Nucleotide analogs, compositions and uses thereof

Abstract

The present invention relates to compounds of formula (I) or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, and pharmaceutical compositions thereof and their use in the treatment and / or prevention of viral infections. [Formula 1] TIFF2025540292000555.tif6171

Description

[Technical Field]

[0001] The present invention belongs to the pharmaceutical field, and particularly relates to nucleotide analogues for treating and / or preventing viral infections, pharmaceutical compositions containing them, and methods for their preparation and use. [Background technology]

[0002] Nucleotide analogs have been demonstrated as compounds capable of exerting antiviral activity both in vitro and in vivo and have been the subject of extensive research for the treatment of viral infections. Nucleotide analogs are generally therapeutically inactive compounds that are converted by host or viral enzymes into the corresponding active antimetabolites, which can inhibit polymerases involved in viral or cellular proliferation. Activation occurs through a variety of mechanisms, including the addition of one or more phosphate groups and / or in combination with other metabolic processes.

[0003] Effective treatments for the Coronaviridae, Paramyxoviridae, Pneumoviridae, Picornaviridae, Flaviviridae, Filoviridae, Arenaviridae, Orthomyxovirus, and Empox viruses that cause human and animal diseases have not yet been established.

[0004] Therefore, there is a need for further development of new nucleotide analogs for the treatment of viral infections. Summary of the Invention

[0005] The present invention provides novel nucleotide analogs that have high inhibitory activity against viral RNA polymerases (particularly RNA-dependent RNA polymerases), are usable for the treatment of infections with Coronaviridae, Paramyxoviridae, Pneumoviridae, Picornaviridae, Flaviviridae, Filoviridae, Arenaviridae, and Orthomyxoviridae families, have excellent PK properties, and can be used for oral administration, as well as compositions containing the compounds and uses thereof.

[0006] To this end, the present invention adopts the following technical solutions:

[0007] In certain aspects, the present invention relates to compounds of formula (I) or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof. [ka] where: R X is H or OH, R X1 , R X2 and R X3 are independently H, D, halogen, -R a , -C(O)R a , -C(O)OR a , -C(O)NR b R c , -NR b R c , -NR a C(O)R b , -NR a C(O)OR b , -NR a C(O)NR b R c , -OR a , -OC(O)R a , -OC(O)NR b R c , -NR a S(O)2R b , -S(O)NR a , -S(O)R a or -S(O)2R a and Here, each R a , R b and R c are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R b and R c together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; X1 and X2 are independently a bond, O, S, or NH; R1 and R2 are independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; L is CH2, CD2 or CHD; W1 is of formula (A), [ka] where: Y1 is O or S; Z1 is O, NH or S; Z2 is O, NH or S; Z3 is a bond, O, NH or S; m1 is 1, 2, 3, 4, 5 or 6; n1 is 0 or 1, n2 is 0 or 1, Each R3 and R4 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R5 is H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; W2 is of formula (B): [ka] where: Y2 is O, NH or S; Z4 is O, NH or S; Z5 is O, NH or S; Z6 is a bond, O, NH or S; m2 is 0, 1, 2, 3, 4, 5, or 6; n3 is 0 or 1, n4 is 0 or 1, Each R6 and R7 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R8 is H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; or any one of W1 and W2 together with the 3' C atom of the sugar group form -Y3-, where Y3 is O, NH or S; Alternatively, W1 and W2 together with the P atom to which they are attached form -Y4(C(R3R4) p ) forming Y4-, where Y4 is O, NH or S, and p is 2, 3, 4 or 5; Each R is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NRd S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R on the same atom or two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R" until fully deuterated; Each R' is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R d , R e and R f are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R e and R f together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R g , -C(O)R g , -C(O)OR g , -C(O)NR h R j , -NR h R j , -NR g C(O)R h , -NR g C(O)OR h , -NR g C(O)NR h R j , -OR g , -OC(O)R g , -OC(O)NR h R j , -NR g S(O)2R h , -S(O)NR g , -S(O)R g or -S(O)2Rg or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R g , R h and R j are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R h and R j together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated.

[0008] In another aspect, the present invention provides a pharmaceutical composition comprising a compound of the present invention, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate, or solvate thereof, and a pharmaceutically acceptable excipient, and optionally other therapeutic agents.

[0009] In another aspect, the present invention relates to the use of a compound of the present invention, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition of the present invention, in the preparation of a medicament for treating and / or preventing a viral infection.

[0010] In another aspect, the present invention relates to a method for treating and / or preventing a viral infection in a subject, comprising administering to the subject a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant thereof, or a pharmaceutical composition of the present invention.

[0011] In another aspect, the present invention relates to the use of a compound of the present invention, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition of the present invention, in the treatment and / or prevention of a viral infection.

[0012] In more specific embodiments, the viral infection according to the present invention is a Coronaviridae infection, a Paramyxoviridae infection, a Pneumoviridae infection, a Picornaviridae infection, a Flaviviridae infection, a Filoviridae infection, an Arenaviridae infection, an Orthomyxoviridae infection or an Empox infection.

[0013] In more specific embodiments, the coronaviruses described in the present invention are SARS-CoV (Severe Acute Respiratory Syndrome Coronaviruses) and their variants, MERS-CoV (Middle East Respiratory Syndrome Coronaviruses) and their variants, and SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronaviruses 2') and their variants, other human coronaviruses (229E, NL63, OC43, HKU1 or WIV1), zoonotic coronaviruses (PEDV or HKU CoV isolates, e.g., HKU3, HKU5 or HKU9), feline coronaviruses (feline enteric coronavirus (FECV) or feline infectious peritonitis virus (FIPV)) or porcine epidemic diarrhea virus (PEDV). In a more specific embodiment, the coronaviruses described in the present invention are SARS-CoV viruses and their mutants, MERS-CoV viruses and their mutants, and SARS-CoV-2 viruses and their mutants. In a more specific embodiment, the coronaviruses described in the present invention are SARS-CoV-2 viruses and their mutants. In a more specific embodiment, the SARS-CoV-2 virus mutants described in the present invention are Alpha mutants, Beta mutants, Delta mutants, Gamma mutants, or Omicron mutants.

[0014] In a more particular embodiment, the Paramyxoviridae according to the present invention is a parainfluenza virus, a measles virus or a mumps virus.

[0015] In a more specific embodiment, the Pneumoviridae according to the present invention is RSV (respiratory syncytial virus) or human metapneumovirus. In a more specific embodiment, the Pneumoviridae according to the present invention is RSV.

[0016] In a more particular embodiment, the Picornaviridae according to the present invention is an Enterovirus or an Erbovirus.

[0017] In more particular embodiments, the Flaviviridae according to the present invention are dengue virus, yellow fever virus, West Nile virus, Zika virus, Japanese encephalitis virus and hepatitis C.

[0018] In more specific embodiments, the Filoviridae described in the present invention is Ebola virus, Zaire ebola virus, Bundibugio ebola virus, Sudan ebola virus, Tai forest ebola virus, Reston ebola virus or Marburg virus. In more specific embodiments, the Filoviridae described in the present invention is Ebola virus or Marburg virus.

[0019] In a more particular embodiment, the Arenavirus according to the present invention is a Lassa (LASA) virus or a Junín (JUNV) virus.

[0020] In another aspect, the present invention provides a method for inhibiting an RNA polymerase, comprising contacting a virally infected cell with a compound of the present invention, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate, or solvate thereof. In a more specific aspect, the RNA polymerase is an RNA-dependent RNA polymerase.

[0021] Other objects and advantages of the present invention will be readily apparent to those skilled in the art from the following specific embodiments, examples, and claims.

[0022] definition chemical definition Specific functional groups and chemical term definitions are discussed in more detail below.

[0023] When a range of numerical values ​​is given, it is intended that each value and all subranges within the stated range be included. For example, "C 1-6 "Alkyl group" refers to C1, C2, C3, C4, C5, C6, C 1-6 , C 1-5 , C 1-4 , C 1-3 , C 1-2 , C 2-6 , C 2-5 , C 2-4 , C 2-3 , C 3-6 , C 3-5 , C 3-4 , C 4-6 , C 4-5 and C 5-6 Contains an alkyl group.

[0024] "C 1-28 "Alkyl group" refers to a straight or branched chain saturated hydrocarbon group containing 1 to 28 carbon atoms, and "C 1-6 An "alkyl group" is referred to as a "lower alkyl group." In some embodiments, C 1-4 Alkyl groups are particularly preferred. Examples of alkyl groups include, but are not limited to, methyl (C1), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), tert-butyl (C4), sec-butyl (C4), isobutyl (C4), n-pentyl (C5), 3-pentyl (C5), pentyl (C5), neopentyl (C5), 3-methyl-2-butyl (C5), sec-pentyl (C5), and n-hexyl (C6). Whether or not the alkyl group is preceded by "substituted," each alkyl group is independently optionally substituted with, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, and suitable substituents are defined below.

[0025] "C 2-28An "alkenyl group" refers to a straight-chain or branched-chain hydrocarbon group having 2 to 28 carbon atoms and one or more carbon-carbon double bonds (e.g., 1, 2, or 3 carbon-carbon double bonds). The one or more carbon-carbon double bonds can be internal (e.g., a 2-butenyl group) or terminal (e.g., a 1-butenyl group). In some embodiments, C 2-4 It is an alkenyl group. Examples of the alkenyl group include, but are not limited to, vinyl (C2), 1-propenyl (C3), 2-propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), pentenyl (C5), pentadienyl (C5), hexenyl (C6), and the like. Whether or not the alkenyl group is preceded by "substituted," each alkenyl group is independently optionally substituted with, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, and suitable substituents are defined as follows:

[0026] "C 2-28 An "alkynyl group" refers to a straight-chain or branched-chain hydrocarbon group having 2 to 28 carbon atoms and one or more carbon-carbon triple bonds (e.g., 1, 2, or 3 carbon-carbon triple bonds) and optionally one or more carbon-carbon double bonds (e.g., 1, 2, or 3 carbon-carbon double bonds). In some embodiments, preferably, C 2-4 An alkynyl group. In some embodiments, an alkynyl group does not contain a double bond. One or more carbon-carbon triple bonds can be internal (e.g., a 2-butynyl group) or terminal (e.g., a 1-butynyl group). Examples of alkynyl groups include, but are not limited to, ethynyl (C2), 1-propynyl (C3), 2-propynyl (C3), 1-butynyl (C4), 2-butynyl (C4), pentynyl (C5), hexynyl (C6), and the like. Whether or not the alkynyl group is preceded by "substituted," each alkynyl group is independently optionally substituted with, for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, and suitable substituents are defined below.

[0027] "C 1-6"Alkoxy group" refers to the group -OR, where R is a substituted or unsubstituted C 1-6 In some embodiments, preferably C 1-4 An alkoxy group. Specifically, the alkoxy group includes, but is not limited to, a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, a tert-butoxy group, a sec-butoxy group, an n-pentyloxy group, an n-hexyloxy group, and a 1,2-dimethylbutoxy group.

[0028] "Halogenated" or "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br), and iodine (I). In some embodiments, the halogen group is F, Cl, or Br. In some embodiments, the halogen group is F or Cl. In some embodiments, the halogen group is F.

[0029] Therefore, "C 1-6 Halogenated alkyl groups" and "C 1-6 The term "halogenated alkoxy group" refers to the "C alkoxy group" substituted with one or more halogen groups. 1-6 alkyl group" and "C 1-6 In some embodiments, preferably, C 1-4 A halogenated alkyl group, more preferably C 1-2 In some embodiments, preferably C 1-4 A halogenated alkoxy group, more preferably C 1-2 It is a halogenated alkoxy group. Examples of the halogenated alkyl group include, but are not limited to, -CF3, -CH2F, -CHF2, -CHFCH2F, -CH2CHF2, -CF2CF3, -CCl3, -CH2Cl, -CHCl2, 2,2,2-trifluoro-1,1-dimethyl-ethyl, etc. Examples of the halogenated alkoxy group include, but are not limited to, -OCH2F, -OCHF2, -OCF3, etc.

[0030] "C 3-10A "cycloalkyl group" refers to a non-aromatic cyclic hydrocarbon group having 3 to 10 ring carbon atoms and 0 heteroatoms. In some embodiments, preferably, C 3-7 Cycloalkyl groups, particularly preferably C 3-6 is a cycloalkyl group, more preferably C 5-6 Cycloalkyl groups also include ring systems in which the cycloalkyl ring is fused to one or more aryl or heteroaryl groups and the point of attachment is on the cycloalkyl ring, in which case the carbon number continues to refer to the number of carbons in the cycloalkyl system. Examples of the cycloalkyl group include a cyclopropyl group (C3), a cyclopropenyl group (C3), a cyclobutyl group (C4), a cyclobutenyl group (C4), a cyclopentyl group (C5), a cyclopentenyl group (C5), a cyclohexyl group (C6), a cyclohexenyl group (C6), a cyclohexadienyl group (C6), a cycloheptyl group (C7), a cycloheptenyl group (C7), a cycloheptadienyl group (C7), a cycloheptatrienyl group (C7), a cyclooctyl group (C8), a cyclooctenyl group (C8), a bicyclo[2.2.1]heptyl group (C7), a bicyclo[2.2.2]octyl group (C8), a cyclononyl group (C9), a cyclononenyl group (C9), a cyclodecyl group (C 10 ), cyclodecenyl group (C 10 ), octahydro-1H-indenyl group (C9), decahydronaphthyl group (C 10 ), spiro[4.5]decyl group (C 10 Whether or not the cycloalkyl group is preceded by "substituted," each cycloalkyl group is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, where suitable substituents are defined below.

[0031] A "3- to 10-membered heterocyclyl group" refers to a 3- to 10-membered non-aromatic ring system having cyclic carbon atoms and 1 to 4 cycloheteroatoms, each heteroatom being independently selected from chlorine, oxygen, sulfur, boron, phosphorus, and silicon. In heterocyclyl groups containing one or more nitrogen atoms, the point of attachment can be a carbon atom or a nitrogen atom, as long as valence permits. In some embodiments, preferred are 3- to 7-membered heterocyclyl groups that are 3- to 7-membered non-aromatic ring systems having cyclic carbon atoms and 1 to 3 cycloheteroatoms. In some embodiments, particularly preferred are 3- to 6-membered heterocyclyl groups that are 3- to 6-membered non-aromatic ring systems having cyclic carbon atoms and 1 to 3 cycloheteroatoms. More preferred are 5- to 6-membered heterocyclyl groups that are 5- to 6-membered non-aromatic ring systems having cyclic carbon atoms and 1 to 3 cycloheteroatoms. Heterocyclyl groups also include ring systems in which the heterocyclyl ring is fused to one or more cycloalkyl, aryl, or heteroaryl groups, and the point of attachment is on the heterocyclyl ring; in such cases, the number of ring members continues to refer to the number of ring members in the heterocyclyl group ring system. Whether or not the heterocyclyl group is preceded by "substituted," each heterocyclyl group is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, and suitable substituents are defined as follows.

[0032] Examples of 3-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azetidinyl, oxetidinyl, and thiorenyl. Examples of 4-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azetidinyl, oxetidinyl, and thiorenyl. Examples of 5-membered heterocyclyl groups containing one heteroatom include, but are not limited to, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, pyrrolidinyl, dihydropyrrolidinyl, and pyrrolidinyl-2,5-dione. Examples of 5-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, dioxasulfuranyl, oxasulfuranyl, disulfuranyl, and oxazolidin-2-one. Examples of 5-membered heterocyclyl groups containing three heteroatoms include, but are not limited to, triazolinyl, diazolinyl, and thiadiazolinyl. Examples of 6-membered heterocyclyl groups containing one heteroatom include, but are not limited to, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Examples of 6-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, piperazinyl, morpholinyl, dithiocyclohexyl, and dialkyl. Examples of 6-membered heterocyclyl groups containing three heteroatoms include, but are not limited to, hexahydrotriazinanyl. Examples of 7-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azepinanyl, oxepinanyl, and thiopinanyl. Examples of 8-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azacyclooctyl, oxacyclooctyl, and thiocyclooctyl. Examples of 5-membered heterocyclyl groups (also referred to herein as 5,6-bicycloheterocyclyl groups) fused to a C6 aryl ring include, but are not limited to, dihydroindolyl, iso-dihydroindolyl, dihydrobenzofuranyl, dihydrobenzothiophene, benzazolidinone, etc.Examples of 6-membered heterocyclyl groups (also referred to herein as 6,6-bicycloheterocyclyl groups) fused to a C6 aryl group include, but are not limited to, tetrahydroquinolinyl groups, tetrahydroisoquinolinyl groups, and the like.

[0033] "C 6-14 An "aryl group" refers to a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aryl ring system (e.g., having 6, 10, or 14 π electrons shared in a cyclic arrangement) having 6 to 14 annular carbon atoms and 0 heteroatoms. In some embodiments, an aryl group has 6 annular carbon atoms (a "C6 aryl group," e.g., a phenyl group). In some embodiments, an aryl group has 10 annular carbon atoms (a "C 10 In some embodiments, the aryl group has 14 ring carbon atoms ("C 14 In some embodiments, preferably, C 6-10 An aryl group is preferably an aryl group, more preferably a C6 aryl group. An aryl group also includes ring systems in which the aryl group is fused to one or more cycloalkyl or heterocyclyl groups, with the point of attachment being on the aryl group ring; in such cases, the number of carbon atoms continues to refer to the number of carbon atoms in the aryl group ring system. Whether or not an aryl group is preceded by "substituted," each aryl group is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, and suitable substituents are defined below.

[0034] A "5- to 10-membered heteroaryl group" refers to a 5- to 10-membered monocyclic or bicyclic 4n+2 aryl ring system (e.g., having 6 or 10 π-electrons shared in a cyclic arrangement) having cyclic carbon atoms and 1-4 cycloheteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur. In heteroaryl groups containing one or more nitrogen atoms, the point of attachment can be a carbon atom or a nitrogen atom, where valence permits. Bicyclic ring systems of heteroaryl groups can contain one or more heteroatoms in one or both rings. Heteroaryl groups also include ring systems in which the heteroaryl group is fused to one or more cycloalkyl or heterocyclyl groups, and the point of attachment is at the heteroaryl ring; in such cases, the number of carbon atoms continues to refer to the number of carbon atoms in the heteroaryl ring system. In some embodiments, preferred are 5- to 6-membered heteroaryl groups that are 5- to 6-membered monocyclic or bicyclic 4n+2 aryl ring systems containing cyclic carbon atoms and 1-4 heteroatoms. Whether or not the heteroaryl group is preceded by "substituted," each heteroaryl group is independently optionally substituted, for example, with 1 to 5 substituents, 1 to 3 substituents, or 1 substituent, where suitable substituents are defined as follows:

[0035] Examples of 5-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyrrolyl, furanyl, and thienyl. Examples of 5-membered heteroaryl groups containing two heteroatoms include, but are not limited to, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Examples of 5-membered heteroaryl groups containing three heteroatoms include, but are not limited to, triazolyl, oxadiazolyl, and thiadiazolyl. Examples of 5-membered heteroaryl groups containing four heteroatoms include, but are not limited to, tetrazolyl. Examples of 6-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyridyl. Examples of 6-membered heteroaryl groups containing two heteroatoms include, but are not limited to, pyridazinyl, pyrimidinyl, and pyrazinyl. Examples of 6-membered heteroaryl groups containing three or four heteroatoms include, but are not limited to, triazinyl and tetrazinyl, respectively. Examples of 7-membered heteroaryl groups containing one heteroatom include, but are not limited to, azetidinyl, oxetidinyl, and thiocycloheptatrienyl. Examples of 5,6-bicycloheteroaryl groups include, but are not limited to, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothienyl, isobenzothienyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzoxadiazolyl, benzothiazolyl, benzoisothiazolyl, benzothiadiazolyl, indoxazinyl, and purinyl. Examples of 6,6-bicycloheteroaryl groups include, but are not limited to, naphthyridinyl, naphthyridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl.

[0036] Examples of substituents on carbon atoms are halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR aa , -ON(R bb )2, -N(R bb )2, -N(R bb )3+ X - 、-N(OR cc )R bb 、-SH、-SR aa 、-SSR cc 、-C(=O)R aa 、-CO2H、-CHO、-C(OR cc )2、-CO2R aa 、-OC(=O)R aa 、-OCO2R aa 、-C(=O)N(R bb )2、-OC(=O)N(R bb )2、-NR bb C(=O)R aa 、-NR bb CO2R aa 、-NR bb C(=O)N(R bb )2、-C(=NR bb )R aa 、-C(=NR bb )OR aa 、-OC(=NR bb )R aa 、-OC(=NR bb )OR aa 、-C(=NR bb )N(R bb )2、-OC(=NR bb )N(R bb )2、-NR bb C(=NR bb )N(R bb )2、-C(=O)NR bb SO2R aa 、-NR bb SO2R aa 、-SO2N(R bb )2、-SO2R aa 、-SO2OR aa 、-OSO2R aa 、-S(=O)R aa 、-OS(=O)R aa 、-Si(R aa )3、-OSi(R aa )3、-C(=S)N(R bb )2、-C(=O)SR aa 、-C(=S)SR aa 、-SC(=S)SR aa 、-SC(=O)SRaa , -OC(=O)SR aa , -SC(=O)OR aa , -SC(=O)R aa , -P(=O)2R aa , -OP(=O)2R aa , -P(=O)(R aa )2, -OP(=O)(R aa )2, -OP(=O)(OR cc )2, -P(=O)2N(R bb )2, -OP(=O)2N(R bb )2, -P(=O)(NR bb )2, -OP(=O)(NR bb )2, -NR bb P(=O)(OR cc )2, -NR bb P(=O)(NR bb )2, -P(R cc )2, -P(R cc )3, -OP(R cc )2, -OP(R cc )3, -B(R aa )2, -B(OR cc )2, -BR aa (OR cc ), alkyl groups, halogenated alkyl groups, alkenyl groups, alkynyl groups, carbocycle groups, heterocyclyl groups, aryl groups, and heteroaryl groups, wherein each alkyl group, alkenyl group, alkynyl group, carbocycle group, heterocyclyl group, aryl group, and heteroaryl group independently has 0, 1, 2, 3, 4, or 5 R dd or substituted by a group Alternatively, the two geminal hydrogens on a carbon atom can be substituted with the groups =O, =S, =NN(R bb )2, =NNR bb C(=O)R aa , =NNR bb C(=O)OR aa , =NNR bb S(=O)2R aa , =NR bb or =NOR cc is replaced by Each R aaare independently selected from alkyl groups, halogenated alkyl groups, alkenyl groups, alkynyl groups, carbocyclic groups, heterocyclyl groups, aryl groups, and heteroaryl groups, or two R aa groups are joined to form a heterocyclyl or heteroaryl ring, where each alkyl, alkenyl, alkynyl, carbocycle, heterocyclyl, aryl, and heteroaryl group independently has 0, 1, 2, 3, 4, or 5 R dd is substituted by a group, Each R bb are independently hydrogen, -OH, or -OR aa , -N(R cc )2, -CN, -C(=O)R aa , -C(=O)N(R cc )2, -CO2R aa , -SO2R aa , -C(=NR cc ) OR aa , -C(=NR cc )N(R cc )2, -SO2N(R cc )2, -SO2R cc , -SO2OR cc , -SOR aa , -C(=S)N(R cc )2, -C(=O)SR cc , -C(=S)SR cc , -P(=O)2R aa , -P(=O)(R aa )2, -P(=O)2N(R cc )2, -P(=O)(NR cc ) 2, selected from alkyl groups, halogenated alkyl groups, alkenyl groups, alkynyl groups, carbocyclic groups, heterocyclyl groups, aryl groups, and heteroaryl groups, or two R bb groups are joined to form a heterocyclyl or heteroaryl ring, where each alkyl, alkenyl, alkynyl, carbocycle, heterocyclyl, aryl, and heteroaryl group independently has 0, 1, 2, 3, 4, or 5 R dd is substituted by a group, Each R ccare independently selected from hydrogen, alkyl groups, halogenated alkyl groups, alkenyl groups, alkynyl groups, carbocyclic groups, heterocyclyl groups, aryl groups, and heteroaryl groups, or two R cc groups are joined to form a heterocyclyl or heteroaryl ring, where each alkyl, alkenyl, alkynyl, carbocycle, heterocyclyl, aryl, and heteroaryl group independently has 0, 1, 2, 3, 4, or 5 R dd is substituted by a group, Each R dd are independently halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR ee , -ON(R ff )2, -N(R ff )2, , -N(R ff )3 + X - , -N(OR ee )R ff , -SH, -SR ee , -SSR ee , -C(=O)R ee , -CO2H, -CO2R ee , -OC(=O)R ee , -OCO2R ee , -C(=O)N(R ff )2, -OC(=O)N(R ff )2, -NR ff C(=O)R ee , -NR ff CO2R ee , -NR ff C(=O)N(R ff )2, -C(=NR ff ) OR ee , -OC(=NR ff )R ee , -OC(=NR ff ) OR ee , -C(=NR ff )N(R ff )2, -OC(=NR ff )N(R ff )2, -NR ff C(=NR ff )N(R ff )2, -NR ff SO2Ree , -SO2N(R ff )2, -SO2R ee , -SO2OR ee , -OSO2R ee , -S(=O)R ee , -Si(R ee )3, -OSi(R ee )3, -C(=S)N(R ff )2, -C(=O)SR ee , -C(=S)SR ee , -SC(=S)SR ee , -P(=O)2R ee , -P(=O)(R ee )2, -OP(=O)(R ee )2, -OP(=O)(OR ee )2, alkyl groups, halogenated alkyl groups, alkenyl groups, alkynyl groups, carbocyclic groups, heterocyclyl groups, aryl groups, and heteroaryl groups, wherein each alkyl group, alkenyl group, alkynyl group, carbocyclic group, heterocyclyl group, aryl group, and heteroaryl group independently has 0, 1, 2, 3, 4, or 5 R gg substituted by a group or two geminal R dd the substituents may be linked to form =O or =S; Each R ee are independently selected from alkyl groups, halogenated alkyl groups, alkenyl groups, alkynyl groups, carbocyclic groups, aryl groups, heterocyclyl groups, and heteroaryl groups, wherein each alkyl group, alkenyl group, alkynyl group, carbocyclic group, heterocyclyl group, aryl group, and heteroaryl group independently has 0, 1, 2, 3, 4, or 5 R gg is substituted by a group, Each R ff are independently selected from hydrogen, alkyl groups, halogenated alkyl groups, alkenyl groups, alkynyl groups, carbocyclic groups, heterocyclyl groups, aryl groups, and heteroaryl groups, or two R ff groups are joined to form a heterocyclyl or heteroaryl ring, where each alkyl, alkenyl, alkynyl, carbocycle, heterocyclyl, aryl, and heteroaryl group independently has 0, 1, 2, 3, 4, or 5 Rgg is substituted by a group, Each R gg are independently halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OC 1-6 Alkyl group, -ON(C 1-6 alkyl group)2, -N(C 1-6 alkyl group)2, -N(C 1-6 alkyl group)3 + X - , -NH(C 1-6 alkyl group)2 + X - , -NH2(C 1-6 alkyl group) + X - , -NH3 + X - , -N(OC 1-6 alkyl group)(C 1-6 alkyl group), -N(OH)(C 1-6 alkyl group), -NH(OH), -SH, -SC 1-6 Alkyl group, -SS(C 1-6 alkyl group), -C(=O)(C 1-6 alkyl group), -CO2H, -CO2(C 1-6 alkyl group), -OC(=O)(C 1-6 alkyl group), -OCO2(C 1-6 alkyl group), -C(=O)NH2, -C(=O)N(C 1-6 alkyl group)2, -OC(=O)NH(C 1-6 alkyl group), -NHC(=O)(C 1-6 alkyl group), -N(C 1-6 alkyl group)C(=O)(C 1-6 alkyl group), -NHCO2(C 1-6 alkyl group), -NHC(=O)N(C 1-6 alkyl group)2, -NHC(=O)NH(C 1-6 alkyl group), -NHC(=O)NH2, -C(=NH)O(C 1-6 alkyl group), -OC(=NH)(C 1-6 alkyl group), -OC(=NH)OC 1-6 Alkyl group, -C(=NH)N(C 1-6 alkyl group)2, -C(=NH)NH(C 1-6alkyl group), -C(=NH)NH2, -OC(=NH)N(C 1-6 alkyl group)2, -OC(NH)NH(C 1-6 alkyl group), -OC(NH)NH2, -NHC(NH)N(C 1-6 alkyl group), -NHC(=NH)NH, -NHSO(C 1-6 alkyl group), -SO2N(C 1-6 alkyl group)2, -SO2NH(C 1-6 alkyl group), -SO2NH2, -SO2C 1-6 Alkyl group, -SO2OC 1-6 Alkyl group, -OSO2C 1-6 Alkyl group, -SOC 1-6 Alkyl group, -Si(C 1-6 alkyl group)3, -OSi(C 1-6 alkyl group)3, -C(=S)N(C 1-6 alkyl group), C(=S)NH(C 1-6 alkyl group), C(=S)NH2, -C(=O)S(C 1-6 alkyl group), -C(=S)SC 1-6 Alkyl group, -SC(=S)SC 1-6 Alkyl group, -P(=O)2(C 1-6 alkyl group), -P(=O)(C 1-6 alkyl group)2, -OP(=O)(C 1-6 alkyl group)2, -OP(=O)(OC 1-6 alkyl group)2, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C2-C6 alkenyl groups, C2-C6 alkynyl groups, C3-C7 carbocyclic groups, C6-C 10 Aryl groups, C3-C7 heterocyclyl groups, C5-C 10 a heteroaryl group or two geminal R gg The substituents may be linked to form =O or =S, where X - is the counter ion.

