Preparation and use of compound capable of inhibiting myopia progression

Abstract

The present invention provides a compound represented by formula (I), or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, or a pharmaceutically acceptable salt thereof. The present invention further provides a method for preparing the compound, a pharmaceutical composition comprising the same, and a use thereof in inhibiting myopia progression.

Description

Preparation and uses of compounds that can inhibit the progression of myopia

[0001] This application claims priority to Chinese Patent Application No. 202411919055.2, filed on December 24, 2024, which is incorporated herein by reference in its entirety. Technical Field

[0002] This invention relates to a class of compounds or pharmaceutically acceptable salts thereof that inhibit the progression of myopia, pharmaceutical compositions thereof and methods of their preparation, and their use in inhibiting the progression of myopia. Background Technology

[0003] Myopia, or nearsightedness, is a type of refractive error that causes blurred vision because parallel light rays, after passing through the eye's refractive system, focus in front of the retina. The exact cause is not yet fully understood, but it is often related to genetic factors and poor eye habits. Myopia manifests as blurred distance vision because parallel light rays cannot focus on the retina. In terms of eye structure, it can result in an excessively long axial length or excessive curvature of the cornea or lens. High-risk groups for myopia include teenagers and those who work long hours doing close-up work.

[0004] Myopia can be classified into low, moderate, and high myopia based on its degree of refractive error, and into axial and refractive myopia based on its refractive components. Furthermore, it can be classified into simple myopia and pathological myopia based on its progression. After developing myopia, vision can be corrected by wearing eyeglasses, contact lenses, or refractive surgery. In addition, low-concentration atropine sulfate eye drops have shown good efficacy in the prevention and treatment of myopia in children and adolescents. However, the conditions of myopic individuals vary greatly, and there is still a strong expectation for an increase in the variety of eye disease treatments to allow for appropriate selection of treatment agents.

[0005] Studies have found that endoplasmic reticulum stress, scleral hypoxia or thinning, and axial elongation are important causes of myopia development and progression. Some medications, such as ophthalmic antioxidants, certain mydriatics, and some traditional Chinese medicine extracts, have been reported to have some effect in inhibiting myopia progression. However, currently only low-concentration atropine sulfate is approved clinically for inhibiting myopia progression, and clinical use has shown that it is not suitable for all myopic individuals. Therefore, the continued development of other types of drugs remains urgent. Summary of the Invention

[0006] In one aspect, the present invention provides a compound of formula (I), or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, or a pharmaceutically acceptable salt thereof:

[0007] in,

[0008] A is either O or S;

[0009] B is O, S, or NR. # ;R # Selected from H, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups;

[0010] R 1 Selected from H, C 1-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, wherein the above groups are optionally substituted by 1, 2, 3, 4 or 5 R's; provided that when A is O and B is O, R's are substituted by 1, 2, 3, 4 or 5 R's. 1 Not H;

[0011] or, These are groups derived from endogenous substances and their derivatives, which are optionally replaced by 1, 2, 3, 4 or 5 R's;

[0012] Each R' is independently selected from halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR a -ON(R) b )2、-N(R b )2、-N(R b )3 + X-, -N(OR) c )R b -SH, -SR a -SSR c -C(=O)R a -CO2H, -CHO, -C(OR) c )2、-CO2R a -OC(=O)R a -OCO2R a -C(=O)N(R) b )2、-OC(=O)N(R b )2、-NR b C(=O)R a -NR b CO2R a -NR b C(=O)N(R b )2、-C(=NR b )R a、-C(=NR b )OR a 、-OC(=NR b )R a 、-OC(=NR b )OR a 、-C(=NR b )N(R b )2、-OC(=NR b )N(R b )2、-NR b C(=NR b )N(R b )2、-C(=O)NR b SO2R a 、-NR b SO2R a 、-SO2N(R b )2、-SO2R a 、-SO2OR a 、-OSO2R a 、-S(=O)R a 、-OS(=O)R a 、-Si(R a )3、-OSi(R a )3、-C(=S)N(R b )2、-C(=O)SR a 、-C(=S)SR a 、-SC(=S)SR a 、-SC(=O)SR a 、-OC(=O)SR a 、-SC(=O)OR a 、-SC(=O)R a 、-P(=O)2R a 、-OP(=O)2R a 、-P(=O)(R a )2、-OP(=O)(R a )2、-OP(=O)(OR c )2、-P(=O)2N(R b )2、-OP(=O)2N(R b )2、-P(=O)(NR b )2、-OP(=O)(NR b )2、-NR b P(=O)(OR c )2、-NR b P(=O)(NR b )2、-P(R c )2、-P(Rc )3、-OP(R c )2、-OP(R c )3、-B(R a 2. -B(OR) c )2、-BR a (OR c C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, =O, =S, =NN(R) b )2、=NNR b C(=O)R a =NNR b C(=O)OR a =NNR b S(=O)2R a =NR b and = NOR c Wherein C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups may be optionally replaced by 1, 2, 3 or 4 R*s;

[0013] And / or, two R' atoms on non-adjacent atoms are connected to form C. 1-6 Alkylene, C 2-6 imide or C 2-6 The ynyl group, wherein the above group is optionally substituted by 1, 2, 3 or 4 R*;

[0014] And / or, two R's on adjacent atoms together with the atoms they are connected to form C. 3-8 A carbocyclic group or a 3-8 membered heterocyclic group, wherein the above groups are optionally substituted by 1, 2, 3 or 4 R*;

[0015] And / or, two R's on the same carbon atom together with that carbon atom form C. 3-8 A carbocyclic group or a 3-8 membered heterocyclic group, wherein the above groups are optionally substituted by 1, 2, 3 or 4 R*;

[0016] Each R* is independently selected from halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR a -ON(R) b)2、-N(R b )2、-N(R b )3 + X - 、-N(OR c )R b 、-SH、-SR a 、-SSR c 、-C(=O)R a 、-CO2H、-CHO、-C(OR c )2、-CO2R a 、-OC(=O)R a 、-OCO2R a 、-C(=O)N(R b )2、-OC(=O)N(R b )2、-NR b C(=O)R a 、-NR b CO2R a 、-NR b C(=O)N(R b )2、-C(=NR b )R a 、-C(=NR b )OR a 、-OC(=NR b )R a 、-OC(=NR b )OR a 、-C(=NR b )N(R b )2、-OC(=NR b )N(R b )2、-NR b C(=NR b )N(R b )2、-C(=O)NR b SO2R a 、-NR b SO2R a 、-SO2N(R b )2、-SO2R a 、-SO2OR a 、-OSO2R a 、-S(=O)R a 、-OS(=O)R a 、-Si(R a )3、-OSi(R a )3、-C(=S)N(R b )2、-C(=O)SR a 、-C(=S)SRa -SC(=S)SR a -SC(=O)SR a -OC(=O)SR a -SC(=O)OR a -SC(=O)R a -P(=O)2R a -OP(=O)2R a -P(=O)(R a )2、-OP(=O)(R a )2、-OP(=O)(OR c )2、-P(=O)2N(R b )2、-OP(=O)2N(R b )2、-P(=O)(NR b )2、-OP(=O)(NR b )2、-NR b P(=O)(OR c )2、-NR b P(=O)(NR b )2、-P(R c )2、-P(R c )3、-OP(R c )2、-OP(R c )3、-B(R a 2. -B(OR) c )2、-BR a (OR c C 1-20 Alkyl, C 1-20 Haloalkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, =O, =S, =NN(R) b )2、=NNR b C(=O)R a =NNR b C(=O)OR a =NNR b S(=O)2R a =NR b and = NOR c ;

[0017] Each R a Selected independently from C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl and 5-10 heteroaryl, or two R a Groups combine to form 3-10 membered heterocyclic groups or 5-10 membered heteroaryl groups;

[0018] Each R b Independently selected from hydrogen, -OH, -OR a -N(R) c )2、-CN、-C(=O)R a -C(=O)N(R) c )2、-CO2R a -SO2R a -C(=NR) c OR a -C(=NR) c )N(R c )2、-SO2N(R c )2、-SO2R c -SO2OR c -SOR a -C(=S)N(R) c )2、-C(=O)SR c -C(=S)SR c -P(=O)2R a -P(=O)(R a )2、-P(=O)2N(R c )2、-P(=O)(NR c 2. C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl and 5-10 heteroaryl, or two R b Groups combine to form 3-10 membered heterocyclic groups or 5-10 membered heteroaryl groups;

[0019] Each R c Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl and 5-10 heteroaryl, or two R c Groups combine to form 3-10 membered heterocyclic groups or 5-10 membered heteroaryl groups;

[0020] X - Selected from F - Cl - ,Br - I - HSO4 - NO3 - HCO3 - and OCl4 - .

[0021] In another aspect, the present invention relates to pharmaceutical compositions comprising the compounds of the invention, or isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates thereof, or pharmaceutically acceptable salts thereof, and pharmaceutically acceptable excipients.

[0022] In another aspect, the present invention relates to the use of compounds of the present invention, or isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates thereof, or pharmaceutically acceptable salts thereof, or the use of pharmaceutical compositions of the present invention in the preparation of medicaments for inhibiting the progression of myopia.

[0023] Invention Details

[0024] Chemical definition

[0025] The definitions of specific functional groups and chemical terms are described in more detail below. Chemical elements are defined according to the CAS version of the periodic table of elements, page 75 of the Handbook of Chemistry and Physics, and generally, specific functional groups are also defined according to that description. Furthermore, general principles of organic chemistry, as well as specific functional groups and reactions, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Smith and March, March's Advanced Organic Chemistry, 5th ed., (John Wiley & Sons, Inc., New York, 2001); Larock, Comprehensive Organic Transformations, (VCH Publishers, Inc., New York, 1989); and Carruthers, Some Modern Methods of Organic Synthesis, 3rd ed., (Cambridge University Press, Cambridge, 1987).

[0026] A hyphen ("-") not between two letters or symbols is used to indicate the attachment point of a substituent. For example, -CONH2 is attached via a carbon atom. A hyphen before or after a chemical group is for convenience; a chemical group may or may not be depicted with one or more hyphens without losing its usual meaning. A wavy line drawn through a line in the structure indicates the attachment point of a group. Unless chemically or structurally required, the order in which chemical groups are written or named does not indicate or imply directionality. A solid line extending from the center of the ring indicates that the attachment point of a substituent on that ring can be on any ring atom. For example, R in the following structure... a It can be attached to any of the five carbon ring atoms, or R a It can replace hydrogen atoms attached to nitrogen ring atoms:

[0027] prefix "C" u-v The colon "" indicates that the following group has between u and v carbon atoms. For example, "C 1-6 "Alkyl" indicates that an alkyl group has 1 to 6 carbon atoms. Similarly, the term "xy-membered" ring, where x and y are numerical ranges, such as "3-12-membered heterocyclic group," refers to a ring containing xy (e.g., 3-12) atoms.

[0028] When listing a range of values, it includes each value and the subranges within that range. For example, "C 1-6 Alkyl groups include C1, C2, C3, C4, C5, C6, and C6. 1-6 C 1-5 C 1-4 C 1-3 C 1-2 C 2-6 C 2-5 C 2-4 C 2-3 C 3-6 C 3-5 C 3-4 C 4-6 C 4-5 and C 5-6 alkyl.

[0029] The following terms are intended to have the meanings provided below and are useful in understanding the specification and intended scope of the invention.

[0030] "alkyl" refers to a straight-chain or branched saturated hydrocarbon group having 1 to 20 carbon atoms ("C"). 1-20 Alkyl group). In some embodiments, the alkyl group has 1 to 12 carbon atoms (“C12”). 1-12 Alkyl group). In some embodiments, the alkyl group has 1 to 10 carbon atoms (“C10”). 1-10Alkyl group). In some embodiments, the alkyl group has 1 to 9 carbon atoms (“C1”). 1-9 Alkyl group). In some embodiments, the alkyl group has 1 to 8 carbon atoms (“C1”). 1-8 Alkyl group). In some embodiments, the alkyl group has 1 to 7 carbon atoms (“C1”). 1-7 Alkyl group (“C”). In some embodiments, the alkyl group has 1 to 6 carbon atoms (“C”). 1-6 Alkyl group (also referred to herein as "lower alkyl group"). In some embodiments, the alkyl group has 1 to 5 carbon atoms ("C1 to 5 C2"). 1-5 Alkyl group). In some embodiments, the alkyl group has 1 to 4 carbon atoms (“C1”). 1-4 Alkyl group). In some embodiments, the alkyl group has 1 to 3 carbon atoms (“C1”). 1-3 Alkyl group (“alkyl”). In some embodiments, the alkyl group has 1 to 2 carbon atoms (“C”). 1-2 Alkyl group (“C1 alkyl”). In some embodiments, the alkyl group has 1 carbon atom (“C1 alkyl”). In some embodiments, the alkyl group has 2 to 6 carbon atoms (“C1 alkyl”). 2-6 Alkyl group). C 1-6 Examples of alkyl groups include: methyl (C1), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), tert-butyl (C4), sec-butyl (C4), isobutyl (C4), n-pentyl (C5), 3-pentyl (C5), pentyl (C5), neopentyl (C5), 3-methyl-2-butyl (C5), tert-pentyl (C5), and n-hexyl (C6). Other examples of alkyl groups include n-heptyl (C7), n-octyl (C8), etc. Unless otherwise stated, each alkyl group is optionally substituted independently, i.e., unsubstituted (“unsubstituted alkyl”) or substituted with one or more substituents (“substituted alkyl”); for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. In some embodiments, the alkyl group is an unsubstituted C1 alkyl group. 1-10 Alkyl group (e.g., -CH3). In some embodiments, the alkyl group is a substituted C-molecule. 1-10 Alkyl. Common abbreviations for alkyl include: Me(-CH3), Et(-CH2CH3), iPr(-CH(CH3)2), nPr(-CH2CH2CH3), n-Bu(-CH2CH2CH2CH3), or i-Bu(-CH2CH(CH3)2). The term "alkyl" also includes heteroalkyl, in which one or more (e.g., 1, 2, 3, or 4) carbon atoms are replaced by heteroatoms (e.g., oxygen (O), sulfur (S), nitrogen (N), boron (B), silicon (Si), phosphorus (P)).

[0031] "Alkenyl" refers to a straight-chain or branched hydrocarbon group having 2 to 20 carbon atoms, one or more carbon-carbon double bonds (e.g., 1, 2, 3, or 4 carbon-carbon double bonds), and optionally one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 carbon-carbon triple bonds). 2-20 Alkenyl group (“Alkenyl”). In some embodiments, the alkenyl group does not contain any triple bonds. In some embodiments, the alkenyl group has 2 to 10 carbon atoms (“C”). 2-10 Alkenyl group (“Alkenyl”). In some embodiments, the alkenyl group has 2 to 9 carbon atoms (“C”). 2-9 Alkenyl group (“Alkenyl”). In some embodiments, the alkenyl group has 2 to 8 carbon atoms (“C”). 2-8 Alkenyl group (“Alkenyl”). In some embodiments, the alkenyl group has 2 to 7 carbon atoms (“C”). 2-7 Alkenyl group (“Alkenyl”). In some embodiments, the alkenyl group has 2 to 6 carbon atoms (“C”). 2-6 Alkenyl group (“Alkenyl”). In some embodiments, the alkenyl group has 2 to 5 carbon atoms (“C”). 2-5 Alkenyl group (“Alkenyl”). In some embodiments, the alkenyl group has 2 to 4 carbon atoms (“C”). 2-4 Alkenyl group (“Alkenyl”). In some embodiments, the alkenyl group has 2 to 3 carbon atoms (“C”). 2-3 The alkenyl group (“C2-alkenyl”) has two carbon atoms in some embodiments. One or more carbon-carbon double bonds may be internal (e.g., in a 2-butenyl group) or terminal (e.g., in a 1-butenyl group). 2-4 Examples of alkenyl groups include: vinyl (C2), 1-propenyl (C3), 2-propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), etc. 2-6 Examples of alkenyl groups include: the C group mentioned above. 2-4 Alkenyl groups, including pentenyl (C5), pentadienyl (C5), hexenyl (C6), etc. Other examples of alkenyl groups include heptenyl (C7), octenyl (C8), octetrinyl (C8), etc. Unless otherwise stated, each alkenyl group is optionally substituted independently, i.e., unsubstituted (“unsubstituted alkenyl”) or substituted by one or more substituents (“substituted alkenyl”); for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. In some embodiments, the alkenyl group is an unsubstituted C10. 2-10 Alkenyl. In some embodiments, the alkenyl group is a substituted C. 2-10 Alkenyl group.

[0032] "Alkyne" refers to a straight-chain or branched hydrocarbon group having 2 to 20 carbon atoms, one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 carbon-carbon triple bonds), and optionally one or more carbon-carbon double bonds (e.g., 1, 2, 3, or 4 carbon-carbon double bonds). 2-20The alkynyl group (“Alynyl”) is present in some embodiments. In some embodiments, the alkynyl group has 2 to 10 carbon atoms (“C”). 2-10 The alkynyl group (“C”) is present in some embodiments. In some embodiments, the alkynyl group has 2 to 9 carbon atoms (“C”). 2-9 The alkynyl group (“acetylenic”) has 2 to 8 carbon atoms in some embodiments. 2-8 The alkynyl group (“acetylation”) has 2 to 7 carbon atoms in some embodiments. 2-7 The alkynyl group (“C”) is present in some embodiments. In some embodiments, the alkynyl group has 2 to 6 carbon atoms (“C”). 2-6 The alkynyl group (“H”) has 2 to 5 carbon atoms in some embodiments. 2-5 The alkynyl group (“C”) is present in some embodiments. In some embodiments, the alkynyl group has 2 to 4 carbon atoms (“C”). 2-4 The alkynyl group (“C”) is present in some embodiments. In some embodiments, the alkynyl group has 2 to 3 carbon atoms (“C”). 2-3 The alkynyl group (“C2-alkynyl”) is present in some embodiments. One or more carbon triple bonds may be internal (e.g., in 2-butynyl) or terminal (e.g., in 1-butynyl). 2-4 Examples of alkynyl groups include, but are not limited to: ethynyl (C2), 1-propynyl (C3), 2-propynyl (C3), 1-butynyl (C4), 2-butynyl (C4), etc. 2-6 Examples of alkenyl groups include: the C group mentioned above. 2-4 The alkynyl group includes pentynyl (C5), hexynyl (C6), etc. Other examples of alkynyl groups include heptynyl (C7), octyynyl (C8), etc. Unless otherwise stated, each alkynyl group is optionally substituted independently, i.e., unsubstituted (“unsubstituted alkynyl”) or substituted by one or more substituents (“substituted alkynyl”); for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. In some embodiments, the alkynyl group is an unsubstituted C5 group. 2-10 Alkynyl group. In some embodiments, the alkynyl group is a substituted C- group. 2-10 Alkyne group.

[0033] "alkylene", "alkenylene", and "alkynylene" refer to divalent groups formed by removing one hydrogen atom from "alkyl", "alkenyl", and "alkynyl". When a specific "alkylene" is provided with a range or number of carbon atoms, it should be understood that the range or number refers to the range or number of carbon atoms in a straight-chain divalent carbon chain. "Alkenylene" may be substituted with one or more of the substituents described herein, or may be unsubstituted.

[0034] "Aryl" refers to a group ("C") that has a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 shared π electrons arranged in a ring) that provides 6-14 ring carbon atoms and zero heteroatoms in the aromatic ring system. 6-14 Aryl group (“C6 aryl”). In some embodiments, the aryl group has six ring carbon atoms (“C6 aryl”; for example, phenyl). In some embodiments, the aryl group has ten ring carbon atoms (“C6 aryl”). 10 Aryl; for example, naphthyl, such as 1-naphthyl and 2-naphthyl). In some embodiments, the aryl group has fourteen cyclic carbon atoms (“C14”). 14 "Aryl"; for example, anthracene. "Aryl" also includes ring systems in which the aryl ring is fused with one or more carbocyclic or heterocyclic groups, wherein the atomic group or connecting point is on the aryl ring, in which case the number of carbon atoms continues to represent the number of carbon atoms in the aryl ring system. Typical aryl groups include, but are not limited to, groups derived from: anthracene, acenaphthene, phenanthrylene, anthracene, azulene, benzene, chlorobenzene, fluorene, benzoxene, hexane, hexane, and other groups. The aryl groups are referred to as indole, symmetric indole, indole, naphthalene, octaphenyl, octylene, octylene, oleophane, pentadiene, pentylene, pentylene, perylene, phenanthracene, phenanthrene, sepium, pyrene, anthracene, rubiginium, benzo[a]phenanthrene, and ternaphthalene. Specifically, the aryl groups include phenyl, naphthyl, indole, and tetrahydronaphthyl. Unless otherwise stated, each aryl group is optionally independently substituted, i.e., unsubstituted (“unsubstituted aryl”) or substituted by one or more substituents (“substituted aryl”). In some embodiments, the aryl group is an unsubstituted C14. 6-14 Aryl. In some embodiments, the aryl group is a substituted C. 6-14 Aryl.

[0035] In some embodiments, the aryl group is substituted with one or more groups selected from halogen, C1-C8 alkyl, C1-C8 haloalkyl, cyano, hydroxyl, C1-C8 alkoxy and amino groups.

[0036] Representative examples of substituted aryl groups include the following:

[0037] Among them, R 56 and R 57 One of them can be hydrogen, R 56 and R 57 At least one of them is independently selected from: C1-C8 alkyl, C 1- C8 haloalkyl, 4-10 membered heterocyclic groups, alkylyl groups, C 1- C8 alkoxy, heteroaryloxy, alkylamino, aromatic amino, heteroarylamino, NR58 COR 59 NR 58 SOR 59 NR 58 SO2R 59 COO alkyl, COO aryl, CONR 58 R 59 CONR 58 OR 59 NR 58 R 59 SO2NR 58 R 59 S-alkyl, SO-alkyl, SO2-alkyl, S-aryl, SO-aryl, SO2-aryl; or R 56 and R 57 They can combine to form rings of 5 to 8 atoms (saturated or unsaturated), which optionally contain one or more heteroatoms selected from N, O, or S. R 60 and R 61 Independently, it is hydrogen, C1-C8 alkyl, C1-C4 haloalkyl, C3-C 10 Cycloalkyl, 4-10 membered heterocyclic, C6-C 10 Aryl, substituted C 6- C 10 Aryl, 5-10 heteroaryl or substituted 5-10 heteroaryl.

[0038] "Fused aryl" refers to an aryl group in which two carbon rings share a second aryl or heteroaryl ring, or a carbocyclic or heterocyