Phosphamide ester monosaccharide, pharmaceutical composition and diagnostic and therapeutic application

Abstract

Provided herein are monosaccharides, e.g., compounds of Formula (I) and pharmaceutical compositions thereof. Also provided herein are methods of their use in cell labeling for diagnostic and / or therapeutic applications. # imgabs0 #

Description

Cross - Reference to Related Applications

[0001] This application claims the benefit of priority of International Application No. PCT / CN2022 / 137519, filed on December 8, 2022, and the entire disclosure thereof is incorporated herein by reference in its entirety pursuant to 35 U.S.C. 119(a). Technical Field

[0002] Provided herein are monosaccharides and their pharmaceutical compositions. Also provided herein are methods of using them for cell labeling for diagnostic and / or therapeutic applications. Background Art

[0003] Glycosylation is an enzymatic process responsible for attaching glycans to glycosyl acceptors (e.g., cell surface proteins). Reily et al., Nat. Rev. Nephrol. 2019, 15, 346 - 66. Glycosylation is crucial for both physiological and pathological cell functions (ibid.). Alterations in glycosylation have been identified in almost every type of cancer and have significant implications for cancer progression, tumor immunity, and clinical outcomes. Hauselmann and Borsig, Front. Oncol. 2014, 4, 28; Stowell et al., Annu. Rev. Pathol.: Mech. Dis. 2015, 10, 473 - 510; Pin and Reis, Nat. Rev. Cancer 2015, 15, 540 - 55; Munkley and Elliott, Oncotarget 2016, 7, 35478 - 89; Reily et al., Nat. Rev. Nephrol. 2019, 15, 346 - 66.

[0004] Metabolic glycoengineering is a technique for introducing unnatural sugars into cellular glycans. Prescher et al., Nature 2004, 430, 873-7; Agatemor et al., Nat. Rev. Chem. 2019, 3, 605-20; Wang and Mooney, Nat. Chem. 2020, 12, 1102-14. Metabolic glycoengineering utilizes the carbohydrate metabolism of cells to tag cells with chemical reporters (ibid.). Then, the chemical reporters (e.g., azides) expressed on the cell surface can be used for targeted drug delivery or in vivo imaging through bioorthogonal chemistry. Laughlin et al., Science 2008, 320, 664-7; Sletten and Bertozzi, Acc. Chem. Res. 2011, 44, 666-76; Wang et al., Nat. Chem. Biol. 2017, 13, 415; Wang and Mooney, Nat. Chem. 2020, 12, 1102-14.

[0005] Despite the progress made in cancer diagnosis and treatment, cancer remains a major public health problem worldwide. Wang and Mooney, Nat. Chem. 2020, 12, 1102-14. It is estimated that in 2022, there will be 1,918,030 new cancer cases and 609,360 cancer deaths in the United States alone. Cancer Facts & Figures 2022. Therefore, effective methods and therapies for cancer diagnosis and treatment are needed. Bargahi et al., Biol. Proced. Online 2022, 24, 5. Summary of the Invention

[0006] This disclosure provides compounds of formula (I): or enantiomers, mixtures of enantiomers, diastereomers, mixtures of two or more diastereomers, tautomers, mixtures of two or more tautomers, or isotopic variants thereof; or pharmaceutically acceptable salts, solvates, hydrates or prodrugs thereof; wherein: R 1 and R 5 are each independently (i) hydrogen; or (ii) -C(O)R 5a , -C(O)OR 5a , -C(O)NR 5b R 5c or -L 2 -P(X)(OR 5a )(NR 5b R5c )); provided that R 1 and R 5 at least one of which is -L 2 -P(X)(OR 5a )(NR 5b R 5c )); R 2 is (i) hydrogen; (ii) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl or heterocyclic group; or (iii) -C(O)R 1a , -C(O)OR 1a , -C(O)NR 1b R 1c , -C(O)SR 1a , -C(NR 1a )NR 1b R 1c , -C(S)R 1a , -C(S)OR 1a , -C(S)NR 1b R 1c , -S(O)R 1a , -S(O)2R 1a , -S(O)NR 1b R 1c , -S(O)2NR 1b R 1c or -Si(R 1a )3; R 3 and R 4 each independently is (i) halogen; or (ii) -OR 5a , -OC(O)R 5a , -OC(O)OR 5a or -OC(O)NR 5b R 5c ; or R 3 and R 4 or R 4 and R 5 are joined together to form a lactone ring; R 5a , R 5b and R 5c each independently is hydrogen, C 1-30 alkyl, C 1-30 heteroalkyl, C 2-30 alkenyl, C2-30 Alkynyl, C 3-30 Cycloalkyl, C 6-30 Aryl, C 7-30 Aralkyl, heteroaryl or heterocyclic group; A is a bond, O or N(R 1b ); L 1 is C 1-6 Alkylene, C 1-6 Heteroalkylene, C 2-6 Alkenylene, C 2-6 Alkynylene, C 3-10 Cycloalkylene, C 6-14 Arylene, C 7-15 Aralkylene, heteroarylene or heterocyclene; L 2 Each is independently (i) a bond; or (ii) -O-C 1-6 Alkylene, -O-C 1-6 Heteroalkylene, -O-C 2-6 Alkenylene, -O-C 2-6 Alkynylene, -O-C 3-10 Cycloalkylene, -O-C 6-14 Arylene, -O-C 7-15 Aralkylene, -O-heteroaryl or -O-heterocyclic group; X is independently O or S; Z is hydrogen, azide, halogen, isocyano, -C=C(R 1a )R 1a , -C≡CR 1a , -C(O)R 1a or -SH; and R 1a 、R 1b and R 1c are each independently hydrogen, deuterium, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 Aryl, C 7-15 Aralkyl, heteroaryl or heterocyclic group; Wherein, alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl, aralkylene, heteroaryl, heteroarylene, heterocyclic group and heterocycloalkylene are each optionally substituted by one or more (in one embodiment, one, two, three or four) substituents Q, wherein Q is independently selected from: (a) deuterium, cyano, halogen, nitro and oxo; (b) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl and heterocyclic group, each of which is further optionally substituted by one or more (in one embodiment, one, two, three or four) substituents Q a ; and (c) –C(O)R a , –C(O)OR a , –C(O)NR b R c , –C(O)SR a , –C(NR a )NR b R c , –C(S)R a , –C(S)OR a , –C(S)NR b R c , –OR a , –OC(O)R a , –OC(O)OR a , –OC(O)NR b R c , –OC(O)SR a , –OC(NR a )NR b R c , –OC(S)R a , –OC(S)OR a , –OC(S)NR b R c , –OP(O)(OR b )OR c , –OS(O)R a , –OS(O)2R a , –OS(O)NR b R c , –OS(O)2NR b R c , –NR b R c , –NRa C(O)R d 、 –NR a C(O)OR d 、 –NR a C(O)NR b R c 、 –NR a C(O)SR d 、 –NR a C(NR d )NR b R c 、 –NR a C(S)R d 、 –NR a C(S)OR d 、 –NR a C(S)NR b R c 、 –NR a S(O)R d 、 –N=S(O)R a R d 、 –NR a S(O)2R d 、 –NR a S(O)NR b R c 、 –NR a S(O)2NR b R c 、 –SR a 、 –S(O)R a 、 –S(O)2R a 、 –S(O)NR b R c and –S(O)2NR b R c wherein, R a 、 R b 、 R c and R d are each independently (i) hydrogen or deuterium; (ii) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 arylalkyl, heteroaryl or heterocyclic group, each of which is optionally substituted by one or more (in one embodiment, by one, two, three or four) substituents Q a substituted; or (iii) R b and R cTogether with the N atom to which they are attached, form a heterocyclic group, which is optionally substituted by one or more (in one embodiment, by one, two, three or four) substituents Q a substituted; wherein Q a are each independently selected from: (a) deuterium, cyano, halogen, nitro and oxo; (b) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl and heterocyclic group; and (c) –C(O)R e , –C(O)OR e , –C(O)NR f R g , –C(O)SR e , –C(NR e )NR f R g , –C(S)R e , –C(S)OR e , –C(S)NR f R g , –OR e , –OC(O)R e , –OC(O)OR e , –OC(O)NR f R g , –OC(O)SR e , –OC(NR e )NR f R g , –OC(S)R e , –OC(S)OR e , –OC(S)NR f R g , –OP(O)(OR f )OR g , –OS(O)R e , –OS(O)2R e , –OS(O)NR f R g , –OS(O)2NR f R g , –NR f R g , –NR e C(O)R h , –NR e C(O)OR f , –NRe C(O)NR f R g ,–NR e C(O)SR f ,–NR e C(NR h )NR f R g ,–NR e C(S)R h ,–NR e C(S)OR f ,–NR e C(S)NR f R g ,–NR e S(O)R h , –N=S(O)R e R h ,–NR e S(O)2R h ,–NR e S(O)NR f R g ,–NR e S(O)2NR f R g ,–SR e , –S(O)R e , –S(O)2R e , –S(O)NR f R g and –S(O)2NR f R g ; Among them, R e , R f , R g and R h are each independently (i) hydrogen or deuterium; (ii) C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 Aryl, C 7-15 aralkyl, heteroaryl or heterocyclic; or (iii) R f and R g Together with the N atom to which they are attached they form a heterocyclyl.

[0007] The present invention also provides a pharmaceutical composition, which comprises a compound of formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof, or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; and a pharmaceutically acceptable excipient.

[0008] In addition, the present invention provides a method for labeling cells in a subject with an azide group, the method comprising administering to a subject in need thereof an effective amount of a compound of formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof.

[0009] In addition, the present invention provides a method for labeling cells with an azide group, the method comprising contacting the cells with an effective amount of a compound of formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof, or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof. Detailed Description

[0010] To facilitate understanding of the disclosure presented herein, a number of terms are defined below.

[0011] Generally, the nomenclature used herein and the experimental procedures described herein in organic chemistry, medicinal chemistry, biochemistry, biology and pharmacology are those well known and commonly used in the art. Unless otherwise defined, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0012] The term "subject" refers to an animal, including (but not limited to) a primate (e.g., a human), a cow, a pig, a sheep, a goat, a horse, a dog, a cat, a rabbit, a rat or a mouse. The terms "subject" and "patient" are used interchangeably herein, e.g., when referring to a mammalian subject, e.g., a human subject. In one embodiment, the subject is a human.

[0013] The term "contacting / contact" means bringing a therapeutic agent and a biomolecule (e.g., a protein, an enzyme, RNA, or DNA), a cell, or a tissue together such that a physiological and / or chemical effect caused by such contact occurs. Contact can occur in vitro, ex vivo, or in vivo. In one embodiment, the therapeutic agent is contacted with the biomolecule in vitro to determine the effect of the therapeutic agent on the biomolecule. In another embodiment, the therapeutic agent is contacted with cells in a cell culture (in vitro) to determine the effect of the therapeutic agent on the cells. In yet another embodiment, contacting the therapeutic agent with the biomolecule, cell, or tissue includes administering the therapeutic agent to a subject having the biomolecule, cell, or tissue to be contacted.

[0014] The term "therapeutically effective amount" or "effective amount" means an amount of a compound that, when administered, is sufficient to prevent the development of one or more symptoms of a disorder, disease, or condition being treated or to alleviate to some extent one or more symptoms of the disorder, disease, or condition being treated. The term "therapeutically effective amount" or "effective amount" also refers to an amount of a compound that is sufficient to elicit a biological or medical response of a biomolecule (e.g., a protein, an enzyme, RNA, or DNA), a cell, a tissue, a system, an animal, or a human that a researcher, veterinarian, physician, or clinician is seeking.

[0015] The terms "pharmaceutically acceptable carrier", "pharmaceutically acceptable excipient", "physiologically acceptable carrier", or "physiologically acceptable excipient" refer to a pharmaceutically acceptable material, composition, or vehicle (e.g., a liquid or solid filler, diluent, solvent, or encapsulating material). In one embodiment, each component is "pharmaceutically acceptable" in the sense of being compatible with the other ingredients of the pharmaceutical formulation and suitable for contact with the tissues or organs of a subject (e.g., a human) without undue toxicity, irritation, allergic response, immunogenicity, or other problems or complications and commensurate with a reasonable benefit / risk ratio. See, e.g., Remington: The Science and Practice of Pharmacy, 23rd Edition; edited by Adejare; Academic Press, 2020; Handbook of Pharmaceutical Excipients, 9th Edition; edited by Sheskey et al.; Pharmaceutical Press, 2020; Handbook of Pharmaceutical Additives, 3rd Edition; edited by Ash and Ash; Synapse Information Resources, 2007; Pharmaceutical Preformulation and Formulation, 2nd Edition; edited by Gibson; CRC Press, 2009.

[0016] The term "about" or "approximately" means an acceptable error of a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined. In certain embodiments, the term "about" or "approximately" means within 1, 2, or 3 standard deviations. In certain embodiments, the term "about" or "approximately" means within 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.05% of a given value or range.

[0017] The term "alkyl" refers to a straight-chain or branched-chain saturated monovalent hydrocarbon group, wherein the alkyl is optionally substituted with one or more substituents Q as described herein. For example, C 1-6 alkyl refers to a straight-chain saturated monovalent hydrocarbon group having 1 to 6 carbon atoms or a branched-chain saturated monovalent hydrocarbon group having 3 to 6 carbon atoms. In certain embodiments, the alkyl is a (C 1-30 ) having 1 to 30 carbon atoms, a (C 1-20 ) having 1 to 20 carbon atoms, a (C 1-15 ) having 1 to 15 carbon atoms, a (C 1-10 ) having 1 to 10 carbon atoms, or a (C 1-6) a straight-chain saturated monovalent hydrocarbon group of carbon atoms, or a branched-chain saturated monovalent hydrocarbon group of 3 to 30 (C 3-30 )、3 to 20 (C 3-20 )、3 to 15 (C 3-15 )、3 to 10 (C 3-10 ) or 3 to 6 (C 3-6 ) carbon atoms. As used herein, straight-chain C 1-6 and branched-chain C 3-6 alkyl groups are also referred to as "lower alkyls". Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl (including all isomeric forms, e.g., n-propyl and isopropyl), butyl (including all isomeric forms, e.g., n-butyl, isobutyl, sec-butyl and tert-butyl), pentyl (including all isomeric forms, e.g., n-pentyl, isopentyl, sec-pentyl, neopentyl and tert-pentyl) and hexyl (including all isomeric forms, e.g., n-hexyl, isohexyl and sec-hexyl).

[0018] The terms "alkylene" and "alkanediyl" are used interchangeably herein when referring to a straight-chain or branched-chain saturated divalent hydrocarbon group, wherein the alkanediyl is optionally substituted by one or more substituents Q as described herein. For example, C 1-6 alkanediyl refers to a straight-chain saturated divalent hydrocarbon group of 1 to 6 carbon atoms or a branched-chain saturated divalent hydrocarbon group of 3 to 6 carbon atoms. In certain embodiments, the alkanediyl is a straight-chain saturated divalent hydrocarbon group having 1 to 30 (C 1-30 )、1 to 20 (C 1-20 )、1 to 15 (C 1-15 )、1 to 10 (C 1-10 ) or 1 to 6 (C 1-6 ) carbon atoms, or a branched-chain saturated divalent hydrocarbon group of 3 to 30 (C 3-30 )、3 to 20 (C 3-20 )、3 to 15 (C 3-15 )、3 to 10 (C 3-10 ) or 3 to 6 (C 3-6 ) carbon atoms. As used herein, straight-chain C 1-6 and branched-chain C 3-6An alkanediyl group is also referred to as a "lower alkanediyl". Examples of alkanediyl groups include, but are not limited to, methanediyl, ethanediyl (including all isomeric forms, e.g., ethane-1,1-diyl and ethane-1,2-diyl), propanediyl (including all isomeric forms, e.g., propane-1,1-diyl, propane-1,2-diyl and propane-1,3-diyl), butanediyl (including all isomeric forms, e.g., butane-1,1-diyl, butane-1,2-diyl, butane-1,3-diyl and butane-1,4-diyl), pentanediyl (including all isomeric forms, e.g., pentane-1,1-diyl, pentane-1,2-diyl, pentane-1,3-diyl and pentane-1,5-diyl) and hexanediyl (including all isomeric forms, e.g., hexane-1,1-diyl, hexane-1,2-diyl, hexane-1,3-diyl and hexane-1,6-diyl). Examples of substituted alkanediyl groups include, but are not limited to, –C(O)CH2–, –C(O)(CH2)2–, –C(O)(CH2)3–, –C(O)(CH2)4–, –C(O)(CH2)5–, –C(O)(CH2)6–, –C(O)(CH2)7–, –C(O)(CH2)8–, –C(O)(CH2)9–, –C(O)(CH2) 10 –, –C(O)CH2C(O)–, –C(O)(CH2)2C(O)–, –C(O)(CH2)3C(O)–, –C(O)(CH2)4C(O)– or –C(O)(CH2)5C(O)–.

[0019] The term "heteroalkyl" refers to a straight-chain or branched-chain saturated monovalent hydrocarbon group containing one or more heteroatoms in its backbone, said heteroatoms being independently selected from O, S and N. The heteroalkyl is optionally substituted with one or more substituents Q as described herein. For example, C 1-6 heteroalkyl refers to a straight-chain saturated monovalent hydrocarbon group having 1 to 6 carbon atoms or a branched-chain saturated monovalent hydrocarbon group having 3 to 6 carbon atoms. In certain embodiments, the heteroalkyl is a straight-chain saturated monovalent hydrocarbon group having 1 to 30 (C 1-30 ), 1 to 20 (C 1-20 ), 1 to 15 (C 1-15 ), 1 to 10 (C 1-10 ) or 1 to 6 (C 1-6 ) carbon atoms, or a branched-chain saturated monovalent hydrocarbon group having 3 to 30 (C 3-30 ), 3 to 20 (C 3-20 ), 3 to 15 (C 3-15 ), 3 to 10 (C 3-10 ) or 3 to 6 (C 3-6 ) carbon atoms. As used herein, straight-chain C 1-6 and branched-chain C 3-6Heteroalkyl groups are also referred to as "lower heteroalkyl". Examples of heteroalkyl groups include, but are not limited to, –OCH3, –OCH2CH3, –CH2OCH3, –NHCH3, –ONHCH3, –NHOCH3, –SCH3, –CH2NHCH2CH3, and –NHCH2CH2CH3. Examples of substituted heteroalkyl groups include, but are not limited to, –CH2NHC(O)CH3 and –NHC(O)CH2CH3.

[0020] The terms "heteroalkylene" and "heteroalkanediyl" are used interchangeably herein when referring to a straight or branched chain saturated divalent hydrocarbon radical having one or more heteroatoms in its backbone, each heteroatom independently selected from O, S, and N. The heteroalkylene is optionally substituted with one or more substituents Q as described herein. For example, C 1-6 Heteroalkylene refers to a straight chain saturated divalent hydrocarbon radical having 1 to 6 carbon atoms or a branched chain saturated divalent hydrocarbon radical having 3 to 6 carbon atoms. In certain embodiments, the heteroalkylene is a straight chain saturated divalent hydrocarbon radical having 1 to 30 (C 1-30 ), 1 to 20 (C 1-20 ), 1 to 15 (C 1-15 ), 1 to 10 (C 1-10 ), or 1 to 6 (C 1-6 ) carbon atoms, or a branched chain saturated divalent hydrocarbon radical having 3 to 30 (C 3-30 ), 3 to 20 (C 3-20 ), 3 to 15 (C 3-15 ), 3 to 10 (C 3-10 ), or 3 to 6 (C 3-6 ) carbon atoms. As used herein, straight chain C 1-6 and branched chain C 3-6 heteroalkylene groups are also referred to as "lower heteroalkylene". Examples of heteroalkylene groups include, but are not limited to, –CH2O–, –CH2CH2O–, –CH2CH2CH2O–, –(CH2)4O–, –(CH2)5O–, –(CH2)6O–, –(CH2)7O–, –(CH2)8O–, –(CH2)9O–, –(CH2) 10O–, –CH2OCH2–, –CH2CH2O–, –(CH2CH2O)2–, –(CH2CH2O)3–, –(CH2CH2O)4–, –(CH2CH2O)5–, –CH2NH–, –CH2NHCH2–, –CH2CH2NH–, –CH2CH2CH2NH–, –(CH2)4NH–, –CH2S–, –CH2SCH2–, and –CH2CH2S–. Examples of substituted heteroalkyl groups include, but are not limited to, –C(O)CH2O–, –C(O)(CH2)2O–, –C(O)CH2CH2CH2O–, –C(O)CH2CH2CH2CH2O–, –C(O)(CH2)5O–, –C(O)(CH2)6O–, –C(O)(CH2)7O–, –C(O)(CH2)8O–, –C(O)(CH2)9O–, –C(O)(CH2) 10 O–, –C(O)CH2OCH2CH2O–, –C(O)CH2O(CH2CH2O)2–, –C(O)CH2O-(CH2-CH2O)3–, –C(O)CH2O(CH2CH2O)4, –C(O)CH2O(CH2CH2O)5–, –CH2NHC(O)CH2–, –CH2CH2C(O)NH–, –CH2N(CH3)–, –(CH2)2N(CH3)–, –(CH2)3N(CH3)–, or –(CH2)4N(CH3)–.

[0021] The term "alkenyl" refers to a straight-chain or branched-chain monovalent hydrocarbon group containing one or more (in one embodiment, one, two, three, or four; in another embodiment, one) carbon-carbon double bonds. The alkenyl is optionally substituted with one or more substituents Q as described herein. As understood by those of ordinary skill in the art, the term "alkenyl" includes groups having "cis" or "trans" configurations or mixtures thereof, or groups having "Z" or "E" configurations or mixtures thereof. For example, C 2-6 alkenyl refers to a straight-chain unsaturated monovalent hydrocarbon group having 2 to 6 carbon atoms or a branched-chain unsaturated monovalent hydrocarbon group having 3 to 6 carbon atoms. In certain embodiments, the alkenyl is a straight-chain monovalent hydrocarbon group having 2 to 30 (C 2-30 ), 2 to 20 (C 2-20 ), 2 to 15 (C 2-15 ), 2 to 10 (C 2-10 ), or 2 to 6 (C 2-6 ) carbon atoms, or a branched-chain monovalent hydrocarbon group having 3 to 30 (C 3-30 ), 3 to 20 (C 3-20 ), 3 to 15 (C 3-15 ), 3 to 10 (C 3-10 ), or 3 to 6 (C3-6 )A branched monovalent hydrocarbon group of carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl, propenyl (including all isomeric forms, e.g., prop-1-en-1-yl, prop-2-en-1-yl, and allyl), and butenyl (including all isomeric forms, e.g., but-1-en-1-yl, but-2-en-1-yl, but-3-en-1-yl, and 2-buten-1-yl).

[0022] The terms "alkenylene" and "alkenediyl" are used interchangeably herein when referring to a straight-chain or branched divalent hydrocarbon group containing one or more (in one embodiment, one, two, three, or four; in another embodiment, one) carbon-carbon double bonds. The alkenediyl is optionally substituted with one or more substituents Q as described herein. As will be understood by those of ordinary skill in the art, the term "alkenediyl" includes groups having "cis" or "trans" configurations or mixtures thereof, or groups having "Z" or "E" configurations or mixtures thereof. For example, C 2-6 Alkenediyl refers to a straight-chain unsaturated divalent hydrocarbon group of 2 to 6 carbon atoms or a branched unsaturated divalent hydrocarbon group of 3 to 6 carbon atoms. In certain embodiments, the alkenediyl is 2 to 30 (C 2-30 ), 2 to 20 (C 2-20 ), 2 to 15 (C 2-15 ), 2 to 10 (C 2-10 ), or 2 to 6 (C 2-6 ) carbon atoms of a straight-chain divalent hydrocarbon group, or 3 to 30 (C 3-30 ), 3 to 20 (C 3-20 ), 3 to 15 (C 3-15 ), 3 to 10 (C 3-10 ), or 3 to 6 (C 3-6 ) carbon atoms of a branched divalent hydrocarbon group. Examples of alkenediyl groups include, but are not limited to, ethylenediyl (including all isomeric forms, e.g., ethene-1,1-diyl and ethene-1,2-diyl), propenediyl (including all isomeric forms, e.g., 1-propene-1,1-diyl, 1-propene-1,2-diyl, and 1-propene-1,3-diyl), butenediyl (including all isomeric forms, e.g., 1-butene-1,1-diyl, 1-butene-1,2-diyl, and 1-butene-1,4-diyl), pentenediyl (including all isomeric forms, e.g., 1-pentene-1,1-diyl, 1-pentene-1,2-diyl, and 1-pentene-1,5-diyl), and hexenediyl (including all isomeric forms, e.g., 1-hexene-1,1-diyl, 1-hexene-1,2-diyl, 1-hexene-1,3-diyl, 1-hexene-1,4-diyl, 1-hexene-1,5-diyl, and hexene-1,6-diyl).

[0023] The term "alkynyl" refers to a straight-chain or branched-chain monovalent hydrocarbon group containing one or more (in one embodiment, one, two, three or four, in another embodiment, one) carbon-carbon triple bonds. The alkynyl group does not contain a carbon-carbon double bond. The alkynyl group is optionally substituted with one or more substituents Q as described herein. For example, C 2-6 Alkynyl refers to a straight-chain unsaturated monovalent hydrocarbon group having 2 to 6 carbon atoms or a branched-chain unsaturated monovalent hydrocarbon group having 4 to 6 carbon atoms. In certain embodiments, the alkynyl group is a straight-chain monovalent hydrocarbon group having 2 to 30 (C 2-30 ), 2 to 20 (C 2-20 ), 2 to 15 (C 2-15 ), 2 to 10 (C 2-10 ) or 2 to 6 (C 2-6 ) carbon atoms, or a branched-chain monovalent hydrocarbon group having 4 to 30 (C 4-30 ), 4 to 20 (C 4-20 ), 4 to 15 (C 4-15 ), 4 to 10 (C 4-10 ) or 4 to 6 (C 4-6 ) carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl (-C≡CH), propynyl (including all isomeric forms, e.g., 1-propynyl (-C≡CCH3) and propargyl (-CH2C≡CH)), butynyl (including all isomeric forms, e.g., 1-butyn-1-yl and 2-butyn-1-yl), pentynyl (including all isomeric forms, e.g., 1-pentyn-1-yl and 1-methyl-2-butyn-1-yl) and hexynyl (including all isomeric forms, e.g., 1-hexyn-1-yl and 2-hexyn-1-yl).

[0024] The terms "alkynylene" and "diynyl" are used interchangeably herein when referring to a straight-chain or branched-chain divalent hydrocarbon group containing one or more (in one embodiment, one, two, three or four, in another embodiment, one) carbon-carbon triple bonds. The alkynylene group does not contain a carbon-carbon double bond. The diynyl group is optionally substituted with one or more substituents Q as described herein. For example, C 2-6 Diynyl refers to a straight-chain unsaturated divalent hydrocarbon group having 2 to 6 carbon atoms or a branched-chain unsaturated divalent hydrocarbon group having 4 to 6 carbon atoms. In certain embodiments, the diynyl group is a straight-chain divalent hydrocarbon group having 2 to 30 (C 2-30 ), 2 to 20 (C 2-20 ), 2 to 15 (C 2-15 ), 2 to 10 (C 2-10 ) or 2 to 6 (C 2-6 ) carbon atoms, or a branched-chain divalent hydrocarbon group having 4 to 30 (C 4-30 ), 4 to 20 (C 4-20 ), 4 to 15 (C 4-15), 4 to 10 (C 4-10 ) or 4 to 6 (C 4-6 ) branched divalent hydrocarbon groups having from 4 to 6 carbon atoms. Examples of the alkynediyl groups include, but are not limited to, ethyne-1,2-diyl, propyne-1,3-diyl (including all isomeric forms, e.g., 1-propyne-1,3-diyl and 1-propyne-3,3-diyl), butyne-1,3-diyl (including all isomeric forms, e.g., 1-butyne-1,3-diyl, 1-butyne-1,4-diyl and 2-butyne-1,1-diyl), pentyne-1,3-diyl (including all isomeric forms, e.g., 1-pentyne-1,3-diyl, 1-pentyne-1,4-diyl and 2-pentyne-1,1-diyl) and hexyne-1,3-diyl (including all isomeric forms, e.g., 1-hexyne-1,3-diyl, 1-hexyne-1,4-diyl and 2-hexyne-1,1-diyl).

[0025] The term "cycloalkyl" refers to a cyclic monovalent hydrocarbon group, which is optionally substituted by one or more substituents Q as described herein. In one embodiment, the cycloalkyl is saturated or unsaturated but non-aromatic, and / or bridged or non-bridged, and / or a fused bicyclic group. In certain embodiments, the cycloalkyl has 3 to 20 (C 3-30 ), 3 to 20 (C 3-20 ), 3 to 15 (C 3-15 ), 3 to 10 (C 3-10 ) or 3 to 7 (C 3-7 ) carbon atoms. In one embodiment, the cycloalkyl is monocyclic. In another embodiment, the cycloalkyl is bicyclic. In yet another embodiment, the cycloalkyl is tricyclic. In still another embodiment, the cycloalkyl is polycyclic. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptenyl, bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, decahydronaphthyl and adamantyl.

[0026] The terms "subcycloalkyl" and "cycloalkanediyl" are used interchangeably herein when referring to a cyclic divalent hydrocarbon group, which may be optionally substituted by one or more substituents Q as described herein. In one embodiment, the cycloalkanediyl may be saturated or unsaturated but non-aromatic, and / or bridged or non-bridged, and / or a fused bicyclic group. In certain embodiments, the cycloalkanediyl has 3 to 30 (C 3-30 ), 3 to 20 (C 3-20 ), 3 to 15 (C 3-15 ), 3 to 10 (C 3-10 ) or 3 to 7 (C 3-7) carbon atoms. Examples of the cycloalkanediyl group include, but are not limited to, cyclopropanediyl (including all isomeric forms, e.g., cyclopropane-1,1-diyl and cyclopropane-1,2-diyl), cyclobutanediyl (including all isomeric forms, e.g., cyclobutane-1,1-diyl, cyclobutane-1,2-diyl and cyclobutane-1,3-diyl), cyclopentanediyl (including all isomeric forms, e.g., cyclopentane-1,1-diyl, cyclopentane-1,2-diyl and cyclopentane-1,3-diyl), cyclohexanediyl (including all isomeric forms, e.g., cyclohexane-1,1-diyl, cyclohexane-1,2-diyl, cyclohexane-1,3-diyl and cyclohex-1,4-diyl), cycloheptanediyl (including all isomeric forms, e.g., cycloheptane-1,1-diyl, cycloheptane-1,2-diyl, cycloheptane-1,3-diyl and cycloheptane-1,4-diyl), decahydronaphthalenediyl (including all isomeric forms, e.g., decahydronaphthalene-1,1-diyl, decahydronaphthalene-1,2-diyl and decahydronaphthalene-1,8-diyl) and adamantanediyl (including all isomeric forms, e.g., adamantane-1,2-diyl, adamantane-1,3-diyl and adamantane-1,8-diyl).

[0027] The term "aryl" refers to a monovalent monocyclic aromatic hydrocarbon group and / or a monovalent polycyclic aromatic hydrocarbon group containing at least one aromatic carbocyclic ring. In certain embodiments, the aryl has 6 to 30 (C 6-30 ), 6 to 20 (C 6-20 ), 6 to 15 (C 6-15 ) or 6 to 10 (C 6-10 ) ring carbon atoms. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, fluorenyl, azulenyl, anthracenyl, phenanthryl, pyrenyl, biphenyl and terphenyl. The aryl also refers to a bicyclic or tricyclic carbocyclic ring, where one ring is aromatic and the rest can be saturated, partially unsaturated or aromatic, e.g., dihydronaphthyl, indenyl, indanyl or tetralinyl. In one embodiment, the aryl is monocyclic. In another embodiment, the aryl is bicyclic. In yet another embodiment, the aryl is tricyclic. In still another embodiment, the aryl is polycyclic. In certain embodiments, the aryl is optionally substituted with one or more substituents Q as described herein.

[0028] The terms "arylene" and "arenediyl" are used interchangeably herein when referring to a divalent monocyclic aromatic hydrocarbon group or a divalent polycyclic aromatic hydrocarbon group containing at least one aromatic hydrocarbon ring. In certain embodiments, the arylene has 6 to 30 (C 6-30 ), 6 to 20 (C 6-20 ), 6 to 15 (C 6-15 ) or 6 to 10 (C 6-10)Ring atoms. Examples of arylene groups include, but are not limited to, phenylene (including all isomeric forms, e.g., benzene-1,2-diyl, benzene-1,3-diyl, and benzene-1,4-diyl), naphthylene (including all isomeric forms, e.g., naphthalene-1,2-diyl, naphthalene-1,3-diyl, and naphthalene-1,8-diyl), fluorenylene (including all isomeric forms, e.g., fluorene-1,2-diyl, fluorene-1,3-diyl, and fluorene-1,8-diyl), azulylene (including all isomeric forms, e.g., azulene-1,2-diyl, azulene-1,3-diyl, and azulene-1,8-diyl), anthrylene (including all isomeric forms, e.g., anthracene-1,2-diyl, anthracene-1,3-diyl, and anthracene-1,8-diyl), phenanthrylene (including all isomeric forms, e.g., phenanthrene-1,2-diyl, phenanthrene-1,3-diyl, and phenanthrene-1,8-diyl), pyrenylene (including all isomeric forms, e.g., pyrene-1,2-diyl, pyrene-1,3-diyl, and pyrene-1,8-diyl), biphenylene (including all isomeric forms, e.g., biphenyl-2,3-diyl, biphenyl-3,4'-diyl, and biphenyl-4,4'-diyl), and terphenylenylene (including all isomeric forms, e.g., terphenyl-2,3-diyl, terphenyl-3,4'-diyl, and terphenyl-4,4'-diyl). Arylene also refers to bicyclic or tricyclic carbocycles where one ring is aromatic and the rest can be saturated, partially unsaturated, or aromatic, e.g., dihydronaphthylene (including all isomeric forms, e.g., dihydronaphthalene-1,2-diyl and dihydronaphthalene-1,8-diyl), indenylene (including all isomeric forms, e.g., indene-1,2-diyl, indene-1,5-diyl, and indene-1,7-diyl), indanyl (including all isomeric forms, e.g., indan-1,2-diyl, indan-1,5-diyl, and indan-1,7-diyl), or tetrahydronaphthylene (tetralinylene) (including all isomeric forms, e.g., tetrahydronaphthalene-1,2-diyl, tetrahydronaphthalene-1,5-diyl, and tetrahydronaphthalene-1,8-diyl). In certain embodiments, the arylene is optionally substituted with one or more substituents Q as described herein.

[0029] The term “aralkyl” or “arylalkyl” refers to a monovalent alkyl group substituted with one or more aryl groups. In certain embodiments, the aralkyl has 7 to 30 (C 7-30 ), 7 to 20 (C 7-20 ), or 7 to 16 (C 7-16 ) carbon atoms. Examples of aralkyl groups include, but are not limited to, benzyl, phenethyl (including all isomeric forms, e.g., 1-phenethyl and 2-phenethyl), and phenylpropyl (including all isomeric forms, e.g., 1-phenylpropyl, 2-phenylpropyl, and 3-phenylpropyl). In certain embodiments, the aralkyl is optionally substituted with one or more substituents Q as described herein.

[0030] The term "aralkylidene" or "arylalkylidene" refers to a divalent alkyl group substituted with one or more aryl groups. In certain embodiments, the aralkylidene has 7 to 30 (C 7-30 ), 7 to 20 (C 7-20 ), or 7 to 16 (C 7-16 ) carbon atoms. Examples of aralkylidene groups include, but are not limited to, benzylidene (including all isomeric forms, e.g., phenylmethanediyl), phenylethylidene (including all isomeric forms, e.g., 2-phenyl-ethane-1,1-diyl and 2-phenyl-ethane-1,2-diyl), and phenylpropylidene (including all isomeric forms, e.g., 3-phenyl-propane-1,1-diyl, 3-phenyl-propane-1,2-diyl, and 3-phenyl-propane-1,3-diyl). In certain embodiments, the aralkylidene is optionally substituted with one or more substituents Q as described herein.

[0031] The term "heteroaryl" refers to a monovalent monocyclic aromatic group or a monovalent polycyclic aromatic group containing at least one aromatic ring, wherein at least one aromatic ring contains one or more heteroatoms in the ring, and each of the heteroatoms is independently selected from O, S, and N. For a heteroaryl group containing a heteroaromatic ring and a non-aromatic heterocyclic ring, the heteroaryl group is not bonded to the rest of the molecule through its non-aromatic heterocyclic ring. Each ring of the heteroaryl group may contain one or two O atoms, one or two S atoms, and / or one to four N atoms; provided that the total number of heteroatoms in each ring is less than four and each ring contains at least one carbon atom. In certain embodiments, the heteroaryl has 5 to 20, 5 to 15, or 5 to 10 ring atoms. In one embodiment, the heteroaryl is monocyclic. Examples of monocyclic heteroaryl groups include, but are not limited to, furyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl, triazinyl, and triazolyl. In another embodiment, the heteroaryl is bicyclic.Examples of bicyclic heteroaryl groups include, but are not limited to, benzofuranyl, benzimidazolyl, benzisoxazolyl, benzopyranyl, benzothiadiazolyl, benzothiazolyl, benzothienyl, benzotriazolyl, benzoxazolyl, furanopyridyl (including all isomeric forms, e.g., furano[2,3-b]pyridyl, furano[2,3-c]pyridyl, furano[3,2-b]pyridyl, furano[3,2-c]pyridyl, furano[3,4-b]pyridyl, and furano[3,4-c]pyridyl), imidazopyridyl (including all isomeric forms, e.g., imidazo[1,2-a]pyridyl, imidazo[4,5-b]pyridyl, and imidazo[4,5-c]pyridyl), imidazothiazolyl (including all isomeric forms, e.g., imidazo[2,1-b]thiazolyl and imidazo[4,5-d]thiazolyl), indazolyl, indolizinyl, indolyl, isobenzofuranyl, isobenzothienyl (i.e., benzo[c]thienyl), isoindolyl, isoquinolinyl, naphthyridinyl (including all isomeric forms, e.g., 1,5-naphthyridinyl, 1,6-naphthyridinyl, 1,7-naphthyridinyl, and 1,8-naphthyridinyl), oxazolopyridyl (including all isomeric forms, e.g., oxazolo[4,5-b]pyridyl, oxazolo[4,5-c]pyridyl, oxazolo[5,4-b]pyridyl, and oxazolo[5,4-c]pyridyl), phthalazinyl, pteridinyl, purinyl, pyrrolopyridyl (including all isomeric forms, e.g., pyrrolo[2,3-b]pyridyl, pyrrolo[2,3-c]pyridyl, pyrrolo[3,2-b]pyridyl, and pyrrolo[3,2-c]pyridyl), quinolinyl, quinoxalinyl, quinazolinyl, thiadiazolopyrimidinyl (including all isomeric forms, e.g., [1,2,5]thiadiazolo[3,4-d]pyrimidinyl and [1,2,3]thiadiazolo[4,5-d]pyrimidinyl), and thiophenopyridyl (including all isomeric forms, e.g., thiopheno[2,3-b]pyridyl, thiopheno[2,3-c]pyridyl, thiopheno[3,2-b]pyridyl, and thiopheno[3,2-c]pyridyl). In yet another embodiment, the heteroaryl is tricyclic. Examples of tricyclic heteroaryl groups include, but are not limited to, acridinyl, benzindolyl, carbazolyl, dibenzofuranyl, perimidinyl, phenanthrolinyl, phenanthridinyl (including all isomeric forms, e.g., 1,5-phenanthrolinyl, 1,6-phenanthrolinyl, 1,7-phenanthrolinyl, 1,9-phenanthrolinyl, and 2,10-phenanthrolinyl), phenarsazinyl, phenazinyl, phenothiazinyl, phenoxazinyl, and xanthenyl. In certain embodiments, the heteroaryl is optionally substituted with one or more substituents Q as described herein.

[0032] The terms "heteroarylene" and "heteroarenediyl" are used interchangeably herein when referring to a divalent monocyclic aromatic group or a divalent polycyclic aromatic group containing at least one aromatic ring, wherein at least one aromatic ring contains one or more heteroatoms in the ring, each of which is independently selected from O, S, and N. For a heteroarylene group containing a heteroaromatic ring and a non-aromatic heterocyclic ring, the heteroarylene group is not bonded to the remainder of the molecule through its non-aromatic heterocyclic ring. Each ring of the heteroarylene group may contain one or two O atoms, one or two S atoms, and / or one to four N atoms, provided that the total number of heteroatoms in each ring is less than four and each ring contains at least one carbon atom. In certain embodiments, the heteroarylene has 5 to 20, 5 to 15, or 5 to 10 ring atoms. Examples of monocyclic heteroarylene include, but are not limited to, furandiyl, imidazolediyl, isothiazolediyl, isoxazolediyl, oxadiazolediyl, oxazolediyl, pyrazinediyl, pyrazolediyl, pyridazinediyl, pyridinediyl, pyrimidinediyl, pyrrolediyl, thiadiazolediyl, thiazolediyl, thiophenediyl, tetrazolediyl, triazinediyl, and triazolediyl.Examples of bicyclic heteroaryl groups include, but are not limited to, benzofurandiyl, benzimidazolediyl, benzisoxazolediyl, chromandiyl, benzothiadiazolediyl, benzothiazolediyl, benzothiophenediyl, benzotriazolediyl, benzoxazolediyl, furopyridinediyl (including all isomeric forms, e.g., furo[2,3-b]pyridinediyl, furo[2,3-c]pyridinediyl, furo[3,2-b]pyridinediyl, furo[3,2-c]pyridinediyl, furo[3,4-b]pyridinediyl, and furo[3,4-c]pyridinediyl), imidazopyridinediyl (including all isomeric forms, e.g., imidazo[1,2-a]pyridinediyl, imidazo[4,5-b]pyridinediyl, and imidazo[4,5-c]pyridinediyl), imidazothiazolediyl (including all isomeric forms, e.g., imidazo[2,1-b]thiazolediyl and imidazo[4,5-d]thiazolediyl), indazolediyl, indolediyl, indolediyl, isobenzofurandiyl, isobenzothiophenediyl (i.e., benzo[c]thiophenediyl), isoindolediyl, isoquinolinediyl, naphthyridinediyl (including all isomeric forms, e.g., 1,5-naphthyridinediyl, 1,6-naphthyridinediyl, 1,7-naphthyridinediyl, and 1,8-naphthyridinediyl), oxazolopyridinediyl (including all isomeric forms, e.g., oxazolo[4,5-b]pyridinediyl, oxazolo[4,5-c]pyridinediyl, oxazolo[5,4-b]pyridinediyl, and oxazolo[5,4-c]pyridinediyl), phthalazinediyl, pteridinediyl, purinediyl, pyrrolopyridinediyl (including all isomeric forms, e.g., pyrrolo[2,3-b]pyridinediyl, pyrrolo[2,3-c]pyridinediyl, pyrrolo[3,2-b]pyridinediyl, and pyrrolo[3,2-c]pyridinediyl), quinolininediyl, quinoxalinediyl, quinazolininediyl, thiadiazolopyrimidinediyl (including all isomeric forms, e.g., [1,2,5]thiadiazolo[3,4-d]pyrimidinediyl and [1,2,3]thiadiazolo[4,5-d]pyrimidinediyl), and thiophenopyridinediyl (including all isomeric forms, e.g., thiopheno[2,3-b]pyridinediyl, thiopheno[2,3-c]pyridinediyl, thiopheno[3,2-b]pyridinediyl, and thiopheno[3,2-c]pyridinediyl). Examples of tricyclic heteroaryl groups include, but are not limited to, acridinediyl, benzindolediyl, carbazolediyl, dibenzofurandiyl, perimidinediyl, phenanthrolinediyl (including all isomeric forms, e.g., 1,5-phenanthrolinediyl, 1,6-phenanthrolinediyl, 1,7-phenanthrolinediyl, 1,9-phenanthrolinediyl, and 2,10-phenanthrolinediyl), phenanthridinediyl, phenopyrazinediyl, phenazinediyl, phenothiazolediyl, phenoxazinediyl, and xanthenediyl. In certain embodiments, the heteroaryl is optionally substituted with one or more substituents Q as described herein.

[0033] The term "heterocyclic group" or "heterocyclic" refers to a monovalent monocyclic non-aromatic ring system or a monovalent polycyclic system containing at least one non-aromatic ring, wherein one or more of the non-aromatic ring atoms are heteroatoms, each of the heteroatoms is independently selected from O, S, and N; and the remaining ring atoms are carbon atoms. For a heterocyclic group containing a heteroaromatic ring and a non-aromatic heterocycle, the heterocyclic group is not bonded to the remainder of the molecule through the heteroaromatic ring. In certain embodiments, the heterocyclic group or heterocyclic group has 3 to 20, 3 to 15, 3 to 10, 3 to 8, 4 to 7, or 5 to 6 ring atoms. In certain embodiments, the heterocyclic group is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may be fused or bridged, and wherein, the nitrogen or sulfur atom may optionally be oxidized, the nitrogen atom may optionally be quaternized, and some rings may be partially or fully saturated or aromatic. The heterocyclic group may be attached to the main structure at any heteroatom or carbon atom that results in a stable compound. Examples of heterocyclic groups and heterocyclic groups include, but are not limited to, azetidinyl, benzodioxolanyl, benzodioxolenyl, benzofuranonyl, chromanyl, decahydroisoquinolinyl, dihydrobenzofuranyl, dihydrobenzisothiazolyl, dihydrobenzisoxazinyl (including all isomeric forms, e.g., 1,4-dihydrobenzo[d][1,3]oxazinyl, 3,4-dihydrobenzo[c][1,2]oxazinyl, and 3,4-dihydrobenzo[d][1,2]oxazinyl), dihydrobenzothiophenyl, dihydroisobenzofuranyl, dihydrobenzo[c]thiophenyl, dihydrofuranyl, dihydroisoindolyl, dihydropyranyl, dihydropyrazolyl, dihydropyrazinyl, dihydropyridyl, dihydropyrimidinyl, dihydropyrrolyl, dioxolanyl, 1,4-dithianyl, furanonyl, imidazolidinyl, imidazolinyl, dihydroindolyl, isochromanyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, oxazolidinonyl, oxazolidinyl, oxiranyl, piperazinyl, piperidinyl, 4-piperidinonyl, pyrazolidinyl, pyrazolinyl, pyrrolidinyl, pyrrolinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydrothiophenyl, thiomorpholinyl, thiazolidinyl, thiochromanyl, tetrahydroquinolinyl, and 1,3,5-trithianyl. In certain embodiments, the heterocyclic group is optionally substituted with one or more substituents Q as described herein. Azetidinyl, benzodioxolanyl, benzodioxolenyl, benzofuranonyl, chromanyl, decahydroisoquinolinyl, dihydrobenzofuranyl, dihydrobenzisothiazolyl, dihydrobenzisoxazinyl (including all isomeric forms, e.g., 1,4-dihydrobenzo[d][1,3]oxazinyl, 3,4-dihydrobenzo[c][1,2]oxazinyl, and 3,4-dihydrobenzo[d][1,2]oxazinyl), dihydrobenzothiophenyl, dihydroisobenzofuranyl, dihydrobenzo[c]thiophenyl, dihydrofuranyl, dihydroisoindolyl, dihydropyranyl, dihydropyrazolyl, dihydropyrazinyl, dihydropyridyl, dihydropyrimidinyl, dihydropyrrolyl, dioxolanyl, 1,4-dithianyl, furanonyl, imidazolidinyl, imidazolinyl, dihydroindolyl, isochromanyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, oxazolidinonyl, oxazolidinyl, oxiranyl, piperazinyl, piperidinyl, 4-piperidinonyl, pyrazolidinyl, pyrazolinyl, pyrrolidinyl, pyrrolinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydrothiophenyl, thiomorpholinyl, thiazolidinyl, thiochromanyl, tetrahydroquinolinyl, and 1,3,5-trithianyl. In certain embodiments, the heterocyclic group is optionally substituted with one or more substituents Q as described herein.

[0034] The term "subheterocyclic group" refers to a divalent monocyclic non-aromatic ring system or a divalent polycyclic ring system containing at least one non-aromatic ring, wherein one or more of the non-aromatic ring atoms are heteroatoms independently selected from O, S, and N; and the remaining ring atoms are carbon atoms. For a subheterocyclic group containing a heteroaromatic ring and a non-aromatic heterocyclic ring, the subheterocyclic group has at least one bond through its non-aromatic heterocyclic ring to the rest of the molecule. In certain embodiments, the subheterocyclic group has 3 to 20, 3 to 15, 3 to 10, 3 to 8, 4 to 7, or 5 to 6 ring atoms. In certain embodiments, the subheterocyclic group is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may be fused or bridged, and wherein a nitrogen or sulfur atom may optionally be oxidized, a nitrogen atom may optionally be quaternized, and some rings may be partially or fully saturated or aromatic. The subheterocyclic group may be attached to the main structure at any heteroatom or carbon atom that results in a stable compound. Examples of such subheterocyclic groups include, but are not limited to, azadiyl, benzodioxanediyl, benzodioxolenediyl, benzofuranonediyl, chromandiyl, decahydroisoquinolinediyl, dihydrobenzofurandiyl, dihydrobenzisothiazolediyl, dihydrobenzisoxazinediyl (including all isomeric forms, e.g., 1,4-dihydrobenzo[d][1,3]oxazinediyl, 3,4-dihydrobenzo[c][1,2]oxazinediyl, and 3,4-dihydrobenzo[d][1,2]oxazinediyl), dihydrobenzothiophenediyl, dihydroisobenzofurandiyl, dihydrobenzo[c]thiophenediyl, dihydrofurandiyl, dihydroisoindolediyl, dihydropyrandiyl, dihydropyrazolediyl, dihydropyrazinediyl, dihydropyridinediyl, dihydropyrimidinediyl, dihydropyrrolediyl, dioxolandiyl, 1,4-dithiandiyl, furanonediyl, imidazolidinediyl, imidazolinediyl, indolindiyl, isochromandiyl, isoindolediyl, isothiazolidinediyl, isoxazolidinediyl, morpholinodiyl, octahydroindolediyl, octahydroisoindolediyl, oxazolidinonediyl, oxazolidinediyl, oxiranyldiyl, piperazinediyl, piperidinediyl, 4-piperidonediyl, pyrazolidinediyl, pyrazolinediyl, pyrrolidinediyl, pyrrolinediyl, quinuclidinediyl, tetrahydrofurandiyl, tetrahydroisoquinolinediyl, tetrahydropyrandiyl, tetrahydrothiophenediyl, thiomorpholinodiyl, thiazolidinediyl, thiochromandiyl, tetrahydroquinolinediyl, and 1,3,5-trithiandiyl. In certain embodiments, the subheterocyclic group is optionally substituted with one or more substituents Q as described herein. Examples include, but are not limited to, azadiyl, benzodioxanediyl, benzodioxolenediyl, benzofuranonediyl, chromandiyl, decahydroisoquinolinediyl, dihydrobenzofurandiyl, dihydrobenzisothiazolediyl, dihydrobenzisoxazinediyl (including all isomeric forms, e.g., 1,4-dihydrobenzo[d][1,3]oxazinediyl, 3,4-dihydrobenzo[c][1,2]oxazinediyl, and 3,4-dihydrobenzo[d][1,2]oxazinediyl), dihydrobenzothiophenediyl, dihydroisobenzofurandiyl, dihydrobenzo[c]thiophenediyl, dihydrofurandiyl, dihydroisoindolediyl, dihydropyrandiyl, dihydropyrazolediyl, dihydropyrazinediyl, dihydropyridinediyl, dihydropyrimidinediyl, dihydropyrrolediyl, dioxolandiyl, 1,4-dithiandiyl, furanonediyl, imidazolidinediyl, imidazolinediyl, indolindiyl, isochromandiyl, isoindolediyl, isothiazolidinediyl, isoxazolidinediyl, morpholinodiyl, octahydroindolediyl, octahydroisoindolediyl, oxazolidinonediyl, oxazolidinediyl, oxiranyldiyl, piperazinediyl, piperidinediyl, 4-piperidonediyl, pyrazolidinediyl, pyrazolinediyl, pyrrolidinediyl, pyrrolinediyl, quinuclidinediyl, tetrahydrofurandiyl, tetrahydroisoquinolinediyl, tetrahydropyrandiyl, tetrahydrothiophenediyl, thiomorpholinodiyl, thiazolidinediyl, thiochromandiyl, tetrahydroquinolinediyl, and 1,3,5-trithiandiyl. In certain embodiments, the subheterocyclic group is optionally substituted with one or more substituents Q as described herein.

[0035] The term "halogen", "halide", or "halo" refers to fluorine, chlorine, bromine, and / or iodine.

[0036] The term "optionally substituted with" means that a group or substituent (e.g., an alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl, aralkylene, heteroaryl, heteroarylene, heterocyclic or heterocycloalkylene group) may be substituted with one or more (in one embodiment, one, two, three or four) substituents Q, each of which is independently selected from, for example, (a) deuterium (-D), cyano (-CN), halogen, nitro (-NO2) and oxo (=O); (b) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl and heterocyclic group, each of which is further optionally substituted with one or more (in one embodiment, one, two, three or four) substituents Q a ; and (c) -C(O)R a , -C(O)OR a , -C(O)NR b R c , -C(O)SR a , -C(NR a )NR b R c , -C(S)R a , -C(S)OR a , -C(S)NR b R c , -OR a , -OC(O)R a , -OC(O)OR a , -OC(O)NR b R c , -OC(O)SR a , -OC(NR a )NR b R c , -OC(S)R a , -OC(S)OR a , -OC(S)NR b R c , -OP(O)(OR b )OR c , -OS(O)R a , -OS(O)2R a , -OS(O)NR b R c , -OS(O)2NR b Rc 、 –NR b R c 、 –NR a C(O)R d 、 –NR a C(O)OR d 、 –NR a C(O)NR b R c 、 –NR a C(O)SR d 、 –NR a C(NR d )NR b R c 、 –NR a C(S)R d 、 –NR a C(S)OR d 、 –NR a C(S)NR b R c 、 –NR a S(O)R d 、 –N=S(O)R a R d 、 –NR a S(O)2R d 、 –NR a S(O)NR b R c 、 –NR a S(O)2NR b R c 、 –SR a 、 –S(O)R a 、 –S(O)2R a 、 –S(O)NR b R c and –S(O)2NR b R c wherein, R a 、 R b 、 R c and R d are each independently (i) hydrogen or deuterium; (ii) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl or heterocyclic group, each of which is optionally substituted by one or more (in one embodiment, by one, two, three or four) substituents Q a ; or (iii) Rb and R c together with the N atom to which they are attached form a heterocyclic group, which is optionally substituted by one or more (in one embodiment, one, two, three or four) substituents Q a Substituted. As used herein, all groups that can be substituted are "optionally substituted".

[0037] In one embodiment, Q a are each independently selected from: (a) deuterium, cyano, halogen, nitro and oxo; (b) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 arylalkyl, heteroaryl and heterocyclic group; and (c) -C(O)R e , -C(O)OR e , -C(O)NR f R g , -C(O)SR e , -C(NR e )NR f R g , -C(S)R e , -C(S)OR e , -C(S)NR f R g , -OR e , -OC(O)R e , -OC(O)OR e , -OC(O)NR f R g , -OC(O)SR e , -OC(NR e )NR f R g , -OC(S)R e , -OC(S)OR e , -OC(S)NR f R g , -OP(O)(OR f )OR g , -OS(O)R e , -OS(O)2R e , -OS(O)NR f R g , -OS(O)2NR f R g , -NR f R g , -NRe C(O)R h ,–NR e C(O)OR f ,–NR e C(O)NR f R g ,–NR e C(O)SR f ,–NR e C(NR h )NR f R g ,–NR e C(S)R h ,–NR e C(S)OR f ,–NR e C(S)NR f R g ,–NR e S(O)R h , –N=S(O)R e R h ,–NR e S(O)2R h ,–NR e S(O)NR f R g ,–NR e S(O)2NR f R g ,–SR e , –S(O)R e , –S(O)2R e , –S(O)NR f R g and –S(O)2NR f R g ; Among them, R e , R f , R g and R h are each independently (i) hydrogen or deuterium; (ii) C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 Aryl, C 7-15 aralkyl, heteroaryl or heterocyclic; or (iii) R f and R g Together with the N atom to which they are attached they form a heterocyclyl.

[0038] In certain embodiments, "optically active" and "enantiomerically active" refer to a collection of molecules having an enantiomeric excess of no less than about 80%, no less than about 90%, no less than about 91%, no less than about 92%, no less than about 93%, no less than about 94%, no less than about 95%, no less than about 96%, no less than about 97%, no less than about 98%, no less than about 99%, no less than about 99.5% or no less than about 99.8%. In certain embodiments, based on the total weight of the enantiomeric mixture under discussion, an optically active compound comprises about 95% or more of one enantiomer and about 5% or less of the other enantiomer. In certain embodiments, based on the total weight of the enantiomeric mixture under discussion, an optically active compound comprises about 98% or more of one enantiomer and about 2% or less of the other enantiomer. In certain embodiments, based on the total weight of the enantiomeric mixture under discussion, an optically active compound comprises about 99% or more of one enantiomer and about 1% or less of the other enantiomer.

[0039] When describing an optically active compound, the prefixes R and S are used to denote the absolute configuration of the compound around its chiral center. (+) and (-) are used to denote the optical rotation of the compound, i.e., the direction in which the optically active compound rotates the plane of polarized light. The (-) prefix indicates that the compound is levorotatory, i.e., the compound rotates the plane of polarized light to the left or counterclockwise. The (+) prefix indicates that the compound is dextrorotatory, i.e., the compound rotates the plane of polarized light to the right or clockwise. However, the signs (+) and (-) of optical rotation are not related to the absolute configuration R and S of the compound.

[0040] The term "isotope-enriched" refers to a compound that contains a non-natural proportion of isotopes at one or more atoms that make up such a compound. In certain embodiments, an isotope-enriched compound contains a non-natural proportion of one or more isotopes, including but not limited to hydrogen ( 1 H), deuterium ( 2 H), tritium ( 3 H), carbon-11 ( 11 C), carbon-12 ( 12 C), carbon-13 ( 13 C), carbon-14 ( 14 C), nitrogen-13 ( 13 N), nitrogen-14 ( 14 N), nitrogen-15 ( 15 N), oxygen-14 ( 14 O), oxygen-15 ( 15 O), oxygen-16 ( 16 O), oxygen-17 ( 17 O), oxygen-18 ( 18 O), fluorine-17 ( 17 F), fluorine-18 (18 F), phosphorus-31 ( 31 P), phosphorus-32 ( 32 P), phosphorus-33 ( 33 P), sulfur-32 ( 32 S), sulfur-33 ( 33 S), sulfur-34 ( 34 S), sulfur-35 ( 35 S), sulfur-36 ( 36 S), chlorine-35 ( 35 Cl), chlorine-36 ( 36 Cl), chlorine-37 ( 37 Cl), bromine-79 ( 79 Br), bromine-81 ( 81 Br), iodine-123 ( 123 I), iodine-125 ( 125 I), iodine-127 ( 127 I), iodine-129 ( 129 I) and iodine-131 ( 131 I). In certain embodiments, the isotope-enriched compound is in a stable form, i.e., it is non-radioactive. In certain embodiments, the isotope-enriched compound contains a non-natural proportion of one or more isotopes, including but not limited to hydrogen ( 1 H), deuterium ( 2 H), carbon-12 ( 12 C), carbon-13 ( 13 C), nitrogen-14 ( 14 N), nitrogen-15 ( 15 N), oxygen-16 ( 16 O), oxygen-17 ( 17 O), oxygen-18 ( 18 O), fluorine-17 ( 17 F), phosphorus-31 ( 31 P), sulfur-32 ( 32 S), sulfur-33 ( 33 S), sulfur-34 ( 34 S), sulfur-36 ( 36 S), chlorine-35 ( 35 Cl), chlorine-37 ( 37 Cl), bromine-79 ( 79 Br), bromine-81 ( 81 Br) and iodine-127 ( 127 I). In certain embodiments, the isotope-enriched compound is in an unstable form, i.e., it is radioactive. In certain embodiments, the isotope-enriched compound contains a non-natural proportion of one or more isotopes, including but not limited to tritium ( 3 H), carbon-11 (11 C), carbon-14 ( 14 C), nitrogen-13 ( 13 N), oxygen-14 ( 14 O), oxygen-15 ( 15 O), fluorine-18 ( 18 F), phosphorus-32 ( 32 P), phosphorus-33 ( 33 P), sulfur-35 ( 35 S), chlorine-36 ( 36 Cl), iodine-123 ( 123 I), iodine-125 ( 125 I), iodine-129 ( 129 I) and iodine-131 ( 131 I). It should be understood that in the compounds provided herein, any hydrogen may, where feasible as determined by one of ordinary skill in the art, be 2 H (by way of example); or any carbon may be 13 C (by way of example); or any nitrogen may be 15 N (by way of example); or any oxygen may be 18 O (by way of example).

[0041] The term "isotope enrichment" refers to the percentage of incorporation of the less prevalent isotope of an element (e.g., D with respect to deuterium or hydrogen-2) in place of the more prevalent isotope of said element (e.g., 1 H with respect to protium or hydrogen-1) at a given position in a molecule. As used herein, when an atom at a specific position in a molecule is designated as a particular less prevalent isotope, it should be understood that the abundance of that isotope at that position is substantially greater than its natural abundance.

[0042] The term "isotope enrichment factor" refers to the ratio between the isotope abundance in an isotope-enriched compound and the natural abundance of a specific isotope.

[0043] The term "hydrogen" or the symbol "H" refers to the composition of the naturally occurring hydrogen isotopes, which includes protium ( 1 H), deuterium ( 2 H or D), and tritium ( 3 H) at their natural abundances. Protium is the most common hydrogen isotope, having a natural abundance of greater than 99.98%. Deuterium is the less prevalent hydrogen isotope, having a natural abundance of approximately 0.0156%.

[0044] The term "deuterium enrichment" refers to the percentage of incorporation of deuterium in place of hydrogen at a given position in a molecule. For example, 1% deuterium enrichment at a given position means that 1% of the molecules in a given sample contain deuterium at that designated position. Since the natural abundance distribution of deuterium is on average about 0.0156%, the deuterium enrichment at any position in a compound synthesized using non-enriched starting materials is on average about 0.0156%. As used herein, when a particular position in an isotopically enriched compound is designated as having deuterium, it is understood that the abundance of deuterium at that position in the compound is substantially greater than its natural abundance (0.0156%).

[0045] The term "carbon" or the symbol "C" refers to the composition of the naturally occurring carbon isotopes, which includes carbon-12 ( 12 C) and carbon-13 ( 13 C) at their natural abundances. Carbon-12 is the most common carbon isotope, having a natural abundance greater than 98.89%. Carbon-13 is a less common carbon isotope, having a natural abundance of about 1.11%.

[0046] The term "carbon-13 enrichment" or " 13 C enrichment" refers to the percentage of incorporation of carbon-13 in place of carbon at a given position in a molecule. For example, 10% carbon-13 enrichment at a given position means that 10% of the molecules in a given sample contain carbon-13 at that designated position. Since the natural abundance distribution of carbon-13 is on average about 1.11%, the carbon-13 enrichment at any position in a compound synthesized using non-enriched starting materials is on average about 1.11%. As used herein, when a particular position in an isotopically enriched compound is designated as having carbon-13, it is understood that the abundance of carbon-13 at that position in the compound is substantially greater than its natural abundance (1.11%).

[0047] The terms "substantially pure" and "substantially homogeneous" mean, when referring to a substance, that it is homogeneous enough to appear free of readily detectable impurities determined by standard analytical methods used by one of ordinary skill in the art, including but not limited to thin layer chromatography (TLC), gel electrophoresis, high performance liquid chromatography (HPLC), gas chromatography (GC), nuclear magnetic resonance (NMR), and mass spectrometry (MS); or pure enough such that further purification will not detectably alter the physical, chemical, biological, and / or pharmacological properties (e.g., enzymatic activity and biological activity) of the substance. In certain embodiments, "substantially pure" or "substantially homogeneous" refers to a collection of molecules in which at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 99.5% by weight of the molecules are a single compound, including a single enantiomer, a racemic mixture, or a mixture of enantiomers, as determined by standard analytical methods. As used herein, when an atom at a particular position in an isotopically enriched molecule is designated as a particular less prevalent isotope, a molecule containing at a designated position an isotope other than the indicated isotope is an impurity relative to the isotopically enriched compound. Thus, for a deuterated compound having an atom designated as deuterium at a particular position, a compound containing protium at the same position is an impurity.

[0048] The term "solvate" refers to a complex or aggregate formed by one or more solute molecules (e.g., the compounds provided herein) and one or more solvent molecules (present in stoichiometric or non-stoichiometric amounts). Suitable solvents include but are not limited to water, methanol, ethanol, n-propanol, isopropanol, and acetic acid. In certain embodiments, the solvent is pharmaceutically acceptable. In one embodiment, the complex or aggregate is in crystalline form. In another embodiment, the complex or aggregate is in non-crystalline form. When the solvent is water, the solvate is a hydrate. Examples of hydrates include but are not limited to hemihydrate, monohydrate, dihydrate, trihydrate, tetrahydrate, and pentahydrate.

[0049] For the divalent groups described herein, the direction in which the divalent group is presented does not imply an orientation. For example, unless a specific orientation is specified, the formula -C(O)NH- represents both -C(O)NH- and -NHC(O)-.

[0050] The phrase "enantiomers, mixtures of enantiomers, diastereomers, mixtures of two or more diastereomers, tautomers, mixtures of two or more tautomers or isotopic variants; or pharmaceutically acceptable salts, solvates, hydrates or prodrugs thereof" has the same meaning as the following phrase: "(i) enantiomers, mixtures of enantiomers, diastereomers, mixtures of two or more diastereomers, tautomers, mixtures of two or more tautomers or isotopic variants of the compound mentioned therein; (ii) pharmaceutically acceptable salts, solvates, hydrates or prodrugs of the compound mentioned therein; or (iii) pharmaceutically acceptable salts, solvates, hydrates or prodrugs of enantiomers, mixtures of enantiomers, diastereomers, mixtures of two or more diastereomers, tautomers, mixtures of two or more tautomers or isotopic variants of the compound mentioned therein". Compound

[0051] In one embodiment, the present invention provides a compound of formula (I): or its enantiomers, mixtures of enantiomers, diastereomers, mixtures of two or more diastereomers, tautomers, mixtures of two or more tautomers, or isotopic variants; or pharmaceutically acceptable salts, solvates, hydrates or prodrugs thereof; wherein: R 1 and R 5 are each independently (i) hydrogen; or (ii) -C(O)R 5a , -C(O)OR 5a , -C(O)NR 5b R 5c or -L 2 -P(X)(OR 5a )(NR 5b R 5c ); provided that at least one of R 1 and R 5 is -L 2 -P(X)(OR 5a )(NR 5b R 5c ); R 2 is (i) hydrogen; (ii) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15an aralkyl, heteroaryl or heterocyclic group; or (iii) -C(O)R 1a , -C(O)OR 1a , -C(O)NR 1b R 1c , -C(O)SR 1a , -C(NR 1a )NR 1b R 1c , -C(S)R 1a , -C(S)OR 1a , -C(S)NR 1b R 1c , -S(O)R 1a , -S(O)2R 1a , -S(O)NR 1b R 1c , -S(O)2NR 1b R 1c or -Si(R 1a )3; R 3 and R 4 each independently is (i) a halogen; or (ii) -OR 5a , -OC(O)R 5a , -OC(O)OR 5a or -OC(O)NR 5b R 5c ; or R 3 and R 4 or R 4 and R 5 are joined together to form a lactone ring; R 5a , R 5b and R 5c each independently is hydrogen, C 1-30 alkyl, C 1-30 heteroalkyl, C 2-30 alkenyl, C 2-30 alkynyl, C 3-30 cycloalkyl, C 6-30 aryl, C 7-30 aralkyl, heteroaryl or heterocyclic group; A is a bond, O or N(R 1b ); L 1 is C 1-6 alkylene, C 1-6 heteroalkylene, C 2-6 alkenylene, C 2-6 alkynylene, C 3-10 cycloalkylene, C 6-14 arylene, C 7-15 aralkylene, heteroarylene or heterocyclene; L 2 is each independently (i) a bond; or (ii) -O-C 1-6 alkylene, -O-C 1-6 heteroalkylene, -O-C 2-6 alkenylene, -O-C 2-6 alkynylene, -O-C 3-10 cycloalkylene, -O-C 6-14 arylene, -O-C 7-15 aralkyl, -O-heteroaryl or -O-heterocyclo; X is each independently O or S; Z is hydrogen, azido, halogen, isocyano, -C═C(R 1a )R 1a 、-C≡CR 1a 、 -C(O)R 1a or -SH; and R 1a 、R 1b and R 1c are each independently hydrogen, deuterium, C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl or heterocyclo; wherein alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl, aralkylene, heteroaryl, heteroarylene, heterocyclo and heterocycloalkylene are each optionally substituted by one or more (in one embodiment, by one, two, three or four) substituents Q, where Q is each independently selected from: (a) deuterium, cyano, halogen, nitro and oxo; (b) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl and heterocyclo, each of which is further optionally substituted by one or more (in one embodiment, by one, two, three or four) substituents Q a substituted; and (c) –C(O)R a 、–C(O)OR a 、–C(O)NR b R c 、–C(O)SRa , –C(NR a )NR b R c , –C(S)R a , –C(S)OR a , –C(S)NR b R c , –OR a , –OC(O)R a , –OC(O)OR a , –OC(O)NR b R c , –OC(O)SR a , –OC(NR a )NR b R c , –OC(S)R a , –OC(S)OR a , –OC(S)NR b R c , –OP(O)(OR b )OR c , –OS(O)R a , –OS(O)2R a , –OS(O)NR b R c , –OS(O)2NR b R c , –NR b R c , –NR a C(O)R d , –NR a C(O)OR d , –NR a C(O)NR b R c , –NR a C(O)SR d , –NR a C(NR d )NR b R c , –NR a C(S)R d , –NR a C(S)OR d , –NR a C(S)NR b R c , –NR a S(O)R d , –N=S(O)R a R d , –NR aS(O)2R d ,–NR a S(O)NR b R c ,–NR a S(O)2NR b R c ,–SR a , –S(O)R a , –S(O)2R a , –S(O)NR b R c and –S(O)2NR b R c , where R a , R b , R c and R d are each independently (i) hydrogen or deuterium; (ii) C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 Aryl, C 7-15 Aralkyl, heteroaryl or heterocyclyl, each of which is optionally substituted by one or more (in one embodiment, by one, two, three or four) substituents Q a or (iii) R b and R c Together with the N atom to which they are attached, they form a heterocyclic group, which is optionally substituted by one or more (in one embodiment, by one, two, three or four) substituents Q a replace; Among them, Q a are each independently selected from: (a) deuterium, cyano, halogen, nitro and oxo; (b) C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 Aryl, C 7-15 Aralkyl, heteroaryl and heterocyclyl; and (c)-C(O)R e , –C(O)OR e , –C(O)NR f R g , –C(O)SR e , –C(NR e )NR f R g , –C(S)R e , –C(S)OR e, –C(S)NR f R g , –OR e , –OC(O)R e , –OC(O)OR e , –OC(O)NR f R g , –OC(O)SR e , –OC(NR e )NR f R g , –OC(S)R e , –OC(S)OR e , –OC(S)NR f R g , –OP(O)(OR f )OR g , –OS(O)R e , –OS(O)2R e , –OS(O)NR f R g , –OS(O)2NR f R g , –NR f R g , –NR e C(O)R h , –NR e C(O)OR f , –NR e C(O)NR f R g , –NR e C(O)SR f , –NR e C(NR h )NR f R g , –NR e C(S)R h , –NR e C(S)OR f , –NR e C(S)NR f R g , –NR e S(O)R h , –N=S(O)R e R h , –NR e S(O)2R h , –NR e S(O)NR f R g , –NR e S(O)2NRf R g ,–SR e , –S(O)R e , –S(O)2R e , –S(O)NR f R g and –S(O)2NR f R g ; Among them, R e , R f , R g and R h are each independently (i) hydrogen or deuterium; (ii) C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 Aryl, C 7-15 aralkyl, heteroaryl or heterocyclic; or (iii) R f and R g Together with the N atom to which they are attached they form a heterocyclyl.

[0052] In certain embodiments, in Formula (I), R 3 In certain embodiments, in formula (I), R 3 In certain embodiments, in formula (I), R 3 For-OR 5a , where R 5a As defined herein. In certain embodiments, in Formula (I), R 3 In certain embodiments, in formula (I), R 3 For –OC(O)R 5a , where R 5a As defined herein. In certain embodiments, in Formula (I), R 3 -OC(O)OR 5a , where R 5a As defined herein. In certain embodiments, in Formula (I), R 3 =–OC(O)NR 5b R 5c , where R 5b and R 5c Each is as defined herein.

[0053] In certain embodiments, in Formula (I), R 4 In certain embodiments, in formula (I), R 4 In certain embodiments, in formula (I), R 4 For –OR 5a, wherein, R 5a is as defined herein. In certain embodiments, in formula (I), R 4 is hydroxy. In certain embodiments, in formula (I), R 4 is –OC(O)R 5a , wherein, R 5a is as defined herein. In certain embodiments, in formula (I), R 4 is –OC(O)OR 5a , wherein, R 5a is as defined herein. In certain embodiments, in formula (I), R 4 is –OC(O)NR 5b R 5c , wherein, R 5b and R 5c are each as defined herein.

[0054] In yet another embodiment, the present invention provides a compound of formula (II): or its enantiomers, mixtures of enantiomers, diastereomers, mixtures of two or more diastereomers, tautomers, mixtures of two or more tautomers, or isotopic variants; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; wherein, R 3a and R 4a are each independently R 5a , –C(O)R 5a , –C(O)OR 5a or –C(O)NR 5b R 5c ; and R 1 , R 2 , R 5 , R 5a , R 5b , R 5c , A, L 1 and Z are each as defined herein.

[0055] In certain embodiments, in formula (I) or formula (II), R 1 is (i) hydrogen; or (ii) -C(O)R 5a , -C(O)OR 5a or -C(O)NR 5b R 5c ; and R 5 is -L 2 -P(X)(OR 5a )(NR 5b R 5c ); wherein, R 5a , R5b , R 5c , L 2 and X are each as defined herein. In certain embodiments, in Formula (I) or Formula (II), R 1 is hydrogen or -C(O)R 5a , and R 5 is -L 2 -P(X)(OR 5a )(NR 5b R 5c ); wherein, R 5a , R 5b , R 5c , L 2 and X are each as defined herein. In certain embodiments, in Formula (I) or Formula (II), R 1 is hydrogen; and R 5 is -L 2 -P(X)(OR 5a )(NR 5b R 5c ); wherein, R 5a , R 5b , R 5c , L 2 and X are each as defined herein. In certain embodiments, in Formula (I) or Formula (II), R 1 is -C(O)R 5a ; and R 5 is -L 2 -P(X)(OR 5a )(NR 5b R 5c ); wherein, R 5a , R 5b , R 5c , L 2 and X are each as defined herein. In certain embodiments, in Formula (I) or Formula (II), R 1 is -C(O)OR 5a ; and R 5 is -L 2 -P(X)(OR 5a )(NR 5b R 5c ); wherein, R 5a , R 5b , R 5c , L 2 and X are each as defined herein. In certain embodiments, in Formula (I) or Formula (II), R 1 is -C(O)NR 5b R 5c ; and R 5 is -L 2-P(X)(OR 5a )(NR 5b R 5c );wherein, R 5a , R 5b , R 5c , L 2 and X are each as defined herein.

[0056] In certain embodiments, in Formula (I) or Formula (II), R 1 is -L 2 -P(X)(OR 5a )(NR 5b R 5c );and R 5 is (i) hydrogen; or (ii) -C(O)R 5a , -C(O)OR 5a or -C(O)NR 5b R 5c ;wherein, R 5a , R 5b , R 5c , L 2 and X are each as defined herein. In certain embodiments, in Formula (I) or Formula (II), R 1 is -L 2 -P(X)(OR 5a )(NR 5b R 5c );and R 5 is hydrogen or -C(O)R 5a ;wherein, R 5a , R 5b , R 5c , L 2 and X are each as defined herein. In certain embodiments, in Formula (I) or Formula (II), R 1 is -L 2 -P(X)(OR 5a )-(NR 5b R 5c );and R 5 is hydrogen; wherein, R 5a , R 5b , R 5c , L 2 and X are each as defined herein. In certain embodiments, in Formula (I) or Formula (II), R 1 is -L 2 -P(X)(OR 5a )(NR 5b R 5c );and R 5 is -C(O)R 5a ;wherein, R5a , R 5b , R 5c , L 2 and X are each as defined herein. In certain embodiments, in Formula (I) or Formula (II), R 1 is -L 2 -P(X)(OR 5a )(NR 5b R 5c ); and R 5 is -C(O)OR 5a ; wherein, R 5a , R 5b , R 5c , L 2 and X are each as defined herein. In certain embodiments, in Formula (I) or Formula (II), R 1 is -L 2 -P(X)-(OR 5a )(NR 5b R 5c ); and R 5 is -C(O)NR 5b R 5c ; wherein, R 5a , R 5b , R 5c , L 2 and X are each as defined herein.

[0057] In certain embodiments, in Formula (I) or Formula (II), R 1((S)-1-Isopropoxycarbonyl-ethylamino)(phenoxy)phosphoryl, ((S)-1-Butoxycarbonylethylamino)(phenoxy)phosphoryl, ((1S)-1-sec-Butoxycarbonylethylamino)(phenoxy)phosphoryl, ((S)-1-tert-Butoxycarbonylethylamino)(phenoxy)phosphoryl, ((S)-1-Pentyloxycarbonylethylamino)(phenoxy)phosphoryl, ((S)-1-Hexyloxycarbonylethylamino)(phenoxy)phosphoryl, ((S)-1-(2-Ethylbutoxy)carbonylethylamino)(phenoxy)phosphoryl, ((1S)-1-(1-Phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl, ((S)-1-Pyridin-3-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl, ((S)-1-Pyridin-4-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl, ((S)-1-Quinolin-4-yl-methoxycarbonylethylamino)(phenoxy)phosphoryl, ((S)-1-Quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl, ((S)-1-(4-Methyltetrahydropyran-4-yloxy)carbonylethylamino)(phenoxy)phosphoryl, ((S)-1-Isopropoxycarbonylethylamino)(quinolin-5-yloxy)phosphoryl, 3-(((S)-1-Isopropoxycarbonylethylamino)(phenoxy)phosphoryloxy)propionyl, (1-Methyl-1-(1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl, (1-Methyl-1-(1-methyl-1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl, ((1S)-1-(1-Phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphoryl, ((1S)-1-(1-(4-(tert-Butoxycarbonylamino)phenyl)ethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphoryl, or ((1S)-1-(1-Methyl-1-phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphoryl.

[0058] In certain embodiments, in Formula (I) or Formula (II), R 1 is (((R)-1-(Benzyloxy)-3-methyl-1-oxobutan-2-yl)amino)(phenoxy)phosphoryl, (((S)-3-Methyl-1-oxo-1-(1-phenyl-cyclopropoxy)butan-2-yl)amino)(phenoxy)phosphoryl, (((S)-1-Oxo-1-((tetrahydro-2H-pyran-4-yl)oxy)propan-2-yl)amino)(phenoxy)phosphoryl, (((S)-1-((1-Methylpiperidin-4-yl)oxy)-1-oxo-propan-2-yl)amino)(phenoxy)phosphoryl, or (((S)-1-Oxo-1-(pentyloxy)propan-2-yl)-amino)-(quinolin-5-yloxy)phosphoryl.

[0059] In certain embodiments, in formula (I) or formula (II), R 5 is ((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-butoxycarbonylethylamino)(phenoxy)phosphinyl, ((1S)-1-sec-butoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-tert-butoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-pentyloxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-hexyloxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-(2-ethylbutoxy)carbonylethylamino)(phenoxy)phosphinyl, ((1S)-1-(1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphinyl, ((S)-1-pyridin-3-ylmethoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-pyridin-4-ylmethoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-quinolin-4-yl-methoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-(4-methyltetrahydropyran-4-yloxy)carbonylethylamino)(phenoxy)phosphinyl, ((S)-1-isopropoxycarbonylethylamino)(quinolin-5-yloxy)phosphinyl, 3-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphinyloxy)propanoyl, (1-methyl-1-(1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphinyl, (1-methyl-1-(1-methyl-1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphinyl, ((1S)-1-(1-phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphinyl, ((1S)-1-(1-(4-(tert-butoxycarbonylamino)phenyl)ethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphinyl, or ((1S)-1-(1-methyl-1-phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphinyl.

[0060] In certain embodiments, in formula (I) or formula (II), R 5 is (((R)-1-(benzyloxy)-3-methyl-1-oxobutan-2-yl)amino)(phenoxy)phosphinyl, (((S)-3-methyl-1-oxo-1-(1-phenyl-cyclopropoxy)butan-2-yl)amino)(phenoxy)phosphinyl, (((S)-1-oxo-1-((tetrahydro-2H-pyran-4-yl)oxy)propan-2-yl)amino)(phenoxy)phosphinyl, (((S)-1-((1-methylpiperidin-4-yl)oxy)-1-oxo-propan-2-yl)amino)(phenoxy)phosphinyl, or (((S)-1-oxo-1-(pentyloxy)propan-2-yl)-amino)(quinolin-5-yloxy)phosphinyl.

[0061] In yet another embodiment, provided herein are compounds of formula (III): or an enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R 1 、R 2 、R 3a 、R 4a 、R 5a 、R 5b 、R 5c 、A, L 1 、L 2 、X, and Z are each as defined herein.

[0062] In yet another embodiment, provided herein are compounds of formula (IV): or an enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R 2 、R 5 、R 3a 、R 4a 、R 5a 、R 5b 、R 5c 、A, L 1 、L 2 、X, and Z are each as defined herein.

[0063] In certain embodiments, in any one of formulas (I) to (IV), R 5c is C 1-10 alkyl or C 7-15 arylalkyl, each of which is optionally substituted with one or more substituents Q. In certain embodiments, in any one of formulas (I) to (IV), R 5c is C 1-10 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, in any one of formulas (I) to (IV), R 5c is methyl, ethyl, propyl, butyl, pentyl, or hexyl, each of which is optionally substituted with one or more substituents Q. In certain embodiments, in any one of formulas (I) to (IV), R 5c is C 7-15An arylalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of formulas (I) to (IV), R 5c is 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-tert-butoxycarbonylethyl, 1-(1-phenylethoxycarbonyl)ethyl, 1-methyl-1-(1-phenylethoxycarbonyl)ethyl, 1-sec-butoxycarbonylethyl, 1-pentyloxycarbonylethyl, 1-hexyloxycarbonylethyl, 1-(2-ethylbutoxy)carbonylethyl, 1-pyridin-3-ylmethoxycarbonylethyl, 1-pyridin-4-ylmethoxycarbonylethyl, 1-quinolin-4-yl-methoxycarbonylethyl, 1-quinolin-5-ylmethoxycarbonylethyl, 1-(4-methyltetrahydropyran-4-yloxy)carbonylethyl, 1-(1-phenylethoxycarbonyl)-2-methylpropyl, 1-(1-methyl-1-phenylethoxycarbonyl)-2-methylpropyl, or 1-(1-(4-(tert-butoxycarbonylamino)phenyl)ethoxycarbonyl)-2-methylpropyl. In certain embodiments, in any one of formulas (I) to (IV), R 5c is 1-isopropoxycarbonylethyl. In certain embodiments, in any one of formulas (I) to (IV), R 5c is 1-((tetrahydropyran-4-yl)oxycarbonyl)ethyl, 1-(benzyloxycarbonyl)-2-methylpropyl, 1-(phenylcyclopropoxycarbonyl)-2-methylpropyl, or 1-((1-methylpiperidin-4-yl)oxycarbonyl)-2-methylpropyl.

[0064] In yet another embodiment, provided herein are compounds of formula (V): or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; wherein, R 6a is C 1-30 alkyl, C 1-30 heteroalkyl, C 2-30 alkenyl, C 2-30 alkynyl, C 3-30 cycloalkyl, C 6-30 aryl, C 7-30 arylalkyl, heteroaryl and heterocyclic group, each of which is optionally substituted by one or more substituents Q; R 6b and R 6c are each independently (i) hydrogen or deuterium; or (ii) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 Aryl, C 7-15 Aralkyl, heteroaryl and heterocyclic group, each of which is optionally substituted by one or more substituents Q; or R 6b and R 6c together with the carbon atom to which they are attached form C 3-10 subcycloalkyl, which is optionally substituted by one or more substituents Q; and R 1 、R 2 、R 3a 、R 4a 、R 5a 、R 5b 、A, L 1 、L 2 、X and Z are each as defined herein.

[0065] In yet another embodiment, compounds of formula (VI) are provided herein: or its enantiomers, mixtures of enantiomers, diastereomers, mixtures of two or more diastereomers, tautomers, mixtures of two or more tautomers, or isotopic variants; or its pharmaceutically acceptable salts, solvates, hydrates or prodrugs; wherein, R 2 、R 5 、R 3a 、R 4a 、R 5a 、R 5b 、R 6a 、R 6b 、R 6c 、A, L 1 、L 2 、X and Z are each as defined herein.

[0066] In certain embodiments, in any one of formulas (I) to (VI), L 2 are each independently a bond or -O-C 1-6 alkylene optionally substituted by one or more substituents Q. In certain embodiments, in any one of formulas (I) to (VI), L 2 is a bond. In certain embodiments, in any one of formulas (I) to (VI), L 2 are each independently -O-C 1-6 alkylene optionally substituted by one or more substituents Q. In certain embodiments, in any one of formulas (I) to (VI), L 2 are each independently -OCH2CH2C(O)-.

[0067] In yet another embodiment, the present disclosure provides a compound of formula (VII): or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; wherein R 1 , R 2 , R 3a , R 4a , R 5a , R 5b , R 6a , R 6b , R 6c , A, L 1 , X and Z are each as defined herein.

[0068] In yet another embodiment, the present disclosure provides a compound of formula (VIII): or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; wherein R 1 , R 2 , R 3a , R 4a , R 5a , R 5b , R 6a , R 6b , R 6c , A, L 1 , X and Z are each as defined herein.

[0069] In yet another embodiment, the present disclosure provides a compound of formula (IX): or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; wherein R 1 , R 2 , R 3 , R 4 , R 5a , R 5b , R 6a , R 6b , R6c 、A, L 1 and X are each as defined herein.

[0070] In certain embodiments, in any of Formulas (I) through (III), (V), and (VII) through (IX), R 1 is hydrogen or -C(O)R 5a , where R 5a is as defined herein. In certain embodiments, in any of Formulas (I) through (III), (V), and (VII) through (IX), R 1 is hydrogen. In certain embodiments, in any of Formulas (I) through (III), (V), and (VII) through (IX), R 1 is -C(O)R 5a , where R 5a is as defined herein. In certain embodiments, in any of Formulas (I) through (III), (V), and (VII) through (IX), R 1 is -C(O)R 5a , where R 5a is C 1-10 alkyl, C 6-14 aryl, heteroaryl or heterocyclic group, each of which is optionally substituted with one or more substituents Q. In certain embodiments, in any of Formulas (I) through (III), (V) and (VII) through (IX), R 1 is -C(O)R 5a , where R 5a is C 1-10 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, in any of Formulas (I) through (III), (V), and (VII) through (IX), R 1 is acetyl, propionyl, butyryl, valeryl, hexanoyl, heptanoyl, octanoyl, nonanoyl or decanoyl, each of which is optionally substituted with one or more substituents Q.

[0071] In certain embodiments, in any of Formulas (I) through (III), (V), and (VII) through (IX), R 1 is -C(O)R 5a , where R 5a is C 6-14 aryl, which is optionally substituted with one or more substituents Q. In certain embodiments, in any of Formulas (I) through (III), (V), and (VII) through (IX), R 1is benzoyl, which is optionally substituted by one or more substituents Q.

[0072] In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R 5a is heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R 5a is monocyclic heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R 5a is a 5- or 6-membered heteroaryl, each of which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R 5a is a 5-membered heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R 5a is a 6-membered heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is pyrrolylcarbonyl or pyridylcarbonyl, each of which is optionally substituted by one or more substituents Q.

[0073] In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R 5a is heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R5a is a monocyclic heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R 5a is a 3-membered, 4-membered, 5-membered, 6-membered or 7-membered heterocyclic group, each of which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R 5a is a 3-membered heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R 5a is a 4-membered heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R 5a is a 5-membered heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R 5a is a 6-membered heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is -C(O)R 5a , wherein R 5a is a 7-membered heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formula (I) to (III), Formula (V), and Formula (VII) to Formula (IX), R 1 is tetrahydropyranylcarbonyl or piperidinylcarbonyl, each of which is optionally substituted by one or more substituents Q.

[0074] In certain embodiments, in any one of Formula (I) to Formula (III), Formula (V), and Formula (VII) to Formula (IX), R 1is acetyl, propionyl, butyryl, valeryl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, benzoyl, pyrrolylcarbonyl, pyridylcarbonyl, tetrahydropyranylcarbonyl or piperidinylcarbonyl, each of which is optionally substituted with one or more substituents Q. In certain embodiments, in any one of formulas (I) to (III), formula (V), and formulas (VII) to (IX), R 1 is acetyl, propionyl, butyryl, valeryl, hexanoyl, nonanoyl, benzoyl, pyrrol-2-ylcarbonyl, pyridin-3-ylcarbonyl, tetrahydropyran-4-ylcarbonyl or piperidin-4-ylcarbonyl, each of which is optionally substituted with one or two substituents, and the substituents are each independently methyl, pyridin-3-yl, pyrrolidin-1-yl, morpholinyl, 4-methylpiperazin-1-yl, 4-acetylpiperazin-1-yl or 4-dimethylamino. In certain embodiments, in any one of formulas (I) to (III), formula (V), and formulas (VII) to (IX), R 1 is acetyl, pyridin-3-ylacetyl, pyrrolidin-1-ylacetyl, 3-morpholinopropionyl, 4-methylpiperazin-1-ylpropionyl, 4-acetylpiperazin-1-ylpropionyl, 2-methylbutyryl, valeryl, hexanoyl, nonanoyl, 4-dimethylaminobenzoyl, pyrrol-2-ylcarbonyl, pyridin-3-ylcarbonyl, tetrahydropyran-4-ylcarbonyl or 1-methylpiperidin-4-ylcarbonyl. In certain embodiments, in any one of formulas (I) to (III), formula (V), and formulas (VII) to (IX), R 1 is acetyl, propionyl or butyryl. In certain embodiments, in any one of formulas (I) to (III), formula (V), and formulas (VII) to (IX), R 1 is acetyl. In certain embodiments, in any one of formulas (I) to (III), formula (V), and formulas (VII) to (IX), R 1 is pivaloyl, 3-(morpholinomethyl)benzoyl, 3-((4-methylpiperazin-1-yl)methyl)benzoyl, 3-morpholinobenzoyl or 3-(4-methylpiperazin-1-yl)benzoyl.

[0075] In yet another embodiment, provided herein are compounds of formula (X): or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; wherein, R 2 、R 5 、R 3a, R 4a , R 5a , R 5b , R 6a , R 6b , R 6c , A, L 1 , X and Z are each as defined herein.

[0076] In yet another embodiment, provided herein is a compound of formula (XI): or an enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; wherein, R 2 , R 5 , R 3a , R 4a , R 5a , R 5b , R 6a , R 6b , R 6c , A, L 1 , X and Z are each as defined herein.

[0077] In yet another embodiment, provided herein is a compound of formula (XII): or an enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; wherein, R 2 , R 5 , R 3a , R 4a , R 5a , R 5b , R 6a , R 6b , R 6c , A, L 1 , X and Z are each as defined herein.

[0078] In certain embodiments, in any one of formulas (I) to (XII), R 2 is hydrogen.

[0079] In certain embodiments, in any one of formulas (I), (II), (IV), (VI), and (X) to (XII), R 5 is hydrogen or -C(O)R 5a, wherein, R 5a is as defined herein. In certain embodiments, in any one of Formula (I), Formula (II), Formula (IV), Formula (VI), and Formula (X) to Formula (XII), R 5 is hydrogen. In certain embodiments, in any one of Formula (I), Formula (II), Formula (IV), Formula (VI), and Formula (X) to Formula (XII), R 5 is -C(O)R 5a , wherein, R 5a is as defined herein. In certain embodiments, in any one of Formula (I), Formula (II), Formula (IV), Formula (VI), and Formula (X) to Formula (XII), R 5 is -C(O)-C 1-6 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formula (I) to (XI), R 4 is hydrogen, acetyl, propionyl or butyryl. In certain embodiments, in any one of Formula (I), Formula (II), Formula (IV), Formula (VI), and Formula (X) to Formula (XII), R 5 is acetyl.

[0080] In certain embodiments, in any one of Formula (II) to Formula (XII), R 3a is hydrogen or -C(O)R 5a , wherein, R 5a is as defined herein. In certain embodiments, in any one of Formula (II) to Formula (XII), R 3a is hydrogen. In certain embodiments, in any one of Formula (II) to Formula (XII), R 3a is -C(O)R 5a , wherein, R 5a is as defined herein. In certain embodiments, in any one of Formula (II) to Formula (XII), R 3a is -C(O)-C 1-6 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, in any one of Formula (II) to Formula (XII), R 3a is acetyl, propionyl or butyryl. In certain embodiments, in any one of Formula (II) to Formula (XII), R 3a is acetyl.

[0081] In certain embodiments, in any one of Formula (II) to Formula (XII), R 4a is hydrogen or -C(O)R 5a , wherein, R 5aAs defined herein. In certain embodiments, in any one of Formulas (II) to (XII), R 4a is hydrogen. In certain embodiments, in any one of Formulas (II) to (XII), R 4a is -C(O)R 5a , wherein R 5a is as defined herein. In certain embodiments, in any one of Formulas (II) to (XII), R 4a is -C(O)-C 1-6 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (II) to (XII), R 4a is acetyl, propionyl or butyryl. In certain embodiments, in any one of Formulas (II) to (XII), R 4a is acetyl.

[0082] In certain embodiments, in any one of Formulas (I) to (XII), R 5a is C 6-14 aryl or heteroaryl, each of which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (I) to (XII), R 5a is C 6-14 aryl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (I) to (XII), R 5a is phenyl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (I) to (XII), R 5a is heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (I) to (XII), R 5a is bicyclic heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (I) to (XII), R 5a is 5,5-, 5,6- or 6,6-fused heteroaryl, each of which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (I) to (XII), R 5a is 5,5-fused heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (I) to (XII), R 5a is 5,6-fused heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (I) to (XII), R 5ais a 6,6-fused heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of formulas (I) to (XII), R 5a is phenyl or quinolin-5-yl. In certain embodiments, in any one of formulas (I) to (XII), R 5a is phenyl.

[0083] In certain embodiments, in any one of formulas (I) to (XII), R 5b is hydrogen.

[0084] In certain embodiments, in any one of formulas (V) to (XII), R 6a is C 1-6 alkyl, C 3-10 cycloalkyl, C 7-15 arylalkyl or heterocyclic group, each of which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of formulas (V) to (XII), R 6a is C 1-6 alkyl or C 7-15 arylalkyl, each of which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of formulas (V) to (XII), R 6a is C 1-6 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of formulas (V) to (XII), R 6a is C 1-6 alkylene-heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of formulas (V) to (XII), R 6a is C 1-6 alkylene-(monocyclic heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of formulas (V) to (XII), R 6a is C 1-6 alkylene-(5-membered or 6-membered heteroaryl), each of which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of formulas (V) to (XII), R 6a is C 1-6 alkylene-(6-membered heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of formulas (V) to (XII), R 6a is C 1-6 alkylene-(bicyclic heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of formulas (V) to (XII), R 6a is C1-6 An alkylene-(5,5-, 5,6- or 6,6-fused heteroaryl), each of which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6a is C 1-6 An alkylene-(6,6-fused heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6a is propyl, butyl, pentyl or hexyl, each of which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6a is C 7-15 An aralkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6a is a monocyclic C 7-15 An aralkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6a is isopropyl, butyl, 2-butyl, tert-butyl, pentyl, hexyl, 2-ethylbutyl, 1-phenylethyl, 2-phenylpropan-2-yl, pyridin-3-ylmethyl, pyridin-4-ylmethyl, quinolin-4-ylmethyl or quinolin-5-ylmethyl. In certain embodiments, in any one of Formulas (V) to (XII), R 6a is isopropyl.

[0085] In certain embodiments, in any one of Formulas (V) to (XII), R 6a is C 3-10 A cycloalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6a is a monocyclic C 3-10 A cycloalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6a is a heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6a is a monocyclic heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6a is a 3-, 4-, 5-, 6- or 7-membered heterocyclic group, each of which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6ais a 6-membered heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, in Formula (I) or Formula (II), R 6a is 1-phenylcyclopropyl, benzyl, tetrahydropyran-4-yl or 1-methylpiperidin-4-yl.

[0086] In certain embodiments, in any one of Formulas (V) to (XII), R 6b is C 1-6 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6a is methyl or isopropyl.

[0087] In certain embodiments, in any one of Formulas (V) to (XII), R 6c is hydrogen or C 1-6 alkyl optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6c is hydrogen or methyl. In certain embodiments, in any one of Formulas (V) to (XII), R 6c is hydrogen. In certain embodiments, in any one of Formulas (V) to (XII), R 6c is methyl.

[0088] In certain embodiments, in any one of Formulas (V) to (XII), R 6b and R 6c together with the carbon atom to which they are attached form a C 3-10 subcycloalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6b and R 6c together with the carbon atom to which they are attached form a monocyclic C 3-10 subcycloalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, in any one of Formulas (V) to (XII), R 6b and R 6c together with the carbon atom to which they are attached form cyclopropane-1,1-diyl, cyclobutene-1,1-diyl, cyclopentane-1,1-diyl or cyclohexane-1,1-diyl, each of which is optionally substituted by one or more substituents Q.

[0089] In certain embodiments, in any one of Formulas (I) to (XII), A is a bond or O. In certain embodiments, in any one of Formulas (I) to (XII), A is a bond. In certain embodiments, in any one of Formulas (I) to (XII), A is O.

[0090] In certain embodiments, in any of Formulas (I) through (XII), L 1 is C 1-6 alkylene, optionally substituted with one or more substituents Q. In certain embodiments, in any of Formulas (I) through (XII), L 1 is methylene, ethane-1,2-diyl, propane-1,2-diyl, or butane-1,4-diyl, each optionally substituted with one or more substituents Q. In certain embodiments, in any of Formulas (I) through (XII), L 1 is methylene.

[0091] In certain embodiments, in any of Formulas (I) through (XII), X is O.

[0092] In certain embodiments, in any of Formulas (I) through (XII), Z is azido, fluoro, iodo, isocyano, -C═CH2, -C≡CH, -C(O)CH3, or -SH. In certain embodiments, in any of Formulas (I) through (XII), Z is azido (-N3).

[0093] In certain embodiments, in any of Formulas (I) through (XII), A is a bond and Z is azido. In certain embodiments, in Formula (I), A is a bond and Z is azido. In certain embodiments, in Formula (II), A is a bond and Z is azido. In certain embodiments, in Formula (III), A is a bond and Z is azido. In certain embodiments, in Formula (IV), A is a bond and Z is azido. In certain embodiments, in Formula (V), A is a bond and Z is azido. In certain embodiments, in Formula (VI), A is a bond and Z is azido. In certain embodiments, in Formula (VII), A is a bond and Z is azido. In certain embodiments, in Formula (VIII), A is a bond and Z is azido. In certain embodiments, in Formula (IX), A is a bond and Z is azido. In certain embodiments, in Formula (X), A is a bond and Z is azido. In certain embodiments, in Formula (XI), A is a bond and Z is azido. In certain embodiments, in Formula (XII), A is a bond and Z is azido.

[0094] The groups R in the chemical formulas described herein (including Formulas (I) through (XII)) 1 、R 2 、R 3 、R 4 、R 5 、R 3a 、R 4a 、R5a , R 5b , R 5c , R 6a , R 6b , R 6c , A, L 1 , L 2 , X and Z are further defined in the embodiments described herein. All combinations of embodiments provided herein for these groups are within the scope of the present disclosure.

[0095] In certain embodiments, R 1 is hydrogen. In certain embodiments, R 1 is -C(O)R 5a , wherein R 5a is as defined herein. In certain embodiments, R 1 is -C(O)-C 1-30 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-20 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-6 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene - heteroaryl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(monocyclic heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(5 - or 6 - membered heteroaryl), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(5 - membered heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(6 - membered heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(bicyclic heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R1 is -C(O)-C 1-10 alkylene-(5,5-, 5,6- or 6,6-heteroaryl), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(5,5-heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(5,6-heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(6,6-heteroaryl), which is optionally substituted with one or more substituents Q.

[0096] In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-heterocyclic group, which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(monocyclic heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(3-, 4-, 5-, 6- or 7-membered heterocyclic group), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(3-membered heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(4-membered heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(5-membered heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(6-membered heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(7-membered heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1is pyrrolidin-1-ylacetyl, 3-morpholinopropionyl, 4-methylpiperazin-1-ylpropionyl or 4-acetylpiperazin-1-ylpropionyl. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(bicyclic heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(bridged, fused or spiro heterocyclic group), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(bridged heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(fused heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 1-10 alkylene-(spiro heterocyclic group), which is optionally substituted with one or more substituents Q.

[0097] In certain embodiments, R 1 is acetyl, propionyl, butyryl, valeryl, hexanoyl, heptanoyl, octanoyl, nonanoyl or decanoyl, each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is acetyl or propionyl, each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is acetyl or propionyl, each of which is optionally substituted with a 5- or 6-membered heteroaryl or a 5- or 6-membered heterocyclic group, and the 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclic group is further substituted with one or more substituents Q a substituted. In certain embodiments, R 1 is acetyl or propionyl, each of which is optionally substituted with pyridin-3-yl, pyrrolidin-1-yl, morpholinyl, 4-methylpiperazin-1-yl or 4-acetylpiperazin-1-yl. In certain embodiments, R 1 is acetyl or pivaloyl.

[0098] In certain embodiments, R 1 is -C(O)-C 1-10 heteroalkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 2-10 alkenyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-C2-10 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 3-10 A cycloalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 6-14 An aryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is benzoyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is 4-dimethylaminobenzoyl. In certain embodiments, R 1 is 3-(morpholinomethyl)benzoyl, 3-((4-methylpiperazin-1-yl)methyl)benzoyl, 3-morpholinobenzoyl or 3-(4-methylpiperazin-1-yl)benzoyl. In certain embodiments, R 1 is -C(O)-(bicyclic C 8-14 aryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is -C(O)-C 7-15 An aralkyl group, which is optionally substituted by one or more substituents Q.

[0099] In certain embodiments, R 1 is -C(O)-heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is -C(O)-(monocyclic heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is -C(O)-(5-membered or 6-membered heteroaryl), each of which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is -C(O)-(5-membered heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is -C(O)-(6-membered heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is pyrrolylcarbonyl or pyridylcarbonyl, each of which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is pyrrol-2-ylcarbonyl or pyridin-3-ylcarbonyl, each of which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is -C(O)-(bicyclic heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 1is -C(O)-(5,5-, 5,6- or 6,6-fused heteroaryl), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-(5,5-fused heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-(5,6-fused heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-(6,6-fused heteroaryl), which is optionally substituted with one or more substituents Q.

[0100] In certain embodiments, R 1 is -C(O)-heterocyclyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-monocyclic heterocyclyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-(3-, 4-, 5-, 6- or 7-membered heterocyclyl), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-(3-membered heterocyclyl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-(4-membered heterocyclyl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-(5-membered heterocyclyl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-(6-membered heterocyclyl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is tetrahydropyranylcarbonyl, piperidinylcarbonyl or piperazinylcarbonyl, each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is tetrahydropyran-4-ylcarbonyl or piperidin-4-ylcarbonyl, each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is tetrahydropyran-4-ylcarbonyl or 1-methylpiperidin-4-ylcarbonyl. In certain embodiments, R 1 is -C(O)-(7-membered heterocyclyl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-bicyclic heterocyclyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 1 is -C(O)-(bridged, fused or spiro heterocyclyl), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R1 is -C(O)-(bridged heterocyclic group), which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is -C(O)-(fused heterocyclic group), which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is -C(O)-(spiro heterocyclic group), which is optionally substituted by one or more substituents Q. In certain embodiments, R 1 is -OC(O)OR 5a , wherein, R 5a is as defined herein. In certain embodiments, R 1 is -OC(O)NR 5b R 5c , wherein, R 5b and R 5c are each as defined herein.

[0101] In certain embodiments, R 1 is -L 2 -P(X)(OR 5a )(NR 5b R 5c ), wherein, R 5a , R 5b , R 5c , L 2 and X are each as defined herein. In certain embodiments, R 1 is -L 2 -P(O)(OR 5a )(NR 5b R 5c ), wherein, R 5a , R 5b , R 5c and L 2 are each as defined herein. In certain embodiments, R 1 is -P(X)(OR 5a )(NR 5b R 5c ), wherein, R 5a , R 5b , R 5c and X are each as defined herein. In certain embodiments, R 1 is -P(O)(OR 5a )(NR 5b R 5c ), wherein, R 5a , R 5b and R 5c are each as defined herein. In certain embodiments, R 1((S)-1-Isopropoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-Butoxycarbonylethylamino)(phenoxy)phosphinyl, ((1S)-1-sec-Butoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-tert-Butoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-Pentyloxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-Hexyloxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-(2-Ethylbutoxy)carbonylethylamino)(phenoxy)phosphinyl, ((1S)-1-(1-Phenylethoxycarbonyl)ethylamino)(phenoxy)phosphinyl, ((S)-1-Pyridin-3-ylmethoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-Pyridin-4-ylmethoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-Quinolin-4-yl-methoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-Quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-(4-Methyltetrahydropyran-4-yloxy)carbonylethylamino)(phenoxy)phosphinyl, ((S)-1-Isopropoxycarbonylethylamino)(quinolin-5-yloxy)phosphinyl, 3-(((S)-1-Isopropoxycarbonylethylamino)(phenoxy)phosphinyloxy)propionyl, (1-Methyl-1-(1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphinyl, (1-Methyl-1-(1-methyl-1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphinyl, ((1S)-1-(1-Phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphinyl, ((1S)-1-(1-(4-(tert-Butoxycarbonylamino)phenyl)ethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphinyl, or ((1S)-1-(1-Methyl-1-phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphinyl. In certain embodiments, R 1 is ((S)-1-Isopropoxycarbonylethylamino)(phenoxy)phosphinyl. In certain embodiments, R 1 is (((R)-1-(Benzyloxy)-3-methyl-1-oxobutan-2-yl)amino)(phenoxy)phosphinyl, (((S)-3-Methyl-1-oxo-1-(1-phenyl-cyclopropoxy)butan-2-yl)amino)(phenoxy)phosphinyl, (((S)-1-Oxo-1-((tetrahydro-2H-pyran-4-yl)oxy)propan-2-yl)amino)(phenoxy)phosphinyl, (((S)-1-((1-Methylpiperidin-4-yl)oxy)-1-oxo-propan-2-yl)amino)(phenoxy)phosphinyl, or (((S)-1-Oxo-1-(pentyloxy)propan-2-yl)-amino)-(quinolin-5-yloxy)phosphinyl).

[0102] In certain embodiments, R 2 is hydrogen. In certain embodiments, R 2 is C 1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, R 2 is methyl, optionally substituted with one or more substituents Q. In certain embodiments, R 2 is C 1-6 heteroalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R 2 is C 2-6 alkenyl, optionally substituted with one or more substituents Q. In certain embodiments, R 2 is C 2-6 alkynyl, optionally substituted with one or more substituents Q. In certain embodiments, R 2 is C 3-10 cycloalkyl, optionally substituted with one or more substituents Q. In certain embodiments, R 2 is C 6-14 aryl, optionally substituted with one or more substituents Q. In certain embodiments, R 2 is C 7-15 aralkyl, optionally substituted with one or more substituents Q. In certain embodiments, R 2 is heteroaryl, optionally substituted with one or more substituents Q. In certain embodiments, R 2 is heterocyclic, optionally substituted with one or more substituents Q.

[0103] In certain embodiments, R 2 is -C(O)R 1a , wherein R 1a is as defined herein. In certain embodiments, R 2 is -C(O)OR 1a , wherein R 1a is as defined herein. In certain embodiments, R 2 is -C(O)NR 1b R 1c , wherein R 1b and R 1c are each as defined herein. In certain embodiments, R 2 is -C(O)SR 1a , wherein R 1a is as defined herein. In certain embodiments, R 2 is -C(NR 1a )NR 1b R 1c , wherein R 1a , R1b and R 1c are each as defined herein. In certain embodiments, R 2 is -C(S)R 1a , wherein R 1a is as defined herein. In certain embodiments, R 2 is -C(S)OR 1a , wherein R 1a is as defined herein. In certain embodiments, R 2 is -C(S)NR 1b R 1c , wherein R 1b and R 1c are each as defined herein. In certain embodiments, R 2 is -S(O)R 1a , wherein R 1a is as defined herein. In certain embodiments, R 2 is -S(O)2R 1a , wherein R 1a is as defined herein. In certain embodiments, R 2 is -S(O)NR 1b R 1c , wherein R 1b and R 1c are each as defined herein. In certain embodiments, R 2 is -S(O)2NR 1b R 1c , wherein R 1b and R 1c are each as defined herein. In certain embodiments, R 2 is -Si(R 1a )3, wherein R 1a are each as defined herein. In certain embodiments, R 2 is -Si(C 1-6 alkyl)3, which are each optionally substituted with one or more substituents Q.

[0104] In certain embodiments, R 3 is a halogen. In certain embodiments, R 3 is fluorine. In certain embodiments, R 3 is -OR 5a , wherein R 5a is as defined herein. In certain embodiments, R 3 is a hydroxyl group. In certain embodiments, R 3 is -OC(O)R 5a , wherein R 5a is as defined herein. In certain embodiments, R3 is -OC(O)-C 1-30 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-C 1-20 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-C 1-10 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-C 1-6 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is acetyloxy, propionyloxy or butyryloxy, each of which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is acetyloxy. In certain embodiments, R 3 is -OC(O)-C 1-10 heteroalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-C 2-10 alkenyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-C 2-10 alkynyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-C 3-10 cycloalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-C 6-14 aryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is benzoyloxy, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-(bicyclic C 8-14 aryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-C 7-15 aralkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-(monocyclic heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 3is -OC(O)-(a 5- or 6-membered heteroaryl), each of which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-(a bicyclic heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-(a 5,5-, 5,6- or 6,6-fused heteroaryl), each of which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-heterocyclyl, which is optionally substituted by one or more substituents Q. In some embodiments, R 3 is -OC(O)-monocyclic heterocyclyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-(a 3-, 4-, 5-, 6- or 7-membered heterocyclyl), each of which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-bicyclic heterocyclyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)-(a bridged, fused or spiro heterocyclyl), each of which is optionally substituted by one or more substituents Q. In certain embodiments, R 3 is -OC(O)OR 5a , wherein R 5a is as defined herein. In certain embodiments, R 3 is -OC(O)NR 5b R 5c , wherein R 5b and R 5c are each as defined herein.

[0105] In certain embodiments, R 4 is halogen. In certain embodiments, R 4 is fluorine. In certain embodiments, R 4 is -OR 5a , wherein R 5a is as defined herein. In certain embodiments, R 4 is hydroxy. In certain embodiments, R 4 is -OC(O)R 5a , wherein R 5a is as defined herein. In certain embodiments, R 4 is -OC(O)-C 1-30 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-C 1-20An alkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-C 1-10 An alkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-C 1-6 An alkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 4 is acetyloxy, propionyloxy or butyryloxy, each optionally substituted by one or more substituents Q. In certain embodiments, R 4 is acetyloxy. In certain embodiments, R 4 is -OC(O)-C 1-10 A heteroalkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-C 2-10 An alkenyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-C 2-10 An alkynyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-C 3-10 A cycloalkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-C 6-14 An aryl group, optionally substituted by one or more substituents Q. In certain embodiments, R 4 is benzoyloxy, optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-(bicyclic C 8-14 aryl), optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-C 7-15 An aralkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-heteroaryl, optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-(monocyclic heteroaryl), optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-(5-membered or 6-membered heteroaryl), each optionally substituted by one or more substituents Q. In certain embodiments, R 4 is -OC(O)-(bicyclic heteroaryl), optionally substituted by one or more substituents Q. In certain embodiments, R 4is -OC(O)-(5,5-, 5,6- or 6,6-fused heteroaryl), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 4 is -OC(O)-heterocyclyl, which is optionally substituted with one or more substituents Q. In some embodiments, R 4 is -OC(O)-monocyclic heterocyclyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 4 is -OC(O)-(3-membered, 4-membered, 5-membered, 6-membered or 7-membered heterocyclyl), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 4 is -OC(O)-bicyclic heterocyclyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 4 is -OC(O)-(bridged, fused or spiro heterocyclyl), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 4 is -OC(O)OR 5a , wherein R 5a is as defined herein. In certain embodiments, R 4 is -OC(O)NR 5b R 5c , wherein R 5b and R 5c are each as defined herein.

[0106] In certain embodiments, R 5 is hydrogen. In certain embodiments, R 5 is -C(O)R 5a , wherein R 5a is as defined herein. In certain embodiments, R 5 is -C(O)-C 1-30 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-20 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-6 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 alkylene-heteroaryl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10Alkylene-(monocyclic heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 Alkylene-(5- or 6-membered heteroaryl), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 Alkylene-(5-membered heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 Alkylene-(6-membered heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 Alkylene-(bicyclic heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 Alkylene-(5,5-, 5,6- or 6,6-heteroaryl), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 Alkylene-(5,5-heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 Alkylene-(5,6-heteroaryl), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 Alkylene-(6,6-heteroaryl), which is optionally substituted with one or more substituents Q.

[0107] In certain embodiments, R 5 is -C(O)-C 1-10 Alkylene-heterocyclic group, which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 Alkylene-(monocyclic heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 Alkylene-(3-, 4-, 5-, 6- or 7-membered heterocyclic group), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 Alkylene-(3-membered heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C1-10 An alkylene-(4-membered heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 An alkylene-(5-membered heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 An alkylene-(6-membered heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 An alkylene-(7-membered heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is pyrrolidin-1-ylacetyl, 3-morpholinopropionyl, 4-methylpiperazin-1-ylpropionyl or 4-acetylpiperazin-1-ylpropionyl. In certain embodiments, R 5 is -C(O)-C 1-10 An alkylene-(bicyclic heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 An alkylene-(bridged, fused or spiro heterocyclic group), each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 An alkylene-(bridged heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 An alkylene-(fused heterocyclic group), which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 1-10 An alkylene-(spiro heterocyclic group), which is optionally substituted with one or more substituents Q.

[0108] In certain embodiments, R 5 is acetyl, propionyl, butyryl, valeryl, hexanoyl, heptanoyl, octanoyl, nonanoyl or decanoyl, each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is acetyl or propionyl, each of which is optionally substituted with one or more substituents Q. In certain embodiments, R 5 is acetyl or propionyl, each of which is optionally substituted with a 5- or 6-membered heteroaryl or a 5- or 6-membered heterocyclic group, and the 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclic group is further substituted with one or more substituents Q a substituted. In certain embodiments, R 5is an acetyl or propionyl group, each optionally substituted by pyridin-3-yl, pyrrolidin-1-yl, morpholinyl, 4-methylpiperazin-1-yl or 4-acetylpiperazin-1-yl.

[0109] In certain embodiments, R 5 is -C(O)-C 1-10 heteroalkyl, optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 2-10 alkenyl, optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 2-10 alkynyl, optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 3-10 cycloalkyl, optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 6-14 aryl, optionally substituted by one or more substituents Q. In certain embodiments, R 5 is benzoyl, optionally substituted by one or more substituents Q. In certain embodiments, R 5 is 4-dimethylaminobenzoyl. In certain embodiments, R 5 is -C(O)-(bicyclic C 8-14 aryl), optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-C 7-15 aralkyl, optionally substituted by one or more substituents Q.

[0110] In certain embodiments, R 5 is -C(O)-heteroaryl, optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-(monocyclic heteroaryl), optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-(5- or 6-membered heteroaryl), each optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-(5-membered heteroaryl), optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-(6-membered heteroaryl), optionally substituted by one or more substituents Q. In certain embodiments, R 5 is pyrrolylcarbonyl or pyridinylcarbonyl, each optionally substituted by one or more substituents Q. In certain embodiments, R 5is pyrrole-2-ylcarbonyl or pyridine-3-ylcarbonyl, each optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-(bicyclic heteroaryl), optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-(5,5-, 5,6- or 6,6-fused heteroaryl), each optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-(5,5-fused heteroaryl), optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-(5,6-fused heteroaryl), optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-(6,6-fused heteroaryl), optionally substituted with one or more substituents Q.

[0111] In certain embodiments, R 5 is -C(O)-heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-monocyclic heterocyclyl, optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-(3-, 4-, 5-, 6- or 7-membered heterocyclyl), each optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-(3-membered heterocyclyl), optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-(4-membered heterocyclyl), optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-(5-membered heterocyclyl), optionally substituted with one or more substituents Q. In certain embodiments, R 5 is -C(O)-(6-membered heterocyclyl), optionally substituted with one or more substituents Q. In certain embodiments, R 5 is tetrahydropyranylcarbonyl, piperidinylcarbonyl or piperazinylcarbonyl, each optionally substituted with one or more substituents Q. In certain embodiments, R 5 is tetrahydropyran-4-ylcarbonyl or piperidin-4-ylcarbonyl, each optionally substituted with one or more substituents Q. In certain embodiments, R 5 is tetrahydropyran-4-ylcarbonyl or 1-methylpiperidin-4-ylcarbonyl. In certain embodiments, R 5 is -C(O)-(7-membered heterocyclyl), optionally substituted with one or more substituents Q. In certain embodiments, R5 is -C(O)-bicyclic heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-(bridged, fused or spiro heterocyclic group), each of which is optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-(bridged heterocyclic group), which is optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-(fused heterocyclic group), which is optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -C(O)-(spiro heterocyclic group), which is optionally substituted by one or more substituents Q. In certain embodiments, R 5 is -OC(O)OR 5a , wherein, R 5a is as defined herein. In certain embodiments, R 5 is -OC(O)NR 5b R 5c , wherein, R 5b and R 5c are each as defined herein.

[0112] In certain embodiments, R 5 is -L 2 -P(X)(OR 5a )(NR 5b R 5c ), wherein, R 5a , R 5b , R 5c , L 2 and X are each as defined herein. In certain embodiments, R 5 is -L 2 -P(O)(OR 5a )(NR 5b R 5c ), wherein, R 5a , R 5b , R 5c and L 2 are each as defined herein. In certain embodiments, R 5 is -P(X)(OR 5a )(NR 5b R 5c ), wherein, R 5a , R 5b , R 5c and X are each as defined herein. In certain embodiments, R 5 is -P(O)(OR 5a )(NR 5b R5c ), wherein R 5a , R 5b and R 5c are each as defined herein. In certain embodiments, R 5 is ((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-butoxycarbonylethylamino)(phenoxy)phosphinyl, ((1S)-1-sec-butoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-tert-butoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-pentyloxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-hexyloxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-(2-ethylbutoxy)carbonylethylamino)(phenoxy)phosphinyl, ((1S)-1-(1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphinyl, ((S)-1-pyridin-3-ylmethoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-pyridin-4-ylmethoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-quinolin-4-yl-methoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphinyl, ((S)-1-(4-methyltetrahydropyran-4-yloxy)carbonylethylamino)(phenoxy)phosphinyl, ((S)-1-isopropoxycarbonylethylamino)(quinolin-5-yloxy)phosphinyl, 3-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphinyloxy)propionyl, (1-methyl-1-(1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphinyl, (1-methyl-1-(1-methyl-1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphinyl, ((1S)-1-(1-phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphinyl, ((1S)-1-(1-(4-(tert-butoxycarbonylamino)phenyl)ethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphinyl, or ((1S)-1-(1-methyl-1-phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphinyl. In certain embodiments, R 5 is ((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphinyl. In certain embodiments, R 5(((R)-1-(Benzyloxy)-3-methyl-1-oxobutan-2-yl)amino)(phenoxy)phosphinyl, (((S)-3-methyl-1-oxo-1-(1-phenyl-cyclopropoxy)butan-2-yl)amino)(phenoxy)phosphinyl, (((S)-1-oxo-1-((tetrahydro-2H-pyran-4-yl)oxy)propan-2-yl)amino)(phenoxy)phosphinyl, (((S)-1-((1-methylpiperidin-4-yl)oxy)-1-oxo-propan-2-yl)amino)(phenoxy)phosphinyl, or (((S)-1-oxo-1-(pentyloxy)propan-2-yl)-amino)-(quinolin-5-yloxy)phosphinyl).

[0113] In certain embodiments, R 3 and R 4 are joined together to form a lactone ring, which is optionally substituted with one or more substituents Q. In certain embodiments, R 4 and R 5 are joined together to form a lactone ring, which is optionally substituted with one or more substituents Q.

[0114] In certain embodiments, R 3a is R 5a as defined herein. In certain embodiments, R 3a is hydrogen. In certain embodiments, R 3a is -C(O)R 5a , wherein R 5a is as defined herein. In certain embodiments, R 3a is -C(O)-C 1-30 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 3a is -C(O)-C 1-20 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 3a is -C(O)-C 1-10 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 3a is -C(O)-C 1-6 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 3a is acetyl, propionyl or butyryl, each optionally substituted with one or more substituents Q. In certain embodiments, R 3a is acetyl. In certain embodiments, R 3a is -C(O)-C 1-10 heteroalkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 3a is -C(O)-C 2-10An alkenyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-C 2-10 An alkynyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-C 3-10 A cycloalkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-C 6-14 An aryl group, optionally substituted by one or more substituents Q. In certain embodiments, R 3a is benzoyl, optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-(bicyclic C 8-14 aryl), optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-C 7-15 An aralkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-heteroaryl, optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-(monocyclic heteroaryl), optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-(5-membered or 6-membered heteroaryl), each optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-(bicyclic heteroaryl), optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-(5,5-, 5,6- or 6,6-fused heteroaryl), each optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-heterocyclic group, optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-monocyclic heterocyclic group, optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-(3-membered, 4-membered, 5-membered, 6-membered or 7-membered heterocyclic group), each optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-bicyclic heterocyclic group, optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)-(bridged, fused or spiro heterocyclic group), each optionally substituted by one or more substituents Q. In certain embodiments, R 3a is -C(O)OR5a , wherein, R 5a is as defined herein. In certain embodiments, R 3a is -C(O)NR 5b R 5c , wherein, R 5b and R 5c are each as defined herein.

[0115] In certain embodiments, R 4a is R 5a as defined herein. In certain embodiments, R 4a is hydrogen. In certain embodiments, R 4a is -C(O)R 5a , wherein, R 5a is as defined herein. In certain embodiments, R 4a is -C(O)-C 1-30 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 4a is -C(O)-C 1-20 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 4a is -C(O)-C 1-10 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 4a is -C(O)-C 1-6 alkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 4a is acetyl, propionyl or butyryl, each optionally substituted with one or more substituents Q. In certain embodiments, R 4a is acetyl. In certain embodiments, R 4a is -C(O)-C 1-10 heteroalkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 4a is -C(O)-C 2-10 alkenyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 4a is -C(O)-C 2-10 alkynyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 4a is -C(O)-C 3-10 cycloalkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 4a is -C(O)-C 6-14 aryl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 4ais benzoyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)-(bicyclic C 8-14 aryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)-C 7-15 aralkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)-heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)-(monocyclic heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)-(5- or 6-membered heteroaryl), each optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)-(bicyclic heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)-(5,5-, 5,6- or 6,6-fused heteroaryl), each optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)-heterocycloalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)-monocyclic heterocycloalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)-(3-, 4-, 5-, 6- or 7-membered heterocycloalkyl), each optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)-bicyclic heterocycloalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)-(bridged, fused or spiro heterocycloalkyl), each optionally substituted by one or more substituents Q. In certain embodiments, R 4a is -C(O)OR 5a , wherein, R 5a is as defined herein. In certain embodiments, R 4a is -C(O)NR 5b R 5c , wherein, R 5b and R 5c are each as defined herein.

[0116] In certain embodiments, R 5a is hydrogen. In certain embodiments, R 5a is C 1-30An alkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 1-20 An alkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 1-10 An alkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 1-6 An alkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is methyl, ethyl, propyl or butyl, each optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 1-30 A heteroalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 1-20 A heteroalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 1-10 A heteroalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 1-6 A heteroalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 2-30 An alkenyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 2-20 An alkenyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 2-10 An alkenyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 2-6 An alkenyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 2-30 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 2-20 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 2-10 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 2-6 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 3-30A cycloalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 3-20 A cycloalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 3-10 A cycloalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 6-30 An aryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 6-14 An aryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is phenyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is bicyclic C 8-14 An aryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 7-30 An aralkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is C 7-15 An aralkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a heteroaryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a monocyclic heteroaryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a 5- or 6-membered heteroaryl group, each optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a 5-membered heteroaryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a 6-membered heteroaryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a bicyclic heteroaryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a 5,5-, 5,6- or 6,6-fused heteroaryl group, each optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a 5,5-fused heteroaryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a 5,6-fused heteroaryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a 6,6-fused heteroaryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5ais a quinolinyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is quinolin-5-yl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a monocyclic heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a 3-, 4-, 5-, 6- or 7-membered heterocyclic group, each optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a bicyclic heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5a is a bridged, fused or spiro heterocyclic group, each optionally substituted by one or more substituents Q.

[0117] In certain embodiments, R 5b is hydrogen. In certain embodiments, R 5b is C 1-30 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 1-20 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 1-10 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 1-6 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is methyl, ethyl, propyl or butyl, each optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 1-30 heteroalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 1-20 heteroalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 1-10 heteroalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 1-6 heteroalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 2-30 alkenyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 2-20An alkenyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 2-10 An alkenyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 2-6 An alkenyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 2-30 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 2-20 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 2-10 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 2-6 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 3-30 A cycloalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 3-20 A cycloalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 3-10 A cycloalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 6-30 An aryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 6-14 An aryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a phenyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is bicyclic C 8-14 An aryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 7-30 An aralkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is C 7-15 An aralkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a heteroaryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a monocyclic heteroaryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5bis a 5- or 6-membered heteroaryl, each optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a 5-membered heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a 6-membered heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a bicyclic heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a 5,5-, 5,6- or 6,6-fused heteroaryl, each optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a 5,5-fused heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a 5,6-fused heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a 6,6-fused heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a quinolinyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a quinolin-5-yl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a monocyclic heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a 3-, 4-, 5-, 6- or 7-membered heterocyclic group, each optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a bicyclic heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5b is a bridged, fused or spiro heterocyclic group, each optionally substituted by one or more substituents Q.

[0118] In certain embodiments, R 5c is hydrogen. In certain embodiments, R 5c is C 1-30 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 1-20 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 1-10 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 1-6An alkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is methyl, ethyl, propyl, butyl, pentyl or hexyl, each optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 1-10 A heteroalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 2-30 An alkenyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 2-20 An alkenyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 2-10 An alkenyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 2-6 An alkenyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 2-30 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 2-20 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 2-10 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 2-6 An alkynyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 3-30 A cycloalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 3-20 A cycloalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 3-10 A cycloalkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 6-30 An aryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 6-14 An aryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is phenyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is bicyclic C 8-14An aryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 7-30 An aralkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is C 7-15 An aralkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is a heteroaryl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is a heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 5c is 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-tert-butoxycarbonylethyl, 1-(1-phenylethoxycarbonyl)ethyl, 1-methyl-1-(1-phenylethoxycarbonyl)ethyl, 1-sec-butoxycarbonylethyl, 1-pentyloxycarbonylethyl, 1-hexyloxycarbonylethyl, 1-(2-ethylbutoxy)carbonylethyl, 1-pyridin-3-ylmethoxycarbonylethyl, 1-pyridin-4-ylmethoxycarbonylethyl, 1-quinolin-4-ylmethoxycarbonylethyl, 1-quinolin-5-ylmethoxycarbonylethyl, 1-(4-methyltetrahydropyran-4-yloxy)carbonylethyl, 1-(1-phenylethoxycarbonyl)-2-methylpropyl, 1-(1-methyl-1-phenylethoxycarbonyl)-2-methylpropyl, or 1-(1-(4-(tert-butoxycarbonylamino)phenyl)ethoxycarbonyl)-2-methylpropyl. In certain embodiments, R 5c is 1-isopropoxycarbonylethyl. In certain embodiments, R 5c is 1-((tetrahydropyran-4-yl)oxycarbonylethyl, 1-(benzyloxycarbonyl)-2-methylpropyl, 1-(phenylcyclopropoxycarbonyl)-2-methylpropyl, or 1-((1-methylpiperidin-4-yl)oxycarbonyl)-2-methylpropyl.

[0119] In certain embodiments, R 6a is C 1-30 An alkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-20 An alkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-10 An alkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-6 An alkyl group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-6Alkylene - heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-6 Alkylene-(monocyclic heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-6 Alkylene-(5 - or 6 - membered heteroaryl), each optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-6 Alkylene-(5 - membered heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-6 Alkylene-(6 - membered heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-6 Alkylene-(bicyclic heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-6 Alkylene-(5,5 -, 5,6 - or 6,6 - fused heteroaryl), each optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-6 Alkylene-(5,5 - fused heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-6 Alkylene-(5,6 - fused heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-6 Alkylene-(6,6 - fused heteroaryl), which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is methyl, ethyl, propyl, butyl, pentyl or hexyl, each optionally substituted by one or more substituents Q. In certain embodiments, R 6a is propyl, butyl, pentyl or hexyl, each optionally substituted by one or more substituents Q.

[0120] In certain embodiments, R 6a is C 1-30 Heteroalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-20 Heteroalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 1-10 Heteroalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C1-6 A heteroalkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 2-30 An alkenyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 2-20 An alkenyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 2-10 An alkenyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 2-6 An alkenyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 2-30 An alkynyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 2-20 An alkynyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 2-10 An alkynyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 2-6 An alkynyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 3-30 A cycloalkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 3-20 A cycloalkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 3-10 A cycloalkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is a monocyclic C 3-10 cycloalkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, each optionally substituted by one or more substituents Q. In certain embodiments, R 6a is a bicyclic C 4-10 cycloalkyl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6a is a bridged, fused or spiro C 4-10 cycloalkyl group, each optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 6-30 An aryl group, optionally substituted by one or more substituents Q. In certain embodiments, R 6ais C 6-14 aryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is phenyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is bicyclic C 8-14 aryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 7-30 aralkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is C 7-15 aralkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is bicyclic C 8-15 aralkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is heterocyclic, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is monocyclic heterocyclic, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is a 3-, 4-, 5-, 6- or 7-membered heterocyclic, each optionally substituted by one or more substituents Q. In certain embodiments, R 6a is a 6-membered heterocyclic, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is bicyclic heterocyclic, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6a is bridged, fused or spiro heterocyclic, each optionally substituted by one or more substituents Q. In certain embodiments, R 6a is isopropyl, butyl, 2-butyl, tert-butyl, pentyl, hexyl, 2-ethylbutyl, 1-phenylethyl, 2-phenylpropan-2-yl, pyridin-3-ylmethyl, pyridin-4-ylmethyl, quinolin-4-ylmethyl or quinolin-5-ylmethyl. In certain embodiments, R 6a is 1-phenylcyclopropyl, benzyl, tetrahydropyran-4-yl or 1-methylpiperidin-4-yl.

[0121] In certain embodiments, R 6b is hydrogen. In certain embodiments, R 6b is deuterium. In certain embodiments, R 6b is C 1-6 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6bis methyl, ethyl, propyl or butyl, each optionally substituted by one or more substituents Q. In certain embodiments, R 6b is methyl, ethyl, isopropyl, 2-methylpropyl or 2-butyl. In certain embodiments, R 6b is methyl or isopropyl. In certain embodiments, R 6b is methyl. In certain embodiments, R 6b is isopropyl. In certain embodiments, R 6b is C 1-6 heteroalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6b is C 2-6 alkenyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6b is C 2-6 alkynyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6b is C 3-10 cycloalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6b is C 6-14 aryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6b is C 7-15 aralkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6b is heteroaryl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6b is heterocyclic group, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6b is hydrogen, methyl, imidazol-4-ylmethyl, indol-3-ylmethyl, carboxymethyl, hydroxymethyl, aminocarbonylmethyl, 2-mercaptomethyl, 2-carboxyethyl, 1-hydroxyethyl, 2-aminocarbonylethyl, 2-methylthioethyl, isopropyl, 2-methylpropyl, 3-guanidinopropyl, 2-butyl, 4-aminobutyl, benzyl or 4-hydroxybenzyl.

[0122] In certain embodiments, R 6c is hydrogen. In certain embodiments, R 6c is deuterium. In certain embodiments, R 6c is C 1-6 alkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, R 6c is methyl, ethyl, propyl or butyl, each optionally substituted by one or more substituents Q. In certain embodiments, R 6c is methyl, ethyl, isopropyl, 2-methylpropyl or 2-butyl. In certain embodiments, R 6cis methyl. In certain embodiments, R 6c is C 1-6 heteroalkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 6c is C 2-6 alkenyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 6c is C 2-6 alkynyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 6c is C 3-10 cycloalkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 6c is C 6-14 aryl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 6c is C 7-15 aralkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 6c is heteroaryl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 6c is heterocyclic, which is optionally substituted with one or more substituents Q. In certain embodiments, R 6c is hydrogen, methyl, imidazol-4-ylmethyl, indol-3-ylmethyl, carboxymethyl, hydroxymethyl, aminocarbonylmethyl, 2-mercaptomethyl, 2-carboxyethyl, 1-hydroxyethyl, 2-aminocarbonylethyl, 2-methylthioethyl, isopropyl, 2-methylpropyl, 3-guanidinopropyl, 2-butyl, 4-aminobutyl, benzyl or 4-hydroxybenzyl. In certain embodiments, R 6c is hydrogen or methyl.

[0123] In certain embodiments, R 6b and R 6c together with the carbon atom to which they are attached form a C 3-10 subcycloalkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 6b and R 6c together with the carbon atom to which they are attached form a monocyclic C 3-10 subcycloalkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 6b and R 6c together with the carbon atom to which they are attached form a bicyclic C 3-10 subcycloalkyl, which is optionally substituted with one or more substituents Q. In certain embodiments, R 6b and R 6c together with the carbon atom to which they are attached form a bridged, fused or spiro C 3-10Subcycloalkyl groups, each optionally substituted by one or more substituents Q. In certain embodiments, R 6b and R 6c together with the carbon atom to which they are attached form cyclopropane-1,1-diyl, cyclobutene-1,1-diyl, cyclopentane-1,1-diyl or cyclohexane-1,1-diyl, each optionally substituted by one or more substituents Q.

[0124] In certain embodiments, A is a bond. In certain embodiments, A is O. In certain embodiments, A is N(R 1b ), where R 1b is as defined herein. In certain embodiments, A is N(H).

[0125] In certain embodiments, L 1 is C 1-6 alkylene, which is optionally substituted by one or more substituents Q. In certain embodiments, L 1 is methylene, ethane-1,2-diyl, propane-1,2-diyl or butane-1,4-diyl, each optionally substituted by one or more substituents Q. In certain embodiments, L 1 is C 1-6 heteroalkylene, which is optionally substituted by one or more substituents Q. In certain embodiments, L 1 is C 2-6 alkenylene, which is optionally substituted by one or more substituents Q. In certain embodiments, L 1 is C 2-6 alkynylene, which is optionally substituted by one or more substituents Q. In certain embodiments, L 1 is C 3-10 subcycloalkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, L 1 is C 6-14 arylene, which is optionally substituted by one or more substituents Q. In certain embodiments, L 1 is C 7-15 aralkyl, which is optionally substituted by one or more substituents Q. In certain embodiments, L 1 is heteroarylene, which is optionally substituted by one or more substituents Q. In certain embodiments, L 1 is heterocyclylene, which is optionally substituted by one or more substituents Q.

[0126] In certain embodiments, L 2 is a bond. In certain embodiments, L 2 is -O-C 1-6 alkylene, which is optionally substituted by one or more substituents Q. In certain embodiments, L2 is -OCH2CH2C(O)-. In certain embodiments, L 2 is -O-C 1-6 a heteroalkylidene, which is optionally substituted with one or more substituents Q. In certain embodiments, L 2 is -O-C 2-6 an alkenylidene, which is optionally substituted with one or more substituents Q. In certain embodiments, L 2 is -O-C 2-6 an alkynylidene, which is optionally substituted with one or more substituents Q. In certain embodiments, L 2 is -O-C 3-10 a cycloalkylidene, which is optionally substituted with one or more substituents Q. In certain embodiments, L 2 is -O-C 6-14 an arylidene, which is optionally substituted with one or more substituents Q. In certain embodiments, L 2 is -O-C 7-15 an aralkylidene, which is optionally substituted with one or more substituents Q. In certain embodiments, L 2 is -O-heteroarylidene, which is optionally substituted with one or more substituents Q. In certain embodiments, L 2 is -O-heterocyclidene, which is optionally substituted with one or more substituents Q.

[0127] In certain embodiments, X is O. In certain embodiments, X is S.

[0128] In certain embodiments, Z is hydrogen. In certain embodiments, Z is azide. In certain embodiments, Z is halogen. In certain embodiments, Z is fluorine or iodine. In certain embodiments, Z is fluorine. In certain embodiments, Z is iodine. In certain embodiments, Z is isocyano (-NC). In certain embodiments, Z is -C=C(R 1a )R 1a , where R 1a are each as defined herein. In certain embodiments, Z is -C=CH2. In certain embodiments, Z is -C≡CR 1a , where R 1a is as defined herein. In certain embodiments, Z is -C≡CH. In certain embodiments, Z is where R 1a is as defined herein. In certain embodiments, Z is In certain embodiments, Z is In certain embodiments, Z is In certain embodiments, Z is where R 1aAs defined herein. In certain embodiments, Z is In certain embodiments, Z is -C(O)R 1a , wherein R 1a As defined herein. In certain embodiments, Z is -C(O)CH3. In certain embodiments, Z is -SH.

[0129] In one embodiment, the present invention provides the following compounds: Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A1; 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A2; 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1S)-1-(1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A3; 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-((1-methyl-1-(1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A4; 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1S)-1-(1-phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphoryl)-D-mannopyranoside A5; 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-((1-methyl-1-(1-methyl-1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A6; 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1S)-1-(1-methyl-1-phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphoryl)-D-mannopyranoside A7; Pyridin-3-ylacetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A8; 3-Morpholinopropionyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A9; 4-Methylpiperazin-1-ylpropionyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A10; 4-Acetylpiperazin-1-ylpropionyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A11; Tetrahydropyran-4-ylcarbonyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A12; 1-Methylpiperidin-4-ylcarbonyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A13; Pyrrolidin-1-ylacetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A14; 4-Dimethylaminobenzoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A15; Pyridin-3-ylcarbonyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A16; Pyrrol-2-ylcarbonyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A17; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-butoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A18; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1S)-1-sec-butoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A19; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-tert-butoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A20; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-pentyloxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A21; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-hexyloxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A22; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-(2-ethylbutoxy)carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A23; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-pyridin-3-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A24; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-pyridin-4-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A25; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-quinolin-4-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A26; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A27; Valeryl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A28; 2-Methylbutanoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-(quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A29; Hexanoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-(quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A30; Nonanoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-(quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A31; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-(4-methyltetrahydropyran-4-yloxy)carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A32; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-((((1S)-1-(1-(4-(tert-butoxycarbonylamino)phenyl)ethoxycarbonyl)-2-methylpropylamino)(phenoxy)-phosphoryl)-D-mannopyranoside A33; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(quinolin-5-yloxy)phosphoryl)-D-mannopyranoside A34; or Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(3-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryloxy)propanoyl)-D-mannopyranoside A35; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0130] In yet another embodiment, the following compounds are provided herein: (3S,4R,5S,6R)-3-(2-azidoacetamido)-6-((((((R)-1-(benzyloxy)-3-methyl-1-oxobutan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A36; (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-3-Methyl-1-oxo-1-(1-phenyl-cyclopropoxy)butan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A37; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)-6-((tetrahydro-2H-pyran-4-carbonyl)oxy)tetrahydro-2H-pyran-3,4-diyl diacetate A38; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((3-Morpholinobenzoyl)oxy)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A39; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((3-(4-Methylpiperazin-1-yl)benzoyl)oxy)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A40; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((3-(Morpholinomethyl)benzoyl)oxy)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A41; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((3-((4-Methylpiperazin-1-yl)methyl)benzoyl)oxy)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A42; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)-6-(valeryloxy)tetrahydro-2H-pyran-3,4-diyl diacetate A43; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((2-methylbutanoyl)oxy)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A44; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-(hexanoyloxy)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A45; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-(nonanoyloxy)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A46; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)-6-((tetrahydro-2H-pyran-4-carbonyl)oxy)tetrahydro-2H-pyran-3,4-diyl diacetate A47; (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-1-oxo-1-((tetrahydro-2H-pyran-4-yl)oxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A48; (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-1-((1-methylpiperidin-4-yl)oxy)-1-oxopropan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A49; (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-1-isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A50; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-Isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)-6-(valeryloxy)tetrahydro-2H-pyran-3,4-diyl diacetate A51; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-Isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)-6-(pivaloyloxy)tetrahydro-2H-pyran-3,4-diyl diacetate A52; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-(hexanoyloxy)-2-((((((S)-1-Isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A53; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-Isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)-6-(nonanoyloxy)tetrahydro-2H-pyran-3,4-diyl diacetate A54; or (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-1-Oxo-1-(pentyloxy)propan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A55; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof.

[0131] In yet another embodiment, provided herein is (((1S)-1-(1-Phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl) 2-(2-Azidoacetylamino)-2-deoxy-3,4,6-tri-O-acetyl-D-mannopyranoside B1; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof.

[0132] In certain embodiments, the compounds provided herein are isolated or purified. In certain embodiments, the compounds provided herein have a purity of at least about 90%, at least about 95%, at least about 98%, at least about 99% or at least about 99.5% by weight. In certain embodiments, the compounds provided herein have a purity of at least about 90% by weight. In certain embodiments, the compounds provided herein have a purity of at least about 95% by weight. In certain embodiments, the compounds provided herein have a purity of at least about 98% by weight. In certain embodiments, the compounds provided herein have a purity of at least about 99% by weight. In certain embodiments, the compounds provided herein have a purity of at least about 99.5% by weight.

[0133] The compounds provided herein are intended to include all possible stereoisomers, unless a specific stereochemistry is specified. In the case where the compounds provided herein contain an alkenyl group, the compounds may exist as one or a mixture of geometric cis / trans (or Z / E) isomers. Where structural isomers are interconvertible, the compounds may exist as a single tautomer or a mixture of tautomers. This may take the form of proton tautomerism in the compounds containing, for example, imino, keto or oxime groups; or the so-called valence tautomerism in compounds containing an aromatic moiety. Thus, a single compound may exhibit more than one type of isomerism.

[0134] The compounds provided herein may be enantiomerically pure, e.g., a single enantiomer or a single diastereomer, or a stereoisomeric mixture, e.g., a mixture of enantiomers, e.g., a racemic mixture of two enantiomers; or a mixture of more than two diastereomers. Thus, one of ordinary skill in the art will recognize that for compounds that undergo epimerization in vivo, administering the compound in its (R) form is equivalent to administering the compound in its (S) form. Conventional techniques for preparing / isolating individual enantiomers include synthesis from a suitable optically pure precursor, asymmetric synthesis from achiral starting materials, or resolution of enantiomeric mixtures, e.g., chiral chromatography, recrystallization, resolution, formation of diastereomeric salts, or derivatization to form diastereomeric adducts followed by separation.

[0135] When the compounds provided herein contain acidic or basic moieties, they may also be provided as pharmaceutically acceptable salts. See, Berge et al., J. Pharm. Sci. 1977, 66, 1-19; Handbook of Pharmaceutical Salts: Properties, Selection, and Use, 2nd Edition; edited by Stahl and Wermuth; John Wiley & Sons, 2011. In certain embodiments, the pharmaceutically acceptable salts of the compounds provided herein are solvates. In certain embodiments, the pharmaceutically acceptable salts of the compounds provided herein are hydrates.

[0136] Suitable acids for preparing the pharmaceutically acceptable salts of the compounds provided herein include, but are not limited to, acetic acid, 2,2-dichloroacetic acid, acylated amino acids, adipic acid, alginic acid, ascorbic acid, L-aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, boric acid, (+)-camphoric acid, camphorsulfonic acid, (+)-(1S)-camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, cinnamic acid, citric acid, cyclamic acid, cyclohexanesulfamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, D-gluconic acid, D-glucuronic acid, L-glutamic acid, α-oxoglutaric acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid, (+)-L-lactic acid, (±)-DL-lactic acid, lactobionic acid, lauric acid, maleic acid, (-)-L-malic acid, malonic acid, (±)-DL-mandelic acid, methanesulfonic acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, nitric acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, perchloric acid, phosphoric acid, L-pyroglutamic acid, saccharic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, sulfuric acid, tannic acid, (+)-L-tartaric acid, thiocyanic acid, p-toluenesulfonic acid, undecylenic acid, and valeric acid.