[0037] Examples of substituents on nitrogen atoms are hydrogen, -OH, -OR aa , -N(R cc )2, -CN, -C(=O)R aa, -C(=O)N(R cc )2, -CO2R aa , -SO2R aa , -C(=NR bb )R aa , -C(=NR cc ) OR aa , -C(=NR cc )N(R cc )2, -SO2N(R cc )2, -SO2R cc , -SO2OR cc , -SOR aa , -C(=S)N(R cc )2, -C(=O)SR cc , -C(=S)SR cc , -P(=O)2R aa , -P(=O)(R aa )2, -P(=O)2N(R cc )2, -P(=O)(NR cc )2, including but not limited to alkyl groups, halogenated alkyl groups, alkenyl groups, alkynyl groups, carbocyclic groups, heterocyclyl groups, aryl groups, and heteroaryl groups, or two R cc groups are joined to form a heterocyclyl or heteroaryl ring, where each alkyl, alkenyl, alkynyl, carbocycle, heterocyclyl, aryl, and heteroaryl group independently has 0, 1, 2, 3, 4, or 5 R dd substituted by a group and R aa , R bb , R cc and R dd is as described above.

[0038] "Deuterated" or "D" refers to one or more hydrogens in a compound or group being replaced by deuterium, and the deuteration can be mono-, di-, poly-, or fully substituted. The terms "substituted by one or more deuteriums" and "single or multiply substituted" can be used interchangeably.

[0039] "Non-deuterated compound" refers to a compound containing deuterium atoms in a proportion not greater than the natural deuterium isotope content (0.015%).

[0040] The isotopic content of deuterium at the deuterium substitution positions is at least 0.015% greater than the isotopic content of natural deuterium, preferably greater than 30%, more preferably greater than 50%, more preferably greater than 75%, more preferably greater than 95%, and more preferably greater than 99%.

[0041] The term "pharmaceutically acceptable salt" refers to a salt that is, within the scope of sound medical judgment, suitable for contact with the tissues of humans and lower animals without excessive toxicity, irritation, or hypersensitivity, commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known to those skilled in the art. For example, pharmaceutically acceptable salts include those described in detail by Berge et al. in J. Pharmaceutical Sciences (1977) 66:1-19. Pharmaceutically acceptable salts of the compounds of the present invention include salts derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, and malonic acid. Also included are salts formed using methods conventional in the art, such as ion exchange methods. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, gluconate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxyethanesulfonate, lanthanide, thiazolinone ... Pharmaceutically acceptable salts derived from appropriate bases include alkali metal salts, alkaline earth metal salts, ammonium salts, and ammonium salts. + (C 1-4Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Other pharmaceutically acceptable salts include non-toxic ammonium, quaternary ammonium, and amine cations, where appropriate, formed with counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, aryl sulfonates, and the like.

[0042] A "subject" to be administered includes, but is not limited to, a human (i.e., male or female of any age, e.g., a pediatric subject (e.g., infant, child, junior) or an adult subject (e.g., young adult, middle-aged adult, or elderly adult)) and / or a non-human animal, e.g., a mammal, e.g., a primate (e.g., cynomolgus monkey, rhesus monkey), cow, pig, horse, sheep, goat, rodent, cat, and / or dog. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human animal. As used herein, the terms "human," "patient," and "subject" are used interchangeably.

[0043] The terms "disease," "disorder," and "symptom" are used interchangeably herein.

[0044] Unless otherwise specified, the term "treatment" as used herein includes actions taken when a subject is suffering from a particular disease, disorder or condition to reduce the severity of the disease, disorder or condition, or to slow or alleviate the progression of the disease, disorder or condition ("therapeutic treatment"), and actions taken before a subject acquires a particular disease, disorder or condition ("prophylactic treatment").

[0045] "Combination" and related terms refer to simultaneous or sequential administration of therapeutic agents of the invention. For example, a compound of the invention can be administered simultaneously or sequentially with another therapeutic agent in separate unit dosage forms, or simultaneously with another therapeutic agent in a single unit dosage form. DETAILED DESCRIPTION OF THE INVENTION

[0046] compound As used herein, the term "compound of the present invention" refers to a compound represented by the following formula (I) (including subsets of each formula), or a pharmaceutically acceptable salt, hydrate, or solvate thereof:

[0047] In certain embodiments, the present invention relates to compounds of formula (I), or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof. [ka] where: R X is H or OH, R X1 , R X2 and R X3 are independently H, D, halogen, -R a , -C(O)R a , -C(O)OR a , -C(O)NR b R c , -NR b R c , -NR a C(O)R b , -NR a C(O)OR b , -NR a C(O)NR b R c , -OR a , -OC(O)R a , -OC(O)NR b R c , -NR a S(O)2R b , -S(O)NR a , -S(O)R aor -S(O)2R a and Here, each R a , R b and R c are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R b and R c together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; X1 and X2 are independently a bond, O, S, or NH; R1 and R2 are independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; L is CH2, CD2 or CHD; W1 is of formula (A), [ka] where: Y1 is O or S; Z1 is O, NH or S; Z2 is O, NH or S; Z3 is a bond, O, NH or S; m1 is 1, 2, 3, 4, 5 or 6; n1 is 0 or 1, n2 is 0 or 1, Each R3 and R4 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R5 is H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; W2 is of formula (B): [ka] where: Y2 is O, NH or S; Z4 is O, NH or S; Z5 is O, NH or S; Z6 is a bond, O, NH or S; m2 is 0, 1, 2, 3, 4, 5, or 6; n3 is 0 or 1, n4 is 0 or 1, Each R6 and R7 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R8 is H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; or any one of W1 and W2 together with the 3' C atom of the sugar group form -Y3-, where Y3 is O, NH or S; Alternatively, W1 and W2 together with the P atom to which they are attached form -Y4(C(R3R4) p ) forming Y4-, where Y4 is O, NH or S, and p is 2, 3, 4 or 5; Each R is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)Rd , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R on the same atom or two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R" until fully deuterated; Each R' is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 Forms an aryl group or a 5- to 10-membered heteroaryl group, wherein C 3-6Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R d , R e and R f are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R e and R f together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R g , -C(O)R g , -C(O)OR g , -C(O)NR h R j , -NR h R j , -NR g C(O)R h , -NR g C(O)OR h , -NR g C(O)NR h R j , -OR g , -OC(O)R g , -OC(O)NR h R j , -NR g S(O)2R h , -S(O)NRg , -S(O)R g or -S(O)2R g or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R g , R h and R j are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R h and R j together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated.

[0048] R X In certain embodiments, R X is H, and in another embodiment, R X is OH.

[0049] R X1 、R X2 and R X3 In certain embodiments, R X1 / R X2 / R X3 is H, and in another embodiment, R X1 / R X2 / R X3 is D, and in another embodiment, R X1 / R X2 / R X3 is halogen, and in another embodiment, R X1 / R X2 / R X3 -R a and in another embodiment, R X1 / R X2 / R X3 is -C(O)R a and in another embodiment, R X1 / R X2 / R X3 is -C(O)OR a and in another embodiment, R X1 / R X2 / R X3 is -C(O)NR b R c and in another embodiment, R X1 / R X2 / R X3 is -NR b R c and in another embodiment, R X1 / R X2 / R X3 is -NR a C(O)R b and in another embodiment, R X1 / R X2 / R X3 is -NR a C(O)OR b and in another embodiment, R X1 / R X2 / R X3 is -NR a C(O)NR b R cand in another embodiment, R X1 / R X2 / R X3 -OR a and in another embodiment, R X1 / R X2 / R X3 is -OC(O)R a and in another embodiment, R X1 / R X2 / R X3 is -OC(O)NR b R c and in another embodiment, R X1 / R X2 / R X3 is -NR a S(O)2R b and in another embodiment, R X1 / R X2 / R X3 is -S(O)NR a and in another embodiment, R X1 / R X2 / R X3 is -S(O)R a and in another embodiment, R X1 / R X2 / R X3 is -S(O)2R a is.

[0050] In certain specific embodiments, R X1 , R X2 and R X3 are independently H, D, halogen or C 1-6 alkyl group, wherein the C 1-6 The alkyl group is optionally substituted with one or more deuterium atoms until fully deuterated, and in another specific embodiment, R X1 , R X2 and R X3 is independently H, D or halogen, and in another specific embodiment, R X1 , R X2 and R X3 is independently H, D, I, Br, Cl, F, CH3, or CD3; and in another specific embodiment, R X1 , R X2and R X3 is independently H, D, I, or Br, and in another specific embodiment, R X1 , R X2 and R X3 is independently H or D, and in another specific embodiment, R X1 , R X2 and R X3 are independently H or D.

[0051] R a 、R b and R c In certain embodiments, R a / R b / R c is H, and in another embodiment, R a / R b / R c is D, and in another embodiment, R a / R b / R c is C 1-6 In another embodiment, R a / R b / R c is C 1-6 In another embodiment, R a / R b / R c is C 3-6 is a cycloalkyl group, and in another embodiment, R a / R b / R c is a 3- to 7-membered heterocyclyl group, and in another embodiment, R a / R b / R c is C 2-6 alkenyl group, and in another embodiment, R a / R b / R c is C 2-6 In another embodiment, R a / R b / R c is C 6-10 is an aryl group, and in another embodiment, Ra / R b / R c is a 5-10 membered heteroaryl group, and in another embodiment, R b and R c together with the N atom to which they are attached form a 3-7 membered heterocyclyl group, and in another embodiment, R b and R c together with the N atom to which they are attached form a 3-7 membered heterocyclyl group, and in another embodiment, R a / R b / R c Each group defined in is optionally substituted by one or more R.

[0052] In certain specific embodiments, R a , R b and R c independently C 1-6 Alkyl group, C 6-10 In another specific embodiment, R a , R b and R c independently C 1-6 It is an alkyl group.

[0053] X 1 and X 2 In certain embodiments, X 1 is a bond; in other embodiments, X 1 is O; in other embodiments, X 1 is S; and in other embodiments, X 1 is NH.

[0054] In certain embodiments, X2 is a bond; in other embodiments, X2 is O; in other embodiments, X2 is S; and in other embodiments, X2 is NH.

[0055] In certain specific embodiments, X1 and X2 are independently a bond, O, S, or NH; in other specific embodiments, X1 and X2 are independently a bond or O; in other specific embodiments, X1 and X2 are a bond; in other specific embodiments, X1 and X2 are O.

[0056] R 1 and R 2 In certain embodiments, R and R are independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

[0057] In certain specific embodiments, R and R are independently C 1-28 Alkyl group, C 3-6 Cycloalkyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group or C 6-10 an aryl group, wherein said C 1-28 Alkyl group, C 3-6 Cycloalkyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group or C 6-10 The aryl group is optionally substituted by one or more R, and in another specific embodiment, R and R are independently C 1-6 Alkyl group, C 3-6 Cycloalkyl group or C 6-10 an aryl group, wherein said C 1-6 Alkyl group, C 3-6 Cycloalkyl group or C 6-10 The aryl group is optionally substituted by one or more R, and in another specific embodiment, R and R are independently C 1-6alkyl group, wherein the C 1-6 The alkyl group is optionally substituted by one or more R, and in another specific embodiment, R and R are independently C 1-6 In another specific embodiment, R and R are independently C 1-3 In another specific embodiment, R1 and R2 are independently a methyl group, an ethyl group, an isopropyl group, or a tert-butyl group, and in another specific embodiment, R1 and R2 are independently a methyl group, an ethyl group, or an isopropyl group.

[0058] L In certain embodiments, L is CH2, in other embodiments L is CD2, and in other embodiments L is CHD.

[0059] In certain specific embodiments, L is CH2, CD2 or CHD; in other specific embodiments, L is CH2 or CD2; in other specific embodiments, L is CH2.

[0060] W 1 and W 2 In certain embodiments, W1 is independently of formula (A): [ka] where: Y1 is O or S; Z1 is O, NH or S; Z2 is O, NH or S; Z3 is a bond, O, NH or S; m1 is 1, 2, 3, 4, 5 or 6; n1 is 0 or 1, n2 is 0 or 1, Each R3 and R4 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R5 is H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

[0061] In certain embodiments, Y 1 is O; in other embodiments, Y 1 is S.

[0062] In certain specific embodiments, Y 1 is O or S; in other specific embodiments, Y 1 is O.

[0063] In certain embodiments, Z 1 is O; in other embodiments, Z 1 is NH; and in other embodiments, Z 1 is S.

[0064] In certain specific embodiments, Z 1 is O, NH or S; in other specific embodiments, Z 1 is O or S.

[0065] In certain embodiments, Z2 is O; in other embodiments, Z2 is NH; and in other embodiments, Z2 is S.

[0066] In certain specific embodiments, Z2 is O, NH or S; in other specific embodiments, Z2 is O or S.

[0067] In certain embodiments, Z3 is a bond; in other embodiments, Z3 is O; in other embodiments, Z3 is NH; and in other embodiments, Z3 is S.

[0068] In certain specific embodiments, Z3 is a bond, O, NH or S; in other specific embodiments, Z3 is a bond or O.

[0069] In certain embodiments, m1 is 1, in other embodiments, m1 is 2, in other embodiments, m1 is 3, in other embodiments, m1 is 4, in other embodiments, m1 is 5, and in other embodiments, m1 is 6.

[0070] In certain specific embodiments, m1 is 1, 2, 3, 4, 5 or 6; in other specific embodiments, m1 is 1, 2, 3 or 4; in other specific embodiments, m1 is 1, 2 or 3; in other specific embodiments, m1 is 1 or 3.

[0071] In certain embodiments, n1 is 0; in other embodiments, n1 is 1.

[0072] In certain embodiments, n2 is 0; in other embodiments, n2 is 1.

[0073] In certain embodiments, each R and R is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R', and in another specific embodiment, each R3 and R4 is independently selected from H, D, C ... 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl group and the 3- to 7-membered heterocyclyl group are optionally substituted by one or more R', and in another specific embodiment, each R3 and R4 is independently selected from H, D, C, 1-6 Alkyl group, C 3-6a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 3-6 The cycloalkyl group and the 3- to 7-membered heterocyclyl group are optionally substituted by one or more R', and in another specific embodiment, each R and R is independently H, D, a methyl group, a benzyl group, -CHC(O)OCH 11 , [ka] or R3 and R4 together with the C atom to which they are attached form a cyclobutane.

[0074] In certain embodiments, each R5 is independently H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R, and in another specific embodiment, each R is independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R, and in another specific embodiment, each R is independently C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group or C 2-6 an alkynyl group, wherein the C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl groups and C 2-6 The alkynyl group is optionally substituted by one or more R, and in another specific embodiment, each R is independently C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 The cycloalkyl group and the 3- to 7-membered heterocyclyl group are optionally substituted by one or more R, and in another specific embodiment, each R is independently C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 The alkynyl group is optionally substituted by one or more R, and in another specific embodiment, each R is independently C 8-28 Alkyl group or C 8-28alkenyl group, wherein C 8-28 Alkyl groups and C 8-28 The alkenyl group is optionally substituted by one or more R, and in another specific embodiment, each R is independently C 8-28 alkyl group, wherein the C 8-28 The alkyl group is optionally substituted by one or more R, and in another specific embodiment, each R is independently C 8-28 alkenyl group, wherein C 8-28 The alkenyl group is optionally substituted by one or more R, and in another specific embodiment, each R is independently C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl or 5- to 10-membered heteroaryl group is optionally substituted by one or more R, and in another specific embodiment, each R is independently C 6-10 an aryl group, wherein said C 6-10 The aryl group is optionally substituted with one or more R, and in another specific embodiment, each R is independently a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, [ka] n-pentyl group, [ka] Cyclobutane, -CH2(CH2) 10 CH3, -CH2(CH2) 12 CH3, -CH2(CH2) 14 CH3, -CH2(CH2) 16 and in another specific embodiment, each R is independently a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, [ka] n-pentyl group, [ka] and in another specific embodiment, each R5 is independently an isopropyl group, a tert-butyl group, or [ka] and in another specific embodiment, each R5 is independently an isopropyl group or [ka] is.

[0075] In certain embodiments, W1 independently represents [ka] and where: m1 is 1, 2, 3, 4, 5 or 6; Each R3 and R4 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R5 is C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Lipid-like is C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl groups and C 8-28 The alkynyl group is optionally substituted by one or more R; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

[0076] In certain specific embodiments, W1 is [ka] and where R3 and R4 are independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; R5 is independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group or C 2-28 an alkynyl group, wherein the C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl groups and C 2-28 The alkynyl group is optionally substituted by one or more R.

[0077] In another specific embodiment, W1 is [ka] and where R3 and R4 are H; R5 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 It is an alkenyl group.

[0078] In another specific embodiment, W1 is [ka] is.

[0079] In certain specific embodiments, W1 is [ka] and where R3 and R4 are independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; R5 is independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group or C 2-28 an alkynyl group, wherein the C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl groups and C 2-28 The alkynyl group is optionally substituted by one or more R.

[0080] In another specific embodiment, W1 is [ka] and where R3 and R4 are H; R5 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 It is an alkenyl group.

[0081] In another specific embodiment, W1 is [ka] and Preferably, W2 is [ka] is.

[0082] In certain specific embodiments, W1 is [ka] and where m1 is 1, 2, 3 or 4; Each R3 and R4 is independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; R5 is independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group or C 2-28 an alkynyl group, wherein the C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl groups and C 2-28 The alkynyl group is optionally substituted by one or more R.

[0083] In another specific embodiment, W1 is [ka] and where m1 is 1 or 2, R3 and R4 are H; R5 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 It is an alkenyl group.

[0084] In another specific embodiment, W1 is [ka] is.

[0085] In certain specific embodiments, W1 is [ka] and where m1 is 1, 2, 3 or 4; Each R3 and R4 is independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; Lipid-like is C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl groups and C 8-28The alkynyl group is optionally substituted by one or more R.

[0086] In certain specific embodiments, W1 is [ka] and where m1 is 2, 3 or 4; R3 and R4 are independently H or C 1-6 an alkoxy group, wherein 1-6 The alkoxy group is optionally C 6-10 aryl group or 5- to 10-membered heteroaryl group, wherein 6-10 The aryl group or 5- to 10-membered heteroaryl group may optionally be halogen or C 1-6 substituted by one or more groups selected from alkoxy groups, Lipid-like is C 8-28 Alkyl group or C 8-28 It is an alkenyl group.

[0087] In another specific embodiment, W1 is [ka] and In another specific embodiment, W1 is [ka] is.

[0088] In certain specific embodiments, W1 is [ka] and where m1 is 1, 2, 3 or 4; Each R3 and R4 is independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; Lipid-like is C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl groups and C 8-28 The alkynyl group is optionally substituted by one or more R.

[0089] In another specific embodiment, W1 is [ka] and where m1 is 2, 3 or 4; R3 and R4 are H; Lipid-like is C 8-28 It is an alkenyl group.

[0090] In another specific embodiment, W1 is [ka] is.

[0091] In certain specific embodiments, W1 is [ka] and where R3 and R4 are independently H, D, C 1-6 Alkyl group, C1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

[0092] In another specific embodiment, W1 is [ka] and where R3 and R4 are H; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl group or 5- to 10-membered heteroaryl group is optionally C 1-6 Alkyl group or -C(O)OC 1-6 It is substituted with one or more groups selected from alkyl groups.

[0093] In another specific embodiment, W1 is [ka] is.

[0094] In certain specific embodiments, W1 is [ka] is.

[0095] In another specific embodiment, W1 is [ka] is.

[0096] In certain embodiments, W2 is independently of formula (B): [ka] where: Y2 is O, NH or S; Z4 is O, NH or S; Z2 is O, NH or S; Z6 is a bond, O, NH or S; m2 is 0, 1, 2, 3, 4, 5, or 6; n3 is 0 or 1, n4 is 0 or 1, Each R6 and R7 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R8 is H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

[0097] In certain embodiments, Y2 is O; in other embodiments, Y2 is NH; and in other embodiments, Y2 is S.

[0098] In certain specific embodiments, Y2 is O, NH or S, and in other specific embodiments, Y2 is O or NH.

[0099] In certain embodiments, Z 4 is O; in other embodiments, Z 4 is NH; and in other embodiments, Z 4 is S.

[0100] In certain specific embodiments, Z4 is O, NH or S; in other specific embodiments, Z4 is O or S.

[0101] In certain embodiments, Z5 is O; in other embodiments, Z5 is NH; and in other embodiments, Z5 is S.

[0102] In certain specific embodiments, Z5 is O, NH or S; in other specific embodiments, Z5 is O or S.

[0103] In certain embodiments, Z6 is a bond; in other embodiments, Z6 is O; in other embodiments, Z6 is NH; and in other embodiments, Z6 is S.

[0104] In certain specific embodiments, Z6 is a bond, O, NH or S; in other specific embodiments, Z6 is a bond or O.

[0105] In certain embodiments, m2 is 0; in other embodiments, m2 is 1; in other embodiments, m2 is 2; in other embodiments, m2 is 3; in other embodiments, m2 is 4; in other embodiments, m2 is 5; and in other embodiments, m2 is 6.

[0106] In certain specific embodiments, m2 is 0, 1, 2, 3, 4, 5 or 6; in other specific embodiments, m2 is 0, 1, 2, 3 or 4; in other specific embodiments, m2 is 0, 1, 2 or 3; in other specific embodiments, m2 is 0, 1 or 3.

[0107] In certain embodiments, n3 is 0; in other embodiments, n3 is 1.

[0108] In certain embodiments, n4 is 0; in other embodiments, n4 is 1.

[0109] In certain embodiments, each R and R is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R', and in another specific embodiment, each R6 and R7 is independently selected from H, D, C, 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl group and the 3- to 7-membered heterocyclyl group are optionally substituted by one or more R', and in another specific embodiment, each R6 and R7 is independently selected from H, D, C, 1-6 Alkyl group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 3-6 The cycloalkyl group and the 3- to 7-membered heterocyclyl group are optionally substituted by one or more R', and in another specific embodiment, each R and R is independently H, D, a methyl group, a benzyl group, -CHC(O)OCH 11 , [ka] or R6 and R7 together with the C atom to which they are attached form a cyclobutane.

[0110] In certain embodiments, each R is independently H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R, and in another specific embodiment, each R is independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R, and in another specific embodiment, each R is independently C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group or C 2-6 an alkynyl group, wherein the C1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl groups and C 2-6 The alkynyl group is optionally substituted by one or more R, and in another specific embodiment, each R is independently C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 The cycloalkyl group and the 3- to 7-membered heterocyclyl group are optionally substituted by one or more R, and in another specific embodiment, each R is independently C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 The alkynyl group is optionally substituted by one or more R, and in another specific embodiment, each R is independently C 8-28 Alkyl group or C 8-28 alkenyl group, wherein C 8-28 Alkyl groups and C 8-28 The alkenyl group is optionally substituted by one or more R, and in another specific embodiment, each R is independently C 8-28 alkyl group, wherein the C 8-28 The alkyl group is optionally substituted by one or more R, and in another specific embodiment, each R is independently C 8-28 alkenyl group, wherein C 8-28 The alkenyl group is optionally substituted by one or more R, and in another specific embodiment, each R is independently C 6-10 an aryl group or a 5- to 10-membered heteroaryl group,6-10 The aryl or 5- to 10-membered heteroaryl group is optionally substituted by one or more R, and in another specific embodiment, each R is independently C 6-10 an aryl group, wherein said C 6-10 The aryl group is optionally substituted with one or more R, and in another specific embodiment, each R is independently a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, [ka] n-pentyl group, [ka] Cyclobutane, -CH2(CH2) 10 CH3, -CH2(CH2) 12 CH3, -CH2(CH2) 14 CH3, -CH2(CH2) 16 and in another specific embodiment, each R is independently a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, [ka] n-pentyl group, [ka] and in another specific embodiment, each R is independently an isopropyl group, a tert-butyl group, or [ka] and in another specific embodiment, each R8 is independently an isopropyl group or [ka] is.

[0111] In certain embodiments, W2 independently represents [ka] and where: m2 is 1, 2, 3, 4, 5 or 6; Each R6 and R7 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R8 is C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Lipid-like is C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl groups and C 8-28 The alkynyl group is optionally substituted by one or more R; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

[0112] In certain specific embodiments, W2 is [ka] and where R6 and R7 are independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; R8 is independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group or C 2-28 an alkynyl group, wherein the C1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl groups and C 2-28 The alkynyl group is optionally substituted by one or more R.

[0113] In another specific embodiment, W2 is [ka] and where R6 is C 1-6 is an alkyl group and R7 is H, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group, wherein said C 1-6 Alkyl groups and C 3-6 The cycloalkyl group is optionally a phenyl group or -C(O)OC 1-6 substituted with one or more groups selected from alkyl groups, R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 alkenyl group, wherein C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 The alkenyl group may optionally contain one or more C 1-6 It is substituted by an alkoxy group.

[0114] In another specific embodiment, W2 is [ka] and where R6 is C 1-6 alkyl group, wherein the C 1-6 The alkyl group is optionally a phenyl group or -C(O)OC 1-6 substituted with one or more groups selected from alkyl groups, R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 alkenyl group, wherein C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 The alkenyl group may optionally contain one or more C 1-6 It is substituted by an alkoxy group.

[0115] In another specific embodiment, W2 is [ka] and where R6 is C 1-6 alkyl group, wherein the C 1-6 The alkyl group is optionally a phenyl group or -C(O)OC 1-6 substituted with one or more groups selected from alkyl groups, R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 alkenyl group, wherein C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 The alkenyl group may optionally contain one or more C 1-6 It is substituted by an alkoxy group.

[0116] In another specific embodiment, W2 is [ka] and In another specific embodiment, W2 is [ka] is.

[0117] In another specific embodiment, W2 is [ka] is.

[0118] In another specific embodiment, W2 is [ka] is.

[0119] In certain specific embodiments, W2 is [ka] and where R6 and R7 are independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; R8 is independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group or C 2-28 an alkynyl group, wherein the C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl groups and C 2-28 The alkynyl group is optionally substituted by one or more R.

[0120] In another specific embodiment, W2 is [ka] and where R6 and R7 are H; R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 It is an alkenyl group.

[0121] In another specific embodiment, W2 is [ka] is.

[0122] In certain specific embodiments, W2 is [ka] and where R6 and R7 are independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; R8 is independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group or C 2-28 an alkynyl group, wherein the C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl groups and C 2-28 The alkynyl group is optionally substituted by one or more R.

[0123] In another specific embodiment, W2 is [ka] and where R6 and R7 are H; R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 It is an alkenyl group.

[0124] In another specific embodiment, W2 is [ka] is.

[0125] In certain specific embodiments, W2 is [ka] and where m2 is 1, 2, 3 or 4; Each R6 and R7 is independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; R8 is independently C 1-28 Alkyl group, C 1-28Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group or C 2-28 an alkynyl group, wherein the C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl groups and C 2-28 The alkynyl group is optionally substituted by one or more R.

[0126] In another specific embodiment, W2 is [ka] and where R6 and R7 are H; m2 is 1 or 2, R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 It is an alkenyl group.

[0127] In another specific embodiment, W2 is [ka] is.

[0128] In certain specific embodiments, W2 is [ka] and where m2 is 1, 2, 3 or 4; Each R6 and R7 is independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; Lipid-like is C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl groups and C 8-28 The alkynyl group is optionally substituted by one or more R.

[0129] In certain specific embodiments, W2 is [ka] and where m2 is 2, 3, or 4; R6 and R7 are independently H or C 1-6 an alkoxy group, wherein 1-6 The alkoxy group is optionally C 6-10 aryl group or 5- to 10-membered heteroaryl group, wherein 6-10 The aryl group or 5- to 10-membered heteroaryl group may optionally be halogen or C 1-6 substituted by one or more groups selected from alkoxy groups, Lipid-like is C 8-28 Alkyl group or C 8-28 It is an alkenyl group.

[0130] In another specific embodiment, W2 is [ka] and In another specific embodiment, W2 is [ka] is.

[0131] In certain specific embodiments, W2 is [ka] and where m2 is 1, 2, 3 or 4; Each R6 and R7 is independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; Lipid-like is C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl groups and C 8-28 The alkynyl group is optionally substituted by one or more R.

[0132] In another specific embodiment, W2 is [ka] and where R6 and R7 are H; m2 is 2, 3, or 4; Lipid-like is C8-28 It is an alkenyl group.

[0133] In another specific embodiment, W2 is [ka] is.

[0134] In certain specific embodiments, W2 is [ka] and where Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

[0135] In another specific embodiment, W2 is [ka] and where Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl or 5- to 10-membered heteroaryl group may optionally contain one or more C 1-6 It is substituted by an alkyl group.

[0136] In another specific embodiment, W2 is [ka] is.

[0137] In certain specific embodiments, W2 is [ka] and where R6 and R7 are independently H, D, C 1-6 Alkyl group, C1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

[0138] In another specific embodiment, W2 is [ka] and where R6 and R7 are H; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl group or 5- to 10-membered heteroaryl group is optionally C 1-6 Alkyl group or -C(O)OC 1-6 It is substituted with one or more groups selected from alkyl groups.

[0139] In another specific embodiment, W2 is [ka] is.

[0140] In certain specific embodiments, W2 is [ka] [ka] is.

[0141] In another specific embodiment, W2 is [ka] [ka] is.

[0142] In another specific embodiment, W2 is [ka] [ka] is.

[0143] In another specific embodiment, W2 is [ka] [ka] is.

[0144] In certain embodiments, any one of W1 and W2 together with the C atom at position 3 in the sugar group forms -Y3-, where Y3 is O, NH or S; in certain specific embodiments, any one of W1 and W2 together with the C atom at position 3 in the sugar group forms -O-; in another specific embodiment, any one of W1 and W2 together with the C atom at position 3 in the sugar group forms -NH-; in another specific embodiment, any one of W1 and W2 together with the C atom at position 3 in the sugar group forms -S-.

[0145] In another embodiment, W1 and W2 together with the P atom to which they are attached form -Y4(C(R3R4) p)Y4-, where Y4 is O, NH or S, p is 2, 3, 4 or 5, and in certain specific embodiments, W1 and W2 together with the P atom to which they are attached form -O(C(R3R4) p )O—, where p is 2, 3, 4, or 5, and in certain specific embodiments, W1 and W2 together with the P atom to which they are attached form —O(C(R3R4)3)O—.

[0146] R In certain embodiments, R is D, in other embodiments, R is halogen, and in other embodiments, R is -R d and in another embodiment, R is —C(O)R d and in another embodiment, R is —C(O)OR d and in another embodiment, R is —C(O)NR e R f and in another embodiment, R is -NR e R f and in another embodiment, R is -NR d C(O)R e and in another embodiment, R is -NR d C(O)OR e and in another embodiment, R is -NR d C(O)NR e R f and in another embodiment, R is -OR d and in another embodiment, R is —OC(O)R d and in another embodiment, R is —OC(O)NR e R f and in another embodiment, R is -NR d S(O)2R e and in another embodiment, R is -S(O)NR d and in another embodiment, R is —S(O)R d and in another embodiment, R is -S(O)R d and in another embodiment, two R on the same atom or on two adjacent atoms together with the atoms to which they are attached form C3-6 In another embodiment, two R on the same atom or two adjacent atoms together with the atom to which they are attached form a 3-7 membered heterocyclyl group; in another embodiment, two R on the same atom or two adjacent atoms together with the atom to which they are attached form a C 6-10 In another embodiment, two Rs on the same atom or two adjacent atoms together with the atoms to which they are attached form a 5- to 10-membered heteroaryl group; in another embodiment, the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″.

[0147] R’ In certain embodiments, R' is D, in other embodiments, R' is halogen, and in other embodiments, R' is -R d and in another embodiment, R' is -C(O)R d and in another embodiment, R' is -C(O)OR d and in another embodiment, R' is -C(O)NR e R f and in another embodiment, R' is -NR e R f and in another embodiment, R' is -NR d C(O)R e and in another embodiment, R' is -NR d C(O)OR e and in another embodiment, R' is -NR d C(O)NR e R f and in another embodiment, R' is -OR d and in another embodiment, R' is -OC(O)R d and in another embodiment, R' is -OC(O)NR e R f and in another embodiment, R' is -NR d S(O)2R eand in another embodiment, R' is -S(O)NR d and in another embodiment, R' is -S(O)R d and in another embodiment, R' is -S(O)R d and in another embodiment, two R' on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 In another embodiment, two R' on the same atom or two adjacent atoms together with the atom to which they are attached form a 3-7 membered heterocyclyl group; in another embodiment, two R' on the same atom or two adjacent atoms together with the atom to which they are attached form a C 6-10 In another embodiment, two R' on the same atom or two adjacent atoms together with the atom to which they are attached form a 5-10 membered heteroaryl group; in another embodiment, the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″.

[0148] R d 、R e and R f In certain embodiments, R d / R e / R f is H, and in another embodiment, R d / R e / R f is D, and in another embodiment, R d / R e / R f is C 1-6 In another embodiment, R d / R e / R f is C 1-6 In another embodiment, R d / R e / R f is C3-6 is a cycloalkyl group, and in another embodiment, R d / R e / R f is a 3- to 7-membered heterocyclyl group, and in another embodiment, R d / R e / R f is C 2-6 alkenyl group, and in another embodiment, R d / R e / R f is C 2-6 In another embodiment, R d / R e / R f is C 6-10 is an aryl group, and in another embodiment, R d / R e / R f is a 5-10 membered heteroaryl group, and in another embodiment, R e and R f together with the N atom to which they are attached form a 3-7 membered heterocyclyl group, and in another embodiment, R e and R f together with the N atom to which they are attached form a 5-10 membered heteroaryl group, and in another embodiment, the C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″.

[0149] R” In certain embodiments, R" is D, in other embodiments, R" is halogen, and in other embodiments, R" is -R g and in another embodiment, R″ is —C(O)R g and in another embodiment, R″ is —C(O)OR g and in another embodiment, R″ is —C(O)NR h Rj and in another embodiment, R″ is —NR h R j and in another embodiment, R″ is —NR g C(O)R h and in another embodiment, R″ is —NR g C(O)OR h and in another embodiment, R″ is —NR g C(O)NR h R j and in another embodiment, R″ is —OR g and in another embodiment, R″ is —OC(O)R g and in another embodiment, R″ is —OC(O)NR h R j and in another embodiment, R″ is —NR g S(O)2R h and in another embodiment, R″ is —S(O)NR g and in another embodiment, R″ is —S(O)R g and in another embodiment, R″ is —S(O)R g and in another embodiment, two R″ on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 In another embodiment, two R″ on the same atom or two adjacent atoms together with the atom to which they are attached form a 3-7 membered heterocyclyl group; in another embodiment, two R″ on the same atom or two adjacent atoms together with the atom to which they are attached form a C 6-10 In another embodiment, two R″ on the same atom or on two adjacent atoms together with the atom to which they are attached form a 5-10 membered heteroaryl group; in another embodiment, the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated.

[0150] Rg 、R h and R j In certain embodiments, R g / R h / R j is H, and in another embodiment, R g / R h / R j is D, and in another embodiment, R g / R h / R j is C 1-6 In another embodiment, R g / R h / R j is C 1-6 In another embodiment, R g / R h / R j is C 3-6 is a cycloalkyl group, and in another embodiment, R g / R h / R j is a 3- to 7-membered heterocyclyl group, and in another embodiment, R g / R h / R j is C 2-6 alkenyl group, and in another embodiment, R g / R h / R j is C 2-6 In another embodiment, R g / R h / R j is C 6-10 is an aryl group, and in another embodiment, R g / R h / R j is a 5-10 membered heteroaryl group, and in another embodiment, R h and R j together with the N atom to which they are attached form a 3-7 membered heterocyclyl group, and in another embodiment, R h and R j together with the N atom to which they are attached form a 5-10 membered heteroaryl group, and in another embodiment, the C 1-6Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are substituted with one or more deuterium atoms until fully deuterated.

[0151] Any technical solution in any of the above specific embodiments, or any combination thereof, can be combined with any technical solution in other specific embodiments, or any combination thereof. For example, R X ,R X1 ,R X2 ,R X3 , X1, X2, R1, R2, L, W1, W2, R, R' and R" or any combination thereof. The present invention is intended to consist of combinations of all these technical solutions, which will not be enumerated due to the length of the text.

[0152] In a more specific embodiment, the present invention provides a compound of formula (I): [ka] where: R X is H or OH, R X1 , R X2 and R X3 are independently H, D, halogen, -R a , -C(O)R a , -C(O)OR a , -C(O)NR b R c , -NR b R c , -NR a C(O)R b , -NR a C(O)OR b , -NR a C(O)NR bR c , -OR a , -OC(O)R a , -OC(O)NR b R c , -NR a S(O)2R b , -S(O)NR a , -S(O)R a or -S(O)2R a and Here, each R a , R b and R c are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R b and R c together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; X1 and X2 are independently a bond, O, S, or NH; R1 and R2 are independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; L is CH2, CD2 or CHD; W1 is of formula (A), [ka] where: Y1 is O or S; Z1 is O, NH or S; Z2 is O, NH or S; Z3 is a bond, O, NH or S; m1 is 1, 2, 3, 4, 5 or 6; n1 is 0 or 1, n2 is 0 or 1, Each R3 and R4 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R5 is H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; W2 is of formula (B): [ka] where: Y2 is O, NH or S; Z4 is O, NH or S; Z5 is O, NH or S; Z6 is a bond, O, NH or S; m2 is 0, 1, 2, 3, 4, 5, or 6; n3 is 0 or 1, n4 is 0 or 1, Each R6 and R7 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10an aryl group or a 5- to 10-membered heteroaryl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R8 is H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; or any one of W1 and W2 together with the 3' C atom of the sugar group form -Y3-, where Y3 is O, NH or S; Alternatively, W1 and W2 together with the P atom to which they are attached form -Y4(C(R3R4) p ) forming Y4-, where Y4 is O, NH or S, and p is 2, 3, 4 or 5; Each R is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NRe R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R on the same atom or two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R" until fully deuterated; Each R' is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d, -S(O)R d or -S(O)2R d or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R d , R e and R f are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R e and R f together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R g , -C(O)R g , -C(O)OR g , -C(O)NR h R j , -NR h R j , -NR g C(O)R h , -NR gC(O)OR h , -NR g C(O)NR h R j , -OR g , -OC(O)R g , -OC(O)NR h R j , -NR g S(O)2R h , -S(O)NR g , -S(O)R g or -S(O)2R g or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R g , R h and R j are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R h and R j together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0153] In a more specific embodiment, the present invention provides a compound of formula (Ia) or (Ib): [ka] or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0154] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein W1 is [ka] and Here, lipid-like is C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl groups and C 8-28 The alkynyl group is optionally substituted by one or more R; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; R3, R4, R5, m1 and R are as defined in claim 1.

[0155] In a more specific embodiment, the present invention provides a compound of formula (II), (III) or (IV): [ka] where: R X is H or OH, R X1 , R X2 and R X3 are independently H, D, halogen, -R a , -C(O)R a , -C(O)OR a , -C(O)NR b R c , -NR b R c , -NR a C(O)R b , -NR a C(O)OR b , -NR a C(O)NR b R c , -OR a , -OC(O)R a , -OC(O)NR b R c , -NR a S(O)2R b , -S(O)NR a , -S(O)R a or -S(O)2R a and Here, each R a , R b and R c are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R b and R c together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; X1 and X2 are independently a bond, O, S, or NH; R1 and R2 are independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; L is CH2, CD2 or CHD; m1 is 1, 2, 3, 4, 5 or 6; R3 and R4 are independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R5 is H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; W2 is of formula (B): [ka] where: Y2 is O, NH or S; Z4 is O, NH or S; Z5 is O, NH or S; Z6 is a bond, O, NH or S; m2 is 0, 1, 2, 3, 4, 5, or 6; n3 is 0 or 1, n4 is 0 or 1, Each R6 and R7 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R8 is H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; or W2 together with the 3' C atom of the sugar group forms -Y3-, where Y3 is O, NH or S; Each R is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NRe R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R on the same atom or two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R" until fully deuterated; Each R' is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d, -S(O)R d or -S(O)2R d or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R d , R e and R f are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R e and R f together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R g , -C(O)R g , -C(O)OR g , -C(O)NR h R j , -NR h R j , -NR g C(O)R h , -NR gC(O)OR h , -NR g C(O)NR h R j , -OR g , -OC(O)R g , -OC(O)NR h R j , -NR g S(O)2R h , -S(O)NR g , -S(O)R g or -S(O)2R g or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R g , R h and R j are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R h and R j together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0156] In a more specific embodiment, the present invention provides a compound of formula (IIa), formula (IIb), formula (IIIa), formula (IIIb), formula (IV) or formula (IVb): [ka] [ka] or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0157] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: R X is H or OH, R X1 , R X2 and R X3 are independently H, D, halogen or C 1-6 alkyl group, wherein the C 1-6 The alkyl group is optionally substituted with one or more deuterium atoms until fully deuterated; X1 and X2 are independently a bond, O, S, or NH; R1 and R2 are independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; L is CH2, CD2 or CHD; m1 is 1, 2 or 3; R3 and R4 are independently H, D, C 1-6 Alkyl group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; R5 is C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 alkenyl group, wherein C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3- to 7-membered heterocyclyl groups and C 2-28 The alkenyl group is optionally substituted by one or more R; W2 is [ka] and where: m2 is 1, 2, 3, 4, 5 or 6; Each R6 and R7 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R8 is C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Lipid-like is C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl groups and C8-28 The alkynyl group is optionally substituted by one or more R; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Each R is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R on the same atom or two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R" until fully deuterated; Each R' is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e Rf , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R d , R e and R f are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R e and R f together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R g , -C(O)R g , -C(O)OR g , -C(O)NR h R j , -NR h R j , -NR g C(O)R h , -NR g C(O)OR h , -NR g C(O)NR h R j , -OR g , -OC(O)R g , -OC(O)NR h R j , -NR g S(O)2R h , -S(O)NR g , -S(O)R g or -S(O)2R g or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R g , R h and R j are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or Rh and R j together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated.

[0158] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where m2 is 1, 2, 3 or 4; Each R6 and R7 is independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; Each R8 is independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group or C 2-28 an alkynyl group, wherein the C 1-28Alkyl group, C 1-28 Halogenated alkyl groups, C3-6 cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl groups and C 2-28 The alkynyl group is optionally substituted by one or more R; Lipid-like is C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl groups and C 8-28 The alkynyl group is optionally substituted by one or more R; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

[0159] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where R6 is C 1-6 is an alkyl group and R7 is H, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group, wherein said C 1-6 Alkyl groups and C 3-6 The cycloalkyl group is optionally a phenyl group or -C(O)OC 1-6 substituted with one or more groups selected from alkyl groups, R8 is independently C 1-28 Alkyl group, C 3-6a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 alkenyl group, wherein C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 The alkenyl group may optionally contain one or more C 1-6 substituted by an alkoxy group, Preferably, W2 is [ka] and Preferably, W2 is [ka] and Preferably, W2 is [ka] and Preferably, W2 is [ka] and Preferably, W2 is [ka] and Preferably, W2 is [ka] 8. The compound according to any one of claims 4 to 7, wherein:

[0160] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where R6 and R7 are H; R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 is an alkenyl group, Preferably, W2 is [ka] is.

[0161] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where R6 and R7 are H; R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 is an alkenyl group, Preferably, W2 is [ka] and Preferably, W2 is [ka] is.

[0162] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where m2 is 1 or 2, R6 and R7 are H; R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 is an alkenyl group, Preferably, W2 is [ka] is.

[0163] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where m2 is 2, 3, or 4; R6 and R7 are independently H or C 1-6 an alkoxy group, wherein 1-6 The alkoxy group is optionally C 6-10 aryl group or 5- to 10-membered heteroaryl group, wherein 6-10 The aryl group or 5- to 10-membered heteroaryl group may optionally be halogen or C 1-6 substituted by one or more groups selected from alkoxy groups, Lipid-like is C 8-28 Alkyl group or C 8-28 is an alkenyl group, Preferably, W2 is [ka] and Preferably, W2 is [ka] is.

[0164] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where m2 is 2, 3, or 4; R6 and R7 are H; Lipid-like is C 8-28 is an alkenyl group, Preferably, W2 is [ka] is.

[0165] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl or 5- to 10-membered heteroaryl group may optionally contain one or more C 1-6 substituted by alkyl groups, Preferably, W2 is [ka] is.

[0166] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where R6 and R7 are H; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl group or 5- to 10-membered heteroaryl group is optionally C 1-6 Alkyl group or -C(O)OC 1-6 substituted with one or more groups selected from alkyl groups, Preferably, W2 is [ka] is.

[0167] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein W2 is [ka] [ka] and Preferably, W2 is [ka] [ka] and Preferably, W2 is [ka] [ka] and Preferably, W2 is [ka] [ka] is.

[0168] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: R X is H, R X1 , R X2 and R X3 are independently H, D or halogen; X1 and X2 are independently a bond or O; R1 and R2 are independently C 1-6 Alkyl group, C 3-6 Cycloalkyl group or C 6-10 is an aryl group, L is CH2, CD2 or CHD; m1 is 1, 2 or 3; R3 and R4 are independently H, D or C 1-6 is an alkyl group, R5 is C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 It is an alkenyl group.

[0169] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: R X is H, R X1 , R X2 and R X3 are independently H or D, X1 and X2 are independently a bond or O; R1 and R2 are independently C 1-6 is an alkyl group, L is CH2, CD2 or CHD; m1 is 1, 2 or 3; R3 and R4 are independently H or D; R5 is C 1-6 It is an alkyl group.

[0170] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein the compound has formula (IIa) or formula (IIb): [ka] where: R X is H or OH, preferably H, R X1 , R X2 and R X3 are independently H, D or halogen, preferably H or D; X1 and X2 are independently a bond, O, S or NH, preferably a bond or O, more preferably a bond; R1 and R2 are independently C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group), L is CH2, CD2 or CHD; R3 and R4 are independently H, D, halogen, C 1-6 Alkyl group or C 1-6 a halogenated alkyl group, preferably H or D; R5 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 an alkyl group (preferably an isopropyl group), W2 is [ka] and Each R6 and R7 is independently selected from H, D, C, optionally substituted by one or more R', optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group) or -OR d or R6 and R7 together with the C atom to which they are attached form C 3-6 forming a cycloalkyl group or a 3- to 7-membered heterocyclyl group, Each R' is independently -C(O)OC 1-6 Alkyl group, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group, preferably —C(O)OC 1-6 is an alkyl group or a phenyl group, R is optionally substituted by one or more R, which is optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, preferably C 1-6 Alkyl group or C 3-6 is a cycloalkyl group, Ar is a phenyl group optionally substituted by one or more R; R independently represents D, C, optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group or -OC 1-6 is an alkyl group, m2 is 1, 2, 3, 4, 5 or 6, preferably 2, 3 or 4; The lipid-like is optionally substituted by one or more deuterium atoms until fully deuterated. 8-28 Alkyl group or C 8-28 alkenyl group, preferably C 12-20 is an alkyl group, R d is independently optionally substituted by one or more R″ (CH) 1-3 -C 6-10Aryl group or (CH2) 1-3 - a 5- to 10-membered heteroaryl group, preferably a CH2-phenyl group; R″ is independently D, halogen, or —OC, optionally substituted by one or more deuteriums until fully deuterated. 1-6 is an alkyl group, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0171] In a more specific embodiment, the present invention relates to a compound represented by formula (IIa) or formula (IIb) above, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein: R X is H or OH, preferably H, R X1 , R X2 and R X3 are independently H, D or halogen, preferably H or D; X1 and X2 are independently a bond or O, preferably a bond; R1 and R2 are independently C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group), L is CH2, CD2 or CHD; R3 and R4 are independently H, D, halogen, C 1-6 Alkyl group or C 1-6 a halogenated alkyl group, preferably H or D; R5 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 an alkyl group (preferably an isopropyl group), W2 is [ka] and Each R6 and R7 is independently H, D, or C, optionally substituted by one or more R', optionally substituted by one or more deuterium atoms until fully deuterated. 1-3 alkyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 forming a cycloalkyl group or a 3- to 7-membered heterocyclyl group, Each R' is independently -C(O)OC 1-6 Alkyl group or C 6-10 An aryl group, preferably —C(O)OC 1-6 is an alkyl group or a phenyl group, R8 is optionally substituted by one or more R, and optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group or C 3-6 is a cycloalkyl group, R is independently -OC 1-6 is an alkyl group, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0172] In a more specific embodiment, the present invention relates to a compound represented by formula (IIa) or formula (IIb) above, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein: R X is H or OH, preferably H, R X1 , R X2 and R X3 are independently H, D or halogen, preferably H or D; X1 and X2 are independently a bond or O, preferably a bond; R1 and R2 are independently C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group), L is CH2, CD2 or CHD; R3 and R4 are independently H, D, halogen, C 1-6 Alkyl group or C 1-6 a halogenated alkyl group, preferably H or D; R5 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 an alkyl group (preferably an isopropyl group), W2 is [ka] and Each R6 and R7 independently represents H, D, or C, optionally substituted by one or more deuterium atoms until fully deuterated. 1-3 is an alkyl group, R8 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group or C 3-6 is a cycloalkyl group, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0173] In a more specific embodiment, the present invention relates to a compound represented by formula (IIa) or formula (IIb) above, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein: R X is H or OH, preferably H, R X1 , R X2 and R X3 are independently H, D or halogen, preferably H or D; X1 and X2 are independently a bond or O, preferably a bond; R1 and R2 are independently C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3alkyl group), L is CH2, CD2 or CHD; R3 and R4 are independently H, D, halogen, C 1-6 Alkyl group or C 1-6 a halogenated alkyl group, preferably H or D; R5 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 an alkyl group (preferably an isopropyl group), W2 is [ka] and Ar is a phenyl group optionally substituted by one or more R; R independently represents a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 is an alkyl group, Each R6 and R7 independently represents H, D, or C, optionally substituted by one or more deuterium atoms until fully deuterated. 1-3 is an alkyl group, R8 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group or C 3-6 is a cycloalkyl group, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0174] In a more specific embodiment, the present invention relates to a compound represented by formula (IIa) or formula (IIb) above, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein: R X is H or OH, preferably H, R X1 , R X2 and R X3are independently H, D or halogen, preferably H or D; X1 and X2 are independently a bond or O, preferably a bond; R1 and R2 are independently C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group), L is CH2, CD2 or CHD; R3 and R4 are independently H or D; R5 is an isopropyl group optionally substituted with one or more deuterium atoms until fully deuterated; W2 is [ka] and each R6 and R7 is independently H or D; R8 is an isopropyl group optionally substituted with one or more deuterium atoms until fully deuterated; or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0175] In more specific embodiments, the present invention relates to the above-mentioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein the compound is represented by formula (IIIa) or formula (IIIb): [ka] where: R X is H or OH, preferably H, R X1 , R X2 and R X3 are independently H, D or halogen, preferably H or D; X1 and X2 are independently a bond or O, preferably a bond; R1 and R2 are independently C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group), L is CH2, CD2 or CHD; R3 and R4 are independently H or D; R5 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 is an alkyl group, W2 is [ka] and Each R6 and R7 independently represents H, D, or C, optionally substituted by one or more deuterium atoms until fully deuterated. 1-3 is an alkyl group, R8 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 is an alkyl group, Ar is a phenyl group optionally substituted by one or more R; R independently represents a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 is an alkyl group, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0176] In a more specific embodiment, the present invention relates to a compound represented by formula (IIIa) or formula (IIIb) above, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein: where: R X is H or OH, preferably H, R X1 , R X2 and R X3are independently H, D or halogen, preferably H or D; X1 and X2 are independently a bond or O, preferably a bond; R1 and R2 are independently C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group), L is CH2, CD2 or CHD; R3 and R4 are independently H or D; R5 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 an alkyl group (preferably a tert-butyl group), W2 is [ka] and Each R6 and R7 independently represents H, D, or C, optionally substituted by one or more deuterium atoms until fully deuterated. 1-3 is an alkyl group, R8 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 is an alkyl group, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0177] In a more specific embodiment, the present invention relates to a compound represented by formula (IIIa) or formula (IIIb) above, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein: R X is H or OH, preferably H, R X1 , R X2 and R X3 are independently H, D or halogen, preferably H or D; X1 and X2 are independently a bond or O, preferably a bond; R1 and R2 are independently C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group), L is CH2, CD2 or CHD; R3 and R4 are independently H or D; R5 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group, preferably an isopropyl group), W2 is [ka] and Ar is a phenyl group optionally substituted by one or more R; R independently represents a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 is an alkyl group, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0178] In a more specific embodiment, the present invention relates to a compound represented by formula (IIIa) or formula (IIIb) above, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein: R X is H or OH, preferably H, R X1 , R X2 and R X3 are independently H, D or halogen, preferably H or D; X1 and X2 are independently a bond or O, preferably a bond; R1 and R2 are independently C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group), L is CH2, CD2 or CHD; R3 and R4 are independently H or D; R5 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group, preferably a tert-butyl group, more preferably an isopropyl group), W2 is [ka] and each R6 and R7 is independently H or D; R8 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group, preferably a tert-butyl group, more preferably an isopropyl group), or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0179] In more specific embodiments, the present invention relates to the above-mentioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein the compound has formula (IVa) or formula (IVb): [ka] where: R X is H or OH, preferably H, R X1 , R X2 and R X3 are independently H, D or halogen, preferably H or D; X1 and X2 are independently a bond or O, preferably a bond; R1 and R2 are independently C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group), L is CH2, CD2 or CHD; m1 is 1, 2 or 3; R3 and R4 are independently H or D; R5 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 an alkyl group (preferably a tert-butyl group), W2 is [ka] and m2 is 1, 2, or 3; each R and R is independently H or D, optionally substituted by one or more deuterium atoms until fully deuterated; R8 is a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 an alkyl group (preferably a tert-butyl group), Ar is a phenyl group optionally substituted by one or more R; R independently represents a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 is an alkyl group, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0180] In a more specific embodiment, the present invention provides a compound of formula (V) or (VI): [ka] where: RX is H or OH, R X1 , R X2 and R X3 are independently H, D, halogen, -R a , -C(O)R a , -C(O)OR a , -C(O)NR b R c , -NR b R c , -NR a C(O)R b , -NR a C(O)OR b , -NR a C(O)NR b R c , -OR a , -OC(O)R a , -OC(O)NR b R c , -NR a S(O)2R b , -S(O)NR a , -S(O)R a or -S(O)2R a and Here, each R a , R b and R c are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R b and R c together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; X1 and X2 are independently a bond, O, S, or NH; R1 and R2 are independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; L is CH2, CD2 or CHD; m1 is 1, 2, 3, 4, 5 or 6; R3 and R4 are independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; Lipid-like is C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 The alkynyl group is optionally substituted by one or more R; W2 is of formula (B): [ka] where: Y2 is O, NH or S; Z4 is O, NH or S; Z5 is O, NH or S; Z6 is a bond, O, NH or S; m2 is 0, 1, 2, 3, 4, 5, or 6; n3 is 0 or 1, n4 is 0 or 1, Each R6 and R7 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R8 is H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; or W2 together with the 3' C atom of the sugar group forms -Y3-, where Y3 is O, NH or S; Each R is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR eR f , -NR d S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R on the same atom or two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R" until fully deuterated; Each R' is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R d , R e and R f are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R e and R f together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R g , -C(O)R g , -C(O)OR g , -C(O)NR h R j , -NR h R j , -NR g C(O)R h , -NR g C(O)OR h , -NR g C(O)NR h R j , -OR g , -OC(O)R g , -OC(O)NR h R j , -NR g S(O)2R h , -S(O)NR g , -S(O)R g or -S(O)2Rg or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R g , R h and R j are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R h and R j together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0181] In more specific embodiments, the present invention provides a compound of formula (Va), formula (Vb), formula (VIa) or formula (VIb): [ka] or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0182] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: R X is H or OH, R X1 , R X2 and R X3 are independently H, D, halogen or C 1-6 alkyl group, wherein the C 1-6 The alkyl group is optionally substituted with one or more deuterium atoms until fully deuterated; X1 and X2 are independently a bond, O, S, or NH; R1 and R2 are independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; L is CH2, CD2 or CHD; m1 is 2, 3, or 4; R3 and R4 are independently H, D, C 1-6 Alkyl group, C 3-6a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; Lipid-like is C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 2-28 Alkenyl group or C 2-28 an alkynyl group, wherein the C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 2-28 Alkenyl groups and C 2-28 The alkynyl group is optionally substituted by one or more R; W2 is [ka] and where: m2 is 1, 2, 3, 4, 5 or 6; Each R6 and R7 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R8 is C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Each R is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e, -S(O)NR d , -S(O)R d or -S(O)2R d or two R on the same atom or two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R" until fully deuterated; Each R' is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 Forms an aryl group or a 5- to 10-membered heteroaryl group, wherein C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R d , R e and R f are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R e sum R f together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl group and the 5-10 membered heteroaryl group are optionally substituted by one or more R"; Each R" is independently D, halogen, -R g , -C(O)R g , -C(O)OR g , -C(O)NR h R j , -NR h R j , -NR g C(O)R h , -NR g C(O)OR h , -NR g C(O)NR h R j , -OR g , -OC(O)R g , -OC(O)NR h R j , -NR g S(O)2R h , -S(O)NR g , -S(O)R g or -S(O)2R gor two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R g , R h and R j are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R h and R j together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated.

[0183] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where m2 is 1, 2, 3 or 4; Each R6 and R7 is independently H, D, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; Each R8 is independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group or C 2-28 an alkynyl group, wherein the C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl groups and C 2-28 The alkynyl group is optionally substituted by one or more R; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 32. The compound of any one of claims 29-31, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the aryl group and the 5- to 10-membered heteroaryl group are optionally substituted by one or more R.

[0184] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where R6 is C 1-6 is an alkyl group and R7 is H, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group, wherein said C 1-6 Alkyl groups and C 3-6 The cycloalkyl group is optionally a phenyl group or -C(O)OC 1-6 substituted with one or more groups selected from alkyl groups, R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 alkenyl group, wherein C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 The alkenyl group may optionally contain one or more C 1-6 substituted by an alkoxy group, Preferably, W2 is [ka] and Preferably, W2 is [ka] and Preferably, W2 is [ka] and Preferably, W2 is [ka] is.

[0185] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where R6 and R7 are H; R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 is an alkenyl group, Preferably, W2 is [ka] is.

[0186] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where R6 and R7 are H; R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 is an alkenyl group, Preferably, W2 is [ka] is.

[0187] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where m2 is 1 or 2, R6 and R7 are H; R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 is an alkenyl group, Preferably, W2 is [ka] is.

[0188] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl or 5- to 10-membered heteroaryl group may optionally contain one or more C 1-6 substituted by alkyl groups, Preferably, W2 is [ka] is.

[0189] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where R6 and R7 are H; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10The aryl group or 5- to 10-membered heteroaryl group is optionally C 1-6 Alkyl group or -C(O)OC 1-6 substituted with one or more groups selected from alkyl groups, Preferably, W2 is [ka] is.

[0190] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates, or solvates thereof, wherein W2 is [ka] and Preferably, W2 is [ka] is.

[0191] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: R X is H, R X1 , R X2 and R X3 are independently H, D or halogen; X1 and X2 are independently a bond or O; R1 and R2 are independently C 1-6 Alkyl group, C 3-6 Cycloalkyl group or C 6-10 is an aryl group, L is CH2, CD2 or CHD; m1 is 2, 3, or 4; R3 and R4 are independently H, D or C 1-6 an alkoxy group, wherein the C 1-6 The alkoxy group is optionally C6-10 aryl group or 5- to 10-membered heteroaryl group, wherein 6-10 The aryl group or 5- to 10-membered heteroaryl group may optionally be halogen or C 1-6 substituted by one or more groups selected from alkoxy groups, Lipid-like is C 1-28 Alkyl group or C 2-28 It is an alkenyl group.

[0192] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: R X is H, R X1 , R X2 and R X3 are independently H or D, X1 and X2 are independently a bond or O; R1 and R2 are independently C 1-6 is an alkyl group, L is CH2, CD2 or CHD; m1 is 2, 3, or 4; R3 and R4 are independently H, D or C 1-6 an alkoxy group, wherein the C 1-6 The alkoxy group is optionally C 6-10 aryl group or 5- to 10-membered heteroaryl group, wherein 6-10 The aryl group or 5- to 10-membered heteroaryl group may optionally be halogen or C 1-6 substituted by one or more groups selected from alkoxy groups, Lipid-like is C 1-28 Alkyl group or C 2-28 It is an alkenyl group.

[0193] In a more specific embodiment, the present invention provides a compound of formula (VII): [ka] where: R X is H or OH, R X1 , R X2 and R X3 are independently H, D, halogen, -R a , -C(O)R a , -C(O)OR a , -C(O)NR b R c , -NR b R c , -NR a C(O)R b , -NR a C(O)OR b , -NR a C(O)NR b R c , -OR a , -OC(O)R a , -OC(O)NR b R c , -NR a S(O)2R b , -S(O)NR a , -S(O)R a or -S(O)2R a and Here, each R a , R b and R c are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R b and R c together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; X1 and X2 are independently a bond, O, S, or NH; R1 and R2 are independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; L is CH2, CD2 or CHD; R3 and R4 are independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; W2 is of formula (B): [ka] where: Y2 is O, NH or S; Z4 is O, NH or S; Z5 is O, NH or S; Z6 is a bond, O, NH or S; m2 is 0, 1, 2, 3, 4, 5, or 6; n3 is 0 or 1, n4 is 0 or 1, Each R6 and R7 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R8 is H, D, C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; or W2 together with the 3' C atom of the sugar group forms -Y3-, where Y3 is O, NH or S; Each R is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d , -S(O)R dor -S(O)2R d or two R on the same atom or two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R" until fully deuterated; Each R' is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R d , R e and Rf are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R e and R f together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R g , -C(O)R g , -C(O)OR g , -C(O)NR h R j , -NR h R j , -NR g C(O)R h , -NR g C(O)OR h , -NR g C(O)NR h R j , -OR g , -OC(O)R g , -OC(O)NR h R j , -NR g S(O)2R h , -S(O)NR g , -S(O)R g or -S(O)2R g or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R g , R h and R j are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R h and R j together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0194] In a more specific embodiment, the present invention provides a compound of formula (VIIa) or formula (VIIb): [ka] or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0195] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: R X is H or OH, R X1 , R X2 and R X3 are independently H, D, halogen or C 1-6 alkyl group, wherein the C 1-6 The alkyl group is optionally substituted with one or more deuterium atoms until fully deuterated; X1 and X2 are independently a bond, O, S, or NH; R1 and R2 are independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; L is CH2, CD2 or CHD; R3 and R4 are independently H, D, C 1-6 Alkyl group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R3 and R4 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 3-6The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; W2 is [ka] and where: m2 is 1, 2, 3, 4, 5 or 6; Each R6 and R7 is independently H, D, halogen, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 1-6 Alkoxy group, C 1-6 Halogenated alkoxy groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R8 is C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group, C 2-28 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Lipid-like is C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl groups and C 8-28 The alkynyl group is optionally substituted by one or more R; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Each R is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d, -S(O)R d or -S(O)2R d or two R on the same atom or two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R" until fully deuterated; Each R' is independently D, halogen, -R d , -C(O)R d , -C(O)OR d , -C(O)NR e R f , -NR e R f , -NR d C(O)R e , -NR d C(O)OR e , -NR d C(O)NR e R f , -OR d , -OC(O)R d , -OC(O)NR e R f , -NR d S(O)2R e , -S(O)NR d , -S(O)R d or -S(O)2R d or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R d , Re and R f are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R e and R f together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R g , -C(O)R g , -C(O)OR g , -C(O)NR h R j , -NR h R j , -NR g C(O)R h , -NR g C(O)OR h , -NR g C(O)NR h R j , -OR g , -OC(O)R g , -OC(O)NR h R j , -NR g S(O)2R h , -S(O)NR g , -S(O)R g or -S(O)2R g or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C 3-6Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 An aryl group or a 5- to 10-membered heteroaryl group is formed, wherein the C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 6-10 Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R g , R h and R j are independently H, D, C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, or R h and R j together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C 1-6 Alkyl group, C 1-6 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated.

[0196] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where m2 is 1, 2, 3 or 4; Each R6 and R7 is independently H, D, C 1-6Alkyl group, C 1-6 Alkoxy group, C 3-6 a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C 1-6 Alkyl group, C 1-6 Alkoxy group, C 3-6 The cycloalkyl and 3- to 7-membered heterocyclyl groups are optionally substituted by one or more R'; Each R8 is independently C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl group or C 2-28 an alkynyl group, wherein the C 1-28 Alkyl group, C 1-28 Halogenated alkyl groups, C 3-6 Cycloalkyl groups, 3-7 membered heterocyclyl groups, C 2-28 Alkenyl groups and C 2-28 The alkynyl group is optionally substituted by one or more R; Lipid-like is C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl group or C 8-28 an alkynyl group, wherein the C 8-28 Alkyl group, C 8-28 Halogenated alkyl groups, C 8-28 Alkenyl groups and C 8-28 The alkynyl group is optionally substituted by one or more R; Ar is C 6-10 an aryl group or a 5- to 10-membered heteroaryl group, 6-10 The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

[0197] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where R6 is C 1-6 is an alkyl group and R7 is H, or R6 and R7 together with the C atom to which they are attached form a C 3-6 Forms a cycloalkyl group, wherein said C 1-6 Alkyl groups and C 3-6 The cycloalkyl group is optionally a phenyl group or -C(O)OC 1-6 substituted with one or more groups selected from alkyl groups, R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 alkenyl group, wherein C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 The alkenyl group may optionally contain one or more C 1-6 substituted by an alkoxy group, Preferably, W2 is [ka] and Preferably, W2 is [ka] and Preferably, W2 is [ka] and Preferably, W2 is [ka] is.

[0198] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where R6 and R7 are H; R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 is an alkenyl group, Preferably, W2 is [ka] is.

[0199] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where R6 and R7 are H; R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 is an alkenyl group, Preferably, W2 is [ka] is.

[0200] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where m2 is 1 or 2, R6 and R7 are H; R8 is independently C 1-28 Alkyl group, C 3-6 a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C 2-28 is an alkenyl group, Preferably, W2 is [ka] is.

[0201] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where m2 is 2, 3, or 4; R6 and R7 are independently H or C 1-6 an alkoxy group, wherein 1-6 The alkoxy group is optionally C 6-10 aryl group or 5- to 10-membered heteroaryl group, wherein 6-10 The aryl group or 5- to 10-membered heteroaryl group may optionally be halogen or C 1-6 substituted by one or more groups selected from alkoxy groups, Lipid-like is C 8-28 Alkyl group or C 8-28 is an alkenyl group, Preferably, W2 is [ka] and Preferably, W2 is [ka] is.

[0202] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: W2 is [ka] and where m2 is 2, 3, or 4; R6 and R7 are H; Lipid-like is C 8-28 is an alkenyl group, Preferably, W2 is [ka] is.

[0203] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein W2 is [ka] [ka] and Preferably, W2 is [ka] [ka] is.

[0204] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: R X is H, R X1 , R X2 and R X3 are independently H, D or halogen; X1 and X2 are independently a bond or O; R1 and R2 are independently C 1-6 Alkyl group, C 3-6 Cycloalkyl group or C 6-10 is an aryl group, L is CH2, CD2 or CHD; R3 and R4 are independently H, D or C 1-6 is an alkyl group, Ar is C 6-10 It is an aryl group or a 5- to 10-membered heteroaryl group.

[0205] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein: R X is H, R X1 , R X2 and R X3 are independently H or D, X1 and X2 are independently a bond or O; R1 and R2 are independently C 1-6 is an alkyl group, L is CH2, CD2 or CHD; R3 and R4 are independently H or D; Ar is C 6-10 It is an aryl group.

[0206] In a more specific embodiment, the present invention provides a compound of formula (VIIa), formula (VIIa) or formula (VIIb): [ka] where: R X is H or OH, preferably H, R X1 , R X2 and R X3 are independently H, D or halogen, preferably H or D; X1 and X2 are independently a bond, O, S or NH, preferably a bond or O, more preferably a bond; R1 and R2 are independently C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group), L is CH2, CD2 or CHD; R9 is CH2-C 6-10 Aryl group, CH2-5 to 10-membered heteroaryl group, CH2C(O)OC 1-6 Alkyl group, CH2C(O)OC 3-6 a cycloalkyl group or a CH2C(O)O-3 to 7-membered heteroaryl group, preferably a CH2-phenyl group, CH2C(O)OC optionally substituted by one or more deuterium atoms until fully deuterated; 1-6 Alkyl group or CH2C(O)OC 3-6 is a cycloalkyl group, and R 10 is H or D, Or, R9 and R 10 are optionally substituted by one or more deuterium atoms until they, together with the C atoms to which they are attached, are fully deuterated. 3-6 forming a cycloalkyl group or a 3- to 7-membered heterocyclyl group, Ar is a phenyl group optionally substituted by one or more R; R independently represents D, C, optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group or -OC 1-6 is an alkyl group, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0207] In a more specific embodiment, the present invention relates to a compound of formula (VIIa), formula (VIIa) or formula (VIIb), or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein: R X is H or OH, preferably H, R X1 , R X2 and R X3 are independently H, D or halogen, preferably H or D; X1 and X2 are independently a bond or O, preferably a bond; R1 and R2 are independently C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 Alkyl group (preferably C 1-3 alkyl group, more preferably an isopropyl group), L is CH2, CD2 or CHD; R9 is a CH2-phenyl group optionally substituted by one or more deuterium atoms until fully deuterated, CH2C(O)OC 1-6 Alkyl group or CH2C(O)OC 3-6 is a cycloalkyl group, and R 10 is H or D, Ar is a phenyl group optionally substituted by one or more R; R independently represents a C optionally substituted by one or more deuterium atoms until fully deuterated. 1-6 an alkyl group (preferably a tert-butyl group), or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

[0208] In more specific embodiments, the present invention relates to the aforementioned compounds, or tautomers, stereoisomers, prodrugs, crystalline forms, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein the compound is [ka] [ka] [ka] [ka] [ka] [ka] [ka] Selected from Preferably the compound is [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] Selected from.

[0209] an intermediate compound, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the intermediate compound is [ka] [ka] [ka] [ka] [ka] [ka] [ka] Selected from.

[0210] The compounds of the present invention may contain one or more asymmetric centers and may exist in multiple stereoisomeric forms, such as enantiomeric and / or diastereomeric forms. For example, the compounds of the present invention may be in the form of a single enantiomer, diastereomer, or geometric isomer (e.g., cis and trans isomers), or may be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomers. Isomers can be isolated from mixtures by methods well known to those skilled in the art, including chiral high-pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts. Alternatively, and preferably, isomers can be prepared by asymmetric synthesis.

[0211] "Tautomer" refers to a case where a functional group in a compound changes its structure to become another functional isomer, which rapidly converts into each other, producing two isomers in dynamic equilibrium; these two isomers are called tautomers.

[0212] Those skilled in the art will recognize that organic compounds can form complexes with solvents in which they react or from which they precipitate or crystallize. These complexes are referred to as "solvates." When the solvent is water, the complex is referred to as a "hydrate." The present invention encompasses all solvates of the compounds of the present invention.

[0213] The term "solvate" refers to a form of a compound or its salt associated with a solvent, typically formed by a decomposition reaction of the solvent. This physical association may include hydrogen bonding. Common solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, and the like. The compounds described herein may be prepared, for example, in crystalline form, and may be solvated. Suitable solvates include pharmaceutically acceptable solvates, and further include stoichiometric and non-stoichiometric solvates. In certain embodiments, the solvate may be dissociated, for example, by incorporating one or more solvent molecules into the lattice of a crystalline solid. "Solvate" includes solution-state solvates and dissociable solvates. Representative solvates include hydrates, ethanolates, and ethanolates.

[0214] The term "hydrate" refers to a compound combined with water. It is usually determined by the ratio of the number of water molecules contained in a hydrate of a compound to the number of compound molecules in the hydrate. Hydrates of compounds can be represented by the general formula R·xH2O, where R is the compound and x is a number greater than 0. A given compound may form multiple types of hydrates, including, for example, monohydrates (x is 1), hypohydrates (x is a number greater than 0 but less than 1, e.g., hemihydrate (R·0.5H2O)), and polyhydrates (x is a number greater than 1, e.g., dihydrate (R·2H2O) and hexahydrate (R·6H2O)).

[0215] The compounds of the present invention may be in amorphous or crystalline form (crystal or polymorph). Furthermore, the compounds of the present invention may exist in one or more crystalline forms. Thus, the present invention includes within its scope all amorphous or crystalline forms of the compounds of the present invention. The term "polymorph" refers to a crystalline form of a compound (or its salt, hydrate, or solvate) having a specific crystalline stacking sequence. All polymorphs have the same elemental composition. Different crystalline forms typically have different X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optoelectronic properties, stability, and solubility. The recrystallization solvent, crystallization rate, storage temperature, and other factors may result in one crystalline form predominating. Various polymorphs of a compound may be prepared by crystallization under different conditions.

[0216] The present invention also includes isotopically labeled compounds equivalent to those described in formula (I), except that one or more atoms are replaced with atoms having different atomic masses or mass numbers than those typically found in nature. Examples of isotopes that can be introduced into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, such as isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, respectively. 2 H, 3 H, 13 C. 11 C. 14 C. 15 N, 18 O. 17 O. 31 P, 32 P, 35 S, 18 F and 36 Compounds of the present invention, prodrugs thereof, and pharmaceutically acceptable salts of said compounds or said prodrugs, which contain the above isotopes and / or isotopes of other atoms, are within the scope of the present invention. 3 H and 14 Certain isotopically labeled compounds of the present invention, such as those incorporating tritium, i.e., C), may be used to measure the tissue distribution of drugs and / or substrates. 3 H and carbon-14, i.e. 14C isotopes are particularly preferred because they are easily prepared and detectable. 2 Substitution with H may be preferred in some cases due to the fact that greater metabolic stability may provide therapeutic advantages such as increased in vivo half-life or reduced dosage requirements. Isotopically labeled compounds of formula (I) of the present invention and prodrugs thereof can generally be prepared in such a way that readily available isotopically labeled reagents are substituted for non-isotopically labeled reagents when carrying out the steps disclosed in the following processes and / or embodiments and preparations.

[0217] Furthermore, prodrugs are included in the context of the present invention. As used herein, the term "prodrug" refers to a compound that is converted into its pharmaceutically effective active form in vivo, for example, by hydrolysis in the bloodstream. Pharmaceutically acceptable prodrugs are described in T. Higuchi and V. Stella, "Prodrugs as Novel Delivery Systems," ACS Symposium Series, Vol. 14, Edward B. Roche, ed., "Bioreversible Carriers in Drug Design," American Pharmaceutical Association and Pergamon Press, 1987, and D. Fleisher, S. Ramon, and H. Barbra, "Improved oral drug delivery: solubility limitations overcome by the use of prodrugs," Advanced Drug Delivery Reviews (1996) 19(2) 115-130, which are incorporated herein by reference.

[0218] A prodrug refers to a covalently bonded compound of the present invention that releases the parent compound in vivo upon administration to a patient. Prodrugs are typically prepared by modifying functional groups, which allow for conventional manipulation or cleavage in vivo to produce the parent compound. Prodrugs include compounds of the present invention having a hydroxyl, amino, or sulfhydryl group bonded to any group that can be broken down to form the hydroxyl, amino, or sulfhydryl group upon administration to a patient. Representative examples of prodrugs therefore include, but are not limited to, acetate / amide, formate / amide, and benzoate / amide derivatives of the hydroxyl, sulfhydryl, and amino functional groups of compounds of Formula (I). In addition, in the case of carboxylic acids (—COOH), esters such as methyl esters and ethyl esters may be used. The esters themselves may be active and / or may be hydrolyzed under in vivo conditions in a living organism. Suitable pharmaceutically acceptable in vivo hydrolyzable ester groups include those that readily break down in vivo to release the parent acid or its salt.

[0219] Pharmaceutical compositions, formulations and kits In another aspect, the present invention provides pharmaceutical compositions comprising a compound of the present invention (also referred to as an "active ingredient") and a pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition comprises an effective amount of the active ingredient. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of the active ingredient. In some embodiments, the pharmaceutical composition comprises a prophylactically effective amount of the active ingredient.

[0220] The pharmaceutically acceptable excipient used in the present invention refers to a non-toxic carrier, adjuvant or vehicle that does not destroy the pharmacological activity of the compound that is prepared together.The pharmaceutically acceptable carrier, adjuvant or vehicle that can be used in the composition of the present invention includes but is not limited to ion exchanger, alumina, aluminum stearate, lecithin, serum protein (for example, human serum albumin), buffer substance (for example, phosphate), glycine, sorbic acid, potassium sorbate, the miglyceride mixture of saturated vegetable fatty acid, water, salt or electrolyte (such as protamine sulfate), disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, silica gel, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based material, polyethylene glycol, carmellose sodium, polyacrylic acid ester, wax, polyethylene-polyoxypropylene-block polymer, polyethylene glycol and lanolin.

[0221] The present invention also includes kits (e.g., pharmaceutical packages). The provided kits may include a compound of the present invention, another therapeutic agent, and first and second containers (e.g., vials, ampoules, bottles, syringes, and / or bulk packages, or other suitable containers) containing the compound of the present invention and the other therapeutic agent. In some embodiments, the provided kits may also optionally include a third container containing a pharmaceutical excipient for diluting or suspending the compound of the present invention and / or the other therapeutic agent. In some embodiments, the combination of the compound of the present invention and the other therapeutic agent provided in the first container and the second container forms a unit dosage form.

[0222] The pharmaceutical compositions provided herein can be administered by many routes, including, but not limited to, oral, parenteral, inhalation, topical, rectal, nasal, buccal, vaginal, via implants, or other administration means. For example, parenteral administration as used herein includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intraarterial, intrasynovial, intrapleural, intrathecal, intralesional, and intracranial injection or infusion techniques.

[0223] Typically, an effective amount of the compound provided herein is administered. The amount of the compound actually administered can be determined by a physician according to relevant circumstances, including the disease to be treated, the selected administration route, the compound actually administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, etc.

[0224] When used for the prevention of the conditions described herein, the compounds provided herein are typically administered at the dosage levels described above to subjects at risk of developing the conditions described, based on a physician's recommendation and under the supervision of a physician. Subjects at risk of developing the conditions described typically include subjects with a family history of the condition, or subjects determined by genetic testing or screening to be particularly susceptible to developing the condition.

[0225] The pharmaceutical compositions provided herein can also be administered long-term ("long-term administration"). Long-term administration refers to administering a compound or pharmaceutical composition thereof for an extended period of time, such as, for example, 3 months, 6 months, 1 year, 2 years, 3 years, 5 years, etc., or may continue indefinitely, for example, for the remainder of the subject's life. In some embodiments, long-term administration is intended to provide a constant level of the compound in the bloodstream for an extended period of time, for example, during the therapeutic window.

[0226] Various administration methods can be used to further deliver the pharmaceutical compositions of the present invention. For example, in some embodiments, the pharmaceutical compositions can be administered by injection, for example, to rapidly increase the concentration of the compound in the blood to an effective level. The injection dose varies depending on the target systemic level of the active ingredient. For example, an intramuscular or subcutaneous injection dose will slowly release the active ingredient, while an injection administered directly into a vein (e.g., an IV drip) can deliver the active ingredient more quickly, allowing the blood concentration of the active ingredient to rapidly increase to an effective level. In other embodiments, the pharmaceutical composition can be administered by continuous infusion, for example, by IV drip, to provide a steady concentration of the active ingredient in the subject's body. Furthermore, in other embodiments, an injection dose of the pharmaceutical composition can be administered first, followed by continuous infusion.

[0227] Oral compositions may take the form of bulk liquid solutions, suspensions, or bulk powder formulations. However, more commonly, the compositions are provided in unit dosage forms to facilitate accurate dosing. The term "unit dosage form" refers to a physically discrete unit suitable for use as a unitary dosage in human patients and other mammals, each unit containing a predetermined amount of active agent and suitable pharmaceutical excipients appropriate for producing the desired therapeutic effect. Typical unit dosage forms include prefilled, premeasured ampoules or syringes for liquid compositions, or pills, tablets, capsules, and the like for solid compositions. In such compositions, the compound is typically the minor component (about 0.1 to about 50 wt%, preferably about 1 to about 40 wt%), with the remainder being various carriers or excipients, as well as processing aids, useful for forming the desired dosage form.

[0228] For oral doses, representative embodiments are 1 to 5 oral doses per day, particularly 2 to 4 oral doses, typically 3 oral doses. Using these modes of dose delivery, each dose provides from about 0.01 to about 20 mg / kg of a compound of the invention, with preferred doses providing from about 0.1 to about 10 mg / kg, particularly from about 1 to about 5 mg / kg each.

[0229] To provide a blood concentration similar to or lower than that obtained when an injectable dose is used, the transdermal dose is generally selected in an amount of about 0.01 to about 20 wt%, preferably about 0.01 to about 20 wt%, preferably about 0.01 to about 10 wt%, and more preferably about 0.5 to about 15 wt%.

[0230] Injectable dose levels range from about 0.1 mg / kg / hour to at least 10 mg / kg / hour for about 1 hour to about 120 hours, particularly 24 to 96 hours. A preload push of about 0.1 mg / kg to about 10 mg / kg or more may be administered to achieve adequate steady-state levels. For a 40-80 kg human patient, the maximum total dose should not exceed about 2 g / day.

[0231] Liquid forms suitable for oral administration may include suitable aqueous or nonaqueous carriers and buffers, suspending and dispersing agents, colorants, flavors, etc. Solid forms may include any of the following ingredients, or compounds with similar properties: binders such as microcrystalline cellulose, yarrow gum, or gelatin; excipients such as starch or lactose; disintegrating agents such as cholic acid, primogel, or corn starch; lubricants such as magnesium stearate; flow agents such as colloidal silicon dioxide; sweeteners such as sucrose or saccharin, or flavors such as peppermint, methyl salicylate, or orange flavoring.

[0232] Injectable compositions are typically based on sterile saline or injectable phosphate-buffered saline, or other injectable excipients known to those skilled in the art. As noted above, in such compositions, the active compound is typically the minor component, usually about 0.05-10 wt%, with the remainder being the injectable excipients, etc.

[0233] Typical transdermal compositions can be prepared as topical ointments or creams containing the active ingredient. When preparing an ointment, the active ingredient is typically combined with paraffin wax or a water-miscible ointment base. Alternatively, the active ingredient can be formulated as a cream, for example, using an oil-in-water cream base. Such transdermal formulations are well known to those skilled in the art and usually contain other ingredients to enhance the consistent skin penetration of the active ingredient or formulation. All such known transdermal formulations and ingredients are within the scope of the present invention.

[0234] The compounds of the present invention can also be administered via a transdermal device. Thus, transdermal administration can be accomplished using either a reservoir or porous membrane type or a solid matrix patch variety.

[0235] The above components of compositions for oral, injectable, or topical administration are merely representative. Additional materials, processing techniques, and the like are described in Remington's Pharmaceutical Sciences, 17th edition, 1985, Mack Publishing Company, Easton, Pennsylvania, Part 8, which is incorporated herein by reference.

[0236] The compounds of this invention can also be administered in sustained release forms or from sustained release delivery systems. A description of representative sustained release materials is found in Remington's Pharmaceutical Sciences.

[0237] The present invention also relates to pharmaceutically acceptable formulations of the compounds of the present invention. In certain embodiments, the formulation comprises water. In other embodiments, the formulation comprises a cyclodextrin derivative. The most common cyclodextrins are α-, β-, and γ-cyclodextrins, which consist of 6, 7, and 8 α-1,4-linked glucose units, respectively. These cyclodextrins optionally contain one or more substituents on the linked sugar moieties, including, but not limited to, methylated, hydroxyalkylated, acylated, and sulfonated alkyl ether substituents. In some embodiments, the cyclodextrin is a sulfoalkyl ether β-cyclodextrin, such as sulfobutyl ether β-cyclodextrin (also known as Captisol). See, e.g., U.S. Pat. No. 5,376,645. In some embodiments, the formulation comprises hexapropyl-β-cyclodextrin (e.g., 10-50% in water).

[0238] Indications In another aspect, the present invention relates to a method for treating and / or preventing a viral infection in a subject, comprising administering to the subject a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant thereof, or a pharmaceutical composition of the present invention.

[0239] In certain embodiments, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, can be used to treat and / or prevent coronavirus infection. In more specific embodiments, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention can inhibit coronavirus replication. In more specific embodiments, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, can be used to treat and / or prevent RNA-dependent RNA polymerase of coronaviruses. In specific embodiments, the coronavirus is SARS-CoV and its variants, MERS-CoV and its variants, SARS-CoV-2 and its variants, other human coronaviruses (e.g., 229E, NL63, OC43, HKU1, or WIV1), zoonotic coronaviruses (e.g., PEDV or HKU CoV isolates, e.g., HKU3, HKU5, or HKU9), feline coronaviruses (e.g., feline enteric coronavirus (FECV) or feline infectious peritonitis virus (FIPV)), or boar epidemic diarrhea virus (PEDV). In specific embodiments, the coronavirus is SARS-CoV and its variants, MERS-CoV and its variants, or SARS-CoV-2 and its variants. In specific embodiments, the coronavirus is SARS-CoV-2 and its variants. In specific embodiments, the SARS-CoV-2 virus variant is an Alpha variant, a Beta variant, a Delta variant, a Gamma variant, or an Omicron variant. In a specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs or isotopic variants thereof, or pharmaceutical compositions of the present invention may be utilized in the treatment and / or prevention of viral infections caused by viruses having polymerase homologues of the SARS-CoV-2 polymerase.For example, they may be used to treat and / or prevent viral infections caused by viruses that share at least 60% sequence identity with SARS-CoV-2 polymerase. In specific embodiments, compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, may be used to treat and / or prevent viral infections caused by viruses that share at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SARS-CoV-2 polymerase. In specific embodiments, compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, may be used to treat and / or prevent viral infections caused by viruses that share a polymerase homolog of SARS-CoV-2 polymerase. For example, they may be used to treat and / or prevent viral infections caused by viruses that share at least 60% sequence identity with SARS-CoV-2 polymerase. In specific embodiments, compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, may be used to treat and / or prevent viral infections caused by viruses that share at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SARS-CoV-2 polymerase. In specific embodiments, compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, may be used to treat and / or prevent viral infections caused by viruses that share at least 60% sequence identity with the entire genome sequence of SARS-CoV-2.In specific embodiments, the compounds of the invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs or isotopic variants thereof, or pharmaceutical compositions of the invention may be used for the treatment and / or prevention of viral infections caused by viruses having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity with the entire genome sequence of SARS-CoV-2.

[0240] In another embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, can be used to treat and / or prevent Paramyxoviridae virus infections. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention can inhibit the replication of Paramyxoviridae viruses. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention can be used to treat and / or prevent the RNA-dependent RNA polymerase of Paramyxoviridae viruses. In a specific embodiment, the Paramyxoviridae virus is parainfluenza virus, measles, or mumps virus.

[0241] In another embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, can be used to treat and / or prevent Pneumoviridae virus infections. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention can inhibit the replication of Pneumoviridae viruses. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention can be used to treat and / or prevent the RNA-dependent RNA polymerase of Pneumoviridae viruses. In a specific embodiment, the Pneumoviridae virus is RSV or human metapneumovirus. In a specific embodiment, the Pneumoviridae virus is RSV.

[0242] In another embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, can be used to treat and / or prevent Picornaviridae virus infections. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention can inhibit the replication of Picornaviridae viruses. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention can be used to treat and / or prevent the RNA-dependent RNA polymerase of Picornaviridae viruses. In a specific embodiment, the Picornaviridae virus is an enterovirus or a rhinovirus.

[0243] In another embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, can be used to treat and / or prevent Flaviviridae virus infections. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention can inhibit the replication of Flaviviridae viruses. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, can be used to treat and / or prevent the RNA-dependent RNA polymerase of Flaviviridae viruses. In specific embodiments, the Flaviviridae virus is dengue virus, Yellow Fever virus, West Nile virus, Zika virus, Japanese encephalitis virus, and Hepatitis C.

[0244] In another embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, can be used to treat and / or prevent Filoviridae virus infections. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention can inhibit the replication of Filoviridae viruses. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, can be used to treat and / or prevent Filoviridae virus RNA-dependent RNA polymerase. In specific embodiments, the Filoviridae virus is Ebola virus, Zaire ebola virus, Bundibugio ebola virus, Sudan ebola virus, Tai forest ebola virus, Reston ebola virus, or Marburg virus. In more specific aspects, the Filoviridae virus according to the present invention is Ebola virus or Marburg virus.

[0245] In another embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, can be used to treat and / or prevent infection with Arenaviridae viruses. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention can inhibit replication of Arenaviridae viruses. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention can be used to treat and / or prevent RNA-dependent RNA polymerase of Arenaviridae viruses. In a specific embodiment, the Arenaviridae virus is Lassa (LASA) virus or Junín (JUNV) virus.

[0246] In another embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, can be used to treat and / or prevent empoxvirus infection. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention can inhibit empoxvirus replication. In a more specific embodiment, the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, can be used to treat and / or prevent empoxvirus RNA-dependent RNA polymerase.

[0247] Administration method The compounds of the present invention (compounds herein serving as the active ingredient) or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, may be administered by any route appropriate to the condition being treated. The preferred route may vary depending on the condition of the subject. An advantage of the compounds of the present invention is that they are orally bioavailable and can be administered orally.

[0248] In certain embodiments, when a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the present invention is utilized to treat a viral infection, the compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the present invention may be administered at any time to a person who may come into contact with a person suffering from a viral infection, or to a person suffering from a viral (e.g., SARS-CoV-2) infection. In another embodiment, the compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the present invention may be administered prophylactically to a person who has come into contact with a person suffering from a viral (e.g., SARS-CoV-2) infection, or to a person at risk of coming into contact with a person suffering from a viral (e.g., SARS-CoV-2) infection, such as a healthcare worker. In another embodiment, a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant thereof, or a pharmaceutical composition of the present invention, can be administered to a person who has tested positive for a viral (e.g., SARS-CoV-2) infection but is not showing symptoms of the viral (e.g., SARS-CoV-2) infection. In another embodiment, a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant thereof, or a pharmaceutical composition of the present invention can be administered to a person who has developed symptoms of a viral (e.g., SARS-CoV-2) infection.

[0249] In certain embodiments, the methods of treating and / or preventing a viral infection disclosed herein comprise event-driven administration of a compound of the invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the invention to a subject.

[0250] As used herein, the terms "event-driven" or "event-driven administration" refer to the administration of a compound of the invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the invention: (1) prior to an event (e.g., 2 hours, 1 day, 2 days, 5 days, or less) in which an individual is exposed to or otherwise increases the risk of an individual becoming infected with a virus (e.g., SARS-CoV-2) (1) or 7 days prior to the event; and / or (2) a period of time during which an event (more than one repeated event) occurs in which the individual is exposed to a virus (e.g., SARS-CoV-2) or otherwise increases the individual's risk of becoming infected with a virus (e.g., SARS-CoV-2); and / or (3) after an event (or after the last event in a series of repeated events) in which the individual is exposed to a virus (e.g., SARS-CoV-2) or otherwise increases the individual's risk of becoming infected with a virus (e.g., SARS-CoV-2). In certain embodiments, event-driven administration occurs before the subject is exposed to a virus (e.g., SARS-CoV-2). In other embodiments, event-driven administration occurs after the subject is exposed to a virus (e.g., SARS-CoV-2). In other embodiments, event-driven administration occurs before the subject is exposed to a virus (e.g., SARS-CoV-2) and after the subject is exposed to a virus (e.g., SARS-CoV-2).

[0251] In certain embodiments, the methods for preventing and / or treating viral infections disclosed herein involve administration before and / or after an event in which an individual is exposed to a virus (e.g., SARS-CoV-2) or otherwise increases the individual's risk of becoming infected with a virus (e.g., SARS-CoV-2), e.g., pre-exposure prophylaxis (PrEP) and / or post-exposure prophylaxis (PEP). In certain specific embodiments, the methods disclosed herein include pre-exposure prophylaxis. In another specific embodiment, the methods disclosed herein include post-exposure prophylaxis.

[0252] In certain embodiments, a compound of the invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant thereof, or a pharmaceutical composition of the invention is administered before the subject is exposed to a virus (e.g., SARS-CoV-2).

[0253] In another embodiment, a compound of the invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the invention is administered before and after a subject is exposed to a virus (e.g., SARS-CoV-2).

[0254] In another embodiment, a compound of the invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the invention is administered after the subject has been exposed to a virus (e.g., SARS-CoV-2).

[0255] An example of an event-driven dosage form includes administering a compound of the invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant thereof, or a pharmaceutical composition of the invention, within 2 hours to 24 hours before exposure to a virus (e.g., SARS-CoV-2), followed by another administration of a compound of the invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant thereof, or a pharmaceutical composition of the invention after the final exposure, and a final administration of a compound of the invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant thereof, or a pharmaceutical composition of the invention, 24 hours later.

[0256] Another example of an event-driven administration mode includes administering a compound of the invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant thereof, or a pharmaceutical composition of the invention within 24 hours before exposure to a virus (e.g., SARS-CoV-2), then daily for the duration of exposure, and then a final administration (which can be increased in doses, e.g., doubled) about 24 hours after the last exposure.

[0257] The effective amount of active ingredient will depend, at least, on the nature of the condition being treated, its toxicity, whether the compound is administered prophylactically or against an active viral infection, the mode of delivery, and the pharmaceutical formulation, and will be determined by the clinician using routine dose-escalation studies. Doses can be expected to be about 0.0001 to about 100 mg / kg body weight per day, typically about 0.01 to about 10 mg / kg body weight per day, more typically about 0.01 to about 5 mg / kg body weight per day, and most typically about 0.05 to about 0.5 mg / kg body weight per day. For example, the daily candidate dose range for an adult weighing about 70 kg is 1 mg to 1000 mg, preferably 5 mg to 500 mg, and can be administered in single or multiple dose form.

[0258] The dosage of the active ingredient of the compound of the present invention for use in treating a viral (e.g., SARS-CoV-2) infection may vary depending on whether it is used prophylactically or to treat a person who already has a viral (e.g., SARS-CoV-2) infection. Furthermore, the dosage may vary depending on whether the person with a viral (e.g., SARS-CoV-2) infection has not yet shown symptoms or is showing symptoms of a viral (e.g., SARS-CoV-2) infection. Treating a person who has tested positive for a viral (e.g., SARS-CoV-2) infection and is showing symptoms of a viral (e.g., SARS-CoV-2) infection may require a higher dose than a person receiving prophylactic treatment.

[0259] Any suitable duration for administering the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, or pharmaceutical compositions of the present invention, is contemplated. For example, administration can last from 1 day to 100 days, including 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, or 90 days. Furthermore, administration can last from 1 week to 15 weeks, including 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 weeks. Longer administration durations are also contemplated. The duration of administration can depend on whether the compound is administered prophylactically or for treatment during normal contact with a person suffering from a viral (e.g., SARS-CoV-2) infection and for an appropriate period of time after last contact with a person suffering from a viral (e.g., SARS-CoV-2) infection. For individuals who already have a viral (e.g., SARS-CoV-2) infection, the administration period may be any period necessary to treat the patient, or an appropriate period after testing negative for the viral (e.g., SARS-CoV-2) infection to ensure that the viral (e.g., SARS-CoV-2) infection does not recur.

[0260] In certain embodiments, the compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or pharmaceutical composition of the present invention, is administered once daily. In some other embodiments, the compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or pharmaceutical composition of the present invention, is administered once every other day. In another embodiment, the compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or pharmaceutical composition of the present invention, is administered once weekly. In another embodiment, the compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or pharmaceutical composition of the present invention, is administered twice weekly.

[0261] In certain embodiments, the methods of the present invention for treating and / or preventing viral (e.g., SARS-CoV-2) infection comprise administering a loading dose of a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the present invention, on day 1, followed by a once-daily maintenance dose of a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the present invention. The once-daily maintenance dose of a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the present invention can be administered for, for example, up to 5 days, up to 7 days, up to 10 days, up to 15 days, up to 20 days, up to 25 days, up to 1 month, or longer, as needed. In another embodiment, the once-daily maintenance dose is administered for about 6-12 days, e.g., about 8-10 days. In another embodiment, the once-daily maintenance dose is administered for about 4 days. In another embodiment, the once-daily maintenance dose is administered for about 5 days. In another embodiment, the once-daily maintenance dose is administered for about 9 days. In another embodiment, the once-daily maintenance dose is administered for about 10 days. The loading dose can be equal to, less than, or greater than the maintenance dose. In another embodiment, the loading dose is greater than the maintenance dose.

[0262] In certain embodiments, the methods of the present invention for preventing and / or treating a viral (e.g., SARS-CoV-2) infection comprise administering a loading dose of 150-250 mg (e.g., about 200 mg) on ​​day 1, followed by a once-daily maintenance dose of about 50-150 mg (e.g., about 100 mg). In another embodiment, the once-daily maintenance dose is administered for about 6-12 days, e.g., about 8-10 days. In another embodiment, the once-daily maintenance dose is administered for about 9 days. In another embodiment, the once-daily maintenance dose is administered for about 2-6 days, e.g., about 3-5 days. In another embodiment, the once-daily maintenance dose is administered for about 4 days.

[0263] In certain embodiments, the methods of the present invention for preventing and / or treating a viral (e.g., SARS-CoV-2) infection comprise administering a loading dose of 50-250 mg (e.g., about 100 mg) on ​​day 1, followed by a once-daily maintenance dose of about 10-100 mg (e.g., about 50 mg). In another embodiment, the once-daily maintenance dose is administered for about 6-12 days, e.g., about 8-10 days. In another embodiment, the once-daily maintenance dose is administered for about 9 days. In another embodiment, the once-daily maintenance dose is administered for about 2-6 days, e.g., about 3-5 days. In another embodiment, the once-daily maintenance dose is administered for about 4 days.

[0264] In another embodiment, the loading dose is the same as the maintenance dose. The equivalent of a single daily dose can be administered as needed, for example, for up to 5 days, up to 7 days, up to 10 days, up to 15 days, up to 20 days, up to 25 days, up to 1 month or more. In another embodiment, the single daily dose is administered for up to 20 days, up to 15 days, up to 14 days, up to 13 days, up to 12 days, up to 10 days, up to 8 days, up to 6 days, up to 4 days, up to 3 days, up to 2 days, or 1 day.

[0265] In a specific embodiment, a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the present invention, is administered once daily for about 6 to 12 days, e.g., about 8 to 10 days. In another embodiment, a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the present invention, is administered once daily for about 9 days. In another embodiment, a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of the present invention, is administered once daily for about 10 days. In another embodiment, about 50 to 150 mg of a compound of the present invention is administered once daily for about 6 to 12 days, e.g., about 10 days. In another embodiment, about 100 mg of a compound of the present invention is administered once daily for about 6 to 12 days, e.g., about 10 days.

[0266] Combination therapy In another aspect, the compounds of the invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs or isotopic variants thereof, or pharmaceutical compositions of the invention may be used in combination with one or more additional agents used in the treatment and / or prevention of Coronaviridae, Paramyxoviridae, Pneumoviridae, Picornaviridae, Flaviviridae, Filoviridae, Arenaviridae, and Orthomyxoviridae infections.

[0267] In certain specific embodiments, a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, may be administered together with one or more additional agents in the form of a single pharmaceutical composition. In another specific embodiment, a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, may be administered together with one or more additional agents in the form of two or more single pharmaceutical compositions. For example, a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, may be administered in the form of one pharmaceutical composition, and at least one of the additional agents may be administered in the form of a second pharmaceutical composition. When at least two additional reagents are present, one or more of the additional reagents may be included in a first pharmaceutical composition of a compound of the invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, and at least one of the other additional reagents may be included in a second pharmaceutical composition.

[0268] When using the compound of the present invention, or its pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant, or the pharmaceutical composition comprising the compound of the present invention, or its pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant and one or more additional reagents, dosage and administration regimen are within the knowledge of those skilled in the art.For example, when the standard treatment for daily practice is carried out using the dosage and administration regimen recognized in the art, in addition to the above-mentioned treatment, the compound of the present invention, or its pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant, or the pharmaceutical composition comprising the compound of the present invention, or its pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant and one or more additional reagents, one of the reagents of alternative combination therapy can be administered with the effective amount or administration regimen described herein.

[0269] The order of administration of a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, and one or more additional reagents may be changed. In certain specific embodiments, a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, may be administered before all additional reagents. In another specific embodiment, a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, may be administered before at least one additional reagent. In another specific embodiment, a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, may be administered simultaneously with one or more additional reagents. In another specific embodiment, a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, may be administered after at least one additional reagent.

[0270] In certain specific embodiments, the combination of a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, with one or more additional reagents may result in an additive effect. In another specific embodiment, the combination of a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, with one or more additional reagents may result in a synergistically enhanced effect. In another specific embodiment, the combination of a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, with one or more additional reagents may result in a synergistically enhanced effect. In some embodiments, the combination of a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, with one or more additional reagents may result in a potent synergistically enhanced effect. Combinations of a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug or isotopic variant thereof with one or more additional agents are not antagonistic.

[0271] As used herein, the term "antagonistic" refers to a decrease in the activity of a combination of compounds compared to the sum of the activities of the combination of compounds when the activity of each compound is measured individually (i.e., as a single compound).

[0272] The term "synergistic" refers to an activity of a combination of compounds that is greater than the sum of the activities of the combination of compounds when the activity of each compound is measured individually.

[0273] The term "additive effect" refers to an activity of a combination of compounds that is approximately equal to the sum of the activities of the combination of compounds when the activity of each compound is measured individually.

[0274] A potential advantage of utilizing a combination of a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, with one or more additional agents is that a reduced amount of the one or more additional agents may be required to effectively treat a viral infection, compared to the amount of the one or more additional agents required to achieve a similar therapeutic effect in the absence of the compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof. Another potential advantage of utilizing a combination of a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, with one or more additional agents is that the use of two or more compounds with different mechanisms of action may result in greater protection against the emergence of resistant viral strains than the protection provided by administering a single compound as a monotherapy.

[0275] Further advantages of utilizing a combination of a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, with one or more additional reagents may include: little or no cross-resistance between a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, and one or more additional reagents; different excretion routes between a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, and one or more additional reagents; little or no cross-toxicity between a compound of the present invention, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, and one or more additional reagents; little or no significant effect on cytochrome P450. A significant or complete absence of pharmacokinetic interactions between the compounds of the present invention, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates, polymorphs, prodrugs, or isotopic variants thereof, and one or more additional agents. A higher proportion of subjects achieving a sustained viral response compared to when the compound is administered as monotherapy, and / or a shorter duration of treatment to achieve a sustained viral response compared to when the compound is administered as monotherapy. [Example]

[0276] The following will describe the present invention in more detail in accordance with specific embodiments. It should be understood that the present invention is only used to explain the present invention and is not used to limit the scope of the present invention. In the following examples, experimental methods without specific conditions are generally performed according to conventional conditions or conditions recommended by manufacturers. Unless otherwise specified, parts and proportions are by weight.

[0277] Typically, in the preparation step, each reaction is carried out in an inert solvent at room temperature to reflux temperature (e.g., 0°C to 100°C, preferably 0°C to 80°C). The reaction time is typically 0.1 to 60 hours, preferably 0.5 to 24 hours.

[0278] The abbreviations used herein have the following meanings: H2SO4: sulfuric acid Acetone: Acetone NIS: N-iodosuccinimide TFA: Trifluoroacetic acid DMF: N,N-dimethylformamide Pd(dppf)Cl2: (1,1'-bis(diphenylphosphino)ferrocene)palladium dichloride TMEDA: Tetramethylethylenediamine NaBD4: sodium borodeuteride T3P: 1-propyl phosphate cyclic anhydride NMM: N-methylmorpholine DMAP: N,N-dimethyl-4-pyridinamine DCM: dichloromethane

[0279] Intermediate A-1 Preparation of the compound (3aR, 4R, 6R, 6aR)-4-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]meso-dioxole-4-carbonitrile [ka]

[0280] The following synthetic route was adopted: [ka]

[0281] GS-441524 (2.0 g, 6.9 mmol) was added to a reaction flask and dissolved in acetone (50 ml). 2,2-Dimethoxypropane (1.09 g, 10.4 mmol) and concentrated sulfuric acid (0.55 ml, 10.4 mmol) were added at room temperature. The mixture was stirred under nitrogen gas protection at room temperature for 4-6 hours. Completion of the reaction was monitored by TLC. Triethylamine (15 ml) was added to quench the reaction. The mixture was concentrated to remove the solvent. The residue was purified by column chromatography and dried under vacuum to give the product (1.7 g white solid, 74% yield). LC-MS (APCI): m / z=332.3 (M+1). + .

[0282] Intermediate A-2 Preparation of compound (3aR, 4R, 6R, 6aR)-4-(4-amino-5-iodopyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]meso-dioxole-4-carbonitrile [ka]

[0283] The following synthetic route was adopted: [ka]

[0284] Intermediate A-1 (11.8 g, 35.6 mmol) was added to a reaction flask and dissolved in anhydrous DMF (70 ml). NIS (8.82 g, 39.2 mmol) and trifluoroacetic acid (0.81 g, 7.1 mmol) were added sequentially. Under nitrogen gas protection, the mixture was heated to 50 °C and reacted for 1-2 hours. Completion was monitored by TLC. The mixture was cooled to room temperature, quenched with saturated aqueous sodium sulfite, and extracted three or four times with ethyl acetate. The combined organic phases were washed with saturated brine, concentrated, and purified by silica gel column chromatography to give the product (14.3 g, 88% yield). LC-MS (APCI): m / z = 458.4 (M+1). + .

[0285] Preparation of Intermediate A-3 Compound (3aR, 4R, 6R, 6aR)-4-(4-amino-5-deuteropyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]meso-dioxole-4-carbonitrile [ka]

[0286] The following synthetic route was adopted: [ka]

[0287] Intermediate A-2 (1.2 g, 2.57 mmol) was added to a reaction flask, and anhydrous tetrahydrofuran (20 ml) and deuterium oxide (2 ml) were added to dissolve the mixture. Pd(dppf)Cl2 (0.1 g, 0.13 mmol) and TMEDA (0.6 g, 5.14 mmol) were added sequentially. The mixture was stirred at room temperature for 10 minutes. Within 30 minutes, NaBD4 (0.22 g, 5.14 mmol) was added in portions and stirred for another 2-3 hours. After completion of the reaction was monitored by TLC, the reaction was quenched with saturated aqueous ammonium chloride and extracted 3-4 times with ethyl acetate. The organic phases were combined, washed with saturated brine, concentrated, and purified by silica gel column chromatography to give the product (0.47 g, yield: 55%). LC-MS (APCI): m / z = 333.6 (M+1). + .

[0288] Intermediate A-4 Preparation of Compound L-arazone Cyclobutyl Ester Hydrochloride [ka]

[0289] The following synthetic route was adopted: [ka]

[0290] Step 1 Synthesis of the compound (tert-butyloxycarbonyl)-L-alanine cyclobutyl ester A reaction flask was charged with (tert-butyloxycarbonyl)-L-alanine (4.91 g, 26 mmol) and cyclobutanol (1.68 g, 23.4 mmol), and anhydrous dichloromethane (50 ml) was added to dissolve the mixture. The mixture was cooled to 0 °C under nitrogen gas protection. NMM (7.08 g, 70.2 mmol), 1-propyl phosphate cyclic anhydride (16.8 ml, 28 mmol), and DMAP (57.6 mg, 0.47 mmol) were added sequentially. The mixture was heated to room temperature and stirred for 2 to 4 hours. Completion of the reaction was monitored by TLC. Water (40 ml) was added to quench the reaction. The organic phase was separated, washed with saturated brine, concentrated, and purified by silica gel column chromatography to give the product (2.4 g, white solid, yield: 42%). 1 H NMR (400 MHz, DMSO) δ 7.95 (s, 1H), 6.95 (s, 1H), 6.86 (s, 1H), 5.92 - 5.76 (m, 1H), 5.50 (d, J = 12.9 Hz, 2H), 4.92 - 4.76 (m, 2H), 4.65 (s, 1H), 4.17 (d, J = 24.2 Hz, 3H), 3.96 (d, J = 36.1 Hz, 3H), 3.67 (s, 2H), 2.22 (s, 2H), 2.06 - 1.87 (m, 2H), 1.70 (d, J = 9.6 Hz, 1H), 1.55 (d, J = 9.3 Hz, 1H), 1.23 (m, 9H).

[0291] Step 2: Synthesis of intermediate A-4 The compound (tert-butyloxycarbonyl)-L-alanine cyclobutyl ester (2.4 g, 9.9 mmol) obtained in the previous step was added to a reaction flask, and 4 N hydrogen chloride-dioxane solution (25 ml, 100 mmol) was added. The mixture was stirred at room temperature for 1-2 hours. The reaction was monitored by TLC for completion, and the mixture was concentrated to remove the solvent. The mixture was directly used in the next reaction without further purification. LC-MS (APCI): m / z=144.4 (M+1). + .

[0292] Intermediate A-5 Preparation of Compound L-Alanine 2,2-Dimethylbutyl Ester Hydrochloride [ka]

[0293] The following synthetic route was adopted: [ka]

[0294] Step 1: Synthesis of the compound (tert-butyloxycarbonyl)-L-alanine 2,2-dimethylbutyl ester A reaction flask was charged with (tert-butyloxycarbonyl)-L-alanine (4.91 g, 26 mmol) and 2,2-dimethyl-1-butanol (2.4 g, 23.4 mmol), and dissolved in anhydrous dichloromethane (50 ml). The mixture was cooled to 0 °C under nitrogen gas protection. NMM (7.08 g, 70.2 mmol), 1-propyl phosphate cyclic anhydride (16.8 ml, 28 mmol), and DMAP (57.6 mg, 0.47 mmol) were added sequentially. The mixture was heated to room temperature and stirred for 2-4 hours. Completion was monitored by TLC. Water (40 ml) was added to quench the reaction. The organic phase was separated, washed with saturated brine, concentrated, and purified by silica gel column chromatography to give the product (1.8 g, white solid, 28% yield). LC-MS (APCI): m / z = 274.6 (M+1). + .

[0295] Step 2: Synthesis of intermediate A-5 The compound (tert-butyloxycarbonyl)-L-alanine 2,2-dimethylbutyl ester (1.8 g, 6.6 mmol) obtained in the previous step was added to a reaction flask, and 4 N hydrogen chloride-dioxane solution (16.5 ml, 66 mmol) was added. The mixture was stirred at room temperature for 1-2 hours. The reaction was monitored by TLC for completion, and the mixture was concentrated to remove the solvent. The mixture was directly used in the next reaction without further purification. LC-MS (APCI): m / z=174.5 (M+1). + .

[0296] Intermediate A-6 Preparation of compound 2,2-dimethylthiopropionic acid S-2-hydroxyethyl ester [ka]

[0297] The following synthetic route was adopted: [ka]

[0298] 2-Mercaptoethanol (3.9 g, 50 mmol) was dissolved in anhydrous dichloromethane (40 ml) and cooled to -78 °C under nitrogen gas protection. Triethylamine (7.6 g, 75 mmol) was added, and a dichloromethane solution (10 ml) of pivaloyl chloride (6.6 g, 55 mmol) was slowly added dropwise. The mixture was stirred at low temperature for 2-3 hours. After completion of the reaction was monitored by TLC, water (20 ml) was added to quench the reaction. The organic phase was separated, washed with saturated brine, concentrated, and purified by column chromatography to give compound 11 as a colorless oily liquid (6.9 g, 86% yield). LC-MS (APCI): m / z = 163.6 (M+1). + .

[0299] Intermediate A-7 Preparation of compound 3-(hexadecyloxy)propan-1-ol [ka]

[0300] The following synthetic route was adopted: [ka]

[0301] Bromohexadecane (1.52 g, 5 mmol) and 1,3-propanediol (1.14 g, 15 mmol) were added to a reaction flask, dissolved in dimethyl sulfoxide (5 ml) and tetrahydrofuran (5 ml), and sodium hydroxide (800 mg, 20 mmol) was added. The mixture was allowed to react at room temperature for 24 hours. The mixture was diluted with water (10 ml), adjusted to neutral pH with 2 M dilute hydrochloric acid, extracted three times with ethyl acetate, and the combined organic phases were washed with saturated brine, concentrated, and purified by silica gel column chromatography to give the compound (1.0 g, yield: 67%). LC-MS (APCI): m / z = 301.3 (M+1). + .

[0302] Intermediate A-8 Preparation of Compound L-Alanine Dodecyl Ester Hydrochloride [ka]

[0303] Intermediate A-8 was obtained by the preparation of Intermediate A-4, replacing cyclobutanol (1.68 g, 23.4 mmol) with n-dodecanol (0.93 g, 5 mmol). LC-MS (APCI): m / z=258.6 (M+1). + .

[0304] Intermediate A-9 Preparation of Compound L-Alanine (9Z,12Z)-Octadecane-9,12-diene-1-Ester Hydrochloride [ka]

[0305] Intermediate A-9 was obtained by the preparation of intermediate A-4, replacing cyclobutanol (1.68 g, 23.4 mmol) with (9Z,12Z)-octadecane-9,12-dien-1-ol (1.33 g, 5 mmol). LC-MS (APCI): m / z=338.6 (M+1). + .

[0306] Intermediate A-10 Preparation of Compound L-Aspartic Acid-1,4-Dicyclobutyl Ester Hydrochloride [ka]

[0307] The following synthetic route was adopted: [ka]

[0308] L-Aspartic acid (1.33 g, 10 mmol), cyclobutanol (10 ml), and trimethylchlorosilane (3.3 g, 30 mmol) were added to a reaction flask, and the mixture was heated to 80°C under nitrogen gas protection and stirred overnight. The reaction was monitored by TLC for completion, and the mixture was concentrated to remove the solvent and directly used in the next reaction without further purification. LC-MS (APCI): m / z=242.5 (M+1). + .

[0309] Intermediate A-11 Preparation of Compound L-Aspartic Acid-1,4-Dicyclopentyl Ester Hydrochloride [ka]

[0310] The following synthetic route was adopted: [ka]

[0311] L-Aspartic acid (1.33 g, 10 mmol), cyclopentanol (10 ml), and trimethylchlorosilane (3.3 g, 30 mmol) were added to a reaction flask, and the mixture was heated to 80°C under nitrogen gas protection and stirred overnight. The reaction was monitored by TLC for completion, and the mixture was concentrated to remove the solvent and directly used in the next reaction without further purification. LC-MS (APCI): m / z=270.1 (M+1). + .

[0312] Intermediate A-12 Preparation of compound L-aspartic acid-1,4-bis(2-ethylbutyl ester) hydrochloride [ka]

[0313] The following synthetic route was adopted: [ka]

[0314] L-Aspartic acid (1.33 g, 10 mmol), 2-ethyl-1-butanol (10 ml), and trimethylchlorosilane (3.3 g, 30 mmol) were added to a reaction flask, and the mixture was heated to 80°C under nitrogen gas protection and stirred overnight. The reaction was monitored by TLC for completion, and the mixture was concentrated to remove the solvent and directly used in the next reaction without further purification. LC-MS (APCI): m / z=302.3 (M+1). + .

[0315] Intermediate A-13 Preparation of Compound L-Phenylalanine Cyclobutyl Ester Hydrochloride [ka]

[0316] Following the procedure for preparing Intermediate A-4, (tert-butyloxycarbonyl)-L-phenylalanine (1.32 g, 5 mmol) was substituted for (tert-butyloxycarbonyl)-L-alanine (4.91 g, 26 mmol) to give Intermediate A-13. LC-MS (APCI): m / z=220.6 (M+1). + .

[0317] Intermediate A-14 Preparation of Compound L-Phenylalanine-2-Methoxy-2-Methylpropyl Ester Hydrochloride [ka]

[0318] Intermediate A-14 was obtained by the same procedure as for the preparation of intermediate A-4, except that (tert-butyloxycarbonyl)-L-phenylalanine (1.32 g, 5 mmol) and 2-methoxy-2-methyl-1-phenylalanine (0.52 g, 5 mmol) were used instead of (tert-butyloxycarbonyl)-L-alanine (4.91 g, 26 mmol) and cyclobutanol (1.68 g, 23.4 mmol), respectively. LC-MS (APCI): m / z=252.4 (M+1). + .

[0319] Intermediate B-1 Compound (S)-2-(((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propanoic acid isopropyl ester, B-1a The compound (S)-2-(((R)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propanoic acid isopropyl ester and B-1b Preparation of compound (S)-2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propanoic acid isopropyl ester [ka]

[0320] The following synthetic route was adopted: [ka]

[0321] Step 1 Synthesis of the compound (hydroxy(4-nitrophenoxy)phosphoryl)-L-alanine isopropyl ester 4-Nitrophenylphosphorodichloride (5.0 g, 19.6 mmol) was added to a reaction flask, and anhydrous dichloromethane (30 ml) was added to dissolve the mixture. The mixture was cooled to -78°C under nitrogen gas protection. L-alanine isopropyl ester hydrochloride (3.3 g, 19.6 mmol) in dichloromethane (10 ml) and triethylamine (5.95 g, 58.8 mmol) were added sequentially. The mixture was stirred at low temperature for 1-2 hours, and the reaction was monitored by TLC for completion. Water (10 ml) was added, the mixture was slowly heated to room temperature, and the reaction was monitored by LC-MS for completion. The mixture was concentrated to remove the solvent and then directly added to the next reaction.

[0322] Step 2 Synthesis of the compound ((((isopropoxycarbonyl)oxy)methoxy)(4-nitrophenoxy)phosphoryl)-L-alanine isopropyl ester The compound (hydroxy(4-nitrophenoxy)phosphoryl)-L-alanine isopropyl ester obtained in the previous step was dissolved in acetonitrile (80 ml), and isopropyl chloromethyl carbonate (5.91 g, 38.7 mmol), potassium bicarbonate (3.88 g, 38.7 mmol), and potassium iodide (6.43 g, 38.7 mmol) were added sequentially. The mixture was heated to 60 °C under nitrogen gas protection and stirred overnight. Completion of the reaction was monitored by TLC. The mixture was concentrated to remove the solvent and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 2:1) to give a colorless oily liquid (3.7 g, yield: 42%). LC-MS (APCI): m / z = 449.7 (M+1). + .

[0323] Step 3 Synthesis of compound (S)-2-(((((3aR,4R,6R,6aR)-6-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-cyano-2,2-dimethyltetrahydrofuro[3,4-d][1,3]meso-dioxol-4-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propanoic acid isopropyl ester Intermediate A-1 (0.83 g, 2.5 mmol) and ((((isopropoxycarbonyl)oxy)methoxy)(4-nitrophenoxy)phosphoryl)-L-alanine isopropyl ester (1.66 g, 3.7 mmol) were added to a reaction flask, and anhydrous tetrahydrofuran (30 ml) was added to dissolve the mixture. The mixture was cooled to 0 °C in an ice bath, and under nitrogen gas protection, a 1 M solution of tert-butylmagnesium chloride (3.7 ml, 3.7 mmol) in tetrahydrofuran was added. The mixture was then slowly heated to room temperature and stirred for 2-4 hours. Completion of the reaction was monitored by TLC, and the reaction was quenched by the addition of saturated aqueous ammonium chloride solution. The mixture was extracted three times with ethyl acetate. The combined organic phases were washed three times with saturated brine, separated, concentrated, and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to give a colorless oily liquid (0.94 g, yield: 59%). LC-MS (APCI): m / z=641.7 (M+1) + .

[0324] Step 4 Synthesis of Compound B-1 The compound (S)-2-(((((3aR,4R,6R,6aR)-6-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-cyano-2,2-dimethyltetrahydrofuro[3,4-d][1,3]meso-dioxol-4-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propanoic acid isopropyl ester (1.15 g, 1.8 mmol) was added to a reaction flask, and formic acid (20 ml) was added. The mixture was stirred at room temperature overnight, and the reaction was monitored by TLC to confirm completion. The mixture was concentrated to remove the solvent, and the mixture was purified by silica gel column chromatography to obtain a white solid (637 mg, yield: 59%). LC-MS (APCI): m / z=601.5 (M+1) + . 1 H NMR (400 MHz, DMSO-d6) δ 7.93 (s, 1H), 6.95 (d, J = 3.6 Hz, 1H), 6.80 (d, J = 4.5 Hz, 1H), 6.02 (d, J = 5.8 Hz, 1H), 5.84 (dd, J = 22.5, 12.4 Hz, 1H), 5.55 - 5.32 (m, 3H), 4.90 - 4.72 (m, 2H), 4.58 (dd, J = 15.2, 3.8 Hz, 1H), 4.26 - 4.04 (m, 2H), 3.59 (ddd, J = 26.9, 16.9, 9.7 Hz, 1H), 1.23 (d, J = 6.2 Hz, 6H), 1.20 - 1.09 (m, 9H).

[0325] Step 5 Synthesis of compounds B-1a and B-1b Racemic compound B-1 was separated by reversed-phase preparative chromatography to give the target products B-1a (retention time: 8.34 min, relative content: 53.3%) and B-1b (retention time: 9.21 min, relative content: 46.7%). Chromatographic separation conditions: Column: Waters, Prep C18 OBD TM , 150×19 mm, 5 μm Column temperature: 30℃ Flow rate: 1.0 mL / min UV detection wavelength: 220 nm Mobile phase: pure water:acetonitrile = 40:60

[0326] Intermediate B-2 Compound (S)-2-(((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propionic acid 2-ethylbutyl ester, B-2a Compound (S)-2-(((R)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propionic acid 2-ethylbutyl ester and B-2b Preparation of compound (S)-2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propionic acid 2-ethylbutyl ester [ka]

[0327] Compound B-2 (white solid, 1.41 g, 22% yield) was obtained by following the procedure for preparing intermediate B-1, substituting L-alanine 2-ethylbutyl ester hydrochloride (2.09 g, 10 mmol) for L-alanine isopropyl ester hydrochloride (3.3 g, 19.6 mmol). LC-MS (APCI): m / z = 643.1 (M+1). + . 1 H NMR (400 MHz, DMSO-d6) δ 7.94 (s, 1H), 6.92 (d, J = 4.5 Hz, 1H), 6.80 (d, J = 4.5 Hz, 1H), 6.06 (d, J = 5.8 Hz, 1H), 5.86 (dd, J = 12.7, 10.1 Hz, 1H), 5.51 - 5.39 (m, 3H), 4.80 (dt, J = 12.5, 6.2 Hz, 1H), 4.60 (d, J = 3.5 Hz, 1H), 4.25 - 4.10 (m, 2H), 3.99 (dd, J = 10.8, 5.9 Hz, 1H), 3.90 (dd, J = 10.8, 5.7 Hz, 1H), 3.65 (dd, J = 16.8, 9.6 Hz, 1H), 1.46 (dt, J = 12.3, 6.1 Hz, 1H), 1.33 - 1.00 (m, 13H), 0.82 (t, J = 7.4 Hz, 6H).

[0328] Racemic compound B-2 was separated by reversed-phase preparative chromatography to give the target products B-2a (retention time: 10.6 min, relative content: 52.9%) and B-2b (retention time: 11.4 min, relative content: 47.1%). Chromatographic separation conditions: Column: Waters, Prep C18 OBD TM , 150×19 mm, 5 μm Column temperature: 30℃ Flow rate: 1.0 mL / min UV detection wavelength: 220 nm Mobile phase: pure water:acetonitrile = 40:60

[0329] Intermediate B-3 Compound (S)-2-(((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)((pivaloyloxy)methoxy)phosphoryl)amino)propionic acid 2-ethylbutyl ester, B-3a Compound (S)-2-(((R)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)((pivaloyloxy)methoxy)phosphoryl)amino)propionic acid 2-ethylbutyl ester and B-3b Preparation of compound (S)-2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)((pivaloyloxy)methoxy)phosphoryl)amino)propionic acid 2-ethylbutyl ester [ka]

[0330] Compound B-3 (white solid, 0.74 g, 23% yield) was obtained by following the procedure for preparing intermediate B-1, replacing L-alanine 2-ethylbutyl ester hydrochloride (1.87 g, 5 mmol) and chloromethyl pivalate (1.5 g, 10 mmol) with L-alanine isopropyl ester hydrochloride (3.3 g, 19.6 mmol) and isopropyl chloromethyl carbonate (5.91 g, 38.7 mmol), respectively. LC-MS (APCI): m / z = 641.2 (M+1). + . 1H NMR (400 MHz, DMSO-d6) δ 7.94 (s, 1H), 6.92 (d, J = 4.5 Hz, 1H), 6.80 (d, J = 4.5 Hz, 1H), 6.06 (d, J = 5.8 Hz, 1H), 5.86 (dd, J = 12.7, 10.1 Hz, 1H), 5.51 - 5.39 (m, 3H), 4.80 (dt, J = 12.5, 6.2 Hz, 1H), 4.60 (d, J = 3.5 Hz, 1H), 4.25 - 4.10 (m, 1H), 3.99 (dd, J = 10.8, 5.9 Hz, 1H), 3.90 (dd, J = 10.8, 5.7 Hz, 1H), 3.65 (dd, J = 16.8, 9.6 Hz, 1H), 1.46 (dt, J = 12.3, 6.1 Hz, 1H), 1.33 - 0.85 (m, 22H).

[0331] Step 2: Synthesis of Compound B-3a and Compound B-3b Racemic compound B-3 was separated by reversed-phase preparative chromatography to give the target products B-3a (retention time: 8.14 min, relative content: 53.8%) and B-3b (retention time: 8.82 min, relative content: 46.2%). Chromatographic separation conditions: Column: Waters, Prep C18 OBD TM , 150×19 mm, 5 μm Column temperature: 30℃ Flow rate: 1.0 mL / min UV detection wavelength: 220 nm Mobile phase: pure water:acetonitrile = 40:60

[0332] Intermediate B-4 Compound (S)-2-(((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propionic acid cyclobutyl ester, B-4a Compound (S)-2-(((R)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propionic acid cyclobutyl ester and B-4b Preparation of compound (S)-2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propionic acid cyclobutyl ester [ka]

[0333] Compound B-4 (white solid 2.26 g, total yield: 37%) was obtained by substituting L-alanine isopropyl ester hydrochloride (3.3 g, 19.6 mmol) for intermediate A-4 (1.43 g, 10 mmol) according to the preparation method of intermediate B-1. LC-MS (APCI): m / z = 613.5 (M+1). + . 1 H NMR (400 MHz, DMSO-d6).

[0334] Step 4 Synthesis of Compound B-4a and Compound B-4b Racemic compound B-4 was separated by reversed-phase preparative chromatography to give the target products B-4a (retention time: 7.82 min, relative content: 54.6%) and B-4b (retention time: 8.35 min, relative content: 45.4%). Chromatographic separation conditions: Column: Waters, Prep C18 OBD TM , 150×19 mm, 5 μm Column temperature: 30℃ Flow rate: 1.0 mL / min UV detection wavelength: 220 nm Mobile phase: pure water:acetonitrile = 40:60

[0335] Intermediate B-5 Compound (S)-2-(((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propionic acid 2,2-dimethylbutyl ester, B-5a Compound (S)-2-(((R)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propionic acid 2,2-dimethylbutyl ester and B-5b Preparation of compound (S)-2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((isopropoxycarbonyl)oxy)methoxy)phosphoryl)amino)propionic acid 2,2-dimethylbutyl ester [ka]

[0336] Compound B-5 (white solid, 1.41 g, 22% yield) was obtained by substituting L-alanine isopropyl ester hydrochloride (3.3 g, 19.6 mmol) for intermediate A-5 (2.09 g, 10 mmol) according to the preparation method of intermediate B-1. LC-MS (APCI): m / z = 643.1 (M+1). + . 1H NMR (400 MHz, DMSO-d6) δ 7.94 (s, 1H), 6.92 (d, J = 4.5 Hz, 1H), 6.80 (d, J = 4.5 Hz, 1H), 6.06 (d, J = 5.8 Hz, 1H), 5.86 (dd, J = 12.7, 10.1 Hz, 1H), 5.51 - 5.39 (m, 3H), 4.80 (dt, J = 12.5, 6.2 Hz, 1H), 4.60 (d, J = 3.5 Hz, 1H), 4.25 - 4.10 (m, 2H), 3.99 (dd, J = 10.8, 5.9 Hz, 1H), 3.90 (dd, J = 10.8, 5.7 Hz, 1H), 3.65 (dd, J = 16.8, 9.6 Hz, 1H), 1.46 (dt, J = 12.3, 6.1 Hz, 1H), 1.33 - 0.88 (m, 19H).

[0337] Racemic compound B-5 was separated by reverse-phase preparative chromatography to give the target products B-5a (retention time: 8.54 min, relative content: 51.2%) and B-5b (retention time: 9.62 min, relative content: 48.8%). Chromatographic separation conditions: Column: Waters, Prep C18 OBD TM , 150×19 mm, 5 μm Column temperature: 30℃ Flow rate: 1.0 mL / min UV detection wavelength: 220 nm Mobile phase: pure water:acetonitrile = 40:60

[0338] Intermediate B-6 Compound 2-((((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((S)-1-(2-ethylbutoxy)-1-oxopropan-2-yl)amino)phosphoryl)oxy)methyl)benzoic acid ethyl ester, B-6a Compound 2-((((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((S)-1-(2-ethylbutoxy)-1-oxopropan-2-yl)amino)phosphoryl)oxy)methyl)benzoic acid ethyl ester and B-6b Preparation of compound 2-((((R)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(((S)-1-(2-ethylbutoxy)-1-oxopropan-2-yl)amino)phosphoryl)oxy)methyl)benzoic acid ethyl ester [ka]

[0339] The following synthetic route was adopted: [ka]

[0340] Step 1 Synthesis of compound 2-((((((S)-1-(2-ethylbutoxy)-1-oxopropan-2-yl)amino)(4-nitrophenoxy)phosphoryl)oxy)methyl)benzoic acid ethyl ester 4-Nitrophenylphosphorodichloride (1.27 g, 5.0 mmol) was dissolved in anhydrous dichloromethane (20 ml) and cooled to -78 °C under nitrogen gas protection. Triethylamine (759 mg, 7.5 mmol) and L-alanine-2-ethylbutyl ester hydrochloride (1.05 g, 5.0 mmol) were added dropwise to a dichloromethane solution (10 ml) containing the mixture. The mixture was stirred at low temperature for 1-2 hours. After the completion of the reaction was confirmed by TLC, the mixture was added with 2-hydroxymethylbenzoic acid ethyl ester (1.08 g, 6.0 mmol), 2,6-dimethylpyridine (1.1 g, 10 mmol), and DMAP (305 mg, 2.5 mmol). The reaction mixture was heated to room temperature and stirred overnight. Completion was monitored by TLC, diluted with excess water, and extracted three or four times with dichloromethane. The combined organic phases were washed with saturated brine, concentrated, and purified by column chromatography to give a pale yellow oily liquid (1.02 g, 38% yield). LC-MS (APCI): m / z = 537.5 (M+1). + .

[0341] Step 2 Synthesis of compound 2-((((((3aR,4R,6R,6aR)-6-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-cyano-2,2-dimethyltetrahydrofuro[3,4-d][1,3]meso-dioxol-4-yl)methoxy)(((S)-1-(2-ethylbutoxy)-1-oxopropan-2-yl)amino)phosphoryl)oxy)methyl)benzoic acid ethyl ester Intermediate A-1 (0.83 g, 2.5 mmol) and compound 2-((((((S)-1-(2-ethylbutoxy)-1-oxopropan-2-yl)amino)(4-nitrophenoxy)phosphoryl)oxy)methyl)benzoic acid ethyl ester (1.98 g, 3.7 mmol) were added to a reaction flask, and anhydrous tetrahydrofuran (30 ml) was added to dissolve the mixture. The mixture was cooled to 0°C in an ice bath, and a 1M tetrahydrofuran solution of tert-butylmagnesium chloride (3.7 ml, 3.7 mmol) was added under nitrogen gas protection. The mixture was then slowly heated to room temperature and stirred for 2 to 4 hours. The reaction was monitored by TLC for completion, and the reaction was quenched by adding saturated aqueous ammonium chloride solution. The mixture was extracted 3 to 4 times with ethyl acetate. The organic phases were combined and washed 3 times with saturated brine. The organic phases were separated and concentrated, and then purified by silica gel column chromatography (petroleum ether:ethyl acetate=1:1) to give a pale yellow oily liquid (1.35 g, yield: 74%). LC-MS (APCI): m / z=729.3 (M+1) + .

[0342] Step 3 Synthesis of intermediate B-6 The compound 2-((((((3aR,4R,6R,6aR)-6-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-cyano-2,2-dimethyltetrahydrofuro[3,4-d][1,3]meso-dioxol-4-yl)methoxy)(((S)-1-(2-ethylbutoxy)-1-oxopropan-2-yl)amino)phosphoryl)oxy)methyl)benzoic acid ethyl ester (320 mg, 0.44 mmol) was added to a reaction flask, and formic acid (10 ml) was added. The mixture was stirred at room temperature overnight, and the reaction was monitored by TLC for completion. The mixture was concentrated to remove the solvent, and the mixture was purified by silica gel column chromatography to obtain a pale yellow solid (154 mg, yield: 51%). LC-MS (APCI): m / z=689.7 (M+1) + . 1H NMR (400 MHz, DMSO-d6) δ 7.93 (s, 1H), 7.44 (d, J = 3.5 Hz,1H), 7.41 (t, J = 3.5 Hz, 1H), 7.22 (m, 2H), 6.90 (d, J = 4.5 Hz, 1H), 6.80 (d, J = 4.5 Hz, 1H), 6.06 (d, J = 5.8 Hz, 1H), 5.86 (dd, J = 12.7, 10.1 Hz, 1H), 5.51 - 5.39 (m, 2H), 4.80 (dt, J = 12.5, 6.2 Hz, 2H), 4.61 (d, J = 3.5 Hz, 2H), 4.25 - 4.10 (m, 6H), 3.99 (dd, J = 10.8, 5.9 Hz, 1H), 2.1 (dd, J = 16.8, 9.6 Hz, 2H), 1.32 - 0.85 (m, 16H).

[0343] Step 4 Synthesis of Compound B-6a and Compound B-6b Racemic compound B-6 was separated by reversed-phase preparative chromatography to give the target products B-6a (retention time: 8.14 min, relative content: 52.2%) and B-6b (retention time: 9.02 min, relative content: 47.8%). Chromatographic separation conditions: Column: Waters, Prep C18 OBD TM , 150×19 mm, 5 μm Column temperature: 30℃ Flow rate: 1.0 mL / min UV detection wavelength: 220 nm Mobile phase: pure water:acetonitrile = 40:60

[0344] Intermediate B-7 Compound (S)-2-(((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)((2-methylbenzyl)oxy)phosphoryl)amino)propionic acid 2-ethylbutyl ester, B-7a Compound (S)-2-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)((2-methylbenzyl)oxy)phosphoryl)amino)propionic acid 2-ethylbutyl ester and B-7b Preparation of compound (S)-2-(((R)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)((2-methylbenzyl)oxy)phosphoryl)amino)propionic acid 2-ethylbutyl ester [ka]

[0345] Compound B-7 (white solid 2.08 g, total yield: 33%) was obtained by following the procedure for preparing intermediate B-6, substituting 2-hydroxymethylbenzoic acid ethyl ester (1.08 g, 6.0 mmol) for 2-methylbenzyl alcohol (1.46 g, 12 mmol). LC-MS (APCI): m / z = 631.1 (M+1). + . 1 H NMR (400 MHz, DMSO-d6) δ 7.93 (s, 1H), 7.44 (d, J = 3.5 Hz,1H), 7.41 (t, J = 3.5 Hz, 1H), 7.22 (m, 2H), 6.90 (d, J = 4.5 Hz, 1H), 6.80 (d, J = 4.5 Hz, 1H), 6.06 (d, J = 5.8 Hz, 1H), 5.86 (dd, J = 12.7, 10.1 Hz, 1H), 5.51 - 5.39 (m, 2H), 4.80 (dt, J = 12.5, 6.2 Hz, 2H), 4.61 (d, J = 3.5 Hz, 2H), 4.25 - 4.10 (m, 4H), 3.99 (dd, J = 10.8, 5.9 Hz, 1H), 2.2 (s, 3H), 2.1 (dd, J = 16.8, 9.6 Hz, 2H), 1.32 - 0.85 (m, 13H).

[0346] Racemic compound B-7 was separated by reversed-phase preparative chromatography to give the target products B-7a (retention time: 8.24 min, relative content: 53.3%) and B-7b (retention time: 9.07 min, relative content: 46.7%). Chromatographic separation conditions: Column: Waters, Prep C18 OBD TM , 150×19 mm, 5 μm Column temperature: 30℃ Flow rate: 1.0 mL / min UV detection wavelength: 220 nm Mobile phase: pure water:acetonitrile = 40:60

[0347] Intermediate B-8 Compound (S)-2-(((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)((4-(tert-butyl)benzyl)oxy)phosphoryl)amino)propionic acid 2-ethylbutyl ester, B-8a Compound (S)-(((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)((4-(tert-butyl)benzyl)oxy)phosphoryl)amino)propionic acid 2-ethylbutyl ester and B-8b Preparation of compound (S)-(((R)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)((4-(tert-butyl)benzyl)oxy)phosphoryl)amino)propionic acid 2-ethylbutyl ester [ka]

[0348] Compound B-8 (white solid 1.61 g, total yield: 24%) was obtained by following the procedure for preparing intermediate B-6, substituting 2-hydroxymethylbenzoic acid ethyl ester (1.08 g, 6.0 mmol) for 4-tert-butylbenzyl alcohol (1.97 g, 12 mmol). LC-MS (APCI): m / z = 673.4 (M+1). + . 1 H NMR (400 MHz, DMSO-d6) δ 7.93 (s, 1H), 7.44 (d, J = 3.5 Hz,1H), 7.41 (t, J = 3.5 Hz, 1H), 7.22 (m, 2H), 6.90 (d, J = 4.5 Hz, 1H), 6.80 (d, J = 4.5 Hz, 1H), 6.06 (d, J = 5.8 Hz, 1H), 5.86 (dd, J = 12.7, 10.1 Hz, 1H), 5.51 - 5.39 (m, 2H), 4.80 (dt, J = 12.5, 6.2 Hz, 2H), 4.61 (d, J = 3.5 Hz, 2H), 4.25 - 4.10 (m, 4H), 3.99 (dd, J = 10.8, 5.9 Hz, 1H), 2.1 (dd, J = 16.8, 9.6 Hz, 2H), 1.35 - 0.88 (m, 22H).

[0349] Racemic compound B-8 was separated by reverse-phase preparative chromatography to give the target products B-8a (retention time: 7.37 min, relative content: 55.0%) and B-8b (retention time: 8.23 ​​min, relative content: 45.0%). Chromatographic separation conditions: Column: Waters, Prep C18 OBD TM , 150×19 mm, 5 μm Column temperature: 30℃ Flow rate: 1.0 mL / min UV detection wavelength: 220 nm Mobile phase: pure water:acetonitrile = 40:60

[0350] Preparation of Intermediate B-9 Compound (((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)phosphoryl)bis(oxy))bis(methylene)diisopropylbis(carbonate) [ka]

[0351] The following synthetic route was adopted: [ka]

[0352] Step 1: Synthesis of the compound (((4-nitrophenoxy)phosphoryl)bis(oxy))bis(methylene)diisopropylbis(carbonate) 4-Nitrophenylphosphorodichloride (2.2 g, 8.6 mmol) was added to a reaction flask, and tetrahydrofuran (25 ml) was added to dissolve it. Purified water (5 ml) was slowly added dropwise, and the mixture was reacted at room temperature with stirring for 2 hours. The mixture was then concentrated to remove the solvent and directly added to the next reaction.

[0353] The intermediate obtained in the previous step was dissolved in acetonitrile (40 ml) and sequentially added with isopropyl chloromethyl carbonate (3.28 g, 21.5 mmol), potassium bicarbonate (2.15 g, 21.5 mmol), and potassium iodide (2.85 g, 17.2 mmol). The mixture was heated to 60°C under nitrogen gas protection and stirred overnight. Completion of the reaction was monitored by TLC. The mixture was concentrated to remove the solvent and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 3:1) to give a colorless oily liquid (1.74 g, yield: 45%). LC-MS (APCI): m / z = 452.7 (M+1). + .

[0354] Step 2 Synthesis of compound (((((2R,3S,4R,5R)-6-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-cyano-2,2-dimethyltetrahydrofuro[3,4-d][1,3]meso-dioxol-4-yl)methoxy)phosphoryl)bis(oxy))bis(methylene)diisopropylbis(carbonate) Intermediate A-1 (0.82 g, 2.5 mmol) and the compound (((4-nitrophenoxy)phosphoryl)bis(oxy))bis(methylene)diisopropylbis(carbonate) (1.68 g, 3.7 mmol) were added to a reaction flask, and anhydrous tetrahydrofuran (30 ml) was added to dissolve the mixture. The mixture was cooled to 0 °C in an ice bath, and under nitrogen gas protection, a 1 M solution of tert-butylmagnesium chloride (3.7 ml, 3.7 mmol) in tetrahydrofuran was added dropwise. The mixture was then slowly heated to room temperature and stirred for 2-4 hours. Completion of the reaction was monitored by TLC, and the reaction was quenched by adding saturated aqueous ammonium chloride solution. The mixture was extracted 3-4 times with ethyl acetate. The combined organic phases were washed 3 times with saturated brine, separated, concentrated, and purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain a colorless oily liquid (1.04 g, yield: 65%). LC-MS (APCI): m / z=644.2 (M+1) + .

[0355] Step 3 Synthesis of Intermediate B-9 The compound (((((2R,3S,4R,5R)-6-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-cyano-2,2-dimethyltetrahydrofuro[3,4-d][1,3]meso-dioxol-4-yl)methoxy)phosphoryl)bis(oxy))bis(methylene)diisopropylbis(carbonate) (1.04 g, 1.6 mmol) was added to a reaction flask, and formic acid (20 ml) was added. The mixture was stirred at room temperature overnight, and the reaction was monitored by TLC to confirm completion. The mixture was concentrated to remove the solvent, and purified by silica gel column chromatography to obtain a white solid (608 mg, yield: 63%). LC-MS (APCI): m / z=604.3 (M+1). + . 1H NMR (400 MHz, DMSO-d6) δ 8.04 (s, 1H), 7.07 (d, J = 4.5 Hz, 1H), 6.87 (d, J = 4.5 Hz, 1H), 5.57 (d, J = 13.6 Hz, 4H), 4.82 (td, J = 12.2, 6.1 Hz, 2H), 4.65 (d, J = 4.7 Hz, 1H), 4.30 (m, 1H), 4.11 (m, 1H), 3.96 - 3.88 (m, 2H), 1.24 (d, J = 6.4 Hz, 12H).

[0356] Preparation of Intermediate B-10 Compound (((((2R,3S,4R,5R)-5-(4-amino-5-deuteropyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)phosphoryl)bis(oxy))bis(methylene)diisopropylbis(carbonate) [ka]

[0357] Compound B-10 (white solid, 521 mg, yield: 54%) was obtained by replacing intermediate A-1 (0.82 g, 2.5 mmol) with intermediate A-3 (0.82 g, 2.5 mmol) according to the preparation method of intermediate B-9. LC-MS (APCI): m / z = 605.5 (M+1). + . 1 H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 6.88 (s, 1H), 5.52 (d, J = 13.6 Hz, 4H), 4.81 (td, J = 12.0, 6.0 Hz, 2H), 4.63 (d, J = 4.7 Hz, 1H), 4.30 (m, 1H), 4.11 (m, 1H), 3.96 - 3.85 (m, 2H), 1.22 (d, J = 6.4 Hz, 12H).

[0358] Preparation of Intermediate B-11 Compound (((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)oxy)methyl isopropyl carbonate [ka]

[0359] The following synthetic route was adopted: [ka]

[0360] Step 1 Synthesis of the compound (4-nitrophenyl)(phenyl) hydrogen phosphate 4-Nitrophenylphosphorodichloride (5.0 g, 19.6 mmol) was added to a reaction flask, dissolved in anhydrous dichloromethane (30 ml), and cooled to -78°C under nitrogen gas protection. Phenol (1.84 g, 19.6 mmol) in dichloromethane (5 ml) and triethylamine (5.95 g, 58.8 mmol) were added dropwise, followed by stirring at low temperature for 1-2 hours. Completion was monitored by TLC. Water (10 ml) was added, the mixture was slowly heated to room temperature, and the mixture was allowed to react for 0.5 hours. Completion was monitored by LC-MS. The mixture was concentrated to remove the solvent and then directly added to the next reaction. LC-MS (APCI): m / z=296.4 (M+1). + .

[0361] Step 2 Synthesis of the compound ((((4-nitrophenoxy)(phenoxy)phosphoryl)oxy)methyl)isopropyl carbonate The compound (4-nitrophenyl) (phenyl) hydrogen phosphate obtained in the previous step was dissolved in acetonitrile (80 ml), and isopropyl chloromethyl carbonate (5.91 g, 38.7 mmol), potassium bicarbonate (3.88 g, 38.7 mmol), and potassium iodide (6.43 g, 38.7 mmol) were added sequentially. The mixture was heated to 60 °C under nitrogen gas protection and stirred overnight. Completion of the reaction was monitored by TLC. The mixture was concentrated to remove the solvent and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1) to obtain a colorless oily liquid (3.4 g, yield: 37%). LC-MS (APCI): m / z = 468.7 (M+1). + .

[0362] Step 3 Synthesis of compound (((((3aR,4R,6R,6aR)-6-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-cyano-2,2-dimethyltetrahydrofuro[3,4-d][1,3]meso-dioxol-4-yl)methoxy)(phenoxy)phosphoryl)oxy)methyl isopropyl carbonate Intermediate A-1 (0.83 g, 2.5 mmol) and the compound ((((4-nitrophenoxy)(phenoxy)phosphoryl)oxy)methyl)isopropyl carbonate (1.52 g, 3.7 mmol) were added to a reaction flask, dissolved in anhydrous tetrahydrofuran (30 ml), cooled to 0 °C in an ice bath, and under nitrogen gas protection, a 1 M solution of tert-butylmagnesium chloride (3.7 ml, 3.7 mmol) in tetrahydrofuran was added dropwise. The mixture was then slowly heated to room temperature and stirred for 2-4 hours. Completion of the reaction w...

Claims

【Request Item 1】 【Chemistry 1】 where: R Ｘ is H or OH, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D, halogen, or —R ａ , -C(O)R ａ , -C(O)OR ａ , —C(O)NR ｂ R ｃ , -NR ｂ R ｃ , -NR ａ C(O)R ｂ , -NR ａ C(O)OR ｂ , -NR ａ C(O)NR ｂ R ｃ , -OR ａ , -OC(O)R ａ , —OC(O)NR ｂ R ｃ , -NR ａ S (O) ２ R ｂ , -S(O) ２ NR ａ , -S(O)R ａ or -S(O) ２ R ａ and Here, each R ａ , R ｂ and R ｃ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｂ and R ｃ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ Aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; X １ and X ２ are independently a bond, O, S, or NH; R １ and R ２ are independently １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; L is CH ２ , CDs ２ or CHD, W １ is formula (A), 【Chemistry 2】 where: Y １ is O or S, Z １ is O, NH or S, Z ２ is O, NH or S, Z ３ is a bond, O, NH or S, m １ is 1, 2, 3, 4, 5 or 6, n １ is 0 or 1, n ２ is 0 or 1, Each R ３ and R ４ are independently H, D, halogen, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ３ and R ４ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R ５ H, D, C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; W ２ is formula (B): 【Transformation 3】 where: Y ２ is O, NH or S, Z ４ is O, NH or S, Z ５ is O, NH or S, Z ６ is a bond, O, NH or S, m ２ is 0, 1, 2, 3, 4, 5 or 6, n ３ is 0 or 1, n ４ is 0 or 1, Each R ６ and R ７ are independently H, D, halogen, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R ８ H, D, C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Or, W １ and W ２ together with the 3'-C atom of the sugar group to form -Y ３ -, where Y ３ is O, NH or S, Or, W １ and W ２ together with the P atom to which they are attached to form -Y ４ (C(R ３ R ４ ) ｐ ) Y ４ -, where Y ４ is O, NH or S, p is 2, 3, 4 or 5, Each R is independently D, halogen, or —R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more R" until fully deuterated; Each R' is independently D, halogen, -R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R ｄ , R ｅ and R ｆ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｅ and R ｆ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R ｇ , -C(O)R ｇ , -C(O)OR ｇ , —C(O)NR ｈ R ｊ , -NR ｈ R ｊ , -NR ｇ C(O)R ｈ , -NR ｇ C(O)OR ｈ , -NR ｇ C(O)NR ｈ R ｊ , -OR ｇ , -OC(O)R ｇ , —OC(O)NR ｈ R ｊ , -NR ｇ S (O) ２ R ｈ , -S(O) ２ NR ｇ , -S(O)R ｇ or -S(O) ２ R ｇ or two R″ on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ Aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R ｇ , R ｈ and R ｊ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｈ and R ｊ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; A compound of formula (I) or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

2. The compound is a compound of formula (Ia) or (Ib): 【Chemistry 4】 10. A compound of claim 1, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

3. W １ teeth, 【Transformation 5】 and Here, lipid-like is C ８－２８ Alkyl group, C ８－２８ Halogenated alkyl group, C ８－２８ Alkenyl group or C ８－２８ an alkynyl group, wherein the C ８－２８ Alkyl group, C ８－２８ Halogenated alkyl group, C ８－２８ Alkenyl groups and C ８－２８ The alkynyl group is optionally substituted by one or more R; Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; R ３ , R ４ , R ５ , m １ and R is as defined in claim 1.

3. A compound according to claim 1 or 2, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

4. The compound is a compound of formula (II), (III) or (IV): 【Transformation 6】 where: R Ｘ is H or OH, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D, halogen, or —R ａ , -C(O)R ａ , -C(O)OR ａ , —C(O)NR ｂ R ｃ , -NR ｂ R ｃ , -NR ａ C(O)R ｂ , -NR ａ C(O)OR ｂ , -NR ａ C(O)NR ｂ R ｃ , -OR ａ , -OC(O)R ａ , —OC(O)NR ｂ R ｃ , -NR ａ S (O) ２ R ｂ , -S(O) ２ NR ａ , -S(O)R ａ or -S(O) ２ R ａ and Here, each R ａ , R ｂ and R ｃ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｂ and R ｃ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ Aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; X １ and X ２ are independently a bond, O, S, or NH; R １ and R ２ are independently １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; L is CH ２ , CDs ２ or CHD, m １ is 1, 2, 3, 4, 5 or 6, R ３ and R ４ are independently H, D, halogen, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ３ and R ４ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R ５ H, D, C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; W ２ is formula (B): 【Transformation 7】 where: Y ２ is O, NH or S, Z ４ is O, NH or S, Z ５ is O, NH or S, Z ６ is a bond, O, NH or S, m ２ is 0, 1, 2, 3, 4, 5 or 6, n ３ is 0 or 1, n ４ is 0 or 1, Each R ６ and R ７ are independently H, D, halogen, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R ８ H, D, C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Or, W ２ together with the 3' C atom of the sugar group to form -Y ３ -, where Y ３ is O, NH or S, Each R is independently D, halogen, or —R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more R" until fully deuterated; Each R' is independently D, halogen, -R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R ｄ , R ｅ and R ｆ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｅ and R ｆ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R ｇ , -C(O)R ｇ , -C(O)OR ｇ , —C(O)NR ｈ R ｊ , -NR ｈ R ｊ , -NR ｇ C(O)R ｈ , -NR ｇ C(O)OR ｈ , -NR ｇ C(O)NR ｈ R ｊ , -OR ｇ , -OC(O)R ｇ , —OC(O)NR ｈ R ｊ , -NR ｇ S (O) ２ R ｈ , -S(O) ２ NR ｇ , -S(O)R ｇ or -S(O) ２ R ｇ or two R″ on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ Aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R ｇ , R ｈ and R ｊ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｈ and R ｊ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; 4. A compound according to any one of claims 1 to 3, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

5. The compound is a compound represented by formula (IIa), formula (IIb), formula (IIIa), formula (IIIb), formula (IVa) or formula (IVb): 【Transformation 8】 【Chemistry 9】 5. The compound of claim 4, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

6. R Ｘ is H or OH, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D, halogen or C １－６ alkyl group, wherein the C １－６ the alkyl group is optionally substituted with one or more deuterium atoms until fully deuterated; X １ and X ２ are independently a bond, O, S, or NH; R １ and R ２ are independently １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; L is CH ２ , CDs ２ or CHD, m １ is 1, 2 or 3, R ３ and R ４ are independently H, D, C １－６ Alkyl group, C ３－６ a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R ３ and R ４ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C ３－６ The cycloalkyl group and the 3- to 7-membered heterocyclyl group are optionally substituted by one or more R'; R ５ is C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ alkenyl group, wherein the C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl groups, 3-7 membered heterocyclyl groups and C ２－２８ The alkenyl group is optionally substituted by one or more R; W ２ teeth, 【Chemistry 10】 and where: m ２ is 1, 2, 3, 4, 5 or 6, Each R ６ and R ７ are independently H, D, halogen, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R ８ is C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Lipid-like is C ８－２８ Alkyl group, C ８－２８ Halogenated alkyl group, C ８－２８ Alkenyl group or C ８－２８ an alkynyl group, wherein the C ８－２８ Alkyl group, C ８－２８ Halogenated alkyl group, C ８－２８ Alkenyl groups and C ８－２８ The alkynyl group is optionally substituted by one or more R; Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Each R is independently D, halogen, or —R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more R" until fully deuterated; Each R' is independently D, halogen, -R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R ｄ , R ｅ and R ｆ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｅ and R ｆ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R ｇ , -C(O)R ｇ , -C(O)OR ｇ , —C(O)NR ｈ R ｊ , -NR ｈ R ｊ , -NR ｇ C(O)R ｈ , -NR ｇ C(O)OR ｈ , -NR ｇ C(O)NR ｈ R ｊ , -OR ｇ , -OC(O)R ｇ , —OC(O)NR ｈ R ｊ , -NR ｇ S (O) ２ R ｈ , -S(O) ２ NR ｇ , -S(O)R ｇ or -S(O) ２ R ｇ or two R″ on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ Aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R ｇ , R ｈ and R ｊ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｈ and R ｊ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; 6. A compound according to claim 4 or 5, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

7. W ２ teeth, 【Chemistry 11】 and Here, m ２ is 1, 2, 3 or 4, Each R ６ and R ７ are independently H, D, C １－６ Alkyl group, C １－６ Alkoxy group, C ３－６ a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Alkoxy group, C ３－６ The cycloalkyl group and the 3- to 7-membered heterocyclyl group are optionally substituted by one or more R'; Each R ８ are independently １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group or C ２－２８ an alkynyl group, wherein the C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl groups and C ２－２８ The alkynyl group is optionally substituted by one or more R; Lipid-like is C ８－２８ Alkyl group, C ８－２８ Halogenated alkyl group, C ８－２８ Alkenyl group or C ８－２８ an alkynyl group, wherein the C ８－２８ Alkyl group, C ８－２８ Halogenated alkyl group, C ８－２８ Alkenyl groups and C ８－２８ The alkynyl group is optionally substituted by one or more R; Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

7. A compound according to any one of claims 4 to 6, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

8. W ２ teeth, 【Chemistry 12】 and Here, R ６ is C １－６ is an alkyl group, and R ７ is H or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group, wherein said C １－６ Alkyl group and C ３－６ The cycloalkyl group is optionally a phenyl group or a —C(O)OC １－６ substituted with one or more groups selected from alkyl groups, R ８ are independently １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ alkenyl group, wherein the C １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ The alkenyl group may optionally contain one or more C １－６ substituted by an alkoxy group, Preferably, W ２ teeth, 【Chemistry 13】 and Preferably, W ２ teeth, 【Chemistry 14】 and Preferably, W ２ teeth, 【Chemistry 15】 and Preferably, W ２ teeth, 【Chemistry 16】 and Preferably, W ２ teeth, 【Chemistry 17】 and Preferably, W ２ teeth, [Chemistry 18] That is, 8. A compound according to any one of claims 4 to 7, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

9. W ２ teeth, 【Chemistry 19】 and Here, R ６ and R ７ is H, R ８ are independently １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ is an alkenyl group, Preferably, W ２ teeth, 【Chemistry 20】 That is, 8. A compound according to any one of claims 4 to 7, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

10. W ２ teeth, 【Chemistry 21】 and Here, R ６ and R ７ is H, R ８ are independently １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ is an alkenyl group, Preferably, W ２ teeth, 【Chemistry 22】 and Preferably, W ２ teeth, 【Chemistry 23】 That is, 8. A compound according to any one of claims 4 to 7, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

11. W ２ teeth, 【Chemistry 24】 and Here, m ２ is 1 or 2, R ６ and R ７ is H, R ８ are independently １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ is an alkenyl group, Preferably, W ２ teeth, 【Chemistry 25】 That is, 8. A compound according to any one of claims 4 to 7, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

12. W ２ teeth, 【Chemistry 26】 and Here, m ２ is 2, 3 or 4, R ６ and R ７ are independently H or C １－６ an alkoxy group, wherein the C １－６ The alkoxy group is optionally C ６－１０ aryl group or 5- to 10-membered heteroaryl group, ６－１０ The aryl or 5- to 10-membered heteroaryl group may optionally be halogen or C １－６ substituted by one or more groups selected from alkoxy groups; Lipid-like is C ８－２８ Alkyl group or C ８－２８ is an alkenyl group, Preferably, W ２ teeth, 【Chemistry 27】 and Preferably, W ２ teeth, 【Chemistry 28】 That is, 8. A compound according to any one of claims 4 to 7, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

13. W ２ teeth, 【Chemistry 29】 and Here, m ２ is 2, 3 or 4, R ６ and R ７ is H, Lipid-like is C ８－２８ is an alkenyl group, Preferably, W ２ teeth, 【Transformation 30】 That is, 8. A compound according to any one of claims 4 to 7, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

14. W ２ teeth, 【Chemistry 31】 and where Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl or 5- to 10-membered heteroaryl group may optionally contain one or more C １－６ substituted by alkyl groups, Preferably, W ２ teeth, 【Chemistry 32】 That is, 8. A compound according to any one of claims 4 to 7, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

15. W ２ teeth, 【Transformation 33】 and Here, R ６ and R ７ is H, Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl group or 5- to 10-membered heteroaryl group is optionally C １－６ Alkyl group or —C(O)OC １－６ substituted with one or more groups selected from alkyl groups, Preferably, W ２ teeth, 【Transformation 34】 That is, 8. A compound according to any one of claims 4 to 7, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

16. W ２ teeth, 【Chemistry 35】 and Preferably, W ２ teeth, 【Transformation 36】 and Preferably, W ２ teeth, 【Chemistry 37】 【Transformation 38】 and Preferably, W ２ teeth, 【Chemistry 39】 【Chemistry 40】 That is, 16. A compound according to any one of claims 4 to 15, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

17. R Ｘ is H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen; X １ and X ２ are independently a bond or O; R １ and R ２ are independently １－６ Alkyl group, C ３－６ Cycloalkyl group or C ６－１０ is an aryl group, L is CH ２ , CDs ２ or CHD, m １ is 1, 2 or 3, R ３ and R ４ are independently H, D or C １－６ is an alkyl group, R ５ is C １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ is an alkenyl group, 17. A compound according to any one of claims 4 to 16, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

18. R Ｘ is H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H or D; X １ and X ２ are independently a bond or O; R １ and R ２ are independently １－６ is an alkyl group, L is CH ２ , CDs ２ or CHD, m １ is 1, 2 or 3, R ３ and R ４ are independently H or D; R ５ is C １－６ is an alkyl group, 18. A compound according to any one of claims 4 to 17, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

19. The compound is a compound of formula (IIa) or (IIb): 【Chemistry 41】 where: R Ｘ is H or OH, preferably H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen, preferably H or D; X １ and X ２ are independently a bond, O, S or NH, preferably a bond or O, more preferably a bond; R １ and R ２ are independently C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group), L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H, D, halogen, C １－６ Alkyl group or C １－６ a halogenated alkyl group, preferably H or D; R ５ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ an alkyl group (preferably an isopropyl group), W ２ teeth, 【Chemistry 42】 and Each R ６ and R ７ are independently optionally substituted by one or more R', H, D, C, optionally substituted by one or more deuteriums until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group) or -OR ｄ or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ forming a cycloalkyl group or a 3- to 7-membered heterocyclyl group, Each R' is independently -C(O)OC １－６ Alkyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, preferably —C(O)OC １－６ is an alkyl group or a phenyl group, R ８ is optionally substituted by one or more R, which is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group, C ３－６ a cycloalkyl group or a 3- to 7-membered heterocyclyl group, preferably C １－６ Alkyl group or C ３－６ is a cycloalkyl group, Ar is a phenyl group optionally substituted by one or more R; R independently represents D, C, optionally substituted with one or more deuterium atoms until fully deuterated. １－６ Alkyl group or —OC １－６ is an alkyl group, m ２ is 1, 2, 3, 4, 5 or 6, preferably 2, 3 or 4, The lipid-like is optionally substituted with one or more deuterium atoms until fully deuterated. ８－２８ Alkyl group or C ８－２８ alkenyl group, preferably C １２－２０ is an alkyl group, R ｄ is independently optionally substituted by one or more R″ (CH ２ ) １－３ -C ６－１０ an aryl group or (CH ２ ) １－３ - a 5- to 10-membered heteroaryl group, preferably CH ２ -phenyl group, R″ is independently D, halogen, or —OC, optionally substituted by one or more deuteriums until fully deuterated. １－６ is an alkyl group, 6. A compound according to claim 5, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

20. R Ｘ is H or OH, preferably H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen, preferably H or D; X １ and X ２ are independently a bond or O, preferably a bond; R １ and R ２ are independently C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group), L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H, D, halogen, C １－６ Alkyl group or C １－６ a halogenated alkyl group, preferably H or D; R ５ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ an alkyl group (preferably an isopropyl group), W ２ teeth, 【Chemistry 43】 and Each R ６ and R ７ are independently H, D or C optionally substituted by one or more R', and optionally substituted by one or more deuteriums until fully deuterated. １－３ is an alkyl group or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ forming a cycloalkyl group or a 3- to 7-membered heterocyclyl group, Each R' is independently -C(O)OC １－６ Alkyl group or C ６－１０ An aryl group, preferably —C(O)OC １－６ is an alkyl group or a phenyl group, R ８ is optionally substituted by one or more R, and optionally substituted by one or more deuteriums until fully deuterated; １－６ Alkyl group or C ３－６ is a cycloalkyl group, R is independently -OC １－６ is an alkyl group, 20. The compound of claim 19, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

21. R Ｘ is H or OH, preferably H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen, preferably H or D; X １ and X ２ are independently a bond or O, preferably a bond; R １ and R ２ are independently C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group), L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H, D, halogen, C １－６ Alkyl group or C １－６ a halogenated alkyl group, preferably H or D; R ５ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ an alkyl group (preferably an isopropyl group), W ２ teeth, 【Chemistry 44】 and Each R ６ and R ７ are independently H, D, or C optionally substituted by one or more deuterium atoms until fully deuterated. １－３ is an alkyl group, R ８ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group or C ３－６ is a cycloalkyl group, 21. The compound of claim 20, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

22. R Ｘ is H or OH, preferably H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen, preferably H or D; X １ and X ２ are independently a bond or O, preferably a bond; R １ and R ２ are independently C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group), L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H, D, halogen, C １－６ Alkyl group or C １－６ a halogenated alkyl group, preferably H or D; R ５ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ an alkyl group (preferably an isopropyl group), W ２ teeth, 【Chemistry 45】 and Ar is a phenyl group optionally substituted by one or more R; R independently represents a C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ is an alkyl group, Each R ６ and R ７ are independently H, D, or C optionally substituted by one or more deuterium atoms until fully deuterated. １－３ is an alkyl group, R ８ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group or C ３－６ is a cycloalkyl group, 20. The compound of claim 19, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

23. R Ｘ is H or OH, preferably H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen, preferably H or D; X １ and X ２ are independently a bond or O, preferably a bond; R １ and R ２ are independently C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group), L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H or D; R ５ is an isopropyl group optionally substituted with one or more deuterium atoms until fully deuterated; W ２ teeth, 【Chemistry 46】 and Each R ６ and R ７ are independently H or D; R ８ is an isopropyl group optionally substituted with one or more deuterium atoms until fully deuterated; 20. The compound of claim 19, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

24. The compound is of formula (IIIa) or (IIIb): 【Chemistry 47】 where: R Ｘ is H or OH, preferably H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen, preferably H or D; X １ and X ２ are independently a bond or O, preferably a bond; R １ and R ２ are independently C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group), L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H or D; R ５ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ is an alkyl group, W ２ teeth, 【Chemistry 48】 and Each R ６ and R ７ are independently H, D, or C optionally substituted by one or more deuterium atoms until fully deuterated. １－３ is an alkyl group, R ８ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ is an alkyl group, Ar is a phenyl group optionally substituted by one or more R; R independently represents a C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ is an alkyl group, 6. A compound according to claim 5, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

25. R Ｘ is H or OH, preferably H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen, preferably H or D; X １ and X ２ are independently a bond or O, preferably a bond; R １ and R ２ are independently C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group), L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H or D; R ５ is optionally substituted by one or more deuteriums D until fully deuterated; １－６ an alkyl group (preferably a tert-butyl group), W ２ teeth, 【Chemistry 49】 and Each R ６ and R ７ are independently H, D, or C optionally substituted by one or more deuterium atoms until fully deuterated. １－３ is an alkyl group, R ８ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ is an alkyl group, 25. The compound of claim 24, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

26. R Ｘ is H or OH, preferably H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen, preferably H or D; X １ and X ２ are independently a bond or O, preferably a bond; R １ and R ２ are independently C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group), L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H or D; R ５ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group, preferably an isopropyl group; W ２ teeth, [Transformation 50] and Ar is a phenyl group optionally substituted by one or more R; R independently represents a C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ is an alkyl group, 25. The compound of claim 24, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

27. R Ｘ is H or OH, preferably H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen, preferably H or D; X １ and X ２ are independently a bond or O, preferably a bond; R １ and R ２ are independently C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group), L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H or D; R ５ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ an alkyl group, preferably a tert-butyl group, more preferably an isopropyl group; W ２ teeth, 【Chemistry 51】 and Each R ６ and R ７ are independently H or D; R ８ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ an alkyl group, preferably a tert-butyl group, more preferably an isopropyl group); 25. The compound of claim 24, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

28. The compound is of formula (IVa) or (IVb): 【Chemistry 52】 where: R Ｘ is H or OH, preferably H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen, preferably H or D; X １ and X ２ are independently a bond or O, preferably a bond; R １ and R ２ are independently C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group), L is CH ２ , CDs ２ or CHD, m １ is 1, 2 or 3, R ３ and R ４ are independently H or D; R ５ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ an alkyl group (preferably a tert-butyl group), W ２ teeth, 【Chemistry 53】 and m ２ is 1, 2 or 3, Each R ６ and R ７ are independently H or D, optionally substituted by one or more deuteriums until fully deuterated; R ８ is optionally substituted by one or more deuterium atoms until fully deuterated. １－６ an alkyl group (preferably a tert-butyl group), Ar is a phenyl group optionally substituted by one or more R; R independently represents a C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ is an alkyl group, 6. The compound of claim 5, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

29. The compound is a compound of formula (V) or (VI): 【Chemistry 54】 where: R Ｘ is H or OH, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D, halogen, or —R ａ , -C(O)R ａ , -C(O)OR ａ , —C(O)NR ｂ R ｃ , -NR ｂ R ｃ , -NR ａ C(O)R ｂ , -NR ａ C(O)OR ｂ , -NR ａ C(O)NR ｂ R ｃ , -OR ａ , -OC(O)R ａ , —OC(O)NR ｂ R ｃ , -NR ａ S (O) ２ R ｂ , -S(O) ２ NR ａ , -S(O)R ａ or -S(O) ２ R ａ and Here, each R ａ , R ｂ and R ｃ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｂ and R ｃ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ Aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; X １ and X ２ are independently a bond, O, S, or NH; R １ and R ２ are independently １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; L is CH ２ , CDs ２ or CHD, m １ is 1, 2, 3, 4, 5 or 6, R ３ and R ４ are independently H, D, halogen, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ３ and R ４ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; Lipid-like is C ８－２８ Alkyl group, C ８－２８ Halogenated alkyl group, C ８－２８ Alkenyl group or C ８－２８ an alkynyl group, wherein the C ８－２８ Alkyl group, C ８－２８ Halogenated alkyl group, C ８－２８ Alkenyl group or C ８－２８ The alkynyl group is optionally substituted by one or more R; W ２ is formula (B): 【Transformation 55】 where: Y ２ is O, NH or S, Z ４ is O, NH or S, Z ５ is O, NH or S, Z ６ is a bond, O, NH or S, m ２ is 0, 1, 2, 3, 4, 5 or 6, n ３ is 0 or 1, n ４ is 0 or 1, Each R ６ and R ７ are independently H, D, halogen, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R ８ H, D, C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Or, W ２ together with the 3' C atom of the sugar group to form -Y ３ -, where Y ３ is O, NH or S, Each R is independently D, halogen, or —R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more R" until fully deuterated; Each R' is independently D, halogen, -R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R ｄ , R ｅ and R ｆ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｅ and R ｆ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R ｇ , -C(O)R ｇ , -C(O)OR ｇ , —C(O)NR ｈ R ｊ , -NR ｈ R ｊ , -NR ｇ C(O)R ｈ , -NR ｇ C(O)OR ｈ , -NR ｇ C(O)NR ｈ R ｊ , -OR ｇ , -OC(O)R ｇ , —OC(O)NR ｈ R ｊ , -NR ｇ S (O) ２ R ｈ , -S(O) ２ NR ｇ , -S(O)R ｇ or -S(O) ２ R ｇ or two R″ on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ Aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R ｇ , R ｈ and R ｊ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｈ and R ｊ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; 4. A compound according to any one of claims 1 to 3, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

30. The compound is a compound represented by formula (Va), formula (Vb), formula (VIa) or formula (VIb): 【Transformation 56】 30. The compound of claim 29, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

31. R Ｘ is H or OH, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D, halogen or C １－６ alkyl group, wherein the C １－６ the alkyl group is optionally substituted with one or more deuterium atoms until fully deuterated; X １ and X ２ are independently a bond, O, S, or NH; R １ and R ２ is independently C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; L is CH ２ , CDs ２ or CHD, m １ is 2, 3 or 4, R ３ and R ４ are independently H, D, C １－６ Alkyl group, C ３－６ a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R ３ and R ４ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C ３－６ The cycloalkyl group and the 3- to 7-membered heterocyclyl group are optionally substituted by one or more R'; Lipid-like is C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ２－２８ Alkenyl group or C ２－２８ an alkynyl group, wherein the C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ２－２８ Alkenyl groups and C ２－２８ The alkynyl group is optionally substituted by one or more R; W ２ teeth, 【Chemistry 57】 and where: m ２ is 1, 2, 3, 4, 5 or 6, Each R ６ and R ７ are independently H, D, halogen, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R ８ is C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Each R is independently D, halogen, or —R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more R" until fully deuterated; Each R' is independently D, halogen, -R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R ｄ , R ｅ and R ｆ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｅ and R ｆ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R ｇ , -C(O)R ｇ , -C(O)OR ｇ , —C(O)NR ｈ R ｊ , -NR ｈ R ｊ , -NR ｇ C(O)R ｈ , -NR ｇ C(O)OR ｈ , -NR ｇ C(O)NR ｈ R ｊ , -OR ｇ , -OC(O)R ｇ , —OC(O)NR ｈ R ｊ , -NR ｇ S (O) ２ R ｈ , -S(O) ２ NR ｇ , -S(O)R ｇ or -S(O) ２ R ｇ or two R″ on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ Aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R ｇ , R ｈ and R ｊ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｈ and R ｊ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; 31. A compound according to claim 29 or 30, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

32. W ２ teeth, 【Transformation 58】 and Here, m ２ is 1, 2, 3 or 4, Each R ６ and R ７ are independently H, D, C １－６ Alkyl group, C １－６ Alkoxy group, C ３－６ a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Alkoxy group, C ３－６ The cycloalkyl group and the 3- to 7-membered heterocyclyl group are optionally substituted by one or more R'; Each R ８ are independently １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group or C ２－２８ an alkynyl group, wherein the C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl groups and C ２－２８ The alkynyl group is optionally substituted by one or more R; Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

32. The compound of any one of claims 29 to 31, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

33. W ２ teeth, 【Chemistry 59】 and Here, R ６ is C １－６ is an alkyl group, and R ７ is H or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group, wherein said C １－６ Alkyl group and C ３－６ The cycloalkyl group is optionally a phenyl group or a —C(O)OC １－６ substituted with one or more groups selected from alkyl groups, R ８ are independently １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ alkenyl group, wherein the C １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ The alkenyl group may optionally contain one or more C １－６ substituted by an alkoxy group, Preferably, W ２ teeth, 【Transformation 60】 and Preferably, W ２ teeth, 【Chemistry 61】 and Preferably, W ２ teeth, 【Transformation 62】 and Preferably, W ２ teeth, 【Transformation 63】 That is, 33. A compound according to any one of claims 29 to 32, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

34. W ２ teeth, 【Chemistry 64】 and Here, R ６ and R ７ is H, R ８ are independently １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ is an alkenyl group, Preferably, W ２ teeth, 【Transformation 65】 That is, 33. A compound according to any one of claims 29 to 32, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

35. W ２ teeth, 【Chemical Formula 66】 and Here, R ６ and R ７ is H, R ８ are independently １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ is an alkenyl group, Preferably, W ２ teeth, 【Transformation 67】 That is, 33. A compound according to any one of claims 29 to 32, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

36. W ２ teeth, 【Transformation 68】 and Here, m ２ is 1 or 2, R ６ and R ７ is H, R ８ are independently １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ is an alkenyl group, Preferably, W ２ teeth, 【Transformation 69】 That is, 33. A compound according to any one of claims 29 to 32, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

37. W ２ teeth, 【Transformation 70】 and where Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl or 5- to 10-membered heteroaryl group may optionally contain one or more C １－６ substituted by alkyl groups, Preferably, W ２ teeth, 【Chemistry 71】 That is, 33. A compound according to any one of claims 29 to 32, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

38. W ２ teeth, 【Chemistry 72】 and Here, R ６ and R ７ is H, Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl group or 5- to 10-membered heteroaryl group is optionally C １－６ Alkyl group or —C(O)OC １－６ substituted with one or more groups selected from alkyl groups, Preferably, W ２ teeth, 【Transformation 73】 That is, 33. A compound according to any one of claims 29 to 32, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

39. W ２ teeth, 【Chemistry 74】 and Preferably, W ２ teeth, 【Chemistry 75】 That is, 39. A compound according to any one of claims 29 to 38, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

40. R Ｘ is H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen; X １ and X ２ are independently a bond or O; R １ and R ２ are independently １－６ Alkyl group, C ３－６ Cycloalkyl group or C ６－１０ is an aryl group, L is CH ２ , CDs ２ or CHD, m １ is 2, 3 or 4, R ３ and R ４ are independently H, D or C １－６ an alkoxy group, wherein the C １－６ The alkoxy group is optionally C ６－１０ aryl group or 5- to 10-membered heteroaryl group, ６－１０ The aryl or 5- to 10-membered heteroaryl group may optionally be halogen or C １－６ substituted by one or more groups selected from alkoxy groups; Lipid-like is C １－２８ Alkyl group or C ２－２８ is an alkenyl group, 40. A compound according to any one of claims 29 to 39, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

41. R Ｘ is H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H or D; X １ and X ２ are independently a bond or O; R １ and R ２ are independently １－６ is an alkyl group, L is CH ２ , CDs ２ or CHD, m １ is 2, 3 or 4, R ３ and R ４ are independently H, D or C １－６ an alkoxy group, wherein the C １－６ The alkoxy group is optionally C ６－１０ aryl group or 5- to 10-membered heteroaryl group, ６－１０ The aryl or 5- to 10-membered heteroaryl group may optionally be halogen or C １－６ substituted by one or more groups selected from alkoxy groups; Lipid-like is C １－２８ Alkyl group or C ２－２８ is an alkenyl group, 41. The compound of any one of claims 29 to 40, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

42. The compound is of formula (VII): 【Transformation 76】 where: R Ｘ is H or OH, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D, halogen, or —R ａ , -C(O)R ａ , -C(O)OR ａ , —C(O)NR ｂ R ｃ , -NR ｂ R ｃ , -NR ａ C(O)R ｂ , -NR ａ C(O)OR ｂ , -NR ａ C(O)NR ｂ R ｃ , -OR ａ , -OC(O)R ａ , —OC(O)NR ｂ R ｃ , -NR ａ S (O) ２ R ｂ , -S(O) ２ NR ａ , -S(O)R ａ or -S(O) ２ R ａ and Here, each R ａ , R ｂ and R ｃ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｂ and R ｃ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ Aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; X １ and X ２ are independently a bond, O, S, or NH; R １ and R ２ are independently １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H, D, halogen, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ３ and R ４ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; W ２ is formula (B): 【Chemical Formula 77】 where: Y ２ is O, NH or S, Z ４ is O, NH or S, Z ５ is O, NH or S, Z ６ is a bond, O, NH or S, m ２ is 0, 1, 2, 3, 4, 5 or 6, n ３ is 0 or 1, n ４ is 0 or 1, Each R ６ and R ７ are independently H, D, halogen, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R ８ H, D, C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Or, W ２ together with the 3' C atom of the sugar group to form -Y ３ -, where Y ３ is O, NH or S, Each R is independently D, halogen, or —R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more R" until fully deuterated; Each R' is independently D, halogen, -R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein said C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R ｄ , R ｅ and R ｆ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｅ and R ｆ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R ｇ , -C(O)R ｇ , -C(O)OR ｇ , —C(O)NR ｈ R ｊ , -NR ｈ R ｊ , -NR ｇ C(O)R ｈ , -NR ｇ C(O)OR ｈ , -NR ｇ C(O)NR ｈ R ｊ , -OR ｇ , -OC(O)R ｇ , —OC(O)NR ｈ R ｊ , -NR ｇ S (O) ２ R ｈ , -S(O) ２ NR ｇ , -S(O)R ｇ or -S(O) ２ R ｇ or two R″ on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ Aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R ｇ , R ｈ and R ｊ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｈ and R ｊ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; 4. A compound according to any one of claims 1 to 3, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

43. The compound is of formula (VIIa) or formula (VIIb): 【Transformation 78】 43. The compound of claim 42, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

44. R Ｘ is H or OH, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D, halogen or C １－６ alkyl group, wherein the C １－６ the alkyl group is optionally substituted with one or more deuterium atoms until fully deuterated; X １ and X ２ are independently a bond, O, S, or NH; R １ and R ２ is independently C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H, D, C １－６ Alkyl group, C ３－６ a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R ３ and R ４ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C ３－６ The cycloalkyl group and the 3- to 7-membered heterocyclyl group are optionally substituted by one or more R'; Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; W ２ teeth, 【Transformation 79】 and where: m ２ is 1, 2, 3, 4, 5 or 6, Each R ６ and R ７ are independently H, D, halogen, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C １－６ Alkoxy group, C １－６ Halogenated alkoxy group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R'; R ８ is C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group, C ２－２８ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Lipid-like is C ８－２８ Alkyl group, C ８－２８ Halogenated alkyl group, C ８－２８ Alkenyl group or C ８－２８ an alkynyl group, wherein the C ８－２８ Alkyl group, C ８－２８ Halogenated alkyl group, C ８－２８ Alkenyl groups and C ８－２８ The alkynyl group is optionally substituted by one or more R; Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R; Each R is independently D, halogen, or —R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more R" until fully deuterated; Each R' is independently D, halogen, -R ｄ , -C(O)R ｄ , -C(O)OR ｄ , —C(O)NR ｅ R ｆ , -NR ｅ R ｆ , -NR ｄ C(O)R ｅ , -NR ｄ C(O)OR ｅ , -NR ｄ C(O)NR ｅ R ｆ , -OR ｄ , -OC(O)R ｄ , —OC(O)NR ｅ R ｆ , -NR ｄ S (O) ２ R ｅ , -S(O) ２ NR ｄ , -S(O)R ｄ or -S(O) ２ R ｄ or two R's on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ forms an aryl group or a 5- to 10-membered heteroaryl group, wherein C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Here, each R ｄ , R ｅ and R ｆ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｅ and R ｆ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R″; Each R" is independently D, halogen, -R ｇ , -C(O)R ｇ , -C(O)OR ｇ , —C(O)NR ｈ R ｊ , -NR ｈ R ｊ , -NR ｇ C(O)R ｈ , -NR ｇ C(O)OR ｈ , -NR ｇ C(O)NR ｈ R ｊ , -OR ｇ , -OC(O)R ｇ , —OC(O)NR ｈ R ｊ , -NR ｇ S (O) ２ R ｈ , -S(O) ２ NR ｇ , -S(O)R ｇ or -S(O) ２ R ｇ or two R″ on the same atom or on two adjacent atoms together with the atoms to which they are attached form C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ aryl group or 5- to 10-membered heteroaryl group, wherein ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ６－１０ Aryl and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; Here, each R ｇ , R ｈ and R ｊ are independently H, D, C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, or R ｈ and R ｊ together with the N atom to which they are attached form a 3- to 7-membered heterocyclyl group or a 5- to 10-membered heteroaryl group, wherein said C １－６ Alkyl group, C １－６ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－６ Alkenyl group, C ２－６ Alkynyl group, C ６－１０ Aryl groups and 5- to 10-membered heteroaryl groups are optionally substituted with one or more deuterium atoms until fully deuterated; 44. A compound of claim 42 or 43, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

45. W ２ teeth, 【Chemistry 80】 and Here, m ２ is 1, 2, 3 or 4, Each R ６ and R ７ are independently H, D, C １－６ Alkyl group, C １－６ Alkoxy group, C ３－６ a cycloalkyl group or a 3- to 7-membered heterocyclyl group, or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group or a 3- to 7-membered heterocyclyl group, wherein said C １－６ Alkyl group, C １－６ Alkoxy group, C ３－６ The cycloalkyl group and the 3- to 7-membered heterocyclyl group are optionally substituted by one or more R'; Each R ８ are independently １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl group or C ２－２８ an alkynyl group, wherein the C １－２８ Alkyl group, C １－２８ Halogenated alkyl group, C ３－６ Cycloalkyl group, 3-7 membered heterocyclyl group, C ２－２８ Alkenyl groups and C ２－２８ The alkynyl group is optionally substituted by one or more R; Lipid-like is C ８－２８ Alkyl group, C ８－２８ Halogenated alkyl group, C ８－２８ Alkenyl group or C ８－２８ an alkynyl group, wherein the C ８－２８ Alkyl group, C ８－２８ Halogenated alkyl group, C ８－２８ Alkenyl groups and C ８－２８ The alkynyl group is optionally substituted by one or more R; Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group, ６－１０ The aryl and 5- to 10-membered heteroaryl groups are optionally substituted by one or more R.

45. A compound according to any one of claims 42 to 44, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

46. W ２ teeth, 【Chemistry 81】 and Here, R ６ is C １－６ is an alkyl group, and R ７ is H or R ６ and R ７ together with the C atoms to which they are attached form C ３－６ Forms a cycloalkyl group, wherein said C １－６ Alkyl group and C ３－６ The cycloalkyl group is optionally a phenyl group or a —C(O)OC １－６ substituted with one or more groups selected from alkyl groups, R ８ are independently １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ alkenyl group, wherein the C １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ The alkenyl group may optionally contain one or more C １－６ substituted by an alkoxy group, Preferably, W ２ teeth, 【Chemistry 82】 and Preferably, W ２ teeth, 【Chemistry 83】 and Preferably, W ２ teeth, 【Chemical 84】 and Preferably, W ２ teeth, 【Chemical 85】 That is, 46. ​​A compound according to any one of claims 42 to 45, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

47. W ２ teeth, 【Chemical 86】 and Here, R ６ and R ７ is H, R ８ are independently １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ is an alkenyl group, Preferably, W ２ teeth, 【Chemistry 87】 That is, 46. ​​A compound according to any one of claims 42 to 45, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

48. W ２ teeth, 【Chemical 88】 and Here, R ６ and R ７ is H, R ８ are independently １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ is an alkenyl group, Preferably, W ２ teeth, 【Chemistry 89】 That is, 46. ​​A compound according to any one of claims 42 to 45, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

49. W ２ teeth, [Chemical 90] and Here, m ２ is 1 or 2, R ６ and R ７ is H, R ８ are independently １－２８ Alkyl group, C ３－６ a cycloalkyl group, a 3- to 7-membered heterocyclyl group, or C ２－２８ is an alkenyl group, Preferably, W ２ teeth, 【Chemistry 91】 That is, 46. ​​A compound according to any one of claims 42 to 45, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

50. W ２ teeth, 【Chemistry 92】 and Here, m ２ is 2, 3 or 4, R ６ and R ７ are independently H or C １－６ an alkoxy group, wherein the C １－６ The alkoxy group is optionally C ６－１０ aryl group or 5- to 10-membered heteroaryl group, ６－１０ The aryl or 5- to 10-membered heteroaryl group may optionally be halogen or C １－６ substituted by one or more groups selected from alkoxy groups; Lipid-like is C ８－２８ Alkyl group or C ８－２８ is an alkenyl group, Preferably, W ２ teeth, 【Chemistry 93】 and Preferably, W ２ teeth, 【Chemical 94】 That is, 46. ​​A compound according to any one of claims 42 to 45, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

51. W ２ teeth, 【Chemical 95】 and Here, m ２ is 2, 3 or 4, R ６ and R ７ is H, Lipid-like is C ８－２８ is an alkenyl group, Preferably, W ２ teeth, 【Chemistry 96】 That is, 46. ​​A compound according to any one of claims 42 to 45, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

52. W ２ teeth, 【Chemistry 97】 【Chem.98】 and Preferably, W ２ teeth, 【Chem.99】 【Chemistry 100】 That is, 52. A compound according to any one of claims 42 to 51, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

53. R Ｘ is H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen; X １ and X ２ are independently a bond or O; R １ and R ２ are independently １－６ Alkyl group, C ３－６ Cycloalkyl group or C ６－１０ is an aryl group, L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H, D or C １－６ is an alkyl group, Ar is C ６－１０ an aryl group or a 5- to 10-membered heteroaryl group; 53. A compound according to any one of claims 42 to 52, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

54. R Ｘ is H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H or D; X １ and X ２ are independently a bond or O; R １ and R ２ are independently １－６ is an alkyl group, L is CH ２ , CDs ２ or CHD, R ３ and R ４ are independently H or D; Ar is C ６－１０ is an aryl group, 54. A compound according to any one of claims 42 to 53, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof. 【Request Item 55】 【Chemistry 101】 where: R Ｘ is H or OH, preferably H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen, preferably H or D; X １ and X ２ are independently a bond, O, S or NH, preferably a bond or O, more preferably a bond; R １ and R ２ are independently C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group), L is CH ２ , CDs ２ or CHD, R ９ is CH ２ -C ６－１０ Aryl group, CH ２ -5 to 10 membered heteroaryl group, CH ２ C(O)O-C １－６ Alkyl group, CH ２ C(O)O-C ３－６ Cycloalkyl group or CH ２ C(O)O--a 3- to 7-membered heteroaryl group, preferably CH optionally substituted by one or more deuterium atoms until fully deuterated. ２ -phenyl group, CH ２ C(O)O-C １－６ Alkyl group or CH ２ C(O)O-C ３－６ is a cycloalkyl group, and R １０ is H or D, Or, R ９ and R １０ are optionally substituted by one or more deuterium atoms until fully deuterated together with the C atoms to which they are attached. ３－６ forming a cycloalkyl group or a 3- to 7-membered heterocyclyl group, Ar is a phenyl group optionally substituted by one or more R; R independently represents D, C, optionally substituted with one or more deuterium atoms until fully deuterated. １－６ Alkyl group or —OC １－６ is an alkyl group, A compound of formula (VIIa), formula (VIIa) or formula (VIIb), or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

56. R Ｘ is H or OH, preferably H, R Ｘ１ , R Ｘ２ and R Ｘ３ are independently H, D or halogen, preferably H or D; X １ and X ２ are independently a bond or O, preferably a bond; R １ and R ２ are independently C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ Alkyl group (preferably C １－３ alkyl group, more preferably an isopropyl group), L is CH ２ , CDs ２ or CHD, R ９ is CH optionally substituted by one or more deuterium atoms until fully deuterated. ２ -phenyl group, CH ２ C(O)O-C １－６ Alkyl group or CH ２ C(O)O-C ３－６ is a cycloalkyl group, and R １０ is H or D, Ar is a phenyl group optionally substituted by one or more R; R independently represents a C optionally substituted by one or more deuterium atoms until fully deuterated. １－６ an alkyl group (preferably a tert-butyl group), 56. The compound of claim 55, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof.

57. The compound is 【Chemical Engineering 102】 【Chemistry 103】 【Chemical 104】 【Chemistry 105】 【Chemistry 106】 【Chemistry 107】 【Chemistry 108】 Selected from Preferably the compound is 【Chemistry 109】 【Chemical 110】 【Chemistry 111】 【Chemistry 112】 【Chemistry 113】 【Chemistry 114】 【Chemical 115】 【Chemistry 116】 【Chemistry 117】 【Chemistry 118】 【Chemical 119】 【Chemical 120】 【Chemistry 121】 or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof selected from:

58. The intermediate compound is 【Chemistry 122】 【Chemical 123】 【Chemistry 124】 【Chemistry 125】 【Chemistry 126】 【Chemistry 127】 【Chemistry 128】 or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof selected from:

59. 60. A pharmaceutical composition comprising a compound of any one of claims 1 to 58, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, and a pharmaceutically acceptable excipient, and optionally other selected therapeutic agents.

60. 60. Use of a compound according to any one of claims 1 to 58, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition according to claim 59, in the preparation of a medicament for treating and / or preventing a viral infection.

61. 60. A method for treating and / or preventing a viral infection in a subject, comprising administering to the subject a compound of any one of claims 1 to 58, or a pharmaceutically acceptable salt, stereoisomer, solvate, hydrate, polymorph, prodrug, or isotopic variant thereof, or a pharmaceutical composition of claim 59.

62. 60. Use of a compound according to any one of claims 1 to 58, or a tautomer, stereoisomer, prodrug, crystalline form, pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition according to claim 59, in the treatment and / or prevention of viral infections.

63. the viral infection comprises a Coronaviridae infection, a Paramyxoviridae infection, a Pneumoviridae infection, a Picornaviridae infection, a Flaviviridae infection, a Filoviridae infection, an Arenaviridae infection, an Orthomyxoviridae infection, or an Empox infection; Preferably, the coronavirus is SARS-CoV virus and its mutants, MERS-CoV virus and its mutants, SARS-CoV-2 virus and its mutants, other human coronaviruses (229E, NL63, OC43, HKU1 or WIV1), zoonotic coronaviruses (PEDV or HKU CoV isolates, for example, HKU3, HKU5 or HKU9), feline coronavirus (feline enteric coronavirus or feline infectious peritonitis virus), or porcine epidemic diarrhea virus; preferably, the coronavirus is SARS-CoV virus and its mutants, MERS-CoV virus and its mutants, or SARS-CoV-2 virus and its mutants; preferably, the coronavirus is SARS-CoV-2 virus and its mutants; preferably, the SARS-CoV-2 virus and its mutants are SARS-CoV-2 virus and its mutants; Beta, Delta, Gamma or Omicron mutants; Preferably, the Paramyxoviridae is a parainfluenza virus, a measles virus, or a mumps virus; Preferably, the Pneumoviridae is RSV or human metapneumovirus, preferably, the Pneumoviridae is RSV; Preferably, the Picornaviridae is an enterovirus or a rhinovirus, Preferably, the Flaviviridae are dengue virus, yellow fever virus, West Nile virus, Zika virus, Japanese encephalitis virus and hepatitis C; Preferably, the Filoviridae is Ebola virus, Zaire Ebola virus, Bundibugye Ebola virus, Sudan Ebola virus, Tai Forest Ebola virus, Reston Ebola virus or Marburg virus; Preferably, the arenavirus is a Lassa virus or a Junin virus.

62. The use according to claim 60, or the method according to claim 61, or the use of a compound or composition according to claim 62.

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