4 '-halogen-containing nucleotide and nucleoside therapeutic compositions and uses related thereto

Abstract

Halogen-containing nucleotide and nucleoside therapeutic compositions and related uses thereof are disclosed. In certain embodiments, the disclosure relates to the treatment or prevention of viral infections. Such viral infections may comprise a tapiviridae, a bunyaviridae, an arenaviridae, a coronaviridae, a flaviviridae, a picornaviridae, eastern equine encephalitis, western equine encephalitis, and Venezuela equine encephalitis (EEE, WEE, and VEE, respectively), Chikungunya fever (CHIK), Ebola, influenza, RSV, and Zika viral infections.

Description

[0001] This application is a divisional application of the Chinese invention patent application with the application date of March 7, 2019, application number 201980030574.4, and invention name “Nucleotide and nucleoside therapeutic compositions containing 4′-halogen and related uses thereof”.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to U.S. Provisional Patent Application No. 62 / 639,725, filed on March 7, 2018, and entitled “4′-HALOGEN CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO,” the entire disclosure of which is incorporated herein by reference.

[0004] Government Support Statement

[0005] This invention was made with government support under Grant Nos. HDTRA1-13-C-0072 and HDTRA1-15-C-0075 awarded by the Defense Threat Reduction Agency and Grant No. HHSN272201500008C awarded by the National Institute of Allergy and Infectious Diseases. The government has certain rights in this invention. Technical Field

[0006] The present disclosure relates to halogen-containing nucleotide and nucleoside therapeutic compositions and related uses thereof. In certain embodiments, the present disclosure relates to the treatment or prevention of viral infections, such as Togaviridae, Bunyaviridae, Arenaviridae, Coronaviridae, Flaviviridae, Picornaviridae, Eastern Equine Encephalitis, Western Equine Encephalitis, and Venezuelan Equine Encephalitis (EEE, WEE, and VEE, respectively), Chikungunya (CHIK), Ebola, influenza, RSV, and Zika virus infections. Background Art

[0007] The causative agents of Eastern, Western, and Venezuelan equine encephalitis (EEE, WEE, and VEE, respectively), as well as Chikungunya (CHIK), are vector-borne viruses (Togaviridae, Alphavirus) that can be transmitted to humans through mosquito bites. Equine encephalitis virus is a CDC Category B pathogen, while CHIK virus is a Category C pathogen. There is considerable concern about the use of virulent strains of VEE virus delivered by aerosol as biological weapons against combat personnel. Animal studies have shown that infection with VEE virus through aerosol exposure rapidly leads to widespread brain infection with high mortality and morbidity. See Roy et al., "Pathogenesis of aerosolized Eastern equine encephalitis virus infection in guinea pigs," Virol J, 2009, 6:170.

[0008] What is needed are new compounds and treatments for viral infections. The compounds and methods disclosed herein meet these needs.

[0009] The citation of references herein is not an admission that prior art is available. Summary of the Invention

[0010] The present disclosure relates to nucleotide and nucleoside therapeutic compositions containing halogens (e.g., 4′-halogens) and related uses thereof. Comprising nucleosides optionally conjugated to phosphorus oxides or salts thereof, prodrugs or conjugated compounds comprising amino acid esters, lipids or sphingolipids or salts thereof, or derivatives thereof linked to nucleotides or nucleosides by phosphorus oxides. In certain embodiments, the present disclosure relates to a compound having formula A,

[0011]

[0012] or a pharmaceutically acceptable salt, derivative or prodrug thereof, as defined herein.

[0013] In certain embodiments, the present disclosure contemplates derivatives of the compounds disclosed herein, such as derivatives containing one or more substituents that are the same or different.

[0014] In certain embodiments, the present disclosure contemplates pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a compound disclosed herein. In certain embodiments, the pharmaceutical composition is in the form of a tablet, capsule, pill, or aqueous buffer (such as saline or phosphate buffer).

[0015] In certain embodiments, the disclosed pharmaceutical compositions may include a compound disclosed herein and a propellant. In certain embodiments, the propellant is an aerosol propellant, such as compressed air, ethanol, nitrogen, carbon dioxide, nitrous oxide, hydrofluoroalkane (HFA), 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane, or a combination thereof.

[0016] In certain embodiments, the present disclosure contemplates a pressurized or non-pressurized container comprising a compound or pharmaceutical composition as described herein. In certain embodiments, the container is a manual pump sprayer, an inhaler, a metered dose inhaler, a dry powder inhaler, a nebulizer, a vibrating mesh nebulizer, a jet nebulizer, or an ultrasonic nebulizer.

[0017] In certain embodiments, the present disclosure relates to methods of increasing the bioavailability for treating or preventing viral infection, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutical composition disclosed herein.

[0018] In certain embodiments, the present disclosure relates to a method for treating or preventing a viral infection, comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutical composition disclosed herein. In certain embodiments, the viral infection is a Togaviridae, Bunyaviridae, Arenaviridae, Coronaviridae, Flaviviridae, Picornaviridae, Zika virus infection, Eastern Equine Encephalitis, Western Equine Encephalitis, and Venezuelan Equine Encephalitis (EEE, WEE, and VEE, respectively), Chikungunya (CHIK), Ebola, influenza, and RSV.

[0019] In certain embodiments, the compound or pharmaceutical composition is administered orally, intravenously, or via the lungs (ie, pulmonary administration).

[0020] In certain embodiments, the disclosure relates to the use of a compound described herein in the production of a medicament for treating or preventing a viral infection, such as Eastern equine encephalitis, Western equine encephalitis, and Venezuelan equine encephalitis (EEE, WEE, and VEE, respectively), Chikungunya (CHIK), Ebola, influenza, RSV, or Zika virus infection.

[0021] In certain embodiments, the present disclosure relates to methods of preparing the compounds disclosed herein by combining the starting materials and reagents disclosed herein under conditions that form the compounds.

[0022] Additional advantages will be set forth in part in the following description and, in part, will be obvious from the description, or may be learned by practice of the aspects described below. The advantages described below will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It should be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The stability of EIDD-02749 in methanol is shown.

[0024] Figure 2 The stability of EIDD-02749 in water is shown.

[0025] Figure 3 The stability of EIDD-02749 in 0.1 N HCl is shown.

[0026] Figure 4 The stability of EIDD-02749 in PBS at pH 7.4 is shown.

[0027] Figure 5 The stability of EIDD-02749 in pH 9 buffer is shown.

[0028] Figure 6 Shown are triphosphate concentrations in Huh-7 cells incubated with EIDD-02749 or the prodrug.

[0029] Figure 7 Shown are triphosphate concentrations in Vero cells incubated with EIDD-02749 or the prodrug.

[0030] Figure 8 Shown are plasma PK profiles from CD-1 mice receiving a single dose of EIDD-02749 at 50, 150, and 500 mg / kg orally (PO) or 10 mg / kg intraperitoneally (ip).

[0031] Figure 9 Shown are body weight changes of AG129 mice dosed once daily (QD) with 10, 30, and 100 mg / kg EIDD-02749 for 10 days. DETAILED DESCRIPTION

[0032] Before describing the present disclosure in more detail, it should be understood that the present disclosure is not limited to the specific embodiments described and, as such, may of course vary. It should also be understood that the terminology used herein is for the purpose of describing specific embodiments only and is not intended to be limiting, as the scope of the present disclosure will be limited only by the appended claims.

[0033] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice and testing of this disclosure, preferred methods and materials are now described.

[0034] All publications and patents cited in this specification are incorporated herein by reference as if each individual publication or patent was specifically and individually indicated to be incorporated by reference, and are incorporated herein by reference to disclose and describe the methods and / or materials in connection with the cited publications. Citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of prior disclosure. Further, the publication dates provided may be different from the actual publication dates, which may need to be independently confirmed.

[0035] As will be apparent to those skilled in the art after reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features that can be readily separated or combined with the features of any of the other several embodiments without departing from the scope or spirit of the disclosure. Any recited method can be carried out in the order of events recited or in any other order that is logically possible.

[0036] Unless otherwise indicated, the embodiments of the present disclosure will employ techniques of medicine, organic chemistry, biochemistry, molecular biology, pharmacology, etc., which are within the skill of the art and are fully explained in the literature.

[0037] The present disclosure relates to 4′-halogen-containing nucleotides and nucleoside therapeutic compositions and related uses thereof. In certain embodiments, the present disclosure relates to nucleosides optionally conjugated to phosphorus oxide or its salts. In certain embodiments, the present disclosure relates to conjugated compounds comprising amino acid esters, lipids or sphingolipids or their salts, or derivatives thereof linked to nucleotides or nucleosides by phosphorus oxide. In certain embodiments, the present disclosure contemplates pharmaceutical compositions comprising these compounds for the treatment of infectious diseases, viral infections, and cancer.

[0038] In certain embodiments, the present disclosure relates to phosphorus oxide prodrugs of 4'-halogen-containing nucleosides for treating positive-sense and negative-sense RNA viral infections by targeting virally encoded RNA-dependent RNA polymerases (RdRp). The present disclosure also provides general uses of lipids and sphingolipids for the delivery of nucleoside analogs for the treatment of infectious diseases and cancer.

[0039] In certain embodiments, the present disclosure relates to conjugated compounds comprising sphingolipids or salts thereof or derivatives thereof linked to nucleotides or nucleosides by phosphorus oxide. In certain embodiments, the phosphorus oxide is phosphate, phosphonate, polyphosphate or polyphosphonate, wherein the phosphate in the phosphate, phosphonate or polyphosphate or polyphosphonate is optionally a phosphorothioate or phosphoramidate. In certain embodiments, the lipid or sphingolipid is covalently bonded to the phosphorus oxide via an amino group or a hydroxyl group.

[0040] Nucleotides or nucleosides include heterocycles containing two or more nitrogen heteroatoms, wherein the substituted heterocycle is optionally substituted with one or more of the same or different alkyl, halogen, or cycloalkyl groups.

[0041] In certain embodiments, the sphingolipid is a saturated or unsaturated 2-aminoalkyl or 2-aminooctadecane optionally substituted with one or more substituents. In certain embodiments, the sphingolipid derivative is a saturated or unsaturated 2-aminooctadecane-3-ol optionally substituted with one or more substituents. In certain embodiments, the sphingolipid derivative is a saturated or unsaturated 2-aminooctadecane-3,5-diol optionally substituted with one or more substituents.

[0042] In certain embodiments, the present disclosure contemplates pharmaceutical compositions comprising any of the compounds disclosed herein and a pharmaceutically acceptable excipient. In certain embodiments, the pharmaceutical composition is in the form of a pill, capsule, tablet, or saline buffer solution containing a carbohydrate. In certain embodiments, the composition may contain a second active agent, such as an analgesic, anti-inflammatory, nonsteroidal anti-inflammatory, antiviral, antibiotic, or anticancer agent.

[0043] In certain embodiments, the present disclosure relates to methods of treating or preventing infection, comprising administering to a subject in need thereof an effective amount of a compound disclosed herein. Typically, the subject is diagnosed with or is at risk of developing a viral, bacterial, fungal, protozoal, or parasitic infection.

[0044] In certain embodiments, the present disclosure relates to a method for treating a viral infection, comprising administering an effective amount of a pharmaceutical composition disclosed herein to a subject in need thereof. In certain embodiments, the subject is a mammal, such as a human. In certain embodiments, the subject is diagnosed with a chronic viral infection. In certain embodiments, administration is performed under conditions where the viral infection is no longer detected. In certain embodiments, the subject is diagnosed with an RNA virus, a DNA virus, or a retrovirus. In certain embodiments, the subject is diagnosed with a virus that is a double-stranded DNA virus, a sense single-stranded DNA virus, a double-stranded RNA virus, a sense single-stranded RNA virus, a negative sense single-stranded RNA virus, a sense single-stranded RNA retrovirus, or a double-stranded DNA retrovirus.

[0045] In certain embodiments, the subject is diagnosed with influenza A virus (including subtypes H1N1, H3N2, H7N9 or H5N1), influenza B virus, influenza C virus, rotavirus A, rotavirus B, rotavirus C, rotavirus D, rotavirus E, human coronavirus, SARS coronavirus, MERS coronavirus, human adenovirus (HAdV-1 to 55), 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59. Human papillomavirus (HPV), parvovirus B19, molluscum contagiosum virus, JC virus (JCV), BK virus, Merkel cell polyomavirus, coxsackievirus A, coxsackievirus B, norovirus, rubella virus, lymphocytic choriomeningitis virus (LCMV), chikungunya virus, Eastern equine encephalitis virus (EEEV), Western equine encephalitis virus (WEEV), Venezuelan equine encephalitis virus (VEEV), Ross River virus, Barmah Forest virus, Forest virus, measles virus, mumps virus, respiratory syncytial virus, rinderpest virus, California encephalitis virus, hantavirus, rabies virus, Ebola virus, Marburg virus, herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes lymphotropic virus, roseolovirus or Kaposi's sarcoma-associated herpesvirus, hepatitis A virus, hepatitis B virus, hepatitis D virus, hepatitis E virus or human immunodeficiency virus (HIV).

[0046] In certain embodiments, the subject is diagnosed with influenza A virus (including subtypes H1N1, H3N2, H7N9, H5N1 (low pathogenicity) and H5N1 (high pathogenicity)), influenza B virus, influenza C virus, rotavirus A, rotavirus B, rotavirus C, rotavirus D, rotavirus E, SARS coronavirus, MERS-CoV, human adenovirus (HAdV-1 to 55), 16, Human papillomavirus (HPV) types 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59, parvovirus B19, molluscum contagiosum virus, JC virus (JCV), BK virus, Merkel cell polyomavirus, coxsackievirus A, coxsackievirus B, norovirus, rubella virus, lymphocytic choriomeningitis virus (LCMV), measles virus, mumps virus, respiratory syncytial virus, 1 and Parainfluenza virus type 3, rinderpest virus, chikungunya virus, Eastern equine encephalitis virus (EEEV), Venezuelan equine encephalitis virus (VEEV), Western equine encephalitis virus (WEEV), California encephalitis virus, Rift Valley fever virus (RVFV), Heartland virus, La Crosse virus, Mapula virus, severe fever with thrombocytopenia syndrome virus, Pichinde virus, Hantavirus, Takarib virus, Junin virus, rabies virus, Ebola virus, Marburg virus, adenovirus, herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus, roseola virus, or Kaposi's sarcoma-associated herpesvirus, hepatitis A virus, hepatitis B virus, hepatitis D virus, hepatitis E virus, or human immunodeficiency virus (HIV).

[0047] In certain embodiments, the present disclosure relates to the use of the compounds disclosed herein for the production or manufacture of a medicament for the treatment or prevention of an infectious disease, a viral infection, or cancer.

[0048] In certain embodiments, the present disclosure relates to compounds disclosed herein, or derivatives of any formula.

[0049] Unless otherwise indicated, the embodiments of the present disclosure will employ techniques of medicine, organic chemistry, biochemistry, molecular biology, pharmacology, etc., which are within the skill of the art and are fully explained in the literature.

[0050] In certain embodiments, the pharmaceutical agent, which may be in the form of a salt or prodrug, is administered in the methods disclosed herein by weight. The weight refers to the weight of the recited compound. If in the form of a salt or prodrug, the weight is the molar equivalent of the corresponding salt or prodrug.

[0051] It must be noted that, as used in the specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. In this specification and the following claims, reference will be made to a number of terms, which will be defined to have the following meanings unless a contrary intention is apparent.

[0052] Before describing various embodiments, the following definitions are provided and should be used unless otherwise indicated.

[0053] As used herein, the term "deuterium" or "D" refers to an isotopic abundance of D relative to H (hydrogen) of at least 50%, at least 75%, or at least 90%.

[0054] As used herein, the term "phosphorus oxide" refers to any type of chemical moiety containing a phosphorus-oxygen (PO or P=O) bond. When used as a linking group in this article, the joined molecule can be bonded to the oxygen or directly bonded to the phosphorus atom. The term is intended to include, but is not limited to, phosphates and phosphonates, in which phosphorus is typically bonded to four oxygens and in which phosphorus is typically bonded to one carbon and three oxygens. "Polyphosphate" generally refers to a phosphate linked together by at least one phosphorus-oxygen-phosphorus (POP) bond. "Polyphosphonate" refers to a polyphosphate containing at least one phosphorus-carbon (CPOP) bond. In addition to containing phosphorus-oxygen bonds, phosphorus oxides can also contain phosphorus-thiol (PS or P=S) bonds and / or phosphorus-amine (PN) bonds, which are referred to as thiophosphates or phosphoramidates, respectively. In phosphorus oxides, the oxygen atom may form a double bond or a single bond or a combination with phosphorus, and the oxygen may be further bonded to other atoms such as carbon, or may exist as an anion in balance with a cation (eg, a metal or a quaternary amine).

[0055] "Subject" refers to any animal, preferably a human patient, livestock, or domestic pet.

[0056] As used herein, the terms "prevent" and "preventing" encompass the prevention of recurrence, spread, or onset. This does not mean that the present disclosure is limited to complete prevention. In some embodiments, onset is delayed, or the severity of the disease is reduced.

[0057] As used herein, the terms "treat" and "treating" are not limited to situations where the subject (e.g., patient) is cured and the disease is eradicated. On the contrary, embodiments of the present disclosure also contemplate treatments that only alleviate symptoms and / or delay disease progression.

[0058] As used herein, the term "in combination with," when used to describe administration with another therapy, means that the agent can be administered before, together with, or after the other therapy, or a combination thereof.

[0059] As used herein, "alkyl" means a straight or branched chain saturated hydrocarbon moiety, such as those containing 1 to 10 carbon atoms. "Higher alkyl" refers to a saturated hydrocarbon having 11 or more carbon atoms. "C6-C 16 ” refers to an alkyl group containing 6 to 16 carbon atoms. Similarly, “C6-C 22 " refers to an alkyl group containing 6 to 22 carbon atoms. Representative saturated straight-chain alkyl groups include methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, etc.; while saturated branched-chain alkyl groups include isopropyl, sec-butyl, isobutyl, tert-butyl, isopentyl, etc.

[0060] As used herein, the term "alkenyl" refers to an unsaturated, straight-chain or branched hydrocarbon moiety containing a double bond. 24 (For example, C2-C 22 、C2-C 20 、C2-C 18 、C2-C 16 、C2-C 14 、C2-C 12 、C2-C 10, C2-C8, C2-C6 or C2-C4) alkenyl is contemplated. Alkenyl groups may contain more than one unsaturated bond. Examples include vinyl, 1-propenyl, 2-propenyl, 1-methylvinyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-Methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl The term "vinyl" refers to a group having the structure -CH=CH2; 1-propenyl refers to a group having the structure -CH=CH-CH3; and 2-propenyl refers to a group having the structure -CH2-CH=CH2. As shown in (Z 1 Z 2 )C=C(Z 3 Z 4) are intended to encompass both E and Z isomers. This may be assumed in formulas where an asymmetric olefin is present, or may be explicitly indicated by the bond notation C=C.

[0061] As used herein, the term "alkynyl" represents a straight or branched chain hydrocarbon moiety containing a triple bond. 24 (For example, C2-C 24 、C2-C 20 、C2-C 18 、C2-C 16 、C2-C 14 、C2-C 12 、C2-C 10 , C2-C8, C2-C6 or C2-C4) alkynyl is contemplated. Alkynyl may contain more than one unsaturated bond. Examples include C2-C6 alkynyl, such as ethynyl, 1-propynyl, 2-propynyl (or propargyl), 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 3-methyl-1-butynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 3-methyl-1-pentynyl, 4-methyl -1-pentynyl, 1-methyl-2-pentynyl, 4-methyl-2-pentynyl, 1-methyl-3-pentynyl, 2-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-4-pentynyl, 3-methyl-4-pentynyl, 1,1-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl and 1-ethyl-1-methyl-2-propynyl.

[0062] Non-aromatic monocyclic or polycyclic alkyl groups are referred to herein as "carbocycles" or "carbocyclyl" groups. Representative saturated carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like; and unsaturated carbocycles include cyclopentenyl and cyclohexenyl, and the like.

[0063] A "heterocarbocycle" or "heterocarbocyclyl" group is a carbocycle containing from one to four heteroatoms independently selected from nitrogen, oxygen, and sulfur, which heteroatoms may be saturated or unsaturated (but not aromatic), monocyclic or polycyclic, and wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized. Heterocarbocycles include morpholinyl, pyrrolidonyl, pyrrolidinyl, piperidinyl, hydantoinyl, valerolactamyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydropyrimidinyl, tetrahydrophenylthio, tetrahydrothiopyranyl, tetrahydropyrimidinyl, tetrahydrophenylthio, tetrahydrothiopyranyl, and the like.

[0064] The term "aryl" refers to an aromatic homocyclic (i.e., hydrocarbon) monocyclic, bicyclic, or tricyclic ring-containing group preferably having 6 to 12 members, such as phenyl, naphthyl, and biphenyl. Phenyl is a preferred aryl group. The term "substituted aryl" refers to an aryl group substituted with one or more groups, preferably selected from alkyl, substituted alkyl, alkenyl (optionally substituted), aryl (optionally substituted), heterocycle (optionally substituted), halogen, hydroxy, alkoxy (optionally substituted), aryloxy (optionally substituted), alkanoyl (optionally substituted), aroyl (optionally substituted), alkyl ester (optionally substituted), aryl ester (optionally substituted), cyano, nitro, amino, substituted amino, amide, lactam, urea, urethane, sulfonyl, and the like, wherein optionally one or more pairs of substituents, taken together with the atoms to which they are bound, form a 3- to 7-membered ring.

[0065] As used herein, "heteroaryl" or "heteroaromatic" refers to an aromatic heterocarbocyclic ring having 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur and containing at least 1 carbon atom, including monocyclic and polycyclic ring systems. Polycyclic ring systems may (but are not required to) contain one or more non-aromatic rings, as long as one of the rings is aromatic. Representative heteroaryl groups are furanyl, benzofuranyl, thiophenyl, benzothiophenyl, pyrrolyl, indolyl, isoindolyl, azaindolyl, pyridyl, quinolyl, isoquinolyl, oxazolyl, isoxazolyl, benzoxazolyl, pyrazolyl, imidazolyl, benzimidazolyl, thiazolyl, benzothiazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, cinnolinyl, phthalazinyl and quinazolinyl. It is contemplated that the use of the term "heteroaryl" includes N-alkylated derivatives such as 1-methylimidazol-5-yl substituents.

[0066] As used herein, "heterocycle" or "heterocyclyl" refers to monocyclic and polycyclic ring systems having 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur and containing at least 1 carbon atom. These monocyclic and polycyclic ring systems can be aromatic, non-aromatic, or a mixture of aromatic and non-aromatic rings. Heterocycle includes heterocarbocycle, heteroaryl, and the like.

[0067] "Alkylthio" refers to an alkyl group as defined above with the indicated number of carbon atoms attached through a sulfur bridge. An example of an alkylthio group is methylthio (ie, -S-CH3).

[0068] "Alkoxy" refers to an alkyl group as defined above with the specified number of carbon atoms attached through an oxygen bridge. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, and sec-pentoxy. Preferred alkoxy groups are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, and tert-butoxy.

[0069] "Alkylamino" refers to an alkyl group as defined above having the indicated number of carbon atoms attached through an amino bridge. An example of an alkylamino group is methylamino (ie, -NH-CH3).

[0070] "Alkanoyl" refers to an alkyl group as defined above having the indicated number of carbon atoms attached through a carbonyl bridge (ie, -(C=O)alkyl).

[0071] "Alkylsulfonyl" refers to an alkyl group as defined above with the specified number of carbon atoms attached through a sulfonyl bridge (i.e., -S(=O)2alkyl), such as methylsulfonyl and the like, and "arylsulfonyl" refers to an aryl group attached through a sulfonyl bridge (i.e., -S(=O)2aryl).

[0072] "Alkylsulfamoyl" refers to an alkyl group as defined above having the indicated number of carbon atoms attached through a sulfamoyl bridge (i.e., -NHS(=O)2alkyl), and "arylsulfamoyl" refers to an aryl group attached through a sulfamoyl bridge (i.e., -NHS(=O)2aryl).

[0073] "Alkylsulfinyl" refers to an alkyl group as defined above having the indicated number of carbon atoms attached through a sulfinyl bridge (ie, -S(=O)alkyl).

[0074] The terms "cycloalkyl" and "cycloalkenyl" refer to mono-, bi-, or tri-isocyclic ring groups having 3 to 15 carbon atoms, fully saturated and partially unsaturated, respectively. The term "cycloalkenyl" encompasses bicyclic and tricyclic ring systems that are not aromatic as a whole but contain aromatic moieties (e.g., fluorene, tetralin, indene, etc.). The rings of polycyclic cycloalkyl groups can be fused, bridged, and / or joined by one or more spirocyclic rings. The terms "substituted cycloalkyl" and "substituted cycloalkenyl" refer to cycloalkyl and cycloalkenyl groups, respectively, substituted with one or more groups, preferably selected from aryl, substituted aryl, heterocycle, substituted heterocycle, carbocycle, substituted carbocycle, halogen, hydroxy, alkoxy (optionally substituted), aryloxy (optionally substituted), alkyl ester (optionally substituted), aryl ester (optionally substituted), alkanoyl (optionally substituted), aroyl (optionally substituted), cyano, nitro, amino, substituted amino, amido, lactam, urea, urethane, sulfonyl, and the like.

[0075] The terms "halogen" and "halo" refer to fluorine, chlorine, bromine and iodine.

[0076] The term "substituted" refers to a molecule in which at least one hydrogen atom is replaced by a substituent. When substituted, one or more of these groups is a "substituent." A molecule can be multiply substituted. In the case of an oxo substituent ("=O"), two hydrogen atoms are replaced. Exemplary substituents within this context can include halogen, hydroxy, alkyl, alkoxy, nitro, cyano, oxo, carbocyclyl, carbocyclylalkyl, heterocarbocyclyl, heterocarbocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, -NRaRb, -NRaC(=O)Rb, -NRaC(=O)NRaNRb, -NRaC(=O)ORb, -NRaS02Rb, -C(=O)Ra, -C(=O)ORa, -C(=O)NRaRb, -OC(=O)NRaRb, -ORa, -SRa, -SORa, -S(=O)2Ra, -OS(=O)2Ra, and -S(=O)2ORa. Ra and Rb in this context may be the same or different and are independently hydrogen, halogen, hydroxy, alkyl, alkoxy, alkyl, amino, alkylamino, dialkylamino, carbocyclyl, carbocyclylalkyl, heterocarbocyclyl, heterocarbocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl.

[0077] As used herein, the term "optionally substituted" means that substitution with another group is optional and thus the designated atom may be unsubstituted. Thus, by using the term "optionally substituted," the disclosure encompasses instances where the group is substituted and instances where it is not substituted.

[0078] Examples of prodrugs that can be used to increase bioavailability include esters, optionally substituted esters, branched esters, optionally substituted branched esters, carbonates, optionally substituted carbonates, carbamates, optionally substituted carbamates, thioesters, optionally substituted thioesters, branched thioesters, optionally substituted branched thioesters, thiocarbonates, optionally substituted thiocarbonates, S-thiocarbonates, optionally substituted S-thiocarbonates, dithiocarbonates, optionally substituted dithiocarbonates, thiocarbamates, optionally substituted thiocarbamates, oxymethoxy carbonyl, optionally substituted oxymethoxycarbonyl, oxymethoxythiocarbonyl, optionally substituted oxymethoxythiocarbonyl, oxymethylcarbonyl, optionally substituted oxymethylcarbonyl, oxymethylthiocarbonyl, optionally substituted oxymethylthiocarbonyl, L-amino acid ester, D-amino acid ester, N-substituted L-amino acid ester, N,N-disubstituted L-amino acid ester, N-substituted D-amino acid ester, N,N-disubstituted D-amino acid ester, sulfenyl, optionally substituted sulfenyl, imidate, optionally substituted imidate, hydrazonate, optionally substituted hydrazonate, oxime, optionally substituted oxime, imidinyl, optionally substituted imidinyl, imidyl, optionally substituted imidyl, aminal, optionally substituted aminal, hemiaminal, optionally substituted hemiaminal, acetal, optionally substituted acetal, hemiacetal, optionally substituted hemiacetal, carbonimidate, optionally substituted carbonimidate, thiocarbonimidate, optionally substituted thiocarbonimidate , carbonimidyl, optionally substituted carbonimidyl, carbamimidate, optionally substituted carbamate, carbamimidyl, optionally substituted carbamate, thioacetal, optionally substituted thioacetal, S-acyl-2-thioethyl, optionally substituted S-acyl-2-thioethyl, bis-(acyloxybenzyl)ester, optionally substituted bis-(acyloxybenzyl)ester, (acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester.

[0079] As used herein, "salts" refer to derivatives of the disclosed compounds wherein the parent compound is modified by preparing acid or base salts thereof. Examples of salts include, but are not limited to, inorganic or organic acid salts of basic residues such as amines, alkylamines, or dialkylamines; alkali metal or organic salts of acidic residues such as carboxylic acids; and the like. In typical embodiments, the salts are conventional non-toxic pharmaceutically acceptable salts comprising quaternary ammonium salts of the parent compound formed with a non-toxic inorganic or organic acid. Preferred salts include those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid, and the like; and salts prepared from organic acids such as acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, pamoic acid, maleic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, p-aminobenzenesulfonic acid, 2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, oxalic acid, isethionic acid, and the like.

[0080] The term "prodrug" refers to an agent that is converted into a biologically active form in vivo. Prodrugs are often useful because, in some cases, they are easier to administer than the parent compound. For example, they can become bioavailable by oral administration, whereas the parent compound is not. Prodrugs can also have improved solubility in pharmaceutical compositions over that of the parent drug. Prodrugs can be converted to the parent drug by various mechanisms, including enzymatic processes and metabolic hydrolysis.

[0081] As used herein, the term "derivative" refers to a structurally similar compound that retains sufficient functional attributes of the identified analog. Derivatives may be structurally similar because they lack one or more atoms and are substituted by one or more substituents, salts in different hydration / oxidation states, for example, replacing a single bond or double bond, replacing a ketone with a hydroxyl group, or because one or more atoms in the molecule are converted, such as, but not limited to, replacing an oxygen atom with a sulfur or nitrogen atom or replacing an amino group with a hydroxyl group, or vice versa. Replacing carbon with nitrogen in an aromatic ring is an expected derivative. The derivative can be a prodrug. Derivatives can be prepared by various synthetic methods or appropriate adaptations presented in chemical literature or as presented in synthesis or organic chemistry textbooks, such as "Advanced Organic Chemistry: Reactions, Mechanisms, and Structure" in March, Wiley Publishing House, 6th edition (2007), Michael B. Smith or "Domino Reactions in Organic Synthesis", Wiley Publishing House (2006), Lutz F. Tietze, the documents of which are incorporated herein by reference.

[0082] Compound

[0083] In certain embodiments, the present disclosure relates to a nucleoside conjugated to a phosphorus moiety, or a pharmaceutically acceptable salt thereof.

[0084] In certain embodiments, the present disclosure relates to compounds of formula I,

[0085]

[0086] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0087] X is CH2, CHMe, CMe2, CHF, CF2 or CD2;

[0088] U is O, S, NH, NR7, CH2, CHF, CF2, CCH2 or CCF2;

[0089] Q is a natural or unnatural nucleobase;

[0090] R 1 Selected from H,

[0091]

[0092]

[0093]

[0094] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0095] Y is O or S;

[0096] Y 1 It's OH, OY 3 or BH3 - M + ;

[0097] Y 2 Is OH or BH3 - M + ;

[0098] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0099] R 2 、R 2′ 、R 3 、R 3′are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0100] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0101] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0102] R 4 is hydrogen or deuterium;

[0103] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0104] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0105] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0106] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0107] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0108] R 7 、R 7′ 、R 8and R 9 can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0109] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0110] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0111] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0112] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0113] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0114] In certain embodiments, the lipid is a fatty alcohol, fatty amine, or fatty thiol derived from essential and / or non-essential fatty acids.

[0115] In certain embodiments, the lipid is an unsaturated, polyunsaturated, omega-unsaturated, or omega-polyunsaturated fatty alcohol, fatty amine, or fatty thiol derived from essential and / or non-essential fatty acids.

[0116] In certain embodiments, the lipid is a fatty alcohol, fatty amine, or fatty thiol derived from essential and non-essential fatty acids in which one or more of the carbon units is substituted with oxygen, nitrogen, or sulfur.

[0117] In certain embodiments, the lipid is an unsaturated, polyunsaturated, omega-unsaturated, or omega-polyunsaturated fatty alcohol, fatty amine, or fatty thiol derived from essential and / or nonessential fatty acids in which one or more of the carbon units is substituted with oxygen, nitrogen, or sulfur.

[0118] In certain embodiments, the lipid is a fatty alcohol, fatty amine, or fatty thiol derived from optionally substituted essential and / or non-essential fatty acids.

[0119] In certain embodiments, the lipid is an unsaturated, polyunsaturated, omega-unsaturated, or omega-polyunsaturated fatty alcohol, fatty amine, or fatty thiol derived from optionally substituted essential and / or non-essential fatty acids.

[0120] In certain embodiments, the lipid is a fatty alcohol, fatty amine, or fatty thiol derived from optionally substituted essential and / or non-essential fatty acids in which one or more of the carbon units are substituted with oxygen, nitrogen, or sulfur.

[0121] In certain embodiments, the lipid is an unsaturated, polyunsaturated, omega-unsaturated, or omega-polyunsaturated fatty alcohol, fatty amine, or fatty thiol derived from essential and / or non-essential fatty acids, one or more of whose carbon units are substituted with oxygen, nitrogen, or sulfur, and optionally substituted.

[0122] In certain embodiments, the lipid is hexadecyloxypropyl.

[0123] In certain embodiments, the lipid is 2-aminohexadecyloxypropyl.

[0124] In certain embodiments, the lipid is 2-aminoeicosyl.

[0125] In certain embodiments, the lipid is 2-benzyloxyhexadecyloxypropyl.

[0126] In certain embodiments, the lipid is lauryl, myristyl, palmityl, stearyl, eicosyl, behenyl, or lignoceryl.

[0127] In certain embodiments, the lipid is a sphingolipid having the formula:

[0128]

[0129] in

[0130] Sphingolipid R 12 is hydrogen, alkyl, C(=O)R 16 、C(=O)OR 16 or C(=O)NHR 16 ;

[0131] Sphingolipid R 13 It is hydrogen, fluorine, OR 16 、OC(=O)R 16 、OC(=O)OR 16 or OC(=O)NHR 16 ;

[0132] Sphingolipid R 14 is a saturated or unsaturated alkyl chain having more than 6 and less than 22 carbons, optionally substituted with one or more halogens or hydroxy groups or a structure having the formula:

[0133]

[0134] wherein n is 8 to 14 or less than or equal to 8 to less than or equal to 14, o is 9 to 15 or less than or equal to 9 to less than or equal to 15, the sum of m and n is 8 to 14 or less than or equal to 8 to less than or equal to 14, and the sum of m and o is 9 to 15 or less than or equal to 9 to less than or equal to 15; or

[0135]

[0136] wherein n is 4 to 10 or less than or equal to 4 to less than or equal to 10, o is 5 to 11 or less than or equal to 5 to less than or equal to 11, the sum of m and n is 4 to 10 or less than or equal to 4 to less than or equal to 10, and the sum of m and o is 5 to 11 or less than or equal to 5 to less than or equal to 11; or

[0137]

[0138] wherein n is 6 to 12, or n is less than or equal to 6 to less than or equal to 12, and the sum of m and n is 6 to 12, or n is less than or equal to 6 to less than or equal to 12;

[0139] Sphingolipid R 15 is OR 16 、OC(=O)R 16 、OC(=O)OR 16 or OC(=O)NHR 16 ;

[0140] Sphingolipid R 16 is hydrogen, cyano, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, or lipid; wherein R 16 Optionally, one or more identical or different R 17 replace; and

[0141] Sphingolipid R 17 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl.

[0142] In certain embodiments, the R 12 is H, methyl, ethyl, propyl, n-butyl, isopropyl, 2-butyl, 1-ethylpropyl, 1-propylbutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, benzyl or phenyl.

[0143] In certain embodiments, the sphingolipid is a sphingolipid having the formula:

[0144]

[0145] in

[0146] Sphingolipid R 12 is hydrogen, hydroxyl, fluorine, OR 16 、OC(=O)R 16 、OC(=O)OR 16 or OC(=O)NHR 16 ;

[0147] Sphingolipid R 13 is hydrogen, hydroxyl, fluorine, OR 16 、OC(=O)R 16 、OC(=O)OR16 or OC(=O)NHR 16 ;

[0148] Sphingolipid R 14 is a saturated or unsaturated alkyl chain having more than 6 and less than 22 carbons, optionally substituted with one or more halogens or a structure having the formula:

[0149]

[0150] wherein n is 8 to 14 or less than or equal to 8 to less than or equal to 14, and the sum of m and n is 8 to 14 or less than or equal to 8 to less than or equal to 14;

[0151] Sphingolipid R 16 is hydrogen, cyano, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, or lipid; wherein R 16 Optionally, one or more identical or different R 17 replace; and

[0152] Sphingolipid R 17 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, ester, formyl, carboxyl, carbamoyl, amino or acyl.

[0153] In certain embodiments, the R 16 is H, methyl, ethyl, propyl, n-butyl, isopropyl, 2-butyl, 1-ethylpropyl, 1-propylbutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or benzyl.

[0154] Suitable sphingolipids include, but are not limited to, sphingosine, ceramide, or sphingomyelin, or 2-aminoalkyl groups optionally substituted with one or more substituents.

[0155] Other suitable sphingolipids include, but are not limited to: 2-aminooctadecane-3,5-diol; (2S,3S,5S)-2-aminooctadecane-3,5-diol; (2S,3R,5S)-2-aminooctadecane-3,5-diol; 2-(methylamino)octadecane-3,5-diol; (2S,3R,5S)-2-(methylamino)octadecane-3,5-diol; 2-(dimethylamino)octadecane-3,5-diol; (2R,3S,5S)-2-(dimethylamino)octadecane-3,5-diol; 1-(pyrrolidin-2-yl)hexadecane-1,3-diol; (1S,3S)-1-( (S)-pyrrolidin-2-yl)hexadecane-1,3-diol; 2-amino-11,11-difluorooctadecane-3,5-diol; (2S,3S,5S)-2-amino-11,11-difluorooctadecane-3,5-diol; 11,11-difluoro-2-(methylamino)octadecane-3,5-diol; (2S,3S,5S)-11,11-difluoro-2-(methylamino)octadecane-3,5-diol; N-((2S,3S,5S)-3,5-dihydroxyoctadecane-2-yl)acetamide; N-((2S,3S,5S)-3,5-dihydroxyoctadecane-2-yl)palmitamide ; 1-(1-aminocyclopropyl)hexadecane-1,3-diol; (1S,3R)-1-(1-aminocyclopropyl)hexadecane-1,3-diol; (1S,3S)-1-(1-aminocyclopropyl)hexadecane-1,3-diol; 2-amino-2-methyloctadecane-3,5-diol; (3S,5S)-2-amino-2-methyloctadecane-3,5-diol; (3S,5R)-2-amino-2-methyloctadecane-3,5-diol; (3S,5S)-2-methyl-2-(methylamino)octadecane-3,5-diol; 2-amino-5-hydroxy-2-methyloctadecane-3-one; (Z )-2-amino-5-hydroxy-2-methyloctadecane-3-one oxime; (2S,3R,5R)-2-amino-6,6-difluorooctadecane-3,5-diol; (2S,3S,5R)-2-amino-6,6-difluorooctadecane-3,5-diol; (2S,3S,5S)-2-amino-6,6-difluorooctadecane-3,5-diol; (2S,3R,5S)-2-amino-6,6-difluorooctadecane-3,5-diol; and (2S,3S,5S)-2-amino-18,18,18-trifluorooctadecane-3,5-diol, which may be optionally substituted with one or more substituents.

[0156] In exemplary embodiments of Formula I, R 1 It is hydrogen,

[0157] In exemplary embodiments of Formula I, X is CH2.

[0158] In exemplary embodiments of Formula I, U is O.

[0159] In exemplary embodiments of Formula I, Q is uracil, cytosine, adenine, and guanine.

[0160] In exemplary embodiments of Formula I, R 2 、R 2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0161] In exemplary embodiments of Formula I, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0162] In exemplary embodiments of Formula I, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0163] In exemplary embodiments of Formula I, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0164] In exemplary embodiments of Formula I, R 8It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0165] In exemplary embodiments of Formula I, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0166] In certain embodiments, the present disclosure relates to compounds of formula II,

[0167]

[0168] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0169] X is CH2, CHMe, CMe2, CHF, CF2 or CD2;

[0170] U is O, S, NH, NR7, CH2, CHF, CF2, CCH2 or CCF2;

[0171] W is N or CR′;

[0172] Z is N or CR”;

[0173] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0174] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0175] R 1 Selected from H,

[0176]

[0177]

[0178]

[0179] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0180] Y is O or S;

[0181] Y 1 It's OH, OY 3 or BH3 - M + ;

[0182] Y 2 Is OH or BH3 - M + ;

[0183] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0184] R 2 、R 2′、R 3 、R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0185] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0186] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0187] R 4 is hydrogen or deuterium;

[0188] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0189] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R10 replace;

[0190] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0191] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0192] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0193] R 7、R 7′ 、R 8 and R 9 can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0194] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0195] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0196] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0197] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0198] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0199] In exemplary embodiments of Formula II, R 1 It is hydrogen,

[0200] In exemplary embodiments of Formula II, X is CH2.

[0201] In exemplary embodiments of Formula II, U is O.

[0202] In exemplary embodiments of Formula II, W is CR'.

[0203] In exemplary embodiments of Formula II, Z is CR".

[0204] In exemplary embodiments of Formula II, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0205] In exemplary embodiments of Formula II, R" is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0206] In exemplary embodiments of Formula II, R 2 、R 2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0207] In exemplary embodiments of Formula II, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0208] In exemplary embodiments of Formula II, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0209] In exemplary embodiments of Formula II, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0210] In exemplary embodiments of Formula II, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0211] In exemplary embodiments of Formula II, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0212] In certain embodiments, the present disclosure relates to compounds of formula III,

[0213]

[0214] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0215] W is N or CR′;

[0216] Z is N or CR”;

[0217] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0218] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0219] R 1 Selected from H,

[0220]

[0221]

[0222]

[0223] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0224] Y is O or S;

[0225] Y 1 It's OH, OY 3 or BH3 - M + ;

[0226] Y2 Is OH or BH3 - M + ;

[0227] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0228] R 2 、R 2′ 、R 3 、R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0229] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0230] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0231] R 4 is hydrogen or deuterium;

[0232] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0233] R 6 、R 6′ 、R 6″ and R 6″′and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0234] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0235] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0236] R9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0237] R 7 、R 7′ 、R 8 and R 9 can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0238] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0239] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0240] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0241] R 11is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0242] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0243] In exemplary embodiments of Formula III, R 1 It is hydrogen,

[0244] In exemplary embodiments of Formula III, W is CR'.

[0245] In exemplary embodiments of Formula III, Z is CR".

[0246] In exemplary embodiments of Formula III, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0247] In exemplary embodiments of Formula III, R" is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0248] In exemplary embodiments of Formula III, R 2 、R 2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0249] In exemplary embodiments of Formula III, R 5are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0250] In exemplary embodiments of Formula III, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0251] In exemplary embodiments of Formula III, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0252] In exemplary embodiments of Formula III, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0253] In exemplary embodiments of Formula III, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0254] In certain embodiments, the present disclosure relates to compounds of formula IV,

[0255]

[0256] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0257] W is N or CR′;

[0258] Z is N or CR”;

[0259] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0260] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0261] R 2 、R 2′ 、R 3 、R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0262] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0263] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0264] R 4 is hydrogen or deuterium;

[0265] R 10is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0266] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0267] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0268] In exemplary embodiments of Formula IV, W is CR'.

[0269] In exemplary embodiments of Formula IV, Z is CR".

[0270] In exemplary embodiments of Formula IV, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0271] In exemplary embodiments of Formula IV, R" is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0272] In exemplary embodiments of Formula IV, R 2 、R 2′ 、R 3 、R3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0273] In certain embodiments, the present disclosure relates to compounds of formula V,

[0274]

[0275] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0276] W is N or CR′;

[0277] Z is N or CR”;

[0278] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0279] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0280] R 2 、R 2′ 、R 3 、R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0281] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0282] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0283] R 4 is hydrogen or deuterium;

[0284] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0285] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0286] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0287] In exemplary embodiments of Formula V, W is CR'.

[0288] In exemplary embodiments of Formula V, Z is CR".

[0289] In exemplary embodiments of Formula V, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0290] In exemplary embodiments of Formula V, R" is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0291] In exemplary embodiments of Formula V, R 2 、R2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0292] In certain embodiments, the present disclosure relates to compounds of formula VI,

[0293]

[0294] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0295] W is N or CR′;

[0296] Z is N or CR”;

[0297] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0298] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0299] R 2 、R 2′ 、R 3 、R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0300] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0301] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0302] R 4 is hydrogen or deuterium;

[0303] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0304] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0305] R 11is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0306] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0307] In exemplary embodiments of Formula VI, W is CR'.

[0308] In exemplary embodiments of Formula VI, Z is CR".

[0309] In exemplary embodiments of Formula VI, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0310] In exemplary embodiments of Formula VI, R" is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0311] In the exemplary embodiment of Formula VI, R 2 、R 2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0312] In the exemplary embodiment of Formula VI, R 6 、R 6′ 、R 6″ and R 6″′ It's all hydrogen.

[0313] In the exemplary embodiment of Formula VI, R 6 、R 6′ and R 6″ is hydrogen, and R 6″′ It's methyl.

[0314] In the exemplary embodiment of Formula VI, R 6 、R6′ and R 6″ is hydrogen, and R 6″′ In the exemplary embodiment of Formula VI, R 6 、R 6″ and R 6″′ is hydrogen, and R 6′ It's methyl.

[0315] In the exemplary embodiment of Formula VI, R 6 、R 6″ and R 6″′ is hydrogen, and R 6′ In the exemplary embodiment of Formula VI, R 6 、R 6″ and R 6″′ is hydrogen, and R 6′ It's fluorine.

[0316] In the exemplary embodiment of Formula VI, R6, R 6″ and R 6″′ is hydrogen, and R 6′ In the exemplary embodiment of Formula VI, R6, R 6″ and R 6″′ is hydrogen, and R 6′ It's chlorine.

[0317] In the exemplary embodiment of Formula VI, R 6 and R 6″ is hydrogen, and R 6′ and R 6″′ It's methyl.

[0318] In the exemplary embodiment of Formula VI, R 6′ 、R 6″ and R 6″′ is hydrogen, and R 6 It's fluorine.

[0319] In the exemplary embodiment of Formula VI, R 6″ is hydrogen, R 6′ and R 6″′ is tert-butyl, and R 6 It's fluorine.

[0320] In certain embodiments, the present disclosure relates to compounds of formula VII,

[0321]

[0322] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0323] X is CH2, CHMe, CMe2, CHF, CF2 or CD2;

[0324] U is O, S, NH, NR7, CH2, CHF, CF2, CCH2 or CCF2;

[0325] Q is a natural or unnatural nucleobase;

[0326] R 1 Selected from H,

[0327]

[0328]

[0329] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0330] Y is O or S;

[0331] Y 1 It's OH, OY 3 or BH3 - M + ;

[0332] Y 2 Is OH or BH3 - M+ ;

[0333] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0334] R 2 、R 2′ 、R 3 、R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0335] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0336] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0337] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0338] R 6 、R 6′ 、R 6″ and R 6″′and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0339] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0340] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0341] R9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0342] R 7 、R 7′ 、R 8 and R 9 can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0343] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0344] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0345] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0346] R 11is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0347] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0348] In exemplary embodiments of Formula VII, R 1 It is hydrogen,

[0349] In exemplary embodiments of Formula VII, X is CH2.

[0350] In exemplary embodiments of Formula VII, U is O.

[0351] In exemplary embodiments of Formula VII, Q is uracil, cytosine, adenine, and guanine.

[0352] In exemplary embodiments of Formula VII, R 2 、R 2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0353] In exemplary embodiments of Formula VII, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0354] In exemplary embodiments of Formula VII, R 6It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0355] In exemplary embodiments of Formula VII, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0356] In exemplary embodiments of Formula VII, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0357] In exemplary embodiments of Formula VII, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0358] In certain embodiments, the present disclosure relates to compounds of formula VIII,

[0359]

[0360] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0361] X is CH2, CHMe, CMe2, CHF, CF2 or CD2;

[0362] U is O, S, NH, NR7, CH2, CHF, CF2, CCH2 or CCF2;

[0363] W is N or CR′;

[0364] Z is N or CR”;

[0365] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0366] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0367] R 1 Selected from H,

[0368]

[0369]

[0370] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0371] Y is O or S;

[0372] Y 1 It's OH, OY 3 or BH3 - M + ;

[0373] Y 2 Is OH or BH3 - M + ;

[0374] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0375] R 2 、R 2′ 、R 3 、R 3′are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0376] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0377] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0378] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0379] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0380] R 7 and R 7′and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0381] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0382] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0383] R 7 、R 7′ 、R 8 and R 9can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0384] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0385] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0386] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0387] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0388] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0389] In exemplary embodiments of Formula VIII, R 1 It is hydrogen,

[0390] In exemplary embodiments of Formula VIII, X is CH2.

[0391] In exemplary embodiments of Formula VIII, U is O.

[0392] In exemplary embodiments of Formula VIII, W is CR'.

[0393] In exemplary embodiments of Formula VIII, Z is CR".

[0394] In exemplary embodiments of Formula VIII, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0395] In exemplary embodiments of Formula VIII, R" is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0396] In exemplary embodiments of Formula VIII, R 2 、R 2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0397] In exemplary embodiments of Formula VIII, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0398] In exemplary embodiments of Formula VIII, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0399] In exemplary embodiments of Formula VIII, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0400] In exemplary embodiments of Formula VIII, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0401] In exemplary embodiments of Formula VIII, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0402] In certain embodiments, the present disclosure relates to compounds of formula IX,

[0403]

[0404] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0405] W is N or CR′;

[0406] Z is N or CR”;

[0407] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0408] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10replace;

[0409] R 1 Selected from H,

[0410]

[0411]

[0412]

[0413] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0414] Y is O or S;

[0415] Y 1 It's OH, OY 3 or BH3 - M + ;

[0416] Y 2 Is OH or BH3 - M + ;

[0417] Y 3is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0418] R 2 、R 2′ 、R 3 、R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0419] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0420] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0421] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0422] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0423] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0424] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0425] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R9 Optionally, one or more identical or different R 10 replace;

[0426] R 7 、R 7′ 、R 8 and R 9 can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0427] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0428] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0429] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0430] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0431] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0432] In exemplary embodiments of Formula IX, R 1 It is hydrogen,

[0433] In exemplary embodiments of Formula IX, W is CR'.

[0434] In exemplary embodiments of Formula IX, Z is CR".

[0435] In exemplary embodiments of Formula IX, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0436] In exemplary embodiments of Formula IX, R" is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0437] In exemplary embodiments of Formula IX, R 2 、R 2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0438] In exemplary embodiments of Formula IX, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0439] In exemplary embodiments of Formula IX, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0440] In exemplary embodiments of Formula IX, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0441] In exemplary embodiments of Formula IX, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0442] In exemplary embodiments of Formula IX, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0443] In certain embodiments, the present disclosure relates to compound X,

[0444]

[0445] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0446] W is N or CR′;

[0447] Z is N or CR”;

[0448] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0449] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0450] R 2 、R 2′ 、R 3 、R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0451] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0452] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0453] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0454] R 11is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0455] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0456] In the exemplary embodiment of Formula X, W is CR'.

[0457] In an exemplary embodiment of Formula X, Z is CR".

[0458] In exemplary embodiments of Formula X, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0459] In exemplary embodiments of Formula X, R″ is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0460] In the exemplary embodiment of Formula X, R 2 、R 2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0461] In certain embodiments, the present disclosure relates to compounds of formula XI,

[0462]

[0463] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0464] W is N or CR′;

[0465] Z is N or CR”;

[0466] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0467] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0468] R 2 、R 2′ 、R 3 、R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0469] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0470] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0471] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0472] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0473] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0474] In exemplary embodiments of Formula XI, W is CR'.

[0475] In exemplary embodiments of Formula XI, Z is CR".

[0476] In exemplary embodiments of Formula XI, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0477] In exemplary embodiments of Formula XI, R" is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0478] In exemplary embodiments of Formula XI, R 2 、R 2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0479] In certain embodiments, the present disclosure relates to compounds of formula XII,

[0480]

[0481] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0482] W is N or CR′;

[0483] Z is N or CR”;

[0484] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0485] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0486] R 2 、R 2′ 、R 3 、R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0487] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0488] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0489] R 6 、R 6′ 、R 6″ and R 6″′and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0490] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0491] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0492] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0493] In exemplary embodiments of Formula XII, W is CR'.

[0494] In exemplary embodiments of Formula XII, Z is CR".

[0495] In exemplary embodiments of Formula XII, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0496] In exemplary embodiments of Formula XII, R″ is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0497] In exemplary embodiments of Formula XII, R 2 、R 2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0498] In exemplary embodiments of Formula XII, R 6 、R 6′ 、R 6″ and R 6″′ It's all hydrogen.

[0499] In exemplary embodiments of Formula XII, R 6 、R 6′ 、R 6″ is hydrogen, and R 6″′ It's methyl.

[0500] In exemplary embodiments of Formula XII, R 6 、R 6′ 、R 6″ is hydrogen, and R 6″′ It's a methoxy group.

[0501] In exemplary embodiments of Formula XII, R 6 、R 6″ and R 6″′ is hydrogen, and R 6′ It's methyl.

[0502] In exemplary embodiments of Formula XII, R 6 、R 6″ and R 6″′ is hydrogen, and R 6′ It's a methoxy group.

[0503] In exemplary embodiments of Formula XII, R6 、R 6″ and R 6″′ is hydrogen, and R 6′ It's fluorine.

[0504] In exemplary embodiments of Formula XII, R 6 、R 6″ and R 6″′ is hydrogen, and R 6′ It is tert-butyl.

[0505] In exemplary embodiments of Formula XII, R 6 、R 6″ and R 6″′ is hydrogen, and R 6′ It's chlorine.

[0506] In exemplary embodiments of Formula XII, R 6 and R 6″ is hydrogen, and R 6′ and R 6″′ It's methyl.

[0507] In exemplary embodiments of Formula XII, R 6′ 、R 6″ and R 6″′ is hydrogen, and R 6 It's fluorine.

[0508] In exemplary embodiments of Formula XII, R 6″ is hydrogen, R 6′ and R 6″′ is tert-butyl, and R 6 It's fluorine.

[0509] In certain embodiments, the present disclosure relates to compounds of formula XIII,

[0510]

[0511] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0512] X is CH2, CHMe, CMe2, CHF, CF2 or CD2;

[0513] U is S, NH, NR7, CH2, CHF, CF2, CCH2 or CCF2;

[0514] W is N or CR′;

[0515] Z is N or CR”;

[0516] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0517] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0518] R 1 Selected from H,

[0519]

[0520]

[0521]

[0522] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0523] Y is O or S;

[0524] Y 1 It's OH, OY 3 or BH3 - M + ;

[0525] Y 2 Is OH or BH3 - M + ;

[0526] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0527] R 2 、R 2′ 、R 3 、R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0528] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0529] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0530] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0531] R 6 、R 6′ 、R 6″ and R 6″′and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0532] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0533] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0534] R9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0535] R 7 、R 7′ 、R 8 and R 9 can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0536] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0537] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0538] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0539] R 11is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0540] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0541] In exemplary embodiments of Formula XIII, R 1 It is hydrogen,

[0542] In exemplary embodiments of Formula XIII, X is CH2.

[0543] In exemplary embodiments of Formula XIII, W is CR'.

[0544] In exemplary embodiments of Formula XIII, Z is CR".

[0545] In exemplary embodiments of Formula XIII, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0546] In exemplary embodiments of Formula XIII, R" is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0547] In exemplary embodiments of Formula XIII, R 2 、R 2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0548] In exemplary embodiments of Formula XIII, R 5are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0549] In exemplary embodiments of Formula XIII, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0550] In exemplary embodiments of Formula XIII, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0551] In exemplary embodiments of Formula XIII, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0552] In exemplary embodiments of Formula XIII, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0553] In certain embodiments, the present disclosure relates to compounds of formula XIV,

[0554]

[0555] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0556] X is CHMe, CMe2, CHF, CF2 or CD2;

[0557] W is N or CR′;

[0558] Z is N or CR”;

[0559] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0560] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0561] R 1 Selected from H,

[0562]

[0563]

[0564]

[0565] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0566] Y is O or S;

[0567] Y 1 It's OH, OY 3 or BH3 - M + ;

[0568] Y 2 Is OH or BH3 - M + ;

[0569] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0570] R 2 、R 2′ 、R 3 、R 3′are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 2 、R 2′ 、R 3 、R 3′ Optionally, one or more identical or different R 10 replace;

[0571] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0572] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0573] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0574] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0575] R 7 and R 7′and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0576] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0577] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0578] R 7 、R 7′ 、R 8 and R 9can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0579] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0580] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0581] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0582] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0583] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0584] In exemplary embodiments of Formula XIV, R 1 It is hydrogen,

[0585] In exemplary embodiments of Formula XIV, W is CR'.

[0586] In exemplary embodiments of Formula XIV, Z is CR".

[0587] In exemplary embodiments of Formula XIV, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0588] In exemplary embodiments of Formula XIV, R" is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0589] In exemplary embodiments of Formula XIV, R 2 、R 2′ 、R 3 、R 3′ are hydrogen, hydroxy, amino, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy, vinyl, ethynyl and chloroethynyl.

[0590] In exemplary embodiments of Formula XIV, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0591] In exemplary embodiments of Formula XIV, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0592] In exemplary embodiments of Formula XIV, R 7It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0593] In exemplary embodiments of Formula XIV, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0594] In exemplary embodiments of Formula XIV, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0595] In certain embodiments, the present disclosure relates to compounds of formula XV,

[0596]

[0597] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0598] W is N or CR′;

[0599] Z is N or CR”;

[0600] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0601] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0602] R1 Selected from H,

[0603]

[0604]

[0605]

[0606] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0607] Y is O or S;

[0608] Y 1 It's OH, OY 3 or BH3 - M + ;

[0609] Y 2 Is OH or BH3 - M + ;

[0610] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3Optionally, one or more identical or different R 10 replace;

[0611] R 2 is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 Optionally, one or more identical or different R 10 replace;

[0612] R 2′ is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2′ Optionally, one or more identical or different R 10 replace;

[0613] R 3 is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 3 Optionally, one or more identical or different R 10 replace;

[0614] R 3′ is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 3′ Optionally, one or more identical or different R 10 replace;

[0615] R 2 and R 2′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0616] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0617] R 5is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0618] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0619] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0620] R 8is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0621] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0622] R 7 、R 7′ 、R 8 and R 9 can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0623] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0624] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0625] R 10is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0626] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0627] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0628] In exemplary embodiments of Formula XV, R 1 It is hydrogen,

[0629] In exemplary embodiments of Formula XV, W is CR'.

[0630] In exemplary embodiments of Formula XV, Z is CR".

[0631] In exemplary embodiments of Formula XV, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0632] In exemplary embodiments of Formula XV, R″ is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0633] In exemplary embodiments of Formula XV, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0634] In exemplary embodiments of Formula XV, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0635] In exemplary embodiments of Formula XV, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0636] In exemplary embodiments of Formula XV, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0637] In exemplary embodiments of Formula XV, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0638] In certain embodiments, the present disclosure relates to compounds of formula XVI,

[0639]

[0640] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0641] W is N or CR′;

[0642] Z is N or CR”;

[0643] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0644] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0645] R 1 Selected from H,

[0646]

[0647]

[0648]

[0649] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0650] Y is O or S;

[0651] Y 1 It's OH, OY 3 or BH3 - M + ;

[0652] Y 2 Is OH or BH3 - M + ;

[0653] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0654] R 3 is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 3Optionally, one or more identical or different R 10 replace;

[0655] R 3′ is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 3′ Optionally, one or more identical or different R 10 replace;

[0656] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0657] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0658] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0659] R 7 and R 7′and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0660] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0661] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0662] R 7 、R 7′ 、R 8 and R 9can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0663] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0664] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0665] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0666] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0667] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0668] In exemplary embodiments of Formula XVI, R 1 It is hydrogen,

[0669] In exemplary embodiments of Formula XVI, W is CR'.

[0670] In exemplary embodiments of Formula XVI, Z is CR".

[0671] In exemplary embodiments of Formula XVI, R' is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0672] In exemplary embodiments of Formula XVI, R″ is H, F, Cl, OH, methyl, hydroxymethyl, fluoromethyl, difluoromethyl, trifluoromethyl, vinyl, ethynyl, or formyl.

[0673] In exemplary embodiments of Formula XVI, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0674] In exemplary embodiments of Formula XVI, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0675] In exemplary embodiments of Formula XVI, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0676] In exemplary embodiments of Formula XVI, R 8It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0677] In exemplary embodiments of Formula XVI, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0678] In certain embodiments, the present disclosure relates to compounds of Formula XVII,

[0679]

[0680] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0681] W is N or CR′;

[0682] Z is N or CR”;

[0683] R′ is deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0684] R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0685] R 1 Selected from H,

[0686]

[0687]

[0688]

[0689] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0690] Y is O or S;

[0691] Y 1 It's OH, OY 3 or BH3 - M + ;

[0692] Y 2 Is OH or BH3 - M + ;

[0693] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0694] R 2 is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2Optionally, one or more identical or different R 10 replace;

[0695] R 3 and R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 3 and R 3′ Optionally, one or more identical or different R 10 replace;

[0696] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0697] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0698] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0699] R 7 and R 7′and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0700] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0701] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0702] R 7 、R 7′ 、R 8 and R 9can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0703] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0704] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0705] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0706] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0707] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0708] In exemplary embodiments of Formula XVII, R 1 It is hydrogen,

[0709] In exemplary embodiments of Formula XVII, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0710] In exemplary embodiments of Formula XVII, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0711] In exemplary embodiments of Formula XVII, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0712] In exemplary embodiments of Formula XVII, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0713] In exemplary embodiments of Formula XVII, R 9It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0714] In certain embodiments, the present disclosure relates to compounds of formula XVIII,

[0715]

[0716] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0717] Z is N or CR”;

[0718] R" is deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0719] R 1 Selected from H,

[0720]

[0721]

[0722]

[0723] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0724] Y is O or S;

[0725] Y 1 It's OH, OY 3 or BH3 - M + ;

[0726] Y 2 Is OH or BH3 - M + ;

[0727] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0728] R 2 is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2Optionally, one or more identical or different R 10 replace;

[0729] R 3 and R 3′ are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 3 and R 3′ Optionally, one or more identical or different R 10 replace;

[0730] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0731] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0732] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0733] R 7 and R 7′and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0734] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0735] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0736] R 7 、R 7′ 、R 8 and R 9can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0737] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0738] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0739] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0740] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0741] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0742] In exemplary embodiments of Formula XVIII, R 1 It is hydrogen,

[0743] In exemplary embodiments of Formula XVIII, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0744] In exemplary embodiments of Formula XVIII, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0745] In exemplary embodiments of Formula XVIII, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0746] In exemplary embodiments of Formula XVIII, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0747] In exemplary embodiments of Formula XVIII, R 9It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0748] In certain embodiments, the present disclosure relates to compounds of formula XIX,

[0749]

[0750] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0751] W is N or CR′;

[0752] Z is N or CR”;

[0753] R′ is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0754] R" is deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace;

[0755] R 1 Selected from H,

[0756]

[0757]

[0758]

[0759] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0760] Y is O or S;

[0761] Y 1 It's OH, OY 3 or BH3 - M + ;

[0762] Y 2 Is OH or BH3 - M + ;

[0763] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0764] R 3 is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 3Optionally, one or more identical or different R 10 replace;

[0765] R 3′ is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 3′ Optionally, one or more identical or different R 10 replace;

[0766] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0767] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0768] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0769] R 7 and R 7′and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0770] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0771] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0772] R 7 、R 7′ 、R 8 and R 9can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0773] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0774] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0775] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0776] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0777] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0778] In exemplary embodiments of Formula XIX, R 1 It is hydrogen,

[0779] In exemplary embodiments of Formula XIX, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0780] In exemplary embodiments of Formula XIX, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0781] In exemplary embodiments of Formula XIX, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0782] In exemplary embodiments of Formula XIX, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0783] In exemplary embodiments of Formula XIX, R 9It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0784] In certain embodiments, the present disclosure relates to compounds of formula XX,

[0785]

[0786] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0787] W is N or CR′;

[0788] R′ is deuterium, chlorine, iodine, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl, or acyl, wherein R′ is optionally replaced by one or more identical or different R 10 replace;

[0789] R 1 Selected from H,

[0790]

[0791]

[0792]

[0793] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0794] Y is O or S;

[0795] Y 1 It's OH, OY 3 or BH3 - M + ;

[0796] Y 2 Is OH or BH3 - M + ;

[0797] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0798] R 3 is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3Optionally, one or more identical or different R 10 replace;

[0799] R 3′ is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 3′ Optionally, one or more identical or different R 10 replace;

[0800] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0801] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0802] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0803] R 7 and R 7′and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0804] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0805] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0806] R 7 、R 7′ 、R 8 and R 9can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0807] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0808] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0809] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0810] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0811] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0812] In the exemplary embodiment of Formula XX, R 1 It is hydrogen,

[0813] In the exemplary embodiment of Formula XX, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0814] In the exemplary embodiment of Formula XX, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0815] In the exemplary embodiment of Formula XX, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0816] In the exemplary embodiment of Formula XX, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0817] In the exemplary embodiment of Formula XX, R 9It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0818] In certain embodiments, the present disclosure relates to compounds of formula XXI,

[0819]

[0820] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0821] R 1 Selected from H,

[0822]

[0823]

[0824] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0825] Y is O or S;

[0826] Y 1 It's OH, OY 3 or BH3 - M + ;

[0827] Y 2 Is OH or BH3 - M + ;

[0828] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0829] R 3 is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 Optionally, one or more identical or different R 10 replace;

[0830] R 3′ is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl, or sulfonyl, wherein R 3′ Optionally, one or more identical or different R 10 replace;

[0831] R 3 and R 3′ can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0832] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0833] R 6 、R 6′ 、R 6″ and R 6″′and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″ ' can each optionally be replaced by one or more identical or different R 10 replace;

[0834] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0835] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0836] R9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0837] R 7 、R 7′ 、R 8 and R 9 can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0838] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0839] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0840] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0841] R 11is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0842] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0843] In exemplary embodiments of Formula XXI, R 1 It is hydrogen,

[0844] In exemplary embodiments of Formula XXI, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0845] In exemplary embodiments of Formula XXI, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0846] In exemplary embodiments of Formula XXI, R 7It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0847] In exemplary embodiments of Formula XXI, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0848] In exemplary embodiments of Formula XXI, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0849] In certain embodiments, the present disclosure relates to compounds of formula XXII,

[0850]

[0851] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0852] R 1 Selected from H,

[0853]

[0854]

[0855]

[0856] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0857] Y is O or S;

[0858] Y 1 It's OH, OY 3 or BH3 - M + ;

[0859] Y 2 Is OH or BH3 - M + ;

[0860] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0861] R 3′ is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3′Optionally, one or more identical or different R 10 replace;

[0862] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0863] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0864] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0865] R 8is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0866] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0867] R 7 、R 7′ 、R 8 and R 9 can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0868] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0869] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0870] R 10is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0871] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0872] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0873] In exemplary embodiments of Formula XXII, R 1 It is hydrogen,

[0874] In exemplary embodiments of Formula XXII, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0875] In exemplary embodiments of Formula XXII, R 6It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0876] In exemplary embodiments of Formula XXII, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0877] In exemplary embodiments of Formula XXII, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0878] In exemplary embodiments of Formula XXII, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0879] In certain embodiments, the present disclosure relates to compounds of formula XXIII,

[0880]

[0881] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0882] R 1 Selected from H,

[0883]

[0884]

[0885]

[0886] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0887] Y is O or S;

[0888] Y 1 It's OH, OY 3 or BH3 - M + ;

[0889] Y 2 Is OH or BH3 - M + ;

[0890] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0891] R 5is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0892] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0893] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0894] R 8is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0895] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0896] R 7 、R 7′ 、R 8 and R 9 can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0897] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0898] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0899] R 10is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0900] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0901] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0902] In exemplary embodiments of Formula XXIII, R 1 It is hydrogen,

[0903] In exemplary embodiments of Formula XXIII, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0904] In exemplary embodiments of Formula XXIII, R 6It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0905] In exemplary embodiments of Formula XXIII, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0906] In exemplary embodiments of Formula XXIII, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0907] In exemplary embodiments of Formula XXIII, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0908] In certain embodiments, the present disclosure relates to compounds of formula XXIV,

[0909]

[0910] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0911] R 1 Selected from H,

[0912]

[0913]

[0914]

[0915] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0916] Y is O or S;

[0917] Y 1 It's OH, OY 3 or BH3 - M + ;

[0918] Y 2 Is OH or BH3 - M + ;

[0919] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0920] R 5is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0921] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0922] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0923] R 8is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0924] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0925] R 7 、R 7′ 、R 8 and R 9 can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0926] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0927] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0928] R 10is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0929] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0930] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0931] In exemplary embodiments of Formula XXIV, R 1 It is hydrogen,

[0932] In exemplary embodiments of Formula XXIV, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0933] In exemplary embodiments of Formula XXIV, R 6It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0934] In exemplary embodiments of Formula XXIV, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0935] In exemplary embodiments of Formula XXIV, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0936] In exemplary embodiments of Formula XXIV, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0937] In certain embodiments, the present disclosure relates to compounds of formula XXV,

[0938]

[0939] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0940] R 1 Selected from

[0941]

[0942]

[0943]

[0944] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0945] Y is O or S;

[0946] Y 1 It's OH, OY 3 or BH3 - M + ;

[0947] Y 2 Is OH or BH3 - M + ;

[0948] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0949] R 5is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0950] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0951] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0952] R 8is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0953] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0954] R 7 、R 7′ 、R 8 and R 9 can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0955] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0956] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0957] R 10is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0958] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0959] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0960] In exemplary embodiments of Formula XXV, R 1 It is hydrogen,

[0961] In exemplary embodiments of Formula XXV, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0962] In exemplary embodiments of Formula XXV, R 6It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0963] In exemplary embodiments of Formula XXV, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0964] In exemplary embodiments of Formula XXV, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0965] In exemplary embodiments of Formula XXV, R 9 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0966] In certain embodiments, the present disclosure relates to compounds of formula XXVI,

[0967]

[0968] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[0969] R 1 Selected from H,

[0970]

[0971]

[0972]

[0973] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[0974] Y is O or S;

[0975] Y 1 It's OH, OY 3 or BH3 - M + ;

[0976] Y 2 Is OH or BH3 - M + ;

[0977] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[0978] R 2is selected from deuterium, C2-C22 alkyl, alkenyl, alkynyl, allenyl, thiol, amino, azido, formyl, acyl, cyano, chlorine, bromine, iodine, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 Optionally, one or more identical or different R 10 replace;

[0979] R 3 is selected from deuterium, C2-C22 alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 and R 3′ Optionally, one or more identical or different R 10 replace;

[0980] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[0981] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′ can each optionally be replaced by one or more identical or different R 10 replace;

[0982] R 7 and R 7′and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace;

[0983] R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace;

[0984] R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace;

[0985] R 7 、R 7′ 、R 8 and R 9can form a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace;

[0986] R 7 and R 7′ can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0987] R 8 and R 9 can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace;

[0988] R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace;

[0989] R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and

[0990] Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

[0991] In exemplary embodiments of Formula XXVI, R 1 It is hydrogen,

[0992] In exemplary embodiments of Formula XXVI, R 5 are lipid, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0993] In exemplary embodiments of Formula XXVI, R 6 It is hydrogen, hydroxy, fluorine, chlorine, amino, lipid, methyl, methoxy, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0994] In exemplary embodiments of Formula XXVI, R 7 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0995] In exemplary embodiments of Formula XXVI, R 8 It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0996] In exemplary embodiments of Formula XXVI, R 9It is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, sec-pentyl, tert-pentyl, neopentyl, 3-pentyl, hexyl, tert-hexyl, 4-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, 2,6-dimethylphenyl, isopropyl alcohol, tert-butanol, N-propylamino, N-isopropylamino, N-tert-butylamino, N,N-dimethylamino, N,N-diethylamino and N,N-dipropylamino.

[0997] In certain embodiments, the present disclosure relates to compounds of formula XXVII,

[0998]

[0999] or a pharmaceutically acceptable salt or physiological salt thereof, wherein

[1000] R 1 Selected from H,

[1001]

[1002]

[1003] optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imide ester, optionally substituted hydrazone ester, optionally substituted oxime, optionally substituted amidino, optionally substituted imide, optionally substituted aminal, optionally substituted hemiaminal, optionally substituted acetal, optionally substituted hemiacetal, optionally substituted carboimidate, optionally substituted thiocarboimidate, optionally substituted carboimidate, optionally substituted carbamate imide ester, optionally substituted carbamate imide, optionally substituted thioacetal, optionally substituted S-acyl-2-thioethyl, optionally substituted bis-(acyloxybenzyl)ester, optionally substituted (acyloxybenzyl)ester, and BAB-ester, wherein R 1 Optionally, one or more identical or different R 10 replace;

[1004] Y is O or S;

[1005] Y 1 It's OH, OY 3 or BH3 - M + ;

[1006] Y 2 Is OH or BH3 - M + ;

[1007] Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace;

[1008] R 3 is selected from deuterium, C2-C22 alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, chlorine, bromine, iodine, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 and R 3′ Optionally, one or more identical or different R 10 replace;

[1009] R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl, or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace;

[1010] R 6 、R 6′ 、R 6″ and R 6″′ and R is independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocyclyl, heterocarbocyclyl, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclyl, heterocarbocyclyl, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano, or lipid, wherein R 6 、R 6′ 、R 6″ and R 6″′can each optionally be replaced by one or more identical or different R 10 replace;

[1011] R 7 and R 7′ and R is independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)amino, carbocycl...

Claims

1. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula I, or a pharmaceutically acceptable salt or physiological salt thereof, wherein X is CH2, CHMe, CMe2, CHF, CF2 or CD2; U is O, S, NH, NR7, CH2, CHF, CF2, CCH2 or CCF2; Q is a natural or unnatural nucleobase; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally substituted sulfenyls, optionally substituted imidates, optionally substituted [0063] The present invention relates to hydrazonates, optionally substituted oximes, optionally substituted imidinyls, optionally substituted imidyls, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carbonimidates, optionally substituted thiocarbonimidates, optionally substituted carbonimidos, optionally substituted carbamimidates, optionally substituted carbamimidyls, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl)esters, optionally substituted (acyloxybenzyl)esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 4 is hydrogen or deuterium; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

2. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula II, or a pharmaceutically acceptable salt or physiological salt thereof, wherein X is CH2, CHMe, CMe2, CHF, CF2 or CD2; U is O, S, NH, NR7, CH2, CHF, CF2, CCH2 or CCF2; W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 4 is hydrogen or deuterium; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

3. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula III, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 4 is hydrogen or deuterium; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

4. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula IV, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 4 is hydrogen or deuterium; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

5. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula V, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 4 is hydrogen or deuterium; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

6. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula VI, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 4 is hydrogen or deuterium; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

7. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula VII, or a pharmaceutically acceptable salt or physiological salt thereof, wherein X is CH2, CHMe, CMe2, CHF, CF2 or CD2; U is O, S, NH, NR7, CH2, CHF, CF2, CCH2 or CCF2; Q is a natural or unnatural nucleobase; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

8. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula VIII, or a pharmaceutically acceptable salt or physiological salt thereof, wherein X is CH2, CHMe, CMe2, CHF, CF2 or CD2; U is O, S, NH, NR7, CH2, CHF, CF2, CCH2 or CCF2; W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

9. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula IX, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

10. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula X, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

11. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XI, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

12. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XII, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

13. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XIII, or a pharmaceutically acceptable salt or physiological salt thereof, wherein X is CH2, CHMe, CMe2, CHF, CF2 or CD2; U is S, NH, NR7, CH2, CHF, CF2, CCH2 or CCF2; W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

14. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XIV, or a pharmaceutically acceptable salt or physiological salt thereof, wherein X is CHMe, CMe2, CHF, CF2 or CD2; W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 , R 2 '、R 3 , R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 , R 2 '、R 3 , R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

15. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XV, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclic, carbocyclic, heterocarbocyclic, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 Optionally, one or more identical or different R 10 replace; R 2 ' is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclic, carbocyclic, heterocarbocyclic, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 'optionally replaced by one or more identical or different R 10 replace; R 3 is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 Optionally, one or more identical or different R 10 replace; R 3 ' is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclic, carbocyclic, heterocarbocyclic, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 'optionally replaced by one or more identical or different R 10 replace; R 2 and R 2 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

16. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XVI, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 3 is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 Optionally, one or more identical or different R 10 replace; R 3 ' is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclic, carbocyclic, heterocarbocyclic, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 'optionally replaced by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

17. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XVII, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; Z is N or CR"; R' is deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is hydrogen, deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 Optionally, one or more identical or different R 10 replace; R 3 and R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 and R 3 'optionally replaced by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

18. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XVIII, or a pharmaceutically acceptable salt or physiological salt thereof, wherein Z is N or CR"; R" is deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 Optionally, one or more identical or different R 10 replace; R 3 and R 3 ' are each independently selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 and R 3 'optionally replaced by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

19. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XIX, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; Z is N or CR"; R' is hydrogen, deuterium, halogen, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R" is deuterium, halogen, hydroxy, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R" is optionally replaced by one or more identical or different R 10 replace; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 3 is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 Optionally, one or more identical or different R 10 replace; R 3 ' is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclic, carbocyclic, heterocarbocyclic, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 'optionally replaced by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

20. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XX, or a pharmaceutically acceptable salt or physiological salt thereof, wherein W is N or CR'; R' is deuterium, chlorine, iodine, hydroxyl, amino, thiol, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocarbocyclyl, cycloalkyl, heterocyclyl or acyl, wherein R' is optionally replaced by one or more identical or different R 10 replace; R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 3 is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclic, carbocyclic, heterocarbocyclic, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 Optionally, one or more identical or different R 10 replace; R 3 ' is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclic, carbocyclic, heterocarbocyclic, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 'optionally replaced by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

21. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XXI, or a pharmaceutically acceptable salt or physiological salt thereof, wherein R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 3 is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 Optionally, one or more identical or different R 10 replace; R 3 ' is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclic, carbocyclic, heterocarbocyclic, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 'optionally replaced by one or more identical or different R 10 replace; R 3 and R 3 ' can form a ring with the carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

22. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XXII, or a pharmaceutically acceptable salt or physiological salt thereof, wherein R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 3 ' is selected from deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclic, carbocyclic, heterocarbocyclic, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 'optionally replaced by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

23. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XXIII, or a pharmaceutically acceptable salt or physiological salt thereof, wherein R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

24. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XXIV, or a pharmaceutically acceptable salt or physiological salt thereof, wherein R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

25. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XXV, or a pharmaceutically acceptable salt or physiological salt thereof, wherein R 1 Selected from optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

26. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XXVI, or a pharmaceutically acceptable salt or physiological salt thereof, wherein R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 is selected from deuterium, C2-C22 alkyl, alkenyl, alkynyl, allenyl, thiol, amino, azido, formyl, acyl, cyano, chlorine, bromine, iodine, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 Optionally, one or more identical or different R 10 replace; R 3 is selected from deuterium, C2-C22 alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 and R 3 'optionally replaced by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

27. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XXVII, or a pharmaceutically acceptable salt or physiological salt thereof, wherein R 1 Selected from H. optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 2 Is OH or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 3 is selected from deuterium, C2-C22 alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, chlorine, bromine, iodine, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 and R 3 'optionally replaced by one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

28. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula XXVIII, or a pharmaceutically acceptable salt or physiological salt thereof, wherein R 1 Selected from optionally substituted esters, optionally substituted branched esters, optionally substituted carbonates, optionally substituted carbamates, optionally substituted thioesters, optionally substituted branched thioesters, optionally substituted thiocarbonates, optionally substituted S-thiocarbonates, optionally substituted dithiocarbonates, optionally substituted thiocarbamates, optionally substituted oxymethoxycarbonyls, optionally substituted oxymethoxythiocarbonyls, optionally substituted oxymethylcarbonyls, optionally substituted oxymethylthiocarbonyls, L-amino acid esters, D-amino acid esters, N-substituted L-amino acid esters, N,N-disubstituted L-amino acid esters, N-substituted D-amino acid esters, N,N-disubstituted D-amino acid esters, optionally optionally substituted sulfenyl, optionally substituted imido esters, optionally substituted hydrazone esters, optionally substituted oximes, optionally substituted amidinos, optionally substituted imidos, optionally substituted aminals, optionally substituted hemiaminals, optionally substituted acetals, optionally substituted hemiacetals, optionally substituted carboimido esters, optionally substituted thiocarboimido esters, optionally substituted carboimidos, optionally substituted carbamic acid imide esters, optionally substituted carbamic acid imide, optionally substituted thioacetals, optionally substituted S-acyl-2-thioethyls, optionally substituted bis-(acyloxybenzyl) esters, optionally substituted (acyloxybenzyl) esters, and BAB-esters, wherein R 1 Optionally, one or more identical or different R 10 replace; Y is O or S; Y 1 It's OH, OY 3 or BH3 - M + ; Y 3 is an aryl, heteroaryl or heterocyclic group, wherein Y 3 Optionally, one or more identical or different R 10 replace; R 2 is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 2 Optionally, one or more identical or different R 10 replace; R 3 is selected from hydrogen, deuterium, alkyl, alkenyl, alkynyl, allenyl, alkoxy, hydroxy, thiol, amino, azido, formyl, acyl, cyano, halogen, aryl, heteroaryl, heterocyclyl, carbocyclyl, heterocarbocyclyl, sulfinyl, sulfamoyl or sulfonyl, wherein R 3 Optionally, one or more identical or different R 10 replace; R 5 is hydrogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, allenyl or lipid, wherein R 5 Optionally, one or more identical or different R 10 replace; R 6 , R 6 '、R 6 ” and R 6 ” and ” are each independently selected from hydrogen, deuterium, hydroxy, amino, azido, thiol, acyl, formyl, halogen, nitro, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, sulfinyl, sulfamoyl, sulfonyl, allenyl, cyano or lipid, wherein R 6 , R 6 '、R 6 ” and R 6 "' can each optionally be replaced by one or more identical or different R 10 replace; R 7 and R 7 ' are each independently selected from hydrogen, deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyl, heterocarbocyclyl, aryloxy, heteroaryloxy, heterocyclyl, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 7 Optionally, one or more identical or different R 10 replace; R 8 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 8 Optionally, one or more identical or different R 10 replace; R 9 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 9 Optionally, one or more identical or different R 10 replace; R 7 , R 7 '、R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached and the amino group attached to the α-carbon, wherein the ring is optionally surrounded by one or more identical or different R 10 replace; R 7 and R 7 ' can form a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 8 and R 9 capable of forming a ring with the α-carbon to which it is attached, wherein the ring is optionally substituted by one or more identical or different R 10 replace; R 10 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro or carbonyl, wherein R 10 Optionally, one or more identical or different R 11 replace; R 11 is deuterium, hydroxy, azido, thiol, amino, cyano, halogen, alkyl, alkenyl, alkynyl, carbocyclyl, heterocarbocyclyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, carbocyclyloxy, heterocarbocyclyloxy, aryloxy, heteroaryloxy, heterocyclyloxy, cycloalkyloxy, cycloalkenyloxy, alkylamino, (alkyl)2amino, carbocyclylamino, heterocarbocyclylamino, arylamino, heteroarylamino, heterocyclylamino, cycloalkylamino, cycloalkenylamino, alkylthio, carbocyclylthio, heterocarbocyclylthio, arylthio, heteroarylthio, heterocyclylthio, cycloalkylthio, cycloalkenylthio, allenyl, sulfinyl, sulfamoyl, sulfonyl, lipid, nitro, or carbonyl; and Lipids are C 11 -C 22 Higher alkyl, C 11 -C 22 Higher alkoxy groups, polyethylene glycol, or aryl groups substituted with alkyl groups, or lipids as described herein.

29. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

30. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

31. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

32. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

33. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

34. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

35. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

36. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

37. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

38. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

39. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

40. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

41. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

42. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

43. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

44. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

45. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

46. ​​A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

47. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

48. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

49. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

50. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

51. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

52. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

53. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

54. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

55. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

56. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

57. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

58. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

59. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

60. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

61. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

62. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

63. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

64. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

65. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

66. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

67. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

68. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

69. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

70. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

71. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

72. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

73. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

74. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

75. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

76. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

77. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

78. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

79. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

80. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

81. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

82. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

83. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

84. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

85. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

86. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

87. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

88. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

89. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

90. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

91. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

92. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

93. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

94. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

95. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

96. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

97. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

98. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

99. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

100. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

101. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

102. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

103. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

104. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

105. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

106. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

107. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

108. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

109. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

110. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

111. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

112. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

113. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

114. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

115. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

116. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

117. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

118. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

119. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

120. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

121. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

122. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

123. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

124. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

125. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

126. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

127. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

128. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

129. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

130. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

131. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

132. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

133. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

134. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

135. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

136. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

137. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

138. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

139. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

140. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

141. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

142. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

143. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

144. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

145. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

146. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

147. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

148. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

149. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

150. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

151. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

152. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

153. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

154. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

155. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

156. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

157. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

158. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

159. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

160. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

161. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

162. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

163. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

164. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

165. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

166. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

167. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

168. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

169. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

170. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

171. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

172. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

173. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

174. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

175. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

176. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

177. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

178. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

179. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

180. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

181. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

182. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

183. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

184. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

185. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

186. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

187. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

188. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

189. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

190. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

191. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

192. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

193. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

194. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

195. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

196. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

197. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

198. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

199. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

200. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

201. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound having the following structure: or a pharmaceutically acceptable salt or physiological salt thereof.

202. The pharmaceutical composition of any one of claims 1 to 201, further comprising a propellant.

203. The pharmaceutical composition of claim 202, wherein the propellant is compressed air, ethanol, nitrogen, carbon dioxide, nitrous oxide, hydrofluoroalkane (HFA), 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane, or a combination thereof.

204. A pressurized container comprising a pharmaceutical composition according to any one of claims 1 to 201.

205. The container of claim 204, which is a manual pump sprayer, an inhaler, a metered dose inhaler, a dry powder inhaler, a nebulizer, a vibrating mesh nebulizer, a jet nebulizer, or an ultrasonic nebulizer.

206. A method of treating or preventing a viral infection, the method comprising administering to a subject in need thereof an effective amount of a compound according to any one of claims 1 to 201.

207. The method of claim 206, wherein the viral infection is of the Togaviridae family.

208. The method of claim 207, wherein the virus is selected from Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Chikungunya virus, and Ross River virus.

209. The method of claim 206, wherein the viral infection is of the Coronaviridae family.

210. The method of claim 209, wherein the viral infection is human coronavirus, SARS coronavirus, and MERS coronavirus.

211. The method of claim 206, wherein the viral infection is with an Orthomyxoviridae virus.

212. The method of claim 211, wherein the viral infection is influenza A virus and influenza B virus.

213. The method of claim 206, wherein the viral infection is Pneumoviridae.

214. The method of claim 213, wherein the viral infection is RSV.

215. The method of claim 206, wherein the viral infection is Arenaviridae.

216. The method of claim 215, wherein the viral infection is Tacaribe virus, Pichinde virus, Junin virus, Lassafever virus, and Lymphocytic Choriomeningitis virus.

217. The method of claim 206, wherein the viral infection is of the Bunyaviridae family.

218. The method of claim 217, wherein the viral infection is Rift Valley fever virus, Punta Toro virus, LaCrosse virus, Maporal virus, Heartland virus, and Severe Fever Thrombocytopenia Syndrome virus.

219. The method of claim 206, wherein the viral infection is of the Flaviviridae family.

220. The method of claim 219, wherein the viral infection is Zika virus, Dengue virus 1, Dengue virus 2, Dengue virus 3, Dengue virus 4, West Nile virus, Yellow Fever virus, Japanese encephalitis virus, Powassen virus, Usutu virus, and tick-borne encephalitis virus.

221. The method of claim 206, wherein the viral infection is Picornaviridae.

222. The method of claim 221, wherein the viral infection is poliovirus, coxsackievirus, enterovirus.

223. A method of treating or preventing a patient from infection with a human coronavirus, SARS coronavirus, MERS coronavirus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Chikungunya virus, Ross River virus, RSV, influenza A virus, influenza B virus, Tacaribe virus, Pichinde virus, Junin virus, Lassa fever virus, lymphocytic choriomeningitis virus, Rift Valley fever virus, Punta Toro virus, La Crosse virus, Mapula virus, Hinterland virus, and severe fever with thrombocytopenia syndrome virus, poliovirus, Coxsackievirus, norovirus, or enterovirus, the method comprising administering to a patient in need thereof an effective amount of a compound having the following structure: or a pharmaceutically acceptable salt or physiological salt thereof.

224. A method of treating or preventing a viral infection in a patient, the method comprising administering to a patient in need thereof an effective amount of a compound having the structure: or a pharmaceutically acceptable salt or physiological salt thereof.

225. The method of claim 224, wherein the viral infection is of the Togaviridae family.

226. The method of claim 225, wherein the virus is selected from Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Chikungunya virus, and Ross River virus.

227. The method of claim 224, wherein the viral infection is of the Coronaviridae family.

228. The method of claim 227, wherein the viral infection is human coronavirus, SARS coronavirus, and MERS coronavirus.

229. The method of claim 224, wherein the viral infection is with an Orthomyxoviridae virus.

230. The method of claim 229, wherein the viral infection is influenza A virus and influenza B virus.

231. The method of claim 224, wherein the viral infection is Alveoviridae.

232. The method of claim 231, wherein the viral infection is RSV.

233. The method of claim 224, wherein the viral infection is Arenaviridae.

234. The method of claim 233, wherein the viral infection is Tacaribe virus, Pichinde virus, Junin virus, Lassa fever virus, and lymphocytic choriomeningitis virus.

235. The method of claim 224, wherein the viral infection is of the Bunyaviridae family.

236. The method of claim 235, wherein the viral infection is Rift Valley fever virus, Punta Toro virus, La Crosse virus, Mapula virus, Heartland virus, and severe fever with thrombocytopenia syndrome virus.

237. The method of claim 224, wherein the viral infection is of the Picornaviridae family.

238. The method of claim 237, wherein the viral infection is poliovirus, coxsackievirus, enterovirus.

239. A method of treating or preventing a patient from infection with a human coronavirus, SARS coronavirus, MERS coronavirus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Chikungunya virus, Ross River virus, RSV, influenza A virus, influenza B virus, Tacaribe virus, Pichinde virus, Junin virus, Lassa fever virus, lymphocytic choriomeningitis virus, Rift Valley fever virus, Punta Toro virus, La Crosse virus, Mapula virus, Hinterlandia virus, and severe fever with thrombocytopenia syndrome virus, poliovirus, Coxsackievirus, Norovirus, or enterovirus, the method comprising administering to a patient in need thereof an effective amount of a compound having the following structure: or a pharmaceutically acceptable salt or physiological salt thereof.

240. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

241. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

242. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

243. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

244. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

245. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

246. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

247. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

248. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

249. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

250. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

251. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

252. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

253. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

254. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

255. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

256. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

257. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

258. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

259. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

260. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

261. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

262. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

263. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

264. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

265. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

266. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

267. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

268. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

269. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

270. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

271. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

272. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

273. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

274. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

275. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

276. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

277. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

278. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

279. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

280. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

281. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

282. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

283. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

284. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

285. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

286. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

287. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

288. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

289. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

290. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

291. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

292. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

293. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

294. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

295. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

296. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

297. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

298. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

299. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

300. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

301. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

302. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

303. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

304. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

305. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

306. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

307. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

308. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

309. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

310. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

311. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

312. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

313. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

314. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

315. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

316. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

317. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

318. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

319. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

320. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

321. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

322. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

323. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

324. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

325. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

326. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

327. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

328. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

329. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

330. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

331. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

332. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

333. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

334. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

335. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

336. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

337. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

338. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

339. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

340. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

341. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

342. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

343. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

344. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

345. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

346. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

347. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

348. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

349. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

350. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

351. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

352. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

353. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

354. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

355. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

356. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

357. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

358. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

359. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

360. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

361. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

362. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

363. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

364. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

365. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

366. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

367. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

368. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

369. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

370. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

371. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

372. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

373. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

374. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

375. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

376. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

377. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

378. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

379. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

380. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

381. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

382. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

383. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

384. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

385. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

386. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

387. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

388. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

389. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

390. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

391. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

392. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

393. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

394. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

395. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

396. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

397. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

398. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

399. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

400. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

401. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

402. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

403. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

404. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

405. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

406. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

407. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from the group consisting of:

408. The pharmaceutical composition of any one of claims 240 to 407, further comprising a propellant.

409. The pharmaceutical composition of claim 408, wherein the propellant is compressed air, ethanol, nitrogen, carbon dioxide, nitrous oxide, hydrofluoroalkane (HFA), 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane, or a combination thereof.

410. A pressurized container comprising a pharmaceutical composition according to any one of claims 240 to 407.

411. The container of claim 410, which is a manual pump sprayer, an inhaler, a metered dose inhaler, a dry powder inhaler, a nebulizer, a vibrating mesh nebulizer, a jet nebulizer, or an ultrasonic nebulizer.

412. A method of treating or preventing a viral infection, the method comprising administering to a subject in need thereof an effective amount of a compound according to any one of claims 240 to 407.

413. The method of claim 412, wherein the viral infection is of the Togaviridae family.

414. The method of claim 413, wherein the virus is selected from Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Chikungunya virus, and Ross River virus.

415. The method of claim 412, wherein the viral infection is of the Coronaviridae family.

416. The method of claim 415, wherein the viral infection is human coronavirus, SARS coronavirus, and MERS coronavirus.

417. The method of claim 412, wherein the viral infection is with an Orthomyxoviridae virus.

418. The method of claim 417, wherein the viral infection is influenza A virus and influenza B virus.

419. The method of claim 412, wherein the viral infection is Alveoviridae.

420. The method of claim 419, wherein the viral infection is RSV.

421. The method of claim 412, wherein the viral infection is Arenaviridae.

422. The method of claim 421, wherein the viral infection is Takarib virus, Pichinde virus, Junin virus, Lassa fever virus, and lymphocytic choriomeningitis virus.

423. The method of claim 412, wherein the viral infection is of the Bunyaviridae family.

424. The method of claim 423, wherein the viral infection is Rift Valley Fever Virus, Punta Toro Virus, La Crosse Virus, Mapula Virus, Heartland Virus, and Severe Febrile Thrombocytopenia Syndrome Virus.

425. The method of claim 412, wherein the viral infection is of the Flaviviridae family.

426. The method of claim 425, wherein the viral infection is Zika virus, dengue virus type 1, dengue virus type 2, dengue virus type 3, dengue virus type 4, West Nile virus, yellow fever virus, Japanese encephalitis virus, Powassan virus, Usutu virus, and tick-borne encephalitis virus.

427. The method of claim 412, wherein the viral infection is of the Picornaviridae family.

428. The method of claim 427, wherein the viral infection is poliovirus, coxsackievirus, enterovirus.

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