[0137] Suitable bases for preparing the pharmaceutically acceptable salts of the compounds provided herein include, but are not limited to, inorganic bases such as magnesium hydroxide, calcium hydroxide, potassium hydroxide, zinc hydroxide, and sodium hydroxide; and organic bases such as primary, secondary, tertiary, and quaternary, aliphatic and aromatic amines, including but not limited to L-arginine, phenylethylbenzylamine, benzathine, choline, deanol, diethanolamine, diethylamine, dimethylamine, dipropylamine, diisopropylamine, 2-(diethylamino)ethanol, ethanolamine, ethylamine, ethylenediamine, isopropylamine, N-methyl-glucamine, hydrabamine, 1H-imidazole, L-lysine, morpholine, 4-(2-hydroxyethyl)-morpholine, methylamine, piperidine, piperazine, propylamine, pyrrolidine, 1-(2-hydroxyethyl)-pyrrolidine, pyridine, quinuclidine, quinoline, isoquinoline, triethanolamine, trimethylamine, triethylamine, N-methyl-D-glucamine, 2-amino-2-(hydroxymethyl)-1,3-propanediol, and tromethamine.

[0138] The compounds provided herein may also be provided as prodrugs, which are functional derivatives of the compounds and are readily convertible in vivo to the parent compound. Prodrugs are generally useful because in some cases they may be more readily administered than the parent compound. For example, they may be bioavailable when administered orally, while the parent compound is not. Prodrugs may also have improved solubility in pharmaceutical compositions compared to the parent compound. Prodrugs can be converted to the parent drug by various mechanisms, including enzymatic processes and metabolic hydrolysis. Pharmaceutical composition

[0139] In one embodiment, provided herein are pharmaceutical compositions that comprise a compound provided herein, such as a compound of formula (I), or an enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; and a pharmaceutically acceptable excipient.

[0140] The pharmaceutical compositions provided herein can be formulated into various dosage forms, including but not limited to dosage forms for oral, parenteral, and topical administration. The pharmaceutical compositions can also be formulated into modified-release dosage forms, including delayed release, sustained release, extended release, continuous release, pulsatile release, controlled release, accelerated release, rapid release, targeted release, programmed release, and gastric retention dosage forms. These dosage forms can be prepared according to conventional methods and techniques known to those skilled in the art. See, for example, Remington: The Science and Practice of Pharmacy, supra; Modified-Release Drug Delivery Technology, 2nd Edition; Rathbone et al., eds.; Drugs and the Pharmaceutical Sciences 184; CRC Press; Boca Raton; FL, 2008.

[0141] In one embodiment, the pharmaceutical compositions provided herein are formulated in a dosage form for oral administration. In another embodiment, the pharmaceutical compositions provided herein are formulated in a dosage form for parenteral administration. In yet another embodiment, the pharmaceutical compositions provided herein are formulated in a dosage form for intravenous administration. In yet another embodiment, the pharmaceutical compositions provided herein are formulated in a dosage form for intramuscular administration. In yet another embodiment, the pharmaceutical compositions provided herein are formulated in a dosage form for subcutaneous administration. In yet another embodiment, the pharmaceutical compositions provided herein are formulated in a dosage form for topical administration.

[0142] The pharmaceutical compositions provided herein can be provided in unit dosage form or in multiple dosage forms. As used herein, a unit dosage form refers to a physically discrete unit suitable for administration to a subject and individually packaged as known in the art. Each unit dose contains a predetermined amount of the active ingredient (e.g., the compounds provided herein) and the required pharmaceutical excipients, which are sufficient to produce the desired therapeutic effect. Examples of unit dosage forms include but are not limited to ampoules, syringes, and individually packaged tablets and capsules. The unit dosage forms can be administered in part or in multiple portions. A multiple dosage form is a plurality of identical unit dosage forms packaged in a single container and administered in separate unit dosage forms. Examples of multiple dosage forms include but are not limited to vials, bottles of tablets or capsules, or pint or gallon bottles.

[0143] The pharmaceutical compositions provided herein can be administered once or in multiple doses at time intervals. It should be understood that the exact dosage and duration of treatment can vary depending on the age, weight, and condition of the subject being treated, and can be determined empirically using known testing protocols or by extrapolation from in vivo or in vitro test or diagnostic data. It should further be understood that for any particular individual, the specific dosage regimen should be adjusted over time according to the needs of the subject and the professional judgment of the person administering or supervising the administration of the pharmaceutical composition. A. Oral administration

[0144] The pharmaceutical compositions provided herein for oral administration can be provided in solid, semi-solid or liquid dosage forms for oral administration. As used herein, oral administration also includes buccal, lingual and sublingual administration. Suitable oral dosage forms include, but are not limited to, tablets, fastmelts, chewable tablets, capsules, pills, strips, troches, lozenges, pastilles, cachets, pellets, medicated chewing gum, powders, effervescent or non-effervescent powders or granules, oral mists, solutions, emulsions, suspensions, wafers, granule sprinkles, elixirs and syrups. In addition to the active ingredient, the pharmaceutical compositions can contain one or more pharmaceutically acceptable carriers or excipients, including but not limited to binders, fillers, diluents, disintegrants, wetting agents, lubricants, glidants, colorants, dye migration inhibitors, sweeteners, flavoring agents, emulsifying agents, suspending and dispersing agents, preservatives, solvents, non-aqueous liquids, organic acids and carbon dioxide sources.

[0145] Binders or granulating agents impart cohesiveness to tablets to ensure that the tablets remain intact after compression. Suitable binders or granulating agents include, but are not limited to, starches such as corn starch, potato starch and pregelatinized starch (e.g., ); gelatin; sugars such as sucrose, glucose, dextrose, molasses and lactose; natural and synthetic gums such as gum arabic, alginic acid, alginates, Irish moss extract, Panwar gum, Ghatti gum, mucilage of isabgol husk, carboxymethyl cellulose, methyl cellulose, polyvinylpyrrolidone (PVP), larch arabinogalactan, powdered tragacanth and guar gum; celluloses such as ethyl cellulose, cellulose acetate, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC); and microcrystalline cellulose such as, and Suitable fillers include, but are not limited to, talc, calcium carbonate, microcrystalline cellulose, powdered cellulose, dextrin, kaolin, mannitol, silicic acid, sorbitol, starch and pregelatinized starch. The amount of binder or filler in the pharmaceutical compositions provided herein varies according to the type of formulation and can be readily discerned by one of ordinary skill in the art. The binder or filler can be present in the pharmaceutical compositions provided herein in an amount of about 50 to about 99% by weight.

[0146] Suitable diluents include, but are not limited to, dicalcium phosphate, calcium sulfate, lactose, sorbitol, sucrose, inositol, cellulose, kaolin, mannitol, sodium chloride, dry starch, and powdered sugar. Certain diluents (e.g., mannitol, lactose, sorbitol, sucrose, and inositol) can impart to some compressed tablets the property of allowing disintegration in the mouth by chewing when present in sufficient amounts. Such compressed tablets can be used as chewable tablets. The amount of diluent in the pharmaceutical compositions provided herein varies according to the type of formulation and is readily discernible to one of ordinary skill in the art.

[0147] Suitable disintegrants include, but are not limited to, agar; bentonite; cellulose, e.g., methylcellulose and carboxymethylcellulose; wood products; natural sponges; cation exchange resins; alginic acid; gums, e.g., guar gum and HV; citrus pulp; cross-linked cellulose, e.g., cross-linked carboxymethylcellulose; cross-linked polymers, e.g., cross-linked polyvinylpyrrolidone; cross-linked starch; calcium carbonate; microcrystalline cellulose, e.g., sodium starch glycolate; polacrilin potassium; starch, e.g., corn starch, potato starch, tapioca starch, and pregelatinized starch; clays; and algins. The amount of disintegrant in the pharmaceutical compositions provided herein varies according to the type of formulation and is readily discernible to one of ordinary skill in the art. The pharmaceutical compositions provided herein can contain from about 0.5 to about 15% or from about 1 to about 5% by weight of the disintegrant.

[0148] Suitable lubricants include, but are not limited to, calcium stearate; magnesium stearate; mineral oil; light mineral oil; glycerin; sorbitol; mannitol; glycols, e.g., glyceryl behenate and polyethylene glycol (PEG); stearic acid; sodium lauryl sulfate; talc; hydrogenated vegetable oils, e.g., peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil, and soybean oil; zinc stearate; ethyl oleate; ethyl laurate; agar; starch; lycopodium; and silica or silica gel, such as 200 and The amount of lubricant in the pharmaceutical compositions provided herein varies according to the type of formulation and is readily discernible to one of ordinary skill in the art. The pharmaceutical compositions provided herein can contain from about 0.1 to about 5% by weight of the lubricant.

[0149] Suitable glidants include, but are not limited to, colloidal silica, And asbestos-free talc. Suitable colorants include, but are not limited to, any approved and certified water-soluble FD&C dyes and water-insoluble FD&C dyes suspended on hydrated alumina, as well as lakes. Lakes are combinations produced by adsorbing water-soluble dyes onto hydrated oxides of heavy metals, resulting in insoluble forms of the dyes. Suitable flavoring agents include, but are not limited to, natural flavorings extracted from plants (e.g., fruits), and synthetic admixtures of compounds that produce a pleasant taste sensation, such as, peppermint and methyl salicylate. Suitable sweeteners include, but are not limited to, sucrose, lactose, mannitol, syrups, glycerin, and artificial sweeteners, such as, saccharin and aspartame. Suitable emulsifiers include, but are not limited to, gelatin, gum arabic, tragacanth, bentonite, and surfactants, such as, polyoxyethylene sorbitan monooleate Polyoxyethylene sorbitan monooleate 80 And triethanolamine oleate. Suitable suspending and dispersing agents include, but are not limited to, sodium carboxymethyl cellulose, pectin, tragacanth, Gum arabic, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, and polyvinylpyrrolidone. Suitable preservatives include, but are not limited to, glycerin, methylparaben and propylparaben, benzoic acid additives, and sodium benzoate and alcohols. Suitable wetting agents include, but are not limited to, propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate, and polyoxyethylene lauryl ether. Suitable solvents include, but are not limited to, glycerin, sorbitol, ethanol, and syrups. Suitable non-aqueous liquids used in emulsions include, but are not limited to, mineral oil and cottonseed oil. Suitable organic acids include, but are not limited to, citric acid and tartaric acid. Suitable carbon dioxide sources include, but are not limited to, sodium bicarbonate and sodium carbonate.

[0150] It should be understood that many carriers and excipients can perform several functions, even in the same formulation.

[0151] The pharmaceutical compositions provided herein for oral administration can be provided as compressed tablets, tablet triturates, chewable lozenges, rapidly dissolving tablets, multi-compressed tablets, or enteric-coated tablets, sugar-coated tablets, or film-coated tablets. Enteric-coated tablets are compressed tablets coated with a material that resists the action of gastric acid but dissolves or disintegrates in the intestine, thereby protecting the active ingredient from the acidic environment of the stomach. Enteric coatings include, but are not limited to, fatty acids, fats, phenyl salicylate, waxes, shellac, ammoniated shellac, and cellulose acetate phthalate. Sugar-coated tablets are compressed tablets coated with a sugar coating, which can be beneficial for covering unpleasant tastes or odors and protecting the tablets from oxidation. Film-coated tablets are compressed tablets covered with a thin layer or film of a water-soluble material. Film coatings include, but are not limited to, hydroxyethyl cellulose, sodium carboxymethyl cellulose, polyethylene glycol 4000, and cellulose acetate phthalate. Film coatings impart the same general characteristics as sugar coatings. Multi-compressed tablets are compressed tablets made by more than one compression cycle, including layered tablets and compressed-coated tablets or dry-coated tablets.

[0152] Tablet dosage forms can be prepared from the active ingredient in powder, crystalline, or granular form, alone or in combination with one or more of the carriers or excipients described herein, including binders, disintegrants, controlled-release polymers, lubricants, diluents, and / or colorants. Flavoring agents and sweetening agents are particularly suitable for forming chewable tablets and lozenges.

[0153] The pharmaceutical compositions provided herein for oral administration can be provided as soft or hard capsules, which can be made of gelatin, methylcellulose, starch, or calcium alginate. Hard gelatin capsules, also known as dry-filled capsules (DFCs), consist of two parts that slide over one another, thereby completely encapsulating the active ingredient. Soft elastic capsules (SECs) are soft, spherical shells, such as gelatin shells, which are plasticized by the addition of glycerol, sorbitol, or similar polyols. Soft gelatin shells can contain preservatives to prevent microbial growth. Suitable preservatives are those described herein, including methyl paraben, propyl paraben, and sorbic acid. The liquid, semi-solid, and solid dosage forms provided herein can be encapsulated in capsules. Suitable liquid and semi-solid dosage forms include solutions and suspensions in propylene carbonate, vegetable oils, or triglycerides. Capsules containing such solutions can be prepared as described in U.S. Patent Nos. 4,328,245, 4,409,239, and 4,410,545. As is known to those skilled in the art, capsules can also be coated to modify or maintain the dissolution of the active ingredient.

[0154] The pharmaceutical compositions for oral administration provided herein can be provided in liquid and semi-solid dosage forms, including emulsions, solutions, suspensions, elixirs, and syrups. An emulsion is a two-phase system in which one liquid is dispersed throughout in the form of small droplets in another liquid, which can be water-in-oil or oil-in-water. The emulsion can include a pharmaceutically acceptable non-aqueous liquid or solvent, an emulsifier, and a preservative. The suspension can include a pharmaceutically acceptable suspending agent and a preservative. An aqueous alcoholic solution can include a pharmaceutically acceptable acetal, for example, a bis(lower alkyl) acetal of a lower alkyl aldehyde, for example, acetaldehyde diethyl acetal; and a water-miscible solvent having one or more hydroxyl groups, for example, propylene glycol and ethanol. An elixir is a clear, sweetened, and hydroalcoholic solution. A syrup is a concentrated aqueous solution of sugar (e.g., sucrose), and can also contain a preservative. For liquid dosage forms, for example, a solution in polyethylene glycol can be diluted with a sufficient amount of a pharmaceutically acceptable liquid carrier (e.g., water) for ease of measurement for administration.

[0155] Other useful liquid and semi-solid dosage forms include, but are not limited to, dosage forms containing an active ingredient and a dialkylated monoalkylene glycol or polyalkylene glycol, including 1,2-dimethoxymethane, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, polyethylene glycol-350-dimethyl ether, polyethylene glycol-550-dimethyl ether, polyethylene glycol-750-dimethyl ether, wherein 350, 550, and 750 refer to the approximate average molecular weight of the polyethylene glycol. These dosage forms can further include one or more antioxidants, for example, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), propyl gallate, vitamin E, hydroquinone, hydroxycoumarins, ethanolamine, lecithin, cephalin, ascorbic acid, malic acid, sorbitol, phosphoric acid, bisulfite, sodium metabisulfite, thiodipropionic acid and its esters, and dithiocarbamates / esters.

[0156] The pharmaceutical compositions for oral administration provided herein can also be provided in the form of liposomes, micelles, microspheres, or nano-systems. The micelle dosage form can be prepared as described in U.S. Patent No. 6,350,458.

[0157] The pharmaceutical compositions for oral administration provided herein can be provided as non-effervescent or effervescent granules and powders for reconstitution into a liquid dosage form. Pharmaceutically acceptable carriers and excipients for non-effervescent granules or powders can include diluents, sweeteners, and wetting agents. Pharmaceutically acceptable carriers and excipients for effervescent granules or powders can include organic acids and a source of carbon dioxide.

[0158] Colorants and flavorants can be used in all dosage forms described herein.

[0159] The pharmaceutical compositions provided herein for oral administration can be formulated into immediate release or modified release dosage forms, including delayed release, sustained release, pulsatile release, controlled release, targeted release, and programmed release forms. B. Parenteral administration

[0160] The pharmaceutical compositions provided herein can be administered parenterally by injection, infusion, or implantation for local or systemic administration. As used herein, parenteral administration includes intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, intraurethral, intrasternal, intracranial, intramuscular, intrasynovial, intravesical, and subcutaneous administration.

[0161] The pharmaceutical compositions provided herein for parenteral administration can be formulated into any dosage form suitable for parenteral administration (including but not limited to solutions, suspension bases, emulsions, micelles, liposomes, microspheres, nanosystems) and solid forms suitable for forming solutions or suspensions in a liquid before injection. Such dosage forms can be prepared by conventional methods known to those skilled in the art of pharmaceutical science. See, e.g., Remington: The Science and Practice of Pharmacy, supra.

[0162] The pharmaceutical compositions provided herein for parenteral administration can include one or more pharmaceutically acceptable carriers and excipients, including but not limited to aqueous media, water-miscible media, non-aqueous media, antimicrobial agents or preservatives against microbial growth, stabilizers, solubilizers, isotonic agents, buffers, antioxidants, local anesthetics, suspending and dispersing agents, wetting or emulsifying agents, complexing agents, masking agents or sequestering or chelating agents, cryoprotectants, lyoprotectants, thickening agents, pH regulators, and inert gases.

[0163] Suitable aqueous media include but are not limited to water, saline, physiological saline or phosphate buffered saline (PBS), sodium chloride injection, Ringer's injection, isotonic dextrose injection, sterile water for injection, dextrose and lactated Ringer's injection. Suitable non-aqueous media include but are not limited to fixed oils of vegetable origin, castor oil, corn oil, cottonseed oil, olive oil, peanut oil, peppermint oil, safflower oil, sesame oil, soybean oil, hydrogenated vegetable oil, hydrogenated soybean oil, medium-chain triglycerides of coconut oil, and palm oil. Suitable water-miscible media include but are not limited to ethanol, 1,3-butanediol, liquid polyethylene glycols (e.g., polyethylene glycol 300 and polyethylene glycol 400), propylene glycol, glycerol, N-methyl-2-pyrrolidone, N,N-dimethylacetamide, and dimethyl sulfoxide.

[0164] Suitable antimicrobial agents or preservatives include, but are not limited to, phenols, cresols, mercurials, benzyl alcohol, chlorobutanol, methylparaben and propylparaben, thimerosal, benzalkonium chloride (e.g., benzethonium chloride), methylparaben and methylpropylparaben, and sorbic acid. Suitable isotonic agents include, but are not limited to, sodium chloride, glycerin, and dextrose. Suitable buffering agents include, but are not limited to, phosphates and citrates. Suitable antioxidants include those described herein, e.g., bisulfites and sodium metabisulfite. Suitable local anesthetics include, but are not limited to, procaine hydrochloride. Suitable suspending and dispersing agents include those described herein, e.g., sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, and polyvinylpyrrolidone. Suitable emulsifying agents include those described herein, e.g., polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monooleate 80, and triethanolamine oleate. Suitable masking or chelating agents include, but are not limited to, EDTA. Suitable pH adjusters include, but are not limited to, sodium hydroxide, hydrochloric acid, citric acid, and lactic acid. Suitable complexing agents include, but are not limited to, cyclodextrins, including α-cyclodextrin, β-cyclodextrin, hydroxypropyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, and sulfobutyl ether-7-β-cyclodextrin

[0165] When the pharmaceutical compositions provided herein are formulated for multi-dose administration, multi-dose parenteral formulations must contain an antimicrobial agent in bacteriostatic or fungistatic concentration. As is known and practiced in the art, all parenteral formulations must be sterile.

[0166] In one embodiment, the pharmaceutical composition for parenteral administration is provided as a ready-to-use sterile solution. In another embodiment, the pharmaceutical composition is provided as a sterile dry soluble product (including freeze-dried powder and subcutaneous tablets) and reconstituted with a vehicle before use. In yet another embodiment, the pharmaceutical composition is provided as a ready-to-use sterile suspension. In yet another embodiment, the pharmaceutical composition is provided as a sterile dry insoluble product and reconstituted with a vehicle before use. In still another embodiment, the pharmaceutical composition is provided as a ready-to-use sterile emulsion.

[0167] The pharmaceutical compositions for parenteral administration provided herein can be formulated in immediate release or modified release dosage forms, including delayed release, sustained release, pulsatile release, controlled release, targeted release, and programmed release forms.

[0168] The pharmaceutical compositions for parenteral administration provided herein can be formulated as a suspension, solid, semi-solid, or thixotropic liquid for administration as an implant depot. In one embodiment, the pharmaceutical composition provided herein is dispersed within a solid internal matrix that is surrounded by an outer polymeric membrane that is insoluble in body fluids but permits diffusion of the active ingredient within the pharmaceutical composition therethrough.

[0169] Suitable internal matrices include, but are not limited to, polymethyl methacrylate, polybutyl methacrylate, plasticized or unplasticized polyvinyl chloride, plasticized nylon, plasticized polyethylene terephthalate, natural rubber, polyisoprene, polyisobutylene, polybutadiene, polyethylene, ethylene-vinyl acetate copolymer, silicone rubber, polydimethylsiloxane, silicone carbonate copolymer, hydrophilic polymers (e.g., hydrogels of esters of acrylic and methacrylic acids), collagen, cross-linked polyvinyl alcohol, and cross-linked partially hydrolyzed polyvinyl acetate.

[0170] Suitable external polymer membranes include, but are not limited to, polyethylene, polypropylene, ethylene / propylene copolymer, ethylene / ethyl acrylate copolymer, ethylene / vinyl acetate copolymer, silicone rubber, polydimethylsiloxane, neoprene, chlorinated polyethylene, polyvinyl chloride, copolymers of vinyl chloride with vinyl acetate, vinylidene chloride, ethylene, and propylene, ionomeric polyethylene terephthalate, butyl rubber, epichlorohydrin rubber, ethylene / vinyl alcohol copolymer, ethylene / vinyl acetate / vinyl alcohol terpolymer, and ethylene / ethyleneoxyethanol copolymer. C. Topical administration

[0171] The pharmaceutical compositions provided herein can be topically administered to the skin, orifice, or mucosa. As used herein, topical administration includes dermal (intradermal), conjunctival, intracorneal, intraocular, ophthalmic, otic, transdermal, nasal, vaginal, urethral, respiratory, and rectal administration.

[0172] The pharmaceutical compositions provided herein can be formulated into any dosage form suitable for topical administration to achieve local or systemic effects, including but not limited to emulsions, solutions, suspensions, creams, gels, hydrogels, ointments, powders, dressings, elixirs, lotions, suspensions, tinctures, pastes, foams, films, aerosols, rinses, sprays, suppositories, bandages, and skin patches. The topical formulations of the pharmaceutical compositions provided herein can also include liposomes, micelles, microspheres, and nanosystems.

[0173] Pharmaceutically acceptable carriers and excipients suitable for use in topical formulations include, but are not limited to, aqueous vehicles, water-miscible vehicles, non-aqueous vehicles, antimicrobial agents or preservatives against microbial growth, stabilizers, solubilizers, isotonic agents, buffers, antioxidants, local anesthetics, suspending and dispersing agents, wetting or emulsifying agents, complexing agents, masking or chelating agents, penetration enhancers, cryoprotectants, lyoprotectants, thickening agents, and inert gases.

[0174] The pharmaceutical compositions can also be topically administered by electroporation, iontophoresis, sonophoresis, sonophoresis, or micro-needle or needleless injection (e.g., POWDERJECT TM and BIOJECT TM ).

[0175] The pharmaceutical compositions provided herein can be provided in the form of ointments, creams, and gels. Suitable ointment vehicles include oily or hydrocarbon vehicles, including lard, hydrogenated lard, olive oil, cottonseed oil, and other oils, white petrolatum; emulsifiable or absorbable vehicles, such as hydrophilic petrolatum, hydroxypropyl stearate, and anhydrous lanolin; water-removable vehicles, such as hydrophilic ointment; water-soluble ointment vehicles, including polyethylene glycols of different molecular weights; emulsion vehicles, water-in-oil (W / O) emulsions or oil-in-water (O / W) emulsions, including cetyl alcohol, glyceryl monostearate, lanolin, and stearic acid. See, e.g., Remington: The Science and Practice of Pharmacy, supra. These vehicles have an emollient effect, but usually require the addition of antioxidants and preservatives.

[0176] Suitable cream bases can be oil-in-water or water-in-oil. Suitable cream vehicles can be washable and contain an oil phase, an emulsifier, and an aqueous phase. The oil phase is also referred to as the "internal" phase and usually includes petrolatum and fatty alcohols (e.g., cetyl alcohol or stearyl alcohol). The aqueous phase usually (but not necessarily) exceeds the oil phase in volume and usually contains a humectant. The emulsifier in the cream formulation can be a nonionic surfactant, anionic surfactant, cationic surfactant, or amphoteric surfactant.

[0177] Gels are semi-solid, suspension-type systems. Monophasic gels contain organic macromolecules that are substantially uniformly distributed in a liquid carrier. Suitable gelling agents include, but are not limited to, cross-linked acrylic polymers, such as carbomers, carboxyalkylenes, and hydrophilic polymers, such as polyethylene oxide, polyoxyethylene-polyoxypropylene copolymers, and polyvinyl alcohol; cellulose polymers, such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose phthalate, and methyl cellulose; gums, such as tragacanth and xanthan gum; sodium alginate; and gelatin. To prepare a homogeneous gel, a dispersant (e.g., alcohol or glycerol) can be added, or the gelling agent can be dispersed by grinding, mechanical mixing, and / or stirring.

[0178] The pharmaceutical compositions provided herein can be administered rectally, urethrally, vaginally, or perivaginally in the form of suppositories, pessaries, bougies, cataplasms, pastes, powders, dressings, creams, plasters, contraceptives, ointments, solutions, emulsions, suspensions, tampons, gels, foams, sprays, or enemas. These dosage forms can be manufactured using conventional procedures as described in Remington: The Science and Practice of Pharmacy (supra).

[0179] Rectal, urethral, and vaginal suppositories are solid objects for insertion into body orifices that are solid at room temperature but melt or soften at body temperature to release the active ingredient within the orifice. Pharmaceutically acceptable carriers used in rectal and vaginal suppositories include a base or vehicle, for example, a hardening agent that, when formulated with the active ingredient, produces a melting point near body temperature; and antioxidants as described herein, including bisulfites and sodium metabisulfite. Suitable vehicles include, but are not limited to, cocoa butter (theobroma oil), glycerin-gelatin, carbowax (polyethylene glycol), cetyl alcohol, paraffin wax, white and yellow waxes, and suitable mixtures of mono-, di-, and triglycerides of fatty acids, as well as hydrogels, for example, polyvinyl alcohol, hydroxyethyl methacrylate, and polyacrylic acid. Combinations of various vehicles can also be used. Rectal and vaginal suppositories can be prepared by compression or molding. The typical weight of rectal and vaginal suppositories is about 2 to about 3 g.

[0180] The pharmaceutical compositions provided herein can be administered ophthalmically in the form of solutions, suspensions, ointments, emulsions, gel-forming solutions, powders for solution, gels, ocular inserts, and implants.

[0181] The pharmaceutical compositions provided herein can be administered intranasally or by inhalation to the respiratory tract. The pharmaceutical compositions can be provided in the form of an aerosol or a solution for use with a pressurized container, pump, nebulizer, atomizer (e.g., an atomizer that produces a fine mist using electrohydrodynamics), or nebulizer alone or in combination with a suitable propellant (e.g., 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoropropane). The pharmaceutical compositions can also be provided alone as a dry powder for insufflation or in combination with an inert carrier (e.g., lactose or phospholipid); and as nasal drops. For intranasal use, the powder can include a bioadhesive (including chitosan or cyclodextrin).

[0182] Solutions or suspensions formulated for a pressurized container, pump, nebulizer, atomizer, or nebulizer contain ethanol, aqueous ethanol, or a suitable alternative reagent for dispersing, dissolving, or retarding the release of the active ingredient; a propellant as a solvent; and / or a surfactant, for example, sorbitan trioleate, oleic acid, or oligolactic acid.

[0183] The pharmaceutical compositions provided herein can be micronized to a size suitable for delivery by inhalation, for example, about 50 microns or less, or about 10 microns or less. Particles of such size can be prepared using comminution methods known to those of skill in the art, for example, spiral jet milling, fluidized bed jet milling, supercritical fluid processing to form nanoparticles, high-pressure homogenization, or spray drying.

[0184] Capsules, blisters, and cartridges for use in an inhaler or insufflator can be formulated to contain a powder mixture comprising: the pharmaceutical compositions provided herein; a suitable powder matrix (e.g., lactose or starch); and a performance modifier (e.g., l-leucine, mannitol, or magnesium stearate). Lactose can be anhydrous or in the form of the monohydrate. Other suitable excipients or carriers include, but are not limited to, dextran, glucose, maltose, sorbitol, xylitol, fructose, sucrose, and trehalose. The pharmaceutical compositions for inhaled / intranasal administration provided herein can further include a suitable flavorant, e.g., menthol and levomenthol; and / or a sweetener, e.g., saccharin and sodium saccharin.

[0185] The pharmaceutical compositions for topical administration provided herein can be formulated as immediate release or modified release, including delayed release, sustained release, pulsatile release, controlled release, targeted release, and programmed release. D. Modified Release

[0186] The pharmaceutical compositions provided herein can be formulated to be provided as a modified release dosage form. As used herein, the term "modified release" refers to a dosage form in which the rate or site of release of the active ingredient is different from that of an immediate release dosage form when administered by the same route. Modified release dosage forms include, but are not limited to, delayed release, retarded release, extended release, sustained release, pulsatile release, controlled release, accelerated release, rapid release, targeted release, programmed release, and gastric retention dosage forms. The pharmaceutical compositions in modified release dosage forms can be prepared using various modified release devices and methods known to those skilled in the art, including, but not limited to, matrix-controlled release devices, osmotic-controlled release devices, multi-particulate controlled release devices, ion exchange resins, enteric coatings, multi-layer coatings, microspheres, liposomes, and combinations thereof. The release rate of the active ingredient can also be altered by changing the particle size and polymorphic phenomena of the active ingredient. 1. Matrix-Controlled Release Devices

[0187] The pharmaceutical compositions of the modified release dosage forms provided herein can be made using matrix-controlled release devices known to those skilled in the art. See, e.g., Takada et al., in Encyclopedia of Controlled Drug Delivery, Mathiowitz, ed.; Wiley, 1999; vol. 2.

[0188] In certain embodiments, the pharmaceutical compositions of the modified release dosage forms provided herein are formulated using an erodible matrix device, which is a water-swellable, erodible, or soluble polymer, including, but not limited to, synthetic polymers and naturally occurring polymers and derivatives, e.g., polysaccharides and proteins.

[0189] Materials that can be used to form an erodible matrix include, but are not limited to, chitin, chitosan, dextran, and pullulan; agarose, gum arabic, gum karaya, locust bean gum, tragacanth gum, carrageenan, ghatti gum, guar gum, xanthan gum, and scleroglucan; starches such as dextrin and maltodextrin; hydrocolloids such as pectin; phospholipids such as lecithin; alginates; propylene glycol alginate; gelatin; collagen; cellulosic materials such as ethyl cellulose (EC), methyl ethyl cellulose (MEC), carboxymethyl cellulose (CMC), CMEC, hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), cellulose acetate (CA), cellulose propionate (CP), cellulose butyrate (CB), cellulose acetate butyrate (CAB), CAP, CAT, hydroxypropyl methyl cellulose (HPMC), HPMCP, HPMCAS, hydroxypropyl methyl cellulose acetate trimellitate (HPMCAT), and ethyl hydroxyethyl cellulose (EHEC); polyvinylpyrrolidone; polyvinyl alcohol; polyvinyl acetate; fatty acid glycerides; polyacrylamide; polyacrylic acid; copolymers of ethyl acrylate or methyl acrylate Poly(2-hydroxyethyl methacrylate); polylactic acid; copolymers of L-glutamic acid and L-glutamic acid ethyl ester; biodegradable lactic acid-glycolic acid copolymers; poly-D-(-)-3-hydroxybutyric acid; and other acrylic derivatives such as homopolymers and copolymers of butyl methacrylate, methyl methacrylate, ethyl methacrylate, ethyl acrylate, (2-dimethylaminoethyl) methacrylate, and (trimethylaminoethyl) methacrylate chloride.

[0190] In certain embodiments, the pharmaceutical compositions provided herein are formulated with non-erosive matrix devices. The active ingredient is dissolved or dispersed in an inert matrix and, upon administration, is released primarily by diffusion through the inert matrix. Materials suitable for use as non-erosive matrix devices include, but are not limited to, insoluble plastics such as polyethylene, polypropylene, polyisoprene, polyisobutylene, polybutadiene, polymethyl methacrylate, polybutyl methacrylate, chlorinated polyethylene, polyvinyl chloride, methyl acrylate-methyl methacrylate copolymer, ethylene-vinyl acetate copolymer, ethylene / propylene copolymer, ethylene / ethyl acrylate copolymer, copolymers of vinyl chloride with vinyl acetate, vinylidene chloride, ethylene and propylene, ionomeric polyethylene terephthalate, butyl rubber, epichlorohydrin rubber, ethylene / vinyl alcohol copolymer, ethylene / vinyl acetate / vinyl alcohol terpolymer, ethylene / ethyleneoxyethanol copolymer, polyvinyl chloride, plasticized nylon, plasticized polyethylene terephthalate, natural rubber, silicone rubber, polydimethylsiloxane, and silicone carbonate copolymer; hydrophilic polymers such as ethyl cellulose, cellulose acetate, cross-linked povidone, and cross-linked partially hydrolyzed polyvinyl acetate; and fatty compounds such as carnauba wax, microcrystalline wax, and triglycerides.

[0191] In matrix-controlled release systems, the desired release kinetics can be controlled, for example, by the type of polymer employed, the polymer viscosity, the particle size of the polymer and / or the active ingredient, the ratio of the active ingredient to the polymer, and other excipients or carriers in the composition.

[0192] The pharmaceutical compositions of the sustained-release dosage forms provided herein can be prepared by methods known to those skilled in the art, including direct compression, dry or wet granulation followed by compression, and melt granulation followed by compression. 2. Osmotic-controlled release devices

[0193] The pharmaceutical compositions of the sustained-release dosage forms provided herein can be made using osmotic-controlled release devices, including but not limited to single-chamber systems, double-chamber systems, asymmetric membrane technology (AMT), and extruding core systems (ECS). Generally, such devices have at least two components: (a) a core containing the active ingredient; and (b) a semi-permeable membrane having at least one delivery port that encapsulates the core. The semi-permeable membrane controls the flow of water from the aqueous environment used into the core, thereby releasing the drug by extrusion through the delivery port.

[0194] In addition to the active ingredient, the core of the osmotic device optionally includes an osmotic agent that creates a driving force for transporting water from the use environment into the core of the device. One class of osmotic agents is water-swellable hydrophilic polymers, which are also referred to as "osmotic polymers" and "hydrogels". Water-swellable hydrophilic polymers suitable as osmotic agents include, but are not limited to, hydrophilic vinyl and acrylic polymers, polysaccharides (e.g., calcium alginate), polyethylene oxide (PEO), polyethylene glycol (PEG), polypropylene glycol (PPG), poly(2-hydroxyethyl methacrylate), poly(acrylic) acid, poly(methacrylic) acid, polyvinylpyrrolidone (PVP), crosslinked PVP, polyvinyl alcohol (PVA), PVA / PVP copolymers, PVA / PVP copolymers having hydrophobic monomers (e.g., methyl methacrylate and vinyl acetate), hydrophilic polyurethanes containing large PEO blocks, crosslinked sodium carboxymethylcellulose, carrageenan, hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC) and carboxyethyl cellulose (CEC), sodium alginate, polycarbophil, gelatin, xanthan gum, and sodium starch glycolate.

[0195] Another class of osmotic agents is osmotica, which are capable of absorbing water to affect the osmotic pressure gradient across the surrounding coating barrier. Suitable osmotica include, but are not limited to, inorganic salts such as magnesium sulfate, magnesium chloride, calcium chloride, sodium chloride, lithium chloride, potassium sulfate, potassium phosphate, sodium carbonate, sodium sulfite, lithium sulfate, potassium chloride, and sodium sulfate; saccharides such as dextrose, fructose, glucose, inositol, lactose, maltose, mannitol, raffinose, sorbitol, sucrose, trehalose, and xylitol; organic acids such as ascorbic acid, benzoic acid, fumaric acid, citric acid, maleic acid, sebacic acid, sorbic acid, adipic acid, edetic acid, glutamic acid, p-toluenesulfonic acid, succinic acid, and tartaric acid; urea; and mixtures thereof.

[0196] Osmotic agents with different dissolution rates can be employed to affect the rate at which the active ingredient is initially delivered from the dosage form. For example, the use of amorphous sugars (e.g., MANNOGEM TM EZ) can provide a faster delivery during the initial few hours, thereby rapidly producing the desired therapeutic effect and gradually and continuously releasing the remaining amount to maintain the desired level of therapeutic or prophylactic effect over a prolonged period. In this case, the active ingredient is released at a rate that replaces the metabolized and excreted active ingredient.

[0197] The core may also include a wide variety of other excipients and carriers as described herein to enhance the performance of the dosage form or to promote stability or processing.

[0198] Materials for forming the semipermeable membrane include various grades of acrylics, vinyls, ethers, polyamides, polyesters, and cellulose derivatives that are water-permeable and water-insoluble at physiologically relevant pHs, or are readily made water-insoluble by chemical changes (e.g., crosslinking). Examples of suitable polymers for forming coatings include plasticized, unplasticized, and reinforced cellulose acetate (CA), diacetate cellulose, triacetate cellulose, CA propionate, cellulose nitrate, cellulose acetate butyrate (CAB), CA urethane, CAP, CA methylcarbamate, CA succinate, cellulose acetate trimellitate (CAT), CA dimethylaminoacetate, CA ethyl carbonate, CA chloroacetate, CA ethyl oxalate, CA methyl sulfonate, CA butyl sulfonate, CA p-toluenesulfonate, agar acetate, amylose triacetate, β-glucan acetate, β-glucan triacetate, glyoxal dimethylacetate, locust bean gum triacetate, hydroxylated ethylene-vinyl acetate, EC, PEG, PPG, PEG / PPG copolymers, PVP, HEC, HPC, CMC, CMEC, HPMC, HPMCP, HPMCAS, HPMCAT, poly(acrylic) acid and esters, and poly(methacrylic) acid and esters and their copolymers, starch, dextran, dextrin, chitosan, collagen, gelatin, polyolefins, polyethers, polysulfones, polyethersulfones, polystyrene, polyvinyl halides, polyvinyl esters and ethers, natural waxes, and synthetic waxes.

[0199] The semipermeable membrane can also be a hydrophobic microporous membrane in which the pores are substantially filled with gas and not wetted by an aqueous medium, but are permeable to water vapor, as disclosed in U.S. Patent No. 5,798,119. Such hydrophobic but water vapor-permeable membranes typically consist of hydrophobic polymers such as polyolefins, polyethylene, polypropylene, polytetrafluoroethylene, polyacrylic acid derivatives, polyethers, polysulfones, polyethersulfones, polystyrene, polyvinyl halides, polyvinylidene fluoride, polyvinyl esters and ethers, natural waxes, and synthetic waxes.

[0200] Delivery ports in the semipermeable membrane can be formed by mechanical drilling or laser drilling after coating. Delivery ports can also be formed in situ by eroding a plug of water-soluble material or by rupturing a thinner portion of the membrane over a notch in the core. Additionally, delivery ports can be formed during the coating process, as in the case of asymmetric membrane coatings of the type disclosed in U.S. Patent Nos. 5,612,059 and 5,698,220.

[0201] The total amount and release rate of the released active ingredient can be substantially regulated by the thickness and porosity of the semipermeable membrane, the composition of the core, and the number, size, and location of the delivery ports.

[0202] Additional conventional excipients or carriers as described herein may further be included in the pharmaceutical compositions of the osmotic controlled release dosage forms to facilitate the performance or processing of the formulations.

[0203] Osmotic controlled release dosage forms can be prepared according to conventional methods and techniques known to those skilled in the art. See, e.g., Remington: The Science and Practice of Pharmacy, supra; Santus and Baker, J. Controlled Release, 1995, 35, 1-21; Verma et al., Drug Dev. Ind. Pharm., 2000, 26, 695-708; Verma et al., J. Controlled Release, 2002, 79, 7-27.

[0204] In certain embodiments, the pharmaceutical compositions provided herein are formulated as AMT controlled release dosage forms, which include an asymmetric osmotic membrane coating a core comprising the active ingredient and other pharmaceutically acceptable excipients or carriers. See, e.g., U.S. Patent No. 5,612,059 and WO 2002 / 17918. AMT controlled release dosage forms can be prepared according to conventional methods and techniques known to those skilled in the art, including direct compression, dry granulation, wet granulation, and dip coating methods.

[0205] In certain embodiments, the pharmaceutical compositions provided herein are formulated as ESC controlled release dosage forms, which include an osmotic membrane coating a core comprising the active ingredient, hydroxyethyl cellulose, and other pharmaceutically acceptable excipients or carriers. 3. Multi-Particulate Controlled Release Devices

[0206] The pharmaceutical compositions provided herein in a modulated release dosage form can be fabricated as a multi-particulate controlled release device, which includes a plurality of particles, granules or pellets having a diameter ranging from about 10 μm to about 3 mm, about 50 μm to about 2.5 mm, or about 100 μm to about 1 mm. Such multi-particulates can be manufactured by methods known to those skilled in the art, including wet and dry granulation, extrusion / spheronization, roller-compaction, melt congealing, and spray-coating seed cores. See, for example, Multiparticulate Oral Drug Delivery; edited by Ghebre-Sellassie; Drugs and the Pharmaceutical Sciences 65; CRC Press: 1994; and Pharmaceutical Palletization Technology; edited by Ghebre-Sellassie; Drugs and the Pharmaceutical Sciences 37; CRC Press: 1989.

[0207] Other excipients or carriers as described herein can be mixed with the pharmaceutical composition to assist in processing and forming the multi-particulates. The resulting particles themselves can constitute the multi-particulate device or can be coated with various film-forming materials (e.g., enteric polymers, water-swellable and water-soluble polymers). The multi-particulates can be further processed into capsules or tablets. 4. Targeted Delivery

[0208] The pharmaceutical compositions provided herein can also be formulated to target specific tissues, receptors or other regions of the body of a subject to be treated, including liposome-based, resealed erythrocyte and antibody-based delivery systems. Examples include, but are not limited to, those disclosed in U.S. Patent Nos. 6,316,652; 6,274,552; 6,271,359; 6,253,872; 6,139,865; 6,131,570; 6,120,751; 6,071,495; 6,060,082; 6,048,736; 6,039,975; 6,004,534; 5,985,307; 5,972,366; 5,900,252; 5,840,674; 5,759,542 and 5,709,874. Methods of Use

[0209] In one embodiment, provided herein is a method of labeling cells with an azide group in a subject, the method comprising administering to a subject in need thereof an effective amount of a compound provided herein, such as a compound of formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0210] In another embodiment, provided herein is a method of labeling the cell surface with an azide group in a subject, the method comprising administering to a subject in need thereof an effective amount of a compound provided herein, such as a compound of formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0211] In certain embodiments, the subject is a mammal. In certain embodiments, the subject is a human.

[0212] In certain embodiments, the cells are cancer cells.

[0213] In certain embodiments, the effective amount of the compound provided herein ranges from about 0.1 to about 100 mg / kg / day, from about 0.1 to about 50 mg / kg / day, from about 0.1 to about 25 mg / kg / day, from about 0.1 to about 20 mg / kg / day, from about 0.1 to about 15 mg / kg / day, from about 0.1 to about 10 mg / kg / day, or from about 0.1 to about 5 mg / kg / day. In one embodiment, the effective amount of the compound provided herein ranges from about 0.1 to about 100 mg / kg / day. In another embodiment, the effective amount of the compound provided herein ranges from about 0.1 to about 50 mg / kg / day. In yet another embodiment, the effective amount of the compound provided herein ranges from about 0.1 to about 25 mg / kg / day. In yet another embodiment, the effective amount of the compound provided herein ranges from about 0.1 to about 20 mg / kg / day. In yet another embodiment, the effective amount of the compound provided herein ranges from about 0.1 to about 15 mg / kg / day. In yet another embodiment, the effective amount of the compound provided herein ranges from about 0.1 to about 10 mg / kg / day. In still another embodiment, the effective amount of the compound provided herein ranges from about 0.1 to about 5 mg / kg / day.

[0214] In certain embodiments, the effective amount of the compounds provided herein ranges from about 1 to about 1000 mg per day, from about 1 to about 500 mg per day, from about 1 to about 200 mg per day, or from about 1 to about 100 mg per day. In one embodiment, the effective amount of the compounds provided herein ranges from about 1 to about 1000 mg per day. In another embodiment, the effective amount of the compounds provided herein ranges from about 1 to about 500 mg per day. In yet another embodiment, the effective amount of the compounds provided herein ranges from about 1 to about 200 mg per day. In still another embodiment, the effective amount of the compounds provided herein ranges from about 1 to about 100 mg per day.

[0215] Depending on the disorder, disease or condition to be treated and the condition of the subject, the compounds provided herein can be administered by the following routes of administration: oral, parenteral (e.g., intramuscular, intraperitoneal, intravenous, CIV, intracisternal injection or infusion, subcutaneous injection, or implantation), inhalation, nasal, vaginal, rectal, sublingual or topical (e.g., transdermal or topical). The compounds provided herein can be formulated with pharmaceutically acceptable excipients, carriers, adjuvants or vehicles into appropriate dosage units suitable for each route of administration.

[0216] In one embodiment, the compounds provided herein are administered orally. In another embodiment, the compounds provided herein are administered parenterally. In yet another embodiment, the compounds provided herein are administered intravenously. In yet another embodiment, the compounds provided herein are administered intramuscularly. In yet another embodiment, the compounds provided herein are administered subcutaneously. In yet another embodiment, the compounds provided herein are administered topically. In still another embodiment, the compounds provided herein are administered by topical infusion.

[0217] The compounds provided herein can be delivered as a single dose, e.g., a single bolus injection, or an oral tablet or pill; or over time, e.g., by continuous infusion over time or by divided bolus doses over time. If necessary, the compounds provided herein can be administered repeatedly, e.g., until the subject shows disease stabilization or regression, or until the subject experiences disease progression or unacceptable toxicity.

[0218] The compounds provided herein can be administered once daily (QD), or divided into multiple daily doses, e.g., twice daily (BID) and three times daily (TID). In addition, the administration can be continuous, i.e., daily or intermittent. As used herein, the terms "intermittent" or "intermittently" are intended to mean stopping and starting at regular or irregular intervals. For example, intermittent administration of the compounds provided herein is administration one to six days per week, cyclic administration (e.g., daily administration for two to eight consecutive weeks, followed by a rest period of up to one week without administration), or alternate day administration.

[0219] The compounds provided herein can also be used in combination or conjunction with therapeutic agents for treating and / or preventing the conditions, disorders or diseases provided herein.

[0220] As used herein, the term "in combination" includes the use of more than one therapy (e.g., one or more prophylactic agents and / or therapeutic agents). However, the use of the term "in combination" does not limit the order in which the therapies (e.g., prophylactic agents and / or therapeutic agents) are administered to a subject having a condition, disorder or disease. The first therapy (e.g., a prophylactic agent or a therapeutic agent, such as a compound provided herein) can be administered before (e.g., 5 minutes, 15 minutes, 50 minutes, 65 minutes, 1 hour, 2 hours, 6 hours, 6 hours, 12 hours, 26 hours, 68 hours, 72 hours, 96 hours, 1 week, 2 weeks, 5 weeks, 6 weeks, 8 weeks or 12 weeks before), simultaneously with or after (e.g., 5 minutes, 15 minutes, 50 minutes, 65 minutes, 1 hour, 2 hours, 6 hours, 12 hours, 26 hours, 68 hours, 72 hours, 96 hours, 1 week, 2 weeks, 5 weeks, 6 weeks, 8 weeks or 12 weeks after) the second therapy (e.g., a prophylactic agent or a therapeutic agent) is administered to the subject. Triple therapy is also contemplated herein.

[0221] The route of administration of the compounds provided herein is not relevant to the route of administration of the second therapy. In one embodiment, the compounds provided herein are administered orally. In another embodiment, the compounds provided herein are administered intravenously. In another embodiment, the compounds provided herein are administered topically. Thus, according to these embodiments, the compounds provided herein are administered orally, intravenously or topically, and the second therapy can be administered orally, parenterally, intraperitoneally, intravenously, intraarterially, transdermally, sublingually, intramuscularly, rectally, buccally, intranasally, liposomally, by inhalation, vaginally, intravitreally, locally via a catheter or a stent, subcutaneously, intradermally, intraarticularly, intrathecally, topically or in a sustained release formulation. In one embodiment, the compounds provided herein and the second therapy are administered by the same route of administration (topically). In another embodiment, the compounds provided herein are administered by one route of administration (e.g., topically), while the second agent (anticancer agent) is administered by another route of administration (e.g., orally).

[0222] In one embodiment, provided herein is a method of labeling a cell with an azide group, the method comprising contacting the cell with an effective amount of a compound provided herein, such as a compound of formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof.

[0223] In another embodiment, provided herein is a method of labeling the cell surface with an azide group, the method comprising contacting the cell with an effective amount of a compound provided herein, such as a compound of formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof.

[0224] In certain embodiments, the cell is a cancer cell.

[0225] The compounds provided herein can also be provided as articles using packaging materials well known to those skilled in the art. See, for example, U.S. Patent Nos. 5,525,907; 5,052,558 and 5,055,252. Examples of pharmaceutical packaging materials include, but are not limited to, blister packs, bottles, tubes, inhalers, pumps, bags, vials, containers, syringes, and any packaging material suitable for the selected formulation and the intended mode and treatment of administration.

[0226] In certain embodiments, provided herein are kits that, when used by a medical practitioner, can simplify the administration of an appropriate amount of a compound provided herein as an active ingredient to a subject. In certain embodiments, the kits provided herein include a container and a dosage form of a compound provided herein.

[0227] The kits provided herein can further include a device for administering the active ingredient. Examples of such devices include, but are not limited to, syringes, needleless injectors, drip bags, patches, and inhalers. The kits provided herein can also include condoms for administering the active ingredient.

[0228] The kits provided herein can further include a pharmaceutically acceptable vehicle that can be used to administer one or more active ingredients. For example, if the active ingredient is provided in a solid form that must be reconstituted for parenteral administration, the kit can include a sealed container of a suitable vehicle in which the active ingredient can be dissolved to form a particulate-free sterile solution suitable for parenteral administration. Examples of pharmaceutically acceptable vehicles include, but are not limited to: aqueous vehicles, including but not limited to water for injection USP, sodium chloride injection, Ringer's injection, dextrose injection, dextrose and sodium chloride injection, and lactated Ringer's injection; water-miscible vehicles, including but not limited to ethanol, polyethylene glycol, and polypropylene glycol; and non-aqueous vehicles, including but not limited to corn oil, cottonseed oil, peanut oil, sesame oil, ethyl oleate, isopropyl myristate, and benzyl benzoate.

[0229] The present disclosure will be further understood by the following non-limiting examples. Examples

[0230] As used herein, the symbols and conventions used in these methods, protocols, and examples, whether or not a particular abbreviation is specifically defined, are consistent with those used in contemporary scientific literature (e.g., Journal of the American Chemical Society, Journal of Medicinal Chemistry, or Journal of Biological Chemistry). Specifically, but not limited to, the following abbreviations may be used in the examples and throughout the specification: g (gram); mg (milligram); mL (milliliter); μL (microliter); mM (millimole); μM (micromole); mmol (millimole); min (minute); h (hour); Ac (acetyl); ACN (acetonitrile); t-Bu (tert-butyl); DCC (N,N'-dicyclohexylcarbodiimide); DCM (dichloromethane); DMAP (4-dimethylaminopyridine); DMSO (dimethyl sulfoxide); EDCI (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide); EtOAc (ethyl acetate); Et2O (diethyl ether); Fmoc (fluorenylmethyloxycarbonyl); IPA (isopropanol); MeOH (methanol); PE (petroleum ether); TBAF (tetra-n-butylammonium fluoride); TEA (triethylamine); THF (tetrahydrofuran); TIPS (triisopropylsilyl); MS (mass spectrometry); NMR (nuclear magnetic resonance); and prep-HPLC (preparative high performance liquid chromatography).

[0231] For all of the following examples, standard processing and purification methods known to those of ordinary skill in the art may be utilized. Unless otherwise indicated, all temperatures are in °C (degrees Celsius). Unless otherwise indicated, all reactions are carried out at room temperature. The synthetic methodologies described herein are intended to illustrate applicable chemical methods by way of specific examples and do not indicate the scope of the disclosure. Example 1 Preparation of Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A1

[0232] Compound A1 was prepared according to Scheme 1.

[0233] (Chloro(phenoxy)phosphoryl)-L-alanine isopropyl ester 1.2 preparation. At -78 °C, under N2, TEA (2.41 g, 23.8 mmol) was added dropwise over 20 minutes to a solution of L-alanine isopropyl ester 1.1 (2 g, 11.9 mmol) and phenyl dichlorophosphate (2.51 g, 11.9 mmol) in anhydrous DCM (30.0 mL). The reaction mixture was stirred at -78 °C for 30 min, then slowly warmed to room temperature and stirred for an additional 3.5 h. The reaction mixture was concentrated in vacuo, diluted with Et2O (20 mL), filtered through Celite, and concentrated in vacuo to afford compound 1.2 (2.51 g), which was used directly in the next step without further purification.

[0234] Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxy-carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A1 preparation. At 0 °C, under N2, 1 M t-BuMgCl in THF (12.4 mL, 12.4 mmol) was added dropwise over 10 minutes to a solution of acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-D-mannopyranoside 1.3 (3.2 g, 8.24 mmol) in anhydrous THF (20.0 mL). After the solution was stirred at 0 °C for 30 minutes, compound 1.2 (2.51 g) in anhydrous THF (10 mL) was added dropwise at 0 °C over 10 minutes. After slowly warming to room temperature and stirring for 12 h, the reaction mixture was concentrated to give a crude product, which was purified by silica gel column chromatography (eluting with EtOAc in PE) to afford compound A1 (4.4 g, α:β ratio: 61:39) in 81% yield. 11H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 8.0 Hz, 1H), 7.38 - 7.34 (m, 2H), 7.19 - 7.15 (m, 3H), 6.06 - 5.91 (m, 1H), 5.87 (dd, J = 8.0, 1.2 Hz, 1H), 5.25 - 5.14 (m, 2H), 4.90 - 4.83 (m, 1H), 4.48 - 4.45 (m, 1H), 4.11 - 4.01 (m, 3H), 3.94 - 3.92 (m, 1H), 3.91 (d, J = 4.0 Hz, 1H), 3.81 - 3.74 (m, 1H), 2.15 (d, J = 8.0 Hz, 3H), 2.06 - 2.04 (m, 3H), 1.95 - 1.93 (m, 3H), 1.22 (d, J = 8.0 Hz, 3H), 1.18 - 1.14 (m, 6H); MS (ESI) m / z: 658.5 [M + H] + . Example 2 Preparation of 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A2 and pyridin-3-ylacetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A8

[0235] Compounds A2 and A8 were prepared according to Scheme 2.

[0236] Preparation of 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A2. At room temperature, ammonium carbonate (87.6 mg, 0.912 mmol) was added in three portions to a solution of compound A1 (200 mg, 0.304 mmol) in MeOH / THF (2 mL / 2 mL). After stirring at room temperature for 3 h, the reaction mixture was concentrated to obtain a crude product, which was purified by silica gel column chromatography (eluting with EtOAc in PE) to give compound A2 (50 mg) in a yield of 26%. MS (ESI) m / z: 616.5 [M + H] + .

[0237] Preparation of pyridin-3-ylacetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A8. To a solution of compound A2 (10 mg, 0.16 mmol) and 2-(pyridin-3-yl)acetic acid (5.62 mg, 0.32 mmol) in anhydrous dioxane (0.50 mL) at 0 °C was added DMAP (0.99 mg, 0.0081 mmol) and EDCI (9.3 mg, 0.049 mmol). After warming to room temperature and stirring for 12 h, the reaction mixture was concentrated in vacuo to give a crude product, which was purified by reverse-phase prep-HPLC to give compound A8 (38.2 mg, α:β ratio: 54:46) in 32% yield. 1 H NMR (400 MHz, DMSO-d6) δ 8.79 - 8.63 (m, 2H), 8.53 (d, J = 8.0 Hz, 1H), 8.24 (dd, J = 8.0, 1.2 Hz, 1H), 7.89 - 7.62 (m, 1H), 7.41 - 7.26 (m, 2H), 7.25 - 7.05 (m, 3H), 6.16 - 5.81 (m, 2H), 5.26 (t, J = 5.2 Hz, 1H), 5.18 - 5.07 (m, 1H), 4.99 - 4.79 (m, 1H), 4.70 - 4.44 (m, 1H), 4.21 - 3.96 (m, 4H), 3.96 - 3.67 (m, 4H), 2.20 - 1.78 (m, 6H), 1.28 - 1.06 (m, 9H); MS (ESI) m / z: 735.4 [M + H] + . Example 3 Preparation of acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-butoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A18

[0238] Compound A18 was prepared according to Scheme 3.

[0239] Preparation of ((9H-fluoren-9-yl)methoxy)carbonyl)-L-alanine butyl ester 3.2. To a solution of Fmoc-L-alanine 3.1 (1 g, 3.21 mmol) and butanol (470 mg, 6.34 mmol) in anhydrous DCM (20 mL) at room temperature was added EDCI (1.84 g, 9.60 mmol) and DMAP (80 mg, 0.655 mmol). After stirring at room temperature for 3 h, the reaction mixture was concentrated to give the crude product, which was purified by silica gel column chromatography (eluting with EtOAc in PE) to give compound 3.2 (310 mg) in 31% yield. MS (ESI) m / z: 368.2 [M+H] + .

[0240] Preparation of L-alanine butyl ester 3.3. To a solution of compound 3.2 (290 mg, 0.789 mmol) in anhydrous ACN (3 mL) at room temperature was added diethylamine (115 mg, 1.58 mmol). After stirring at 60 °C for 12 h, the reaction mixture was concentrated to give the crude product, which was purified by silica gel column chromatography (eluting with acetone in DCM) to give compound 3.3 (69 mg) in 60% yield. MS (ESI) m / z: 146.1 [M+H] + .

[0241] Preparation of (chloro(phenoxy)phosphoryl)-L-alanine butyl ester 3.4. At -78 °C under N2, to a stirred solution of compound 3.3 (69 mg, 0.475 mmol) and phenyl dichlorophosphate (100 mg, 0.474 mmol) in anhydrous DCM (1.0 mL) was added TEA (96 mg, 0.949 mmol). After stirring at -78 °C for 30 min and then at room temperature for 3 h, the reaction mixture was concentrated in vacuo, diluted with anhydrous THF (2 mL), filtered through celite, and concentrated in vacuo to give compound 3.4 (75 mg), which was used directly in the next step without further purification.

[0242] Preparation of Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-butoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A18. At 0 °C under N2, t-BuMgCl (0.7 mL, 0.713 mmol) was added to a solution of Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-D-mannopyranoside 1.3 (185 mg, 0.476 mmol) in anhydrous THF (1 mL). After stirring the mixture at 0 °C for 30 minutes, Compound 3.4 (152 mg, 0.475 mmol) in THF (1 mL) was added. The reaction mixture was slowly warmed to room temperature and stirred for 12 hours. The reaction mixture was purified by reverse phase prep-HPLC to give Compound A18 (50.8 mg, α:β ratio: 65:35) in 16% yield. 1 HNMR (400 MHz, DMSO-d6) δ 8.55 (d, J = 9.2 Hz, 1H), 7.43 - 7.29 (m, 2H), 7.23 - 7.10 (m, 3H), 6.10 - 5.92 (m, 1H), 5.87 (dd, J = 8.0, 1.6 Hz, 1H), 5.33 - 5.00 (m, 2H), 4.71 - 4.35 (m, 1H), 4.16 - 3.96 (m, 5H), 3.96 - 3.87 (m, 2H), 3.87 - 3.76 (m, 1H), 2.05 (d, J = 8.0 Hz, 3H), 1.99 - 1.97 (m, 3H), 1.94 - 1.92 (m, 3H), 1.60 - 1.44 (m, 2H), 1.36 - 1.16 (m, 5H), 0.86 (t, J = 5.4 Hz, 3H); MS (ESI) m / z: 672.3 [M + H] + . Example 4 Preparation of Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-tert-butoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A20

[0243] Compound A20 was prepared according to Scheme 4.

[0244] Preparation of ((perfluorophenoxy)(phenoxy)phosphoryl)-L-alanine tert-butyl ester 4.2. To a mixture of compound 4.1 (700 mg, 4.82 mmol) in THF (20 mL) was added TEA (1.46 g, 14.46 mmol) and phenyl dichlorophosphate (1.02 g, 4.82 mmol). The mixture was stirred at -78 °C under N2 for 1 h and then warmed to 0 °C over 2 h, after which 2,3,4,5,6-pentafluorophenol (887 mg, 4.82 mmol) was added under N2. The reaction mixture was stirred at 0 °C for 2 h and concentrated to give the crude product, which was purified by silica gel column chromatography (eluting with IPA in DCM) to give compound 4.2 (600 mg) in 27% yield. MS (ESI) m / z: 490.1 [M+Na] + .

[0245] Preparation of acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-tert-butoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A20. At 0 °C under N2, t-BuMgCl (1.93 mL, 1.93 mmol) was added dropwise to a mixture of acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-D-mannopyranoside 1.3 (500 mg, 1.28 mmol) in THF (10 mL). The mixture was stirred at 0 °C under N2 for 30 min, after which compound 4.2 (600 mg, 1.28 mmol) was added at 0 °C under N2. After stirring at 0 °C under N2 for 1 h, the reaction was quenched with NH4Cl (20 mL) and the reaction mixture was extracted with EtOAc. The combined organic layers were washed with brine (100 mL x 3), dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was purified by reverse phase prep-HPLC to give compound A20 (102 mg, α:β ratio: 66:34) in 12% yield. 11H NMR (400 MHz, DMSO) δ 8.56 (d, J = 9.2 Hz, 1H), 7.38 - 7.32 (m, 2H), 7.21 - 7.14 (m, 3H), 6.15 - 5.80 (m, 2H), 5.37 - 4.99 (m, 2H), 4.69 - 4.35 (m, 1H), 4.08 - 4.05 (m, 3H), 3.91 (t, J = 5.6 Hz, 2H), 3.75 - 3.58 (m, 1H), 2.16 - 2.13 (m, 2H), 2.11 - 1.98 (m, 4H), 1.95 - 1.92 (m, 3H), 1.40 (s, 9H), 1.22 - 1.15 (m, 3H); MS (ESI) m / z: 694.3 [M+Na] + . Example 5 Preparation of acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxy-carbonylethylamino)(quinolin-5-yloxy)phosphoryl)-D-mannopyranoside A34

[0246] Compound A34 was prepared according to Scheme 5.

[0247] Preparation of quinolin-5-yl dichlorophosphate 5.2. At -78 °C under N2, a solution of POCl3 (1.06 g, 6.9 mmol) in anhydrous DCM (5.00 mL) was added dropwise (over 5 minutes) to a solution of quinolin-5-ol 5.1 (1 g, 6.9 mmol) and TEA (0.7 g, 6.9 mmol) in anhydrous DCM (15.0 mL). After stirring at room temperature for 2 h, the reaction mixture was concentrated in vacuo to give compound 5.2 (2 g), which was used directly in the next step without further purification.

[0248] Preparation of acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxy-carbonylethylamino)(quinolin-5-yloxy)phosphoryl)-D-mannopyranoside A34. Compound A34 (α:β ratio: 57:43) was prepared according to the procedure described in Example 1. 11H NMR (400 MHz, DMSO-d6) δ 8.99 - 8.94 (m, 1H), 8.57 (d, J = 8.0 Hz, 1H), 8.51 (d, J = 12.0 Hz, 1H), 7.87 (d, J = 8.2 Hz, 1H), 7.73 (t, J = 8.0 Hz, 1H), 7.65 - 7.59 (m, 1H), 7.53 (d, J = 7.6 Hz, 1H), 6.30 - 6.15 (m, 1H), 5.94 - 5.81 (m, 1H), 5.32 - 5.22 (m, 1H), 5.20 - 5.11 (m, 1H), 4.90 - 4.79 (m, 1H), 4.48 - 4.42 (m, 1H), 4.18 - 4.06 (m, 3H), 3.93 - 3.85 (m, 3H), 2.16 - 2.11 (m, 3H), 2.04 (d, J = 8.0 Hz, 3H), 1.95 (d, J = 4.0 Hz, 3H), 1.29 - 1.21 (m, 3H), 1.14 - 1.05 (m, 6H); MS (ESI) m / z: 709.2 [M + H] + . Example 6 Preparation of (3S,4R,5S,6R)-3-(2-azidoacetamido)-6-(((3-(((((S)-1-isopropoxy-1-oxopropan-2-yl)amino)(phenoxy)phosphoryl)oxy)propanoyl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A35

[0249] Compound A35 was prepared according to Scheme 6.

[0250] Preparation of (3S,4R,5S,6R)-3-(2-azidoacetamido)-6-(((3-((triisopropylsilyl)-oxy)propanoyl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate 6.2. To a stirred solution of 3-((triisopropylsilyl)oxy)propanoic acid 6.1 (190 mg, 773 μmol) in anhydrous DCM (2 mL) was added DMAP (31.3 mg, 257 μmol) and acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-D-mannopyranoside 1.3 (100 mg, 257 μmol), and then DCC (79.4 mg, 385 μmol) was added at 0 °C. After stirring at 0 °C for 5 minutes and at 30 °C overnight, the reaction mixture was concentrated and purified by silica gel column chromatography (eluting with EtOAc in PE) to give compound 6.2 (60 mg) in 38% yield.1 1H NMR (400 MHz, DMSO-d6) δ 8.57 - 8.54 (m, 1H), 5.83 (s, 1H), 5.28 - 5.11 (m, 2H), 4.46 - 4.42 (m, 1H), 4.11 - 3.94 (m, 4H), 2.09–2.06 (m, 7H), 2.01 - 1.81 (m, 6H), 1.28 - 1.06 (m, 3H), 1.03 - 1.00 (m, 18H); MS (ESI) m / z: 639.3 [M+Na] + .

[0251] Preparation of (3S,4R,5S,6R)-3-(2-azidoacetamido)-6-(((3-hydroxypropanoyl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate 6.3. A mixture of compound 6.2 (200 mg, 324 μmol) and TBAF (0.6 mL) in THF (4.0 mL) was stirred overnight. The reaction mixture was then concentrated and purified by silica gel column chromatography (eluting with EtOAc in PE) to give compound 6.3 (61 mg) in 41% yield. 1 1H NMR (400 MHz, CD3OD) δ 6.34 - 5.74 (m, 1H), 5.46 - 4.98 (m, 2H), 4.80 (s, 1H), 4.66 - 4.48 (m, 1H), 4.41 - 4.04 (m, 3H), 4.03 - 3.69 (m, 4H), 2.64 - 2.43 (m, 2H), 2.22 - 1.85 (m, 9H); MS (ESI) m / z: 483.0 [M+Na] + .

[0252] (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-(((3-(((((S)-1-Isopropoxy-1-oxopropan-2-yl)amino)(phenoxy)phosphoryl)oxy)propanoyl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A35 was prepared. Under Ar, a solution of 1 M t-BuMgCl in THF (0.2 mL) was added dropwise to a solution of compound 6.3 (61 mg, 132 μmol) in THF (3 mL) at 0 °C. After stirring the resulting mixture at 0 °C for 1 h, a solution of compound 6.4 (120 mg, 264 μmol) in THF (2 mL) was added at 0 °C. The reaction mixture was stirred at 0 °C for 1 h, then diluted with saturated aqueous NH4Cl and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was purified by silica gel column chromatography (eluting with EtOAc in PE) and further purified by reverse phase prep-HPLC to give compound A35 (19.3 mg, α:β ratio: 31:69), with a yield of 20%. 1 1H NMR (400 MHz, DMSO-d6) δ 8.60 - 8.52 (m, 1H), 7.40 - 7.35 (m, 2H), 7.30 - 7.06 (m, 4H), 6.00 - 5.81 (m, 2H), 5.25 (s, 1H), 5.18 - 5.10 (m, 1H), 4.90 - 4.84 (m, 1H), 4.50 - 4.42 (m, 2H), 4.25 - 4.22 (m, 1H), 4.20 - 4.15 (m, 1H), 4.12 - 4.08 (m, 1H), 3.95 - 3.90 (m, 1H), 2.73 - 2.69 (m, 2H), 2.15 (s, 3H), 2.14 - 1.67 (m, 8H), 1.25 - 1.13 (m, 9H); MS (ESI) m / z: 752.0 [M+Na] + .

[0253] The following compounds were prepared similarly according to the synthetic procedures or methodologies exemplified herein.

[0254] 2-(2-Azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1S)-1-(1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A3 (α:β ratio: 65:35). 11H NMR (400 MHz, DMSO-d6) δ 8.74 - 8.23 (m, 1H), 7.62 - 7.28 (m, 7H), 7.18 - 7.15 (m, 3H), 6.27 - 5.66 (m, 3H), 5.31 - 5.12 (m, 2H), 4.66 - 4.40 (m, 1H), 4.06 - 3.88 (m, 8H), 2.38 - 1.80 (m, 9H), 1.48 - 1.25 (m, 6H); MS (ESI) m / z: 720.3 [M + H] + .

[0255] 2-(2-Azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1-methyl-1-(1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A4 (α:β ratio: 55:45). 1 1H NMR (400 MHz, DMSO-d6) δ 8.59 - 8.27 (m, 1H), 7.45 - 7.26 (m, 8H), 7.16 (s, 3H), 6.07 - 5.82 (m, 2H), 5.80 - 5.67 (m, 1H), 5.27 - 5.04 (m, 2H), 4.65 - 4.02 (m, 1H), 4.08 - 3.99 (m, 2H), 3.93 - 3.64 (m, 2H), 2.23 - 1.82 (m, 9H), 1.45 - 1.33 (m, 9H); MS (ESI) m / z: 734.3 [M + Na] + .

[0256] 2-(2-Azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1S)-1-(1-phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphoryl)-D-mannopyranoside A5 (α:β ratio: 70:30). 1 1H NMR (400 MHz, DMSO-d6) δ 8.64 - 8.26 (m, 1H), 7.38 - 7.28 (m 7H), 7.14 - 7.02 (m, 3H), 6.12 - 5.67 (m, 3H), 5.24 - 5.13 (m, 2H), 4.65 - 4.41 (m, 1H), 4.16 - 3.44 (m, 6H), 2.22 - 1.84 (m, 9H), 1.46 - 1.43 (m, 3H), 0.92 - 0.62 (m, 6H); MS (ESI) m / z: 748.3 [M + H] + .

[0257] 2-(2-Azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1-methyl-1-(1-methyl-1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A6 (α:β ratio: 64:36). 1 HNMR(400MHz,DMSO-d6)δ8.56 - 8.32(m,1H),7.36 - 6.98(m,10H),6.03 - 5.76(m,2H),5.23 - 5.02(m,2H),4.55 - 4.40(m,1H),4.10 - 4.00(m,3H),3.96 - 3.81(m,2H),2.15 - 1.91(m,9H),1.66(d,J=5.6Hz,6H),1.43 - 1.37(m,6H); MS(ESI)m / z:720.3[M+H] + .

[0258] 2-(2-Azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-((((1S)-1-(1-methyl-1-phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphoryl)-D-mannopyranoside A7 (α:β ratio: 65:35). 1 H NMR(400MHz,DMSO-d6)δ8.56 - 8.32(m,1H),7.36 - 6.98(m,10H),6.03 - 5.76(m,2H),5.23 - 5.02(m,2H),4.55 - 4.40(m,1H),4.10 - 4.00(m,3H),3.96 - 3.81(m,2H),2.15 - 1.91(m,9H),1.66(d,J=5.6Hz,6H),1.43 - 1.37(m,6H).; MS(ESI)m / z:770.3[M+Na] + .

[0259] 3-Morpholinopropionyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-((((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A9 (α:β ratio: 45:55). 1HNMR(400MHz, DMSO-d6) δ 9.80 (br s, 1H), 8.64 - 8.31 (m, 1H), 7.45 (d, J = 7.6 Hz, 2H), 7.23 - 7.11 (m, 3H), 6.19 - 5.87 (m, 2H), 5.32 - 5.09 (m, 2H), 4.85 (t, J = 5.6 Hz, 1H), 4.68 - 4.51 (m, 1H), 4.20 - 3.80 (m, 8H), 3.79 - 3.54 (m, 3H), 3.48 - 3.326 (m, 4H), 3.20 - 2.79 (m, 3H), 2.09 - 1.89 (m, 6H), 1.28 - 1.04 (m, 9H); MS(ESI) m / z: 757.1 [M + H] + .

[0260] 4-Methylpiperazin-1-ylpropanoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxy-carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A10 (α:β ratio: 58:42). 1 H NMR(400MHz, DMSO-d6) δ 8.65 - 8.30 (m, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.23 - 7.11 (m, 3H), 6.12 - 5.83 (m, 2H), 5.31 - 5.04 (m, 2H), 4.82 (t, J = 5.6 Hz, 1H), 4.63 - 4.42 (m, 1H), 4.24 - 4.14 (m, 1H), 4.13 - 3.95 (m, 3H), 3.93 - 3.87 (m, 2H), 3.76 (t, J = 5.2 Hz, 2H), 2.69 - 2.57 (m, 2H), 2.45 - 2.17 (m, 8H), 2.13 (s, 3H), 2.08 - 2.01 (m, 3H), 1.97 - 1.89 (m, 3H), 1.28 - 1.10 (m, 9H); MS(ESI) m / z: 770.2 [M + H] + .

[0261] 4-Acetylpiperazin-1-ylpropanoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxy-carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A11 (α:β ratio: 54:46). 11H NMR (400 MHz, DMSO-d6) δ 9.88 (s, 1H), 8.76 - 8.26 (m, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.23 - 7.10 (m, 3H), 6.18 - 5.84 (m, 2H), 5.35 - 5.10 (m, 2H), 4.82 (t, J = 5.6 Hz, 1H), 4.72 - 4.49 (m, 1H), 4.49 - 4.27 (m, 1H), 4.25 - 3.48 (m, 11H), 3.17 - 2.75 (m, 5H), 2.15 - 1.86 (m, 9H), 1.29 - 1.07 (m, 9H); MS (ESI) m / z: 798.4 [M+H] + .

[0262] Tetrahydropyran-4-yl carbonyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A12 (α:β ratio: 66:34). 1 1H NMR (400 MHz, DMSO-d6) δ 8.66 - 8.39 (m, 1H), 7.43 - 7.12 (m, 5H), 6.12 - 5.83 (m, 1H), 5.32 - 5.07 (m, 2H), 4.84 (t, J = 5.6 Hz, 1H), 4.43 (br s, 1H), 4.18 - 3.98 (m, 3H), 3.94 - 3.70 (m, 5H), 3.44 - 3.24 (m, 3H), 2.87 - 2.62 (m, 1H), 2.17 - 2.02 (m, 3H), 2.00 - 1.90 (m, 3H), 1.86 - 1.44 (m, 4H), 1.25 - 1.09 (m, 9H); MS (ESI) m / z: 728.3 [M+H] + .

[0263] 1-Methylpiperidin-4-yl carbonyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A13 (α:β ratio: 49:51). 11H NMR (400 MHz, DMSO-d6) δ 8.66 - 8.41 (m, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.24 - 7.11 (m, 3H), 6.14 - 5.84 (m, 1H), 5.34 - 5.09 (m, 2H), 4.86 (t, J = 5.2 Hz, 1H), 4.74 - 4.43 (m, 1H), 4.14 - 3.71 (m, 6H), 3.81 - 3.71 (m, 1H), 3.06 - 2.86 (m, 2H), 2.80 - 2.56 (m, 4H), 2.19 - 1.62 (m, 12H), 1.26 - 1.09 (m, 9H); MS (ESI) m / z: 741.4 [M+H] + .

[0264] Pyrrolidin-1-ylacetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A14 (α:β ratio: 54:46). 1 1H NMR (400 MHz, DMSO-d6) δ 10.28 (br s, 1H), 8.71 - 8.21 (m, 1H), 7.43 - 7.06 (m, 5H), 6.24 - 5.89 (m, 2H), 5.38 - 5.12 (m, 2H), 4.86 (t, J = 5.6 Hz, 1H), 4.76 - 4.53 (m, 1H), 4.45 (s, 1H), 4.28 - 3.67 (m, 7H), 3.54 (br s, 2H), 3.13 (br s, 2H), 2.09 - 1.80 (m, 10H), 1.28 - 1.04 (m, 9H); MS (ESI) m / z: 727.2 [M+H] + .

[0265] 4-Dimethylaminobenzoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A15 (α:β ratio: 40:60). 11H NMR (400 MHz, CDCl3) δ 8.26 - 7.83 (m, 3H), 7.32 (d, J = 8.0 Hz, 2H), 7.23 - 7.13 (m, 3H), 7.01 - 6.81 (m, 2H), 6.27 - 6.16 (m, 1H), 5.64 - 5.46 (m, 2H), 5.09 - 4.93 (m, 1H), 4.78 (t, J = 5.2 Hz, 1H), 4.51 - 3.81 (m, 6H), 3.64 - 3.44 (m, 1H), 3.09 (s, 6H), 2.06 (d, J = 12.0 Hz, 6H), 1.44 - 1.34 (m, 3H), 1.31 - 1.19 (m, 6H); MS (ESI) m / z: 763.4 [M+H] + .

[0266] Pyridin-3-ylcarbonyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A16 (α:β ratio: 46:54). δ 9.24 - 9.00 (m, 1H), 8.84 (d, J = 7.2 Hz, 1H), 8.70 - 8.55 (m, 1H), 8.43 - 8.17 (m, 1H), 7.60 (dd, J = 8.0, 1.2 Hz, 1H), 7.38 - 6.97 (m, 5H), 6.42 - 6.14 (m, 1H), 6.03 - 5.84 (m, 1H), 5.41 - 5.15 (m, 2H), 4.90 - 4.57 (m, 2H), 4.32 - 4.02 (m, 3H), 4.01 - 3.88 (m, 2H), 3.81 - 3.67 (m, 1H), 2.11 - 1.91 (m, 6H), 1.21 - 1.03 (m, 9H); MS (ESI) m / z: 721.4 [M+H] + .

[0267] Pyrrol-2-ylcarbonyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A17 (α:β ratio: 36:64). 1HNMR(400MHz,CDCl3)δ9.27(s,1H),8.19 - 7.78(m,1H),7.32(d,J = 8.0Hz,2H),7.24 - 6.95(m,6H),6.36 - 6.26(m,1H),6.22 - 6.03(m,1H),5.57 - 5.39(m,2H),5.04(t,J = 5.6Hz,1H),4.82(t,J = 5.2Hz,1H),4.49 - 3.93(m,3H),3.93 - 3.80(m,2H),3.70 - 3.39(m,1H),2.11 - 2.01(m,6H),1.43 - 1.33(m,3H),1.30 - 1.16(m,6H); MS(ESI)m / z:708.3[M + H] + .

[0268] Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1S)-1-sec-butoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A19 (α:β ratio: 66:34). 1 H NMR(400MHz,DMSO)δ8.56(d,J = 9.2Hz,1H),7.38 - 7.34(m,2H),7.25 - 6.99(m,3H),6.12 - 5.91(m,1H),5.85(dd,J = 8.0,1.6Hz,1H),5.34 - 4.95(m,2H),4.78 - 4.38(m,2H),4.10 - 4.03(m,3H),3.93 - 3.87(m,2H),3.85 - 3.75(m,1H),2.18 - 2.11(m,2H),2.07 - 1.98(m,4H),1.97 - 1.91(m,3H),1.55 - 1.44(m,2H),1.25(d,J = 2.4Hz,3H),1.22(t,J = 6.6Hz,3H),0.85 - 0.80(m,3H); MS(ESI)m / z:672.3[M + H] + .

[0269] Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-pentyloxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A21 (α:β ratio: 67:33). 11H NMR (400 MHz, DMSO-d6) δ 8.59 (d, J = 9.2 Hz, 1H), 7.38 - 7.34 (m, 2H), 7.26 - 7.11 (m, 3H), 6.13 - 5.75 (m, 2H), 5.32 - 5.08 (m, 2H), 4.62 - 4.45 (m, 1H), 4.11 - 3.99 (m, 4H), 3.91 (t, J = 4.4 Hz, 2H), 2.18 - 1.98 (m, 6H), 1.97 - 1.91 (m, 3H), 1.60 - 1.49 (m, 3H), 1.30 - 0.99 (m, 8H), 0.84 (t, J = 2.4 Hz, 3H); MS (ESI) m / z: 686.6 [M+H] + .

[0270] Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-hexyloxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A22 (α:β ratio: 64:36). 1 1H NMR (400 MHz, DMSO-d6) δ 8.57 (d, J = 8.8 Hz, 1H), 7.43 - 7.28 (m, 2H), 7.24 - 7.10 (m, 3H), 6.11 - 5.80 (m, 2H), 5.31 - 5.04 (m, 2H), 4.68 - 4.39 (m, 1H), 4.15 - 4.01 (m, 5H), 3.92 (t, J = 4.4 Hz, 2H), 3.81 - 3.74 (m, 1H), 2.21 - 1.89 (m, 9H), 1.60 - 1.45 (m, 2H), 1.35 - 1.19 (m, 9H), 0.96 - 0.73 (m, 3H); MS (ESI) m / z: 722.3 [M+Na] + .

[0271] Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-(2-ethylbutoxy)carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A23 (α:β ratio: 67:33). 11H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 9.2 Hz, 1H), 7.42 - 7.28 (m, 2H), 7.26 - 7.11 (m, 3H), 6.11 - 5.76 (m, 2H), 5.35 - 5.06 (m, 2H), 4.45 (d, J = 9.2 Hz, 1H), 4.13 - 3.78 (m, 8H), 2.18 - 1.98 (m, 6H), 1.98 - 1.90 (m, 3H), 1.51 - 1.38 (m, 1H), 1.33 - 1.22 (m, 7H), 0.88 - 0.77 (m, 6H); MS (ESI) m / z: 722.3 [M+Na] + .

[0272] Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-pyridin-3-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A24 (α:β ratio: 72:26). 1 1H NMR (400 MHz, DMSO-d6) δ 8.83 - 8.73 (m, 2H), 8.60 (d, J = 9.2 Hz, 1H), 8.25 (d, J = 7.2 Hz, 1H), 7.91 - 7.74 (m, 1H), 7.40 - 7.27 (m, 2H), 7.23 - 7.01 (m, 3H), 6.20 - 6.04 (m, 1H), 5.87 (t, J = 5.2 Hz, 1H), 5.35 - 5.08 (m, 4H), 4.71 - 4.39 (m, 1H), 4.25 - 3.96 (m, 4H), 4.01 - 3.90 (m, 2H), 2.20 - 2.11 (m, 2H), 2.10 - 1.98 (m, 4H), 1.96 - 1.68 (m, 3H), 1.38 - 1.17 (m, 3H); MS (ESI) m / z: 707.5 [M+H] + .

[0273] Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-pyridin-4-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A25 (α:β ratio: 60:40). 1HNMR(400MHz, DMSO-d6) δ 8.58 - 8.53 (m, 2H), 8.25 (d, J = 7.2 Hz, 1H), 7.35 - 7.31 (m, 4H), 7.20 - 7.13 (m, 3H), 6.22 - 6.04 (m, 1H), 5.84 (t, J = 5.2 Hz, 1H), 5.24 - 5.04 (m, 4H), 4.66 - 4.40 (m, 1H), 4.14 - 3.98 (m, 4H), 3.91 (t, J = 6.0 Hz, 2H), 2.16 - 2.12 (m, 2H), 2.06 - 2.00 (m, 4H), 1.95 - 1.92 (m, 3H), 1.33 - 1.28 (m, 3H); MS(ESI) m / z: 707.5 [M + H] + .

[0274] Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-quinolin-4-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A26 (α:β ratio: 70:30). 1 HNMR(400MHz, DMSO-d6 / D2O) δ 9.01 (d, J = 4.4 Hz, 1H), 8.64 - 8.27 (m, 1H), 8.13 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 7.2 Hz, 1H), 7.82 - 7.58 (m, 2H), 7.37 - 7.26 (m, 2H), 7.24 - 7.08 (m, 3H), 6.09 - 5.81 (m, 1H), 5.71 (d, J = 4.0 Hz, 2H), 5.30 - 5.01 (m, 2H), 4.65 - 4.41 (m, 1H), 4.16 - 3.97 (m, 4H), 3.96 - 3.77 (m, 2H), 2.20 - 2.08 (m, 2H), 2.03 - 1.91 (m, 7H), 1.39 - 1.23 (m, 3H); MS(ESI) m / z: 757.1 [M + H] + .

[0275] Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A27 (α:β ratio: 70:30). 1HNMR(400MHz, DMSO-d6 / D2O) δ 9.06 (d, J = 4.4Hz, 1H), 8.73 - 8.54 (m, 1H), 8.16 (d, J = 8.0Hz, 1H), 7.92 (d, J = 7.2Hz, 1H), 7.80 - 7.64 (m, 2H), 7.39 - 7.23 (m, 2H), 7.22 - 7.01 (m, 3H), 6.06 - 5.78 (m, 1H), 5.72 (d, J = 4.0Hz, 2H), 5.34 - 5.02 (m, 2H), 4.67 - 4.41 (m, 1H), 4.19 - 3.98 (m, 3H), 3.96 - 3.81 (m, 3H), 2.17 - 1.90 (m, 9H), 1.29 - 1.18 (m, 3H); MS(ESI) m / z: 757.1 [M+H] + .

[0276] Valeryl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A28 (α:β ratio: 56:44). 1 HNMR(400MHz, DMSO-d6) δ 9.00 (s, 1H), 8.64 - 8.16 (m, 2H), 8.06 (d, J = 8.0Hz, 1H), 7.84 - 7.58 (m, 3H), 7.34 - 7.23 (m, 2H), 7.18 - 6.95 (m, 3H), 6.23 - 5.76 (m, 2H), 5.70 - 5.51 (m, 2H), 5.35 - 4.94 (m, 2H), 4.66 - 4.40 (m, 1H), 4.30 - 4.01 (m, 3H), 3.94 - 3.78 (m, 3H), 2.47 - 2.13 (m, 2H), 2.06 - 1.74 (m, 6H), 1.56 - 1.36 (m, 2H), 1.29 - 1.20 (m, 5H), 0.94 - 0.71 (m, 3H); MS(ESI) m / z: 799.0 [M+H] + .

[0277] 2-Methylbutyryl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A29 (α:β ratio: 33:67). 11H NMR (400 MHz, DMSO-d6) δ 8.94 (d, J = 4.0 Hz, 1H), 8.65 - 8.20 (m, 2H), 8.19 - 7.97 (m, 1H), 7.77 - 7.70 (m, 1H), 7.69 - 7.63 (m, 1H), 7.59 - 7.52 (m, 1H), 7.34 - 7.25 (m, 2H), 7.20 - 7.02 (m, 3H), 6.27 - 5.71 (m, 2H), 5.67 - 5.45 (m, 2H), 5.38 - 4.88 (m, 2H), 4.71 - 4.28 (m, 1H), 4.15 - 3.70 (m, 6H), 2.06 - 1.84 (m, 7H), 1.64 - 1.39 (m, 2H), 1.25 - 1.17 (m, 3H), 1.13 - 0.92 (m, 3H), 0.88 - 0.70 (m, 3H); MS (ESI) m / z: 799.2 [M+H] + .

[0278] Hexanoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A30 (α:β ratio: 55:45). 1 1H NMR (400 MHz, DMSO-d6) δ 8.99 - 8.89 (m, 1H), 8.55 - 8.20 (m, 2H), 8.08 - 7.97 (m, 1H), 7.78 - 7.48 (m, 3H), 7.35 - 7.25 (m, 2H), 7.19 - 7.06 (m, 3H), 6.35 - 6.10 (m, 1H), 6.05 - 5.81 (m, 1H), 5.63 - 5.49 (m, 2H), 5.28 - 5.14 (m, 1H), 4.72 - 4.39 (m, 2H), 4.30 - 3.77 (m, 6H), 2.47 - 2.25 (m, 2H), 2.04 - 1.75 (m, 6H), 1.61 - 1.44 (m, 2H), 1.30 - 1.17 (m, 7H), 0.94 - 0.81 (m, 3H); MS (ESI) m / z: 813.7 [M+H] + .

[0279] Nonanoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A31 (α:β ratio: 45:55). 1HNMR(400MHz, DMSO-d6) δ 8.93 (s, 1H), 8.60 - 8.16 (m, 2H), 8.03 (d, J = 8.4 Hz, 1H), 7.79 - 7.61 (m, 2H), 7.61 - 7.50 (m, 1H), 7.36 - 7.25 (m, 2H), 7.19 - 7.05 (m, 3H), 6.19 - 5.80 (m, 2H), 5.68 - 5.49 (m, 2H), 5.34 - 4.90 (m, 2H), 4.67 - 4.39 (m, 1H), 4.18 - 3.71 (m, 6H), 2.44 - 2.35 (m, 1H), 2.26 - 2.10 (m, 1H), 2.04 - 1.85 (m, 6H), 1.60 - 1.30 (m, 3H), 1.25 - 1.12 (m, 12H), 0.86 - 0.79 (m, 3H); MS(ESI) m / z: 855.8 [M + H] + .

[0280] Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-(4-methyl-tetrahydropyran-4-yloxy)carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A32 (α:β ratio: 90:10). 1 H NMR(400MHz, DMSO-d6) δ 8.63 - 8.26 (m, 1H), 7.35 (d, J = 7.8 Hz, 2H), 7.22 - 7.06 (m, 3H), 6.10 - 5.49 (m, 2H), 5.31 - 5.03 (m, 2H), 4.43 (d, J = 4.0 Hz, 1H), 4.19 - 3.96 (m, 3H), 3.88 (d, J = 7.2 Hz, 2H), 3.81 - 3.69 (m, 1H), 3.63 - 3.47 (m, 4H), 2.16 - 1.90 (m, 11H), 1.70 - 1.58 (m, 2H), 1.46 - 1.36 (m, 3H), 1.27 - 1.20 (m, 3H); MS(ESI) m / z: 736.2 [M + Na] + .

[0281] Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1S)-1-(1-(4-(tert-butoxycarbonylamino)phenyl)ethoxycarbonyl)-2-methylpropylamino)(phenoxy)-phosphoryl)-D-mannopyranoside A33 (α:β ratio: 31:69). 11H NMR (400 MHz, DMSO-d6) δ 9.36 (s, 1H), 8.65 - 8.33 (dd, J = 79.7, 8.9 Hz, 1H), 7.48 - 7.20 (m, 6H), 7.20 - 7.02 (m, 3H), 6.09 - 5.80 (m, 2H), 5.79 - 5.66 (m, 1H), 5.30 - 5.01 (m, 2H), 4.65 - 4.43 (m, 1H), 4.14 - 4.98 (m, 3H), 3.95 - 3.87 (m, 2H), 3.60 - 3.44 (m, 1H), 2.18 - 1.99 (m, 6H), 1.98 - 1.86 (m, 4H), 1.53 - 1.33 (m, 12H), 0.88 - 0.61 (m, 6H); MS (ESI) m / z: 885.2 [M+Na] + .

[0282] (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((R)-1-(Benzyloxy)-3-methyl-1-oxobutan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A36 (α:β ratio: 74:26). 1 1H NMR (400 MHz, DMSO-d6) δ 8.60 - 8.25 (m, 1H), 7.42 - 7.24 (m, 7H), 7.21 - 7.08 (m, 3H), 6.11 - 5.77 (m, 2H), 5.27 - 5.16 (m, 1H), 5.11 - 4.99 (m, 2H), 4.73 - 4.40 (m, 1H), 4.09 - 4.01 (m, 2H), 3.91 (t, J = 8.0 Hz, 2H), 3.75 (s, 2H), 3.62 - 3.53 (m, 1H), 2.17 - 1.78 (m, 10H), 0.86 - 0.67 (m, 6H); MS (ESI) m / z: 756.2 [M+H] + .

[0283] (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-3-methyl-1-oxo-1-(1-phenyl-cyclopropoxy)butan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A37 (α:β ratio: 61:39). 11H NMR (400 MHz, DMSO-d6) δ 8.62 - 8.19 (m, 1H), 7.39 - 7.31 (m, 2H), 7.30 - 7.10 (m, 8H), 6.06 - 5.82 (m, 2H), 5.23 - 5.13 (m, 1H), 4.63 - 4.41 (m, 1H), 4.09 - 4.01 (m, 2H), 3.94 - 3.89 (m, 2H), 3.60 - 3.45 (m, 3H), 2.19 - 1.76 (m, 10H), 1.27 - 1.12 (m, 4H), 0.86 - 0.68 (m, 6H); MS (ESI) m / z: 782.2 [M+Na] + .

[0284] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)-6-((tetrahydro-2H-pyran-4-carbonyl)oxy)tetrahydro-2H-pyran-3,4-diyl diacetate A38 (α:β ratio: 57:43). 1 1H NMR (400 MHz, DMSO-d6) δ 8.64 - 8.22 (m, 1H), 7.41 - 7.31 (m, 2H), 7.23 - 7.12 (m, 3H), 6.19 - 5.83 (m, 2H), 5.42 - 5.05 (m, 2H), 4.72 - 4.41 (m, 1H), 4.25 - 4.03 (m, 3H), 4.03 - 3.95 (m, 2H), 3.94 - 3.87 (m, 2H), 3.86 - 3.74 (m, 3H), 3.35 - 3.27 (m, 2H), 2.07 - 1.91 (m, 6H), 1.88 - 1.80 (m, 1H), 1.78 - 1.40 (m, 6H), 1.26 - 1.18 (m, 7H), 0.87 - 0.80 (m, 3H); MS (ESI) m / z: 778.2. [M+Na] + .

[0285] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((3-morpholinobenzoyl)oxy)-2-((((((S)-1-oxo-1-(pentyl)oxypropan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A39 (α:β ratio: 46:54). 11H NMR (400 MHz, DMSO-d6) δ 8.74 - 8.34 (m, 1H), 7.59 - 7.02 (m, 9H), 6.35 - 5.87 (m, 2H), 5.49 - 5.11 (m, 1H), 4.92 - 4.38 (m, 2H), 4.31 - 4.022 (m, 3H), 4.00 - 3.89 (m, 4H), 3.87 - 3.79 (m, 2H), 3.76 - 3.72 (m, 3H), 3.25 - 3.06 (m, 4H), 2.13 - 1.79 (m, 6H), 1.60 - 1.38 (m, 2H), 1.32 - 1.09 (m, 7H), 0.92 - 0.74 (m, 3H); MS (ESI) m / z: 833.3 [M+H] + .

[0286] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((3-(4-methylpiperazin-1-yl)benzoyl)oxy)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A40 (α:β ratio: 50:50). 1 1H NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.74 - 8.38 (m, 1H), 7.71 - 7.03 (m, 9H), 6.34 - 5.91 (m, 2H), 5.45 - 4.86 (m, 2H), 4.82 - 4.55 (m, 2H), 4.42 - 4.22 (m, 1H), 4.16 - 3.98 (m, 3H), 3.97 - 3.78 (m, 6H), 3.61 - 3.45 (m, 2H), 3.24 - 3.11 (m, 2H), 3.10 - 2.95 (m, 2H), 2.87 (s, 3H), 2.11 - 1.80 (m, 6H), 1.60 - 1.39 (m, 2H), 1.36 - 1.08 (m, 7H), 0.93 - 0.74 (m, 3H); MS (ESI) m / z: 846.3 [M+H] + .

[0287] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((3-(morpholinomethyl)benzoyl)oxy)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A41 (α:β ratio: 48:52). 11H NMR (400 MHz, DMSO-d6) δ 8.82 - 8.37 (m, 1H), 8.33 - 7.92 (m, 2H), 7.91 - 7.53 (m, 2H), 7.46 - 7.25 (m, 2H), 7.24 - 7.02 (m, 3H), 6.38 - 5.93 (m, 2H), 5.42 - 5.23 (m, 1H), 4.84 - 4.40 (m, 3H), 4.33 - 4.06 (m, 3H), 4.02 - 3.79 (m, 6H), 3.61 (s, 4H), 3.17 (s, 4H), 2.10 - 1.84 (m, 6H), 1.55 - 1.42 (m, 2H), 1.27 - 1.19 (m, 7H), 0.91 - 0.75 (m, 3H); MS (ESI) m / z: 847.3 [M + H] + .

[0288] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((3-((4-Methylpiperazin-1-yl)methyl)benzoyl)oxy)-2-((((((S)-1-Oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A42 (α:β ratio: 40:60). 1 1H NMR (400 MHz, DMSO-d6) δ 8.76 - 8.40 (m, 1H), 8.07 - 7.83 (m, 2H), 7.74 - 7.49 (m, 2H), 7.42 - 7.04 (m, 5H), 6.35 - 5.92 (m, 2H), 5.53 - 4.95 (m, 2H), 4.94 - 4.58 (m, 2H), 4.51 - 4.10 (m, 3H), 4.09 - 3.93 (m, 4H), 3.93 - 3.61 (m, 4H), 3.20 - 2.83 (m, 4H), 2.78 (s, 3H), 2.49 - 2.30 (m, 2H), 2.12 - 1.80 (m, 6H), 1.62 - 1.40 (m, 2H), 1.36 - 1.12 (m, 7H), 0.94 - 0.74 (m, 3H); MS (ESI) m / z: 860.3 [M + H] + .

[0289] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-Oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)-6-(valeryloxy)tetrahydro-2H-pyran-3,4-diyl diacetate A43 (α:β ratio: 40:60). 11H NMR (400 MHz, DMSO-d6) δ 8.97 - 8.87 (m, 1H), 8.63 - 8.20 (m, 1H), 8.15 - 8.02 (m, 2H), 7.92 - 7.82 (m, 1H), 7.77 - 7.65 (m, 1H), 7.62 - 7.51 (m, 1H), 7.40 - 7.26 (m, 2H), 7.25 - 7.02 (m, 3H), 6.07 - 5.83 (m, 1H), 5.78 - 5.60 (m, 2H), 5.36 - 5.05 (m, 2H), 4.84 - 4.38 (m, 2H), 4.25 - 3.96 (m, 4H), 3.92 - 3.76 (m, 2H), 2.43 - 2.38 (m, 1H), 2.34 - 2.18 (m, 1H), 2.10 - 1.72 (m, 6H), 1.57 - 1.36 (m, 2H), 1.34 - 1.12 (m, 5H), 0.94 - 0.68 (m, 3H); MS (ESI) m / z: 799.0 [M+H] + .

[0290] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((2-methylbutanoyl)oxy)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A44 (α:β ratio: 40:60). 1 1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.60 - 8.19 (m, 1H), 8.18 - 7.99 (m, 2H), 7.96 - 7.83 (m, 1H), 7.81 - 7.66 (m, 1H), 7.61 (s, 1H), 7.39 - 7.24 (m, 2H), 7.23 - 7.06 (m, 3H), 6.05 - 5.81 (m, 1H), 5.74 - 5.60 (m, 2H), 5.30 - 5.12 (m, 1H), 4.70 - 4.52 (m, 1H), 4.48 - 4.39 (m, 1H), 4.37 - 4.08 (m, 2H), 4.06 - 3.77 (m, 5H), 2.41 - 2.32 (m, 1H), 2.05 - 1.98 (m, 2H), 1.96 - 1.79 (m, 4H), 1.57 - 1.37 (m, 2H), 1.32 - 1.23 (m, 3H), 1.12 - 1.00 (m, 3H), 0.87 - 0.78 (m, 3H); MS (ESI) m / z: 799.2 [M+H] + .

[0291] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-(hexanoyloxy)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A45 (α:β ratio: 39:61). 1 H NMR (400 MHz, DMSO-d6) δ 8.92 - 8.78 (m, 1H), 8.64 - 8.22 (m, 1H), 8.12 - 7.97 (m, 2H), 7.88 - 7.74 (m, 1H), 7.71 - 7.58 (m, 1H), 7.54 - 7.41 (m, 1H), 7.38 - 7.06 (m, 5H), 6.42 - 6.17 (m, 1H), 6.10 - 5.78 (m, 1H), 5.74 - 5.51 (m, 2H), 5.40 - 4.98 (m, 1H), 4.83 - 4.38 (m, 2H), 4.34 - 3.69 (m, 6H), 2.45 - 2.25 (m, 2H), 2.10 - 1.74 (m, 6H), 1.62 - 1.40 (m, 2H), 1.31 - 1.19 (m, 7H), 0.92 - 0.76 (m, 3H); MS (ESI) m / z: 813.6 [M+H] + .

[0292] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-(nonanoyloxy)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A46 (α:β ratio: 46:54). 11H NMR (400 MHz, DMSO-d6) δ 8.91 - 8.78 (m, 1H), 8.59 - 8.17 (m, 1H), 8.11 - 7.96 (m, 2H), 7.86 - 7.75 (m, 1H), 7.71 - 7.58 (m, 1H), 7.53 - 7.44 (m, 1H), 7.38 - 7.25 (m, 2H), 7.25 - 7.04 (m, 3H), 6.41 - 6.18 (m, 1H), 6.11 - 5.77 (m, 1H), 5.73 - 5.50 (m, 2H), 5.33 - 5.16 (m, 1H), 4.72 - 4.54 (m, 1H), 4.46 - 4.35 (m, 1H), 4.28 - 3.70 (m, 6H), 2.37 - 2.23 (m, 2H), 2.02 - 1.78 (m, 6H), 1.48 (s, 3H), 1.27 - 1.19 (m, 12H), 0.87 - 0.82 (m, 3H); MS (ESI) m / z: 855.2 [M+H] + .

[0293] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)-6-((tetrahydro-2H-pyran-4-carbonyl)oxy)tetrahydro-2H-pyran-3,4-diyl diacetate A47 (α:β ratio: 54:46). 1 1H NMR (400 MHz, DMSO-d6) δ 9.01 - 8.85 (m, 1H), 8.67 - 8.25 (m, 1H), 8.20 - 8.04 (m, 2H), 7.94 - 7.81 (m, 1H), 7.75 - 7.65 (m, 1H), 7.62 - 7.49 (m, 1H), 7.41 - 7.27 (m, 2H), 7.22 - 7.14 (m, 2H), 7.13 - 6.94 (m, 1H), 6.28 - 6.08 (m, 1H), 6.06 - 5.84 (m, 1H), 5.75 - 5.62 (m, 2H), 5.25 - 5.16 (m, 1H), 4.69 - 4.58 (m, 1H), 4.50 - 4.41 (m, 1H), 4.11 - 4.00 (m, 3H), 3.94 - 3.86 (m, 2H), 3.85 - 3.65 (m, 2H), 3.39 - 3.15 (m, 2H), 2.84 - 2.62 (m, 1H), 2.19 - 1.80 (m, 7H), 1.80 - 1.38 (m, 4H), 1.34 - 1.24 (m, 3H); MS (ESI) m / z: 827.2 [M+H] +.

[0294] (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-1-oxo-1-((tetrahydro-2H-pyran-4-yl)oxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A48 (α:β ratio: 44:56). 1 H NMR (400 MHz, DMSO-d6) δ 8.66 - 8.21 (m, 1H), 7.45 - 7.28 (m, 2H), 7.24 - 7.04 (m, 3H), 6.23 - 5.78 (m, 2H), 5.34 - 5.14 (m, 1H), 4.88 - 4.66 (m, 2H), 4.63 - 4.37 (m, 2H), 4.30 - 4.13 (m, 1H), 4.10 - 4.02 (m, 1H), 4.01 - 3.89 (m, 2H), 3.87 - 3.68 (m, 3H), 3.52 - 3.35 (m, 2H), 2.23 - 1.65 (m, 11H), 1.56 - 1.36 (m, 2H), 1.32 - 1.15 (m, 3H); MS (ESI) m / z: 722.2 [M+Na] + .

[0295] (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-1-((1-methylpiperidin-4-yl)oxy)-1-oxopropan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A49 (α:β ratio: 28:72). 1 H NMR (400 MHz, DMSO-d6) δ 8.69 - 8.24 (m, 1H), 7.43 - 7.32 (m, 2H), 7.25 - 7.12 (m, 3H), 6.28 - 5.98 (m, 1H), 5.90 - 5.77 (m, 1H), 5.27 - 5.12 (m, 1H), 4.99 - 4.66 (m, 2H), 4.48 - 4.37 (m, 1H), 4.25 - 4.00 (m, 3H), 3.97 - 3.79 (m, 3H), 3.56 - 3.38 (m, 1H), 3.35 - 3.23 (m, 1H), 3.14 - 2.93 (m, 2H), 2.82 - 2.71 (m, 3H), 2.25 - 1.85 (m, 11H), 1.84 - 1.77 (m, 1H), 1.75 - 1.59 (m, 1H), 1.34 - 1.14 (m, 3H); MS (ESI) m / z: 713.3 [M+H] + .

[0296] (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-1-Isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A50 (α:β ratio: 57:43). 1 H NMR (400 MHz, DMSO-d6) δ 8.99 - 8.94 (m, 1H), 8.57 (d, J = 8.0 Hz, 1H), 8.51 (d, J = 12.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.73 (t, J = 8.0 Hz, 1H), 7.65 - 7.59 (m, 1H), 7.53 (d, J = 8.0 Hz, 1H), 6.30 - 6.15 (m, 1H), 5.94 - 5.81 (m, 1H), 5.32 - 5.22 (m, 1H), 5.20 - 5.11 (m, 1H), 4.90 - 4.79 (m, 1H), 4.48 - 4.42 (m, 1H), 4.18 - 4.06 (m, 3H), 3.93 - 3.85 (m, 3H), 2.13 (d, J = 20.0 Hz, 3H), 2.04 (d, J = 8.0 Hz, 3H), 1.95 (d, J = 4.0 Hz, 3H), 1.29 - 1.21 (m, 3H), 1.14 - 1.05 (m, 6H); MS (ESI) m / z: 709.2 [M+H] + .

[0297] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-Isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)-6-(pivaloyloxy)tetrahydro-2H-pyran-3,4-diyl diacetate A51 (α:β ratio: 75:25). 11H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.65 - 8.12 (m, 2H), 7.92 - 7.85 (m, 1H), 7.82 - 7.73 (m, 1H), 7.70 - 7.52 (m, 2H), 6.54 - 6.19 (m, 1H), 6.12 - 5.78 (m, 1H), 5.36 - 5.09 (m, 2H), 4.93 - 4.79 (m, 1H), 4.76 - 4.66 (m, 1H), 4.17 - 4.01 (m, 3H), 3.92 - 3.70 (m, 3H), 2.45 - 2.26 (m, 2H), 2.15 - 1.81 (m, 6H), 1.57 - 1.42 (m, 2H), 1.31 - 1.18 (m, 5H), 1.15 - 0.96 (m, 6H), 0.92 - 0.80 (m, 3H); MS (ESI) m / z: 751.3 [M+H] + .

[0298] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-Isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)-6-(pivaloyloxy)tetrahydro-2H-pyran-3,4-diyl diacetate A52 (α:β ratio: 60:40). 1 1H NMR (400 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.64 - 8.28 (m, 2H), 7.92 - 7.83 (m, 1H), 7.80 - 7.70 (m, 1H), 7.68 - 7.51 (m, 2H), 6.44 - 6.17 (m, 1H), 6.06 - 5.84 (m, 1H), 5.34 - 5.15 (m, 2H), 4.87 - 4.80 (m, 1H), 4.66 - 4.62 (m, 1H), 4.51 - 4.44 (m, 1H), 4.21 - 4.13 (m, 1H), 4.10 - 3.98 (m, 2H), 3.90 - 3.79 (m, 2H), 2.07 - 1.89 (m, 6H), 1.30 - 1.16 (m, 6H), 1.15 - 1.10 (m, 9H), 1.07 - 0.96 (m, 3H); MS (ESI) m / z: 751.3 [M+H] + .

[0299] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-(hexanoyloxy)-2-((((((S)-1-isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A53 (α:β ratio: 56:44). 1 H NMR (400 MHz, DMSO-d6) δ 9.00 - 8.92 (m, 1H), 8.61 - 8.21 (m, 2H), 7.91 - 7.82 (m, 1H), 7.79 - 7.70 (m, 1H), 7.68 - 7.51 (m, 2H), 6.50 - 6.16 (m, 1H), 6.10 - 5.78 (m, 1H), 5.36 - 4.95 (m, 2H), 4.87 - 4.70 (m, 1H), 4.63 - 4.45 (m, 1H), 4.20 - 4.01 (m, 3H), 3.93 - 3.84 (m, 3H), 2.41 - 2.28 (m, 2H), 2.09 - 1.89 (m, 6H), 1.60 - 1.44 (m, 2H), 1.29 - 1.16 (m, 7H), 1.14 - 0.97 (m, 6H), 0.88 - 0.79 (m, 3H); MS (ESI) m / z: 765.2 [M+H] + .

[0300] (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)-6-(nonanoyloxy)tetrahydro-2H-pyran-3,4-diyl diacetate A54 (α:β ratio: 41:59). 11H NMR (400 MHz, DMSO-d6) δ 9.01 - 8.87 (m, 1H), 8.65 - 8.15 (m, 2H), 7.92 - 7.80 (m, 1H), 7.79 - 7.67 (m, 1H), 7.65 - 7.50 (m, 2H), 6.46 - 6.15 (m, 1H), 6.09 - 5.81 (m, 1H), 5.35 - 4.85 (m, 2H), 4.81 - 4.43 (m, 2H), 4.29 - 4.07 (m, 2H), 4.05 - 3.75 (m, 4H), 2.40 - 2.26 (m, 2H), 2.11 - 1.83 (m, 6H), 1.58 - 1.43 (m, 2H), 1.29 - 1.16 (m, 13H), 1.14 - 1.09 (m, 3H), 1.09 - 0.94 (m, 3H), 0.88 - 0.79 (m, 3H); MS (ESI) m / z: 807.3 [M+H] + .

[0301] (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-1-Oxo-1-(pentyloxy)propan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A55 (α:β ratio: 61:38). 1 1H NMR (400 MHz, DMSO-d6) δ 9.06 - 8.95 (m, 1H), 8.66 - 8.25 (m, 2H), 7.92 - 7.85 (m, 1H), 7.81 - 7.73 (m, 1H), 7.71 - 7.55 (m, 2H), 6.46 - 6.25 (m, 1H), 6.05 - 5.81 (m, 1H), 5.31 - 5.16 (m, 1H), 4.92 - 4.57 (m, 1H), 4.50 - 4.38 (m, 1H), 4.34 - 4.08 (m, 2H), 4.07 - 3.68 (m, 6H), 2.20 - 1.67 (m, 9H), 1.54 - 1.24 (m, 4H), 1.22 - 1.03 (m, 5H), 0.87 - 0.72 (m, 3H); MS (ESI) m / z: 737.2 [M+H] + .

[0302] (((1S)-1-(1-Phenylethoxy-carbonyl)ethylamino)(phenoxy)phosphoryl) 2-(2-azidoacetylamino)-2-deoxy-3,4,6-tri-O-acetyl-D-mannopyranoside B1 (α:β ratio: 45:55). 11H NMR (400 MHz, DMSO-d6) δ 8.74 - 8.23 (m, 1H), 7.62 - 7.28 (m, 7H), 7.18 - 7.15 (m, 3H), 6.27 - 5.66 (m, 3H), 5.31 - 5.12 (m, 2H), 4.66 - 4.40 (m, 1H), 4.06 - 3.88 (m, 6H), 2.38 - 1.80 (m, 9H), 1.48 - 1.25 (m, 6H); MS (ESI) m / z: 720.3 [M+H] + . Example B1 Flow cytometry analysis of cell labeling

[0303] Cells (2.0×10 5 cells / mL, 2 mL) were seeded in a 6-well culture plate and allowed to adhere overnight at 37 °C. After washing three times with PBS, the cells were incubated with the azide compound provided herein (25 μM) for 48 h at 37 °C. After washing three times with PBS, the cells were incubated with DBCO-biotin (50 μM) in 500 μL of serum-free DMEM for 1 h at 37 °C. The cells were washed three times with PBS and then incubated with streptavidin-Cy5 (5 μg / mL) in 500 μL of serum-free DMEM for 1 h at 37 °C. The cells were washed three times with PBS and then 300 μL of 1× trypsin / EDTA was added for digestion. The lifted cells were transferred to a 1.5 mL EP tube, centrifuged at 1000 rpm for 3 min, and washed once with PBS. Finally, 500 μL of PBS containing 4% PFA was added to the cell pellet to fix the cells. The cell suspension was transferred to a flow tube and mixed with 10 μL of PI working solution (50 μg / mL) for 30 min at room temperature, and then flow cytometry was performed.

[0304] Flow cytometry was used to characterize the labeling efficiency of the compounds provided herein. After the cells were labeled with azide groups, DBCO-biotin was added to specifically react with the azide groups. Avidin-Cy5 was added to bind to the biotin on the cell surface for flow cytometry analysis. Dead cells were stained with PI and excluded from the analysis. The results are presented as the mean fluorescence of live cells and are compared with PBS as a negative control and with Ac4ManNAz (AAM) as a positive control, Ac4ManNAz (AAM, CAS: 361154-30-5). The results are summarized in Tables 1 to 3. Table 1. Labeling efficiency of azide compounds in A549 cells Compound No. <![CDATA[Average FL (×10 5 )]]> PBS % AAM % A1 16.2 540 89 A3 8.82 294 48 A4 9.32 311 51 A5 3.55 118 20 B1 7.67 256 42 Table 2. Labeling efficiency of azide compounds in MDA-MB-231 Compound No. <![CDATA[Average FL (×10 5 )]]> PBS % AAM % A1 12.6 663 101 A18 12.4 653 99 A20 6.43 338 51 A22 13.0 684 104 A23 12.2 642 98 A26 18.0 947 144 A27 13.6 716 109 Table 3. Labeling efficiency of azide compounds in OVCAR3 Compound No. <![CDATA[Average FL (×10 5 )]]> PBS % AAM % A24 0.77 5923 28.7 A25 0.72 5538 26.9 A26 2.4 18462 89.6 A27 2.5 19231 93.3 Example B2 LCMS analysis of cell labeling

[0305] The labeling efficiency of the azide compounds provided herein was determined using LCMS. After the cells were labeled with the azide compound, the cells were lysed. The protein content in the lysate was quantified by BCA assay, and the cell number was determined by comparing the protein content with a protein content-cell number standard curve. Azido sialic acid (N3-SA) was cleaved from the glycoprotein in the lysate by incubation with acetic acid at 80 °C for 1 h, and then derivatized with the DBCO reagent as shown in the protocol below. The cycloaddition product was quantified by LCMS to obtain the amount of N3-SA in the cell lysate. N3-SA / cell was calculated as n(N3-SA) / cell number.

[0306] Briefly, cells (2.0×10 5 cells / mL, 2 mL) were seeded in a 6-well culture plate and allowed to adhere overnight at 37 °C. After washing three times with PBS, the cells were incubated with the azide compound (25 μM) at 37 °C for 48 h. After washing three times with PBS, the cells were lysed with RIPA (200 μL) at 4 °C for 0.5 h. The protein content of the lysate (20 μL) was determined using a BCA assay kit. The lysate (126 μL) was transferred to an Eppendorf (1.5 mL), mixed with glacial acetic acid (14 μL), and incubated at 80 °C for 1 h. The suspension was centrifuged at 15000 rpm for 5 min, and the supernatant (80 μL) was reacted with DIBO reagent (20 μL, 50 μg / mL in 0.1% formic acid) in 100 μL of 0.1% formic acid at 37 °C for 2 h. The mixture was centrifuged at 15000 rpm for 5 min, and the supernatant (180 μL) was transferred to a sample vial. The cycloaddition product formed was quantified by LC-MS using a standard calibration curve.

[0307] The above-described embodiments are provided to give those of ordinary skill in the art a complete disclosure and description of how to make and use the claimed embodiments, and are not intended to limit the scope of the disclosure herein. Modifications that are obvious to those skilled in the art are intended to fall within the scope of the following claims. All publications, patents, and patent applications cited in this specification are incorporated herein by reference as if each such publication, patent, or patent application was specifically and individually indicated to be incorporated by reference herein.

Claims

1. A compound of formula (I): or an enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; wherein: R 1 is (i) -C(O)R 5a 、-C(O)OR 5a or -C(O)NR 5b R 5c ; or (ii) hydrogen; and R 5 is -L 2 -P(X)(OR 5a )(NR 5b R 5c ); or R 1 is -L 2 -P(X)(OR 5a )(NR 5b R 5c ); and R 5 is (i) hydrogen; or (ii) -C(O)R 5a 、-C(O)OR 5a or -C(O)NR 5b R 5c ; R 2 is (i) hydrogen; (ii) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl or heterocyclic group; or (iii) -C(O)R 1a , -C(O)OR 1a , -C(O)NR 1b R 1c , -C(O)SR 1a , -C(NR 1a )NR 1b R 1c , -C(S)R 1a , -C(S)OR 1a , -C(S)NR 1b R 1c , -S(O)R 1a , -S(O)2R 1a , -S(O)NR 1b R 1c , -S(O)2NR 1b R 1c or -Si(R 1a )3; R 3 and R 4 each independently is (i) -OR 5a , -OC(O)R 5a , -OC(O)OR 5a or -OC(O)NR 5b R 5c ; or (ii) a halogen; or R 3 and R 4 or R 4 and R 5 are joined together to form a lactone ring; R 5a 、 R 5b and R 5c each independently is hydrogen, C 1-30 alkyl, C 1-30 heteroalkyl, C 2-30 alkenyl, C 2-30 alkynyl, C 3-30 cycloalkyl, C 6-30 aryl, C 7-30 aralkyl, heteroaryl or heterocyclic group; A is a key, O or N(R 1b ); L 1 is C 1-6 alkylene, C 1-6 heteroalkylene, C 2-6 alkenylene, C 2-6 alkynylene, C 3-10 cycloalkylene, C 6-14 arylene, C 7-15 aralkyl, heteroaryl or heterocyclic group; L 2 each independently is (i) a key; or (ii) -O-C 1-6 alkylene, -O-C 1-6 heteroalkylene, -O-C 2-6 alkenylene, -O-C 2-6 alkynylene, -O-C 3-10 cycloalkylene, -O-C 6-14 arylene, -O-C 7-15 aralkyl, -O-heteroaryl or -O-heterocyclic group; Each X is independently O or S; Z is an azido group, hydrogen, a halogen, an isocyano group, -C═C(R 1a )R 1a , -C≡CR 1a , –C(O)R 1a or –SH; and R 1a , R 1b and R 1c are independently hydrogen, deuterium, C 1-6 Alkyl, C 1-6 Heteroalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-10 Cycloalkyl, C 6-14 Aryl, C 7-15 Aralkyl, heteroaryl or heterocyclic group; Among them, alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, alkynyl, alkynylene, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl, aralkylene, heteroaryl, heteroarylene, heterocyclic group and heterocycloalkylene are each optionally substituted by one or more (in one embodiment, one, two, three or four) substituents Q, where Q is independently selected from: (a) deuterium, cyano, halogen, nitro and oxo; (b) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl and heterocyclic group, each of which is further optionally substituted by one or more (in one embodiment, one, two, three or four) substituents Q a ; and (c) –C(O)R a , –C(O)OR a , –C(O)NR b R c , –C(O)SR a , –C(NR a )NR b R c , –C(S)R a , –C(S)OR a , –C(S)NR b R c , –OR a , –OC(O)R a , –OC(O)OR a , –OC(O)NR b R c , –OC(O)SR a , –OC(NR a )NR b R c , –OC(S)R a , –OC(S)OR a , –OC(S)NR b R c , –OP(O)(OR b )OR c , –OS(O)R a , –OS(O)2R a , –OS(O)NR b R c , –OS(O)2NR b R c , –NR b R c , –NR a C(O)R d 、 –NR a C(O)OR d 、 –NR a C(O)NR b R c 、 –NR a C(O)SR d 、 –NR a C(NR d )NR b R c 、 –NR a C(S)R d 、 –NR a C(S)OR d 、 –NR a C(S)NR b R c 、 –NR a S(O)R d 、 –N=S(O)R a R d 、 –NR a S(O)2R d 、 –NR a S(O)NR b R c 、 –NR a S(O)2NR b R c 、 –SR a 、 –S(O)R a 、 –S(O)2R a 、 –S(O)NR b R c and –S(O)2NR b R c wherein, R a 、 R b 、 R c and R d are each independently (i) hydrogen or deuterium; (ii) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 arylalkyl, heteroaryl or heterocyclic group, each of which is optionally substituted by one or more (in one embodiment, by one, two, three or four) substituents Q a substituted; or (iii) R b and R c Together with the N atom to which they are attached, form a heterocyclic group, which is optionally substituted by one or more (in one embodiment, by one, two, three or four) substituents Q a substituted; wherein, Q a each independently selected from: (a) deuterium, cyano, halogen, nitro, and oxo; (b) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl, and heterocyclic group; and (c) –C(O)R e , –C(O)OR e , –C(O)NR f R g , –C(O)SR e , –C(NR e )NR f R g , –C(S)R e , –C(S)OR e , –C(S)NR f R g , –OR e , –OC(O)R e , –OC(O)OR e , –OC(O)NR f R g , –OC(O)SR e , –OC(NR e )NR f R g , –OC(S)R e , –OC(S)OR e , –OC(S)NR f R g , –OP(O)(OR f )OR g , –OS(O)R e , –OS(O)2R e , –OS(O)NR f R g , –OS(O)2NR f R g , –NR f R g , –NR e C(O)R h , –NR e C(O)OR f , –NR e C(O)NR f R g , –NR e C(O)SR f , –NR e C(NR h )NR f R g 、–NR e C(S)R h 、–NR e C(S)OR f 、–NR e C(S)NR f R g 、–NR e S(O)R h 、–N=S(O)R e R h 、–NR e S(O)2R h 、–NR e S(O)NR f R g 、–NR e S(O)2NR f R g 、–SR e 、–S(O)R e 、–S(O)2R e 、–S(O)NR f R g and –S(O)2NR f R g ; wherein, R e 、R f 、R g and R h are each independently (i) hydrogen or deuterium; (ii) C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl or heterocyclic group; or (iii) R f and R g together with the N atom to which they are attached form a heterocyclic group.

2. The compound according to claim 1, wherein R 3 is (i) -OR 5a 、-OC(O)R 5a 、-OC(O)OR 5a or -OC(O)NR 5b R 5c ; or (ii) a halogen.

3. The compound according to claim 1 or 2, wherein R 3 is a halogen.

4. The compound according to any one of claims 1-3, wherein, R 3 is fluorine.

5. The compound according to any one of claims 1-4, wherein, R 4 is (i) -OR 5a 、-OC(O)R 5a 、-OC(O)OR 5a or -OC(O)NR 5b R 5c ; or (ii) a halogen.

6. The compound according to any one of claims 1-5, wherein R 4 is a halogen.

7. The compound according to any one of claims 1-6, wherein R 4 is fluorine.

8. The compound according to any one of claims 1, 2 and 5, wherein the compound has the structure of formula (II): or its enantiomers, a mixture of enantiomers, diastereomers, a mixture of two or more diastereomers, tautomers, a mixture of two or more tautomers, or isotopic variants; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; wherein, R 3a and R 4a each independently is -C(O)R 5a -C(O)OR 5a -C(O)NR 5b R 5c or hydrogen.

9. The compound according to any one of claims 1-8, wherein R 1 is (i) -C(O)R 5a 、-C(O)OR 5a or -C(O)NR 5b R 5c ; or (ii) hydrogen; and R 5 is -L 2 -P(X)(OR 5a )(NR 5b R 5c ).

10. The compound according to claim 8 or 9, wherein the compound has the structure of formula (III): or an enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof.

11. The compound according to any one of claims 1-8, wherein R 1 is -L 2 -P(X)(OR 5a )-(NR 5b R 5c );and R 5 is (i) hydrogen; or (ii) -C(O)R 5a , -C(O)OR 5a or -C(O)NR 5b R 5c .

12. The compound according to claim 8 or 11, wherein the compound has the structure of formula (IV): or an enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof.

13. The compound according to any one of claims 1-12, wherein, R 5c is C 1-30 alkyl or C 7-30 arylalkyl, each of which is optionally substituted by one or more substituents Q.

14. The compound according to any one of claims 1-13, wherein, R 5c is C 1-6 alkyl, which is optionally substituted by one or more substituents Q.

15. The compound according to any one of claims 1-14, wherein, R 5c is methyl, ethyl, propyl, butyl, pentyl or hexyl, each of which is optionally substituted by one or more substituents Q.

16. The compound according to any one of claims 1-13, wherein, R 5c is C 7-15 an aralkyl group, which is optionally substituted by one or more substituents Q.

17. The compound according to any one of claims 8-10 and 13-16, wherein the compound has the structure of formula (V): or an enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; wherein: R 6a is C 1-30 alkyl, C 1-30 heteroalkyl, C 2-30 alkenyl, C 2-30 alkynyl, C 3-30 cycloalkyl, C 6-30 aryl, C 7-30 aralkyl, heteroaryl and heterocyclic group, each of which is optionally substituted by one or more substituents Q; and R 6b and R 6c each independently is (i) hydrogen or deuterium; or (ii) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl and heterocyclic group, each of which is optionally substituted by one or more substituents Q; or R 6b and R 6c together with the carbon atom to which they are attached form a C 3-10 subcycloalkyl, which is optionally substituted by one or more substituents Q.

18. The compound according to any one of claims 8 and 11-16, wherein the compound has the structure of formula (V): or an enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof; wherein: R 6a is C 1-30 alkyl, C 1-30 heteroalkyl, C 2-30 alkenyl, C 2-30 alkynyl, C 3-30 cycloalkyl, C 6-30 aryl, C 7-30 aralkyl, heteroaryl and heterocyclic group, each of which is optionally substituted by one or more substituents Q; and R 6b and R 6c each independently is (i) hydrogen or deuterium; or (ii) C 1-6 alkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl and heterocyclic group, each of which is optionally substituted by one or more substituents Q; or R 6b and R 6c together with the carbon atom to which they are attached form a C 3-10 subcycloalkyl, which is optionally substituted by one or more substituents Q.

19. The compound according to any one of claims 1-18, wherein, L 2 each independently is a key or -O-C optionally substituted by one or more substituents Q 1-6 alkylene group.

20. The compound according to any one of claims 1-19, wherein, Each L 2 is a key.

21. The compound according to claim 17, 19 or 20, wherein the compound has the structure of formula (VII): or an enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof.

22. The compound according to any one of claims 17 and 19-21, wherein the compound has the structure of formula (VIII): or an enantiomer, mixture of enantiomers, diastereomer, mixture of two or more diastereomers, tautomer, mixture of two or more tautomers, or isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof.

23. The compound according to any one of claims 17 and 19-21, wherein the compound has the structure of formula (IX): or its enantiomers, mixtures of enantiomers, diastereomers, mixtures of two or more diastereomers, tautomers, mixtures of two or more tautomers, or isotopic variants; or pharmaceutically acceptable salts, solvates, hydrates or prodrugs thereof.

24. A compound according to any one of claims 1 - 10 and 13 - 23, wherein, R 1 is hydrogen.

25. A compound according to any one of claims 1-10 and 13-23, wherein, R 1 is -C(O)R 5a .

26. A compound according to any one of claims 1-10, 13-23 and 25, wherein, R 1 is -C(O)R 5a , wherein R 5a is C 1-10 alkyl, C 6-14 aryl, heteroaryl or heterocyclic group, each of which is optionally substituted by one or more substituents Q.

27. A compound according to any one of claims 1 - 10, 13 - 23, 25 and 26, wherein, R 1 is -C(O)R 5a , wherein R 5a is C 1-10 alkyl, which is optionally substituted by one or more substituents Q.

28. A compound according to any one of claims 1-10, 13-23 and 25-27, wherein, R 1 is acetyl, propionyl, butyryl, valeryl, hexanoyl, heptanoyl, octanoyl, nonanoyl or decanoyl, each of which is optionally substituted with one or more substituents Q.

29. A compound according to any one of claims 1-10, 13-23 and 25-28, wherein, R 1 is an acetyl group, a propionyl group or a butyryl group.

30. A compound according to any one of claims 1 - 10, 13 - 23, 25 and 26, wherein, R 1 is -C(O)R 5a , wherein R 5a is C 6-14 aryl, which is optionally substituted by one or more substituents Q.

31. A compound according to any one of claims 1 - 10, 13 - 23, 25, 26 and 30, wherein, R 1 is -C(O)R 5a , wherein R 5a is benzoyl, which is optionally substituted by one or more substituents Q.

32. A compound according to any one of claims 1-10, 13-23, 25 and 26, wherein, R 1 is -C(O)R 5a , wherein R 5a is a heteroaryl group, which is optionally substituted by one or more substituents Q.

33. A compound according to any one of claims 1-10, 13-23, 25, 26 and 32, wherein, R 1 is -C(O)R 5a , wherein R 5a is a monocyclic heteroaryl optionally substituted with one or more substituents Q.

34. A compound according to any one of claims 1-10, 13-23, 25, 26, 32 and 33, wherein, R 1 is -C(O)R 5a , wherein R 5a is a 5- or 6-membered heteroaryl, each of which is optionally substituted by one or more substituents Q.

35. A compound according to any one of claims 1-10, 13-23, 25, 26 and 32-34, wherein, R 1 is -C(O)R 5a , wherein R 5a is pyrrolylcarbonyl or pyridylcarbonyl, each of which is optionally substituted by one or more substituents Q.

36. A compound according to any one of claims 1 - 10, 13 - 23, 25, and 26, wherein, R 1 is -C(O)R 5a , wherein R 5a is a heterocyclic group, which is optionally substituted by one or more substituents Q.

37. A compound according to any one of claims 1 - 10, 13 - 23, 25, 26 and 36, wherein, R 1 is -C(O)R 5a , wherein R 5a is a monocyclic heterocyclic group, which is optionally substituted by one or more substituents Q.

38. A compound according to any one of claims 1 - 10, 13 - 23, 25, 26, 36 and 37, wherein, R 1 is -C(O)R 5a , wherein R 5a is a 3-, 4-, 5-, 6- or 7-membered heterocyclic group, each of which is optionally substituted by one or more substituents Q.

39. A compound according to any one of claims 1 - 10, 13 - 23, 25, 26 and 36 - 38, wherein, R 1 is -C(O)R 5a , wherein R 5a is pyrrolylcarbonyl or pyridylcarbonyl, each of which is optionally substituted by one or more substituents Q.

40. A compound according to any one of claims 1-10, 13-23, 25 and 26, wherein, R 1 is acetyl, pivaloyl, pyridin-3-ylacetyl, pyrrolidin-1-ylacetyl, propionyl, 3-morpholinopropionyl, 4-methylpiperazin-1-ylpropionyl, 4-acetylpiperazin-1-ylpropionyl, butyryl, 2-methylbutyryl, valeryl, hexanoyl, nonanoyl, 4-dimethylaminobenzoyl, 3-(morpholinomethyl)benzoyl, 3-((4-methylpiperazin-1-yl)methyl)benzoyl, 3-morpholinobenzoyl, 3-(4-methylpiperazin-1-yl)benzoyl, pyrrol-2-ylcarbonyl, pyridin-3-yl-carbonyl, tetrahydropyran-4-ylcarbonyl or 1-methylpiperidin-4-ylcarbonyl.

41. A compound according to any one of claims 1-10, 13-23, 25, 26 and 40, wherein, R 1 is an acetyl group.

42. The compound according to any one of claims 18 - 20, wherein the compound has the structure of formula (X): or its enantiomers, mixtures of enantiomers, diastereomers, mixtures of two or more diastereomers, tautomers, mixtures of two or more tautomers, or isotopic variants; or pharmaceutically acceptable salts, solvates, hydrates or prodrugs thereof.

43. The compound according to any one of claims 18 - 20 and 42, wherein the compound has the structure of formula (XI): or its enantiomers, mixtures of enantiomers, diastereomers, mixtures of two or more diastereomers, tautomers, mixtures of two or more tautomers, or isotopic variants; or pharmaceutically acceptable salts, solvates, hydrates or prodrugs thereof.

44. The compound according to any one of claims 18 - 20 and 42, wherein the compound has the structure of formula (XII): or its enantiomers, mixtures of enantiomers, diastereomers, mixtures of two or more diastereomers, tautomers, mixtures of two or more tautomers, or isotopic variants; or pharmaceutically acceptable salts, solvates, hydrates or prodrugs thereof.

45. A compound according to any one of claims 1-8, 11-16 and 42-44, wherein, R 5 is hydrogen.

46. A compound according to any one of claims 1 - 8, 11 - 16 and 42 - 44, wherein, R 5 is -C(O)R 5a .

47. A compound according to any one of claims 1-8, 11-16, 42-44 and 46, wherein, R 5 is -C(O)-C 1-6 alkyl, which is optionally substituted by one or more substituents Q.

48. A compound according to any one of claims 1-8, 11-16, 42-44, 46 and 47, wherein, R 5 is an acetyl group, a propionyl group or a butyryl group.

49. A compound according to any one of claims 1-8, 11-16, 42-44 and 46-48, wherein, R 5 is an acetyl group.

50. A compound according to any one of claims 1-49, wherein, R 2 is hydrogen.

51. The compound according to any one of claims 8-50, wherein, R 3a is hydrogen.

52. The compound according to any one of claims 8 - 50, wherein, R 3a is -C(O)R 5a .

53. A compound according to any one of claims 8 - 50 and 52, wherein, R 3a is -C(O)-C 1-6 alkyl, which is optionally substituted by one or more substituents Q.

54. A compound according to any one of claims 8 - 50, 52 and 53, wherein, R 3a is an acetyl group, a propionyl group or a butyryl group.

55. A compound according to any one of claims 8 - 50 and 52 - 54, wherein, R 3a is an acetyl group.

56. A compound according to any one of claims 8 - 55, wherein R 4a is hydrogen.

57. The compound according to any one of claims 8 - 55, wherein, R 4a is -C(O)R 5a .

58. A compound according to any one of claims 8 - 55 and 57, wherein, R 4a is -C(O)-C 1-6 alkyl, which is optionally substituted by one or more substituents Q.

59. A compound according to any one of claims 8 - 55, 57 and 58, wherein, R 4a is an acetyl group, a propionyl group or a butyryl group.

60. A compound according to any one of claims 8 - 55 and 57 - 59, wherein, R 4a is an acetyl group.

61. The compound according to any one of claims 1-60, wherein R 5a is C 6-14 an aryl or heteroaryl, each optionally substituted with one or more substituents Q.

62. The compound according to any one of claims 1-61, wherein, R 5a is C 6-14 aryl, which is optionally substituted by one or more substituents Q.

63. The compound according to any one of claims 1-62, wherein, R 5a is phenyl, which is optionally substituted by one or more substituents Q.

64. The compound according to any one of claims 1-61, wherein, R 5a is a heteroaryl optionally substituted with one or more substituents Q.

65. A compound according to any one of claims 1 - 61 and 64, wherein, R 5a is a bicyclic heteroaryl, which is optionally substituted by one or more substituents Q.

66. A compound according to any one of claims 1 - 61, 64 and 65, wherein, R 5a is a 5,5-, 5,6- or 6,6-fused heteroaryl, each of which is optionally substituted by one or more substituents Q.

67. A compound according to any one of claims 1-61 and 64-66, wherein, R 5a is a 6,6-fused heteroaryl which is optionally substituted with one or more substituents Q.

68. A compound according to any one of claims 1-61 and 64-67, wherein R 5a is a quinolinyl group, which is optionally substituted by one or more substituents Q.

69. The compound according to any one of claims 1 - 61, wherein, R 5a is phenyl or quinolin-5-yl.

70. The compound according to any one of claims 1-69, wherein, R 5b is hydrogen.

71. The compound according to any one of claims 1-70, wherein, R 6a is C 1-6 alkyl, C 3-10 cycloalkyl, C 7-15 arylalkyl or heterocyclic group, each of which is optionally substituted by one or more substituents Q.

72. The compound according to any one of claims 1-71, wherein, R 6a is C 1-6 alkyl, which is optionally substituted by one or more substituents Q.

73. A compound according to any one of claims 1-72, wherein, R 6a is C 1-6 alkylene - heteroaryl, which is optionally substituted with one or more substituents Q a substituted.

74. The compound according to any one of claims 1-73, wherein, R 6a is C 1-6 alkylene-(monocyclic heteroaryl), which is optionally substituted with one or more substituents Q a substituted.

75. A compound according to any one of claims 1 - 74, wherein, R 6a is C 1-6 alkylene-(5- or 6-membered heteroaryl), each of which is optionally substituted with one or more substituents Q a substituted.

76. A compound according to any one of claims 1-73, wherein, R 6a is C 1-6 alkylene-(bicyclic heteroaryl), each of which is optionally substituted with one or more substituents Q a substituted.

77. A compound according to any one of claims 1 - 73 and 76, wherein, R 6a is C 1-6 alkylene-(5,5-, 5,6- or 6,6-fused heteroaryl), each of which is optionally substituted by one or more substituents Q a substituted.

78. A compound according to any one of claims 1-71, wherein, R 6a is C 3-10 cycloalkyl, which is optionally substituted with one or more substituents Q.

79. A compound according to any one of claims 1-71 and 78, wherein, R 6a is a monocyclic C 3-10 cycloalkyl group, which is optionally substituted with one or more substituents Q.

80. The compound according to any one of claims 1-71, wherein, R 6a is C 7-15 an aralkyl group, optionally substituted by one or more substituents Q.

81. A compound according to any one of claims 1 - 71 and 80, wherein, R 6a is a monocyclic C 7-15 arylalkyl, which is optionally substituted by one or more substituents Q.

82. A compound according to any one of claims 1 - 71, wherein, R 6a is a heterocyclic group, which is optionally substituted by one or more substituents Q.

83. A compound according to any one of claims 1 - 71 and 82, wherein, R 6a is a monocyclic heterocyclic group, which is optionally substituted by one or more substituents Q.

84. A compound according to any one of claims 1 - 71, 82, and 83, wherein, R 6a is a 3-, 4-, 5-, 6- or 7-membered heterocyclic group, each of which is optionally substituted by one or more substituents Q.

85. A compound according to any one of claims 1-71, wherein, R 6a is isopropyl, butyl, 2-butyl, tert-butyl, pentyl, hexyl, 2-ethylbutyl, 1-phenylcyclopropyl, benzyl, 1-phenylethyl, 2-phenylpropan-2-yl, pyridin-3-ylmethyl, pyridin-4-ylmethyl, quinolin-4-ylmethyl, quinolin-5-ylmethyl, tetrahydropyran-4-yl or 1-methylpiperidin-4-yl.

86. A compound according to any one of claims 1 - 71 and 85, wherein, R 6a is isopropyl.

87. A compound according to any one of claims 1 - 86, wherein, R 6b is C 1-6 alkyl, which is optionally substituted by one or more substituents Q.

88. A compound according to any one of claims 1 - 87, wherein, R 6b is methyl or isopropyl.

89. The compound according to any one of claims 1-88, wherein, R 6b is methyl.

90. A compound according to any one of claims 1 - 89, wherein, R 6c is hydrogen or C 1-6 alkyl optionally substituted by one or more substituents Q.

91. The compound according to any one of claims 1-90, wherein, R 6c is hydrogen or methyl.

92. The compound according to any one of claims 1-91, wherein R 6c is hydrogen.

93. A compound according to any one of claims 1 - 86, wherein, R 6b and R 6c together with the carbon atoms to which they are attached form a C 3-10 subcycloalkyl group, which is optionally substituted by one or more substituents Q.

94. A compound according to any one of claims 1 - 86 and 93, wherein, R 6b and R 6c together with the carbon atoms to which they are attached form a monocyclic C 3-10 subcycloalkyl group which is optionally substituted by one or more substituents Q.

95. The compound according to any one of claims 1-94, wherein, A is a bond or O.

96. A compound according to any one of claims 1-95, wherein, A is a bond.

97. A compound according to any one of claims 1-96, wherein, L 1 is C 1-6 an alkylene group, which is optionally substituted by one or more substituents Q.

98. The compound according to any one of claims 1-97, wherein, L 1 is methanediyl, ethane-1,2-diyl, propane-1,2-diyl or butane-1,4-diyl, each optionally substituted by one or more substituents Q.

99. The compound according to any one of claims 1-98, wherein L 1 is a methanediyl group.

100. The compound according to any one of claims 1-99, wherein, X is O.

101. The compound according to any one of claims 1-100, wherein, Z is hydrogen, azido, fluoro, iodo, isocyano, -C=CH2, -C≡CH, -C(O)CCH3 or -SH.

102. The compound according to any one of claims 1-101, wherein, Z is an azido group.

103. A compound as follows: Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A1; 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A2; 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1S)-1-(1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A3; 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-((1-methyl-1-(1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A4; 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1S)-1-(1-phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphoryl)-D-mannopyranoside A5; 2-(2-Azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1-methyl-1-(1-methyl-1-phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A6; 2-(2-Azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1S)-1-(1-methyl-1-phenylethoxycarbonyl)-2-methylpropylamino)(phenoxy)phosphoryl)-D-mannopyranoside A7; Pyridin-3-ylacetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A8; 3-Morpholinopropionyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxy-carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A9; 4-Methylpiperazin-1-ylpropionyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxy-carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A10; 4-Acetylpiperazin-1-ylpropionyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxy-carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A11; Tetrahydropyran-4-ylcarbonyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxy-carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A12; 1-Methylpiperidin-4-ylcarbonyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxy-carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A13; Pyrrolidin-1-ylacetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxy-carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A14; 4-Dimethylaminobenzoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A15; Pyridin-3-ylcarbonyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A16; Pyrrol-2-ylcarbonyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A17; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-butoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A18; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((1S)-1-sec-butoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A19; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-tert-butoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A20; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-pentyloxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A21; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-hexyloxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A22; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-(2-ethylbutoxy)carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A23; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-pyridin-3-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A24; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-pyridin-4-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A25; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-quinolin-4-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A26; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A27; Valeryl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A28; 2-Methylbutanoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-(quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A29; Hexanoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-(quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A30; Nonanoyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-(quinolin-5-ylmethoxycarbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A31; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-(4-methyltetrahydropyran-4-yloxy)carbonylethylamino)(phenoxy)phosphoryl)-D-mannopyranoside A32; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-((((1S)-1-(1-(4-(tert-butoxycarbonylamino)phenyl)ethoxycarbonyl)-2-methylpropylamino)(phenoxy)-phosphoryl)-D-mannopyranoside A33; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(((S)-1-isopropoxycarbonylethylamino)(quinolin-5-yloxy)phosphoryl)-D-mannopyranoside A34; Acetyl 2-(2-azidoacetylamino)-2-deoxy-3,4-di-O-acetyl-6-O-(3-(((S)-1-isopropoxycarbonylethylamino)(phenoxy)phosphoryloxy)propionyl)-D-mannopyranoside A35; (3S,4R,5S,6R)-3-(2-azidoacetamido)-6-((((((R)-1-(benzyloxy)-3-methyl-1-oxobutan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A36; (3S,4R,5S,6R)-3-(2-azidoacetamido)-6-((((((S)-3-methyl-1-oxo-1-(1-phenyl-cyclopropoxy)butan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A37; (2R,3S,4R,5S)-5-(2-azidoacetamido)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)-6-((tetrahydro-2H-pyran-4-carbonyl)oxy)tetrahydro-2H-pyran-3,4-diyl diacetate A38; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((3-morpholinobenzoyl)oxy)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A39; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((3-(4-methylpiperazin-1-yl)benzoyl)oxy)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A40; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((3-(morpholinomethyl)benzoyl)oxy)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A41; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((3-((4-methylpiperazin-1-yl)methyl)benzoyl)oxy)-2-((((((S)-1-oxo-1-(pentyloxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A42; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)-6-(valeryloxy)tetrahydro-2H-pyran-3,4-diyl diacetate A43; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-((2-methylbutyryl)oxy)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A44; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-(hexanoyloxy)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A45; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-(nonanoyloxy)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A46; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-oxo-1-(quinolin-4-ylmethoxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)-6-((tetrahydro-2H-pyran-4-carbonyl)oxy)tetrahydro-2H-pyran-3,4-diyl diacetate A47; (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-1-oxo-1-((tetrahydro-2H-pyran-4-yl)oxy)propan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A48; (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-1-((1-methylpiperidin-4-yl)oxy)-1-oxopropan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A49; (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-1-isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A50; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)-6-(valeryloxy)tetrahydro-2H-pyran-3,4-diyl diacetate A51; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)-6-(pivaloyloxy)tetrahydro-2H-pyran-3,4-diyl diacetate A52; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-6-(hexanoyloxy)-2-((((((S)-1-isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-3,4-diyl diacetate A53; (2R,3S,4R,5S)-5-(2-Azidoacetamido)-2-((((((S)-1-isopropoxy-1-oxopropan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)-6-(nonanoyloxy)tetrahydro-2H-pyran-3,4-diyl diacetate A54; (3S,4R,5S,6R)-3-(2-Azidoacetamido)-6-((((((S)-1-Oxo-1-(pentyloxy)propan-2-yl)amino)(quinolin-5-yloxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate A55; or (((1S)-1-(1-Phenylethoxycarbonyl)ethylamino)(phenoxy)phosphoryl) 2-(2-azidoacetylamino)-2-deoxy-3,4,6-tri-O-acetyl-D-mannopyranoside B1; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof.

104. A pharmaceutical composition, said pharmaceutical composition comprising a compound according to any one of claims 1-103, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate or hydrate thereof; and a pharmaceutically acceptable excipient.

105. The pharmaceutical composition according to claim 104, wherein, The composition is in a single dosage form.

106. The pharmaceutical composition according to claim 104 or 105, wherein, The composition is in an oral, parenteral or intravenous dosage form.

107. The pharmaceutical composition according to claim 106, wherein, The composition is formulated as an oral dosage form.

108. The pharmaceutical composition according to claim 107, wherein, The oral dosage form is a tablet or a capsule.

109. A method of labeling cells in a subject with an azide group, said method comprising administering to a subject in need thereof an effective amount of a compound according to any one of claims 1-103 or a pharmaceutical composition according to any one of claims 104-108.

110. The method according to claim 109, wherein, The subject is a human.

111. A method of labeling cells with an azide group, said method comprising contacting the cells with an effective amount of a compound according to any one of claims 1-103 or a pharmaceutical composition according to any one of claims 104-108.

112. The method according to any one of claims 109-111, wherein, The cells are cancer cells.

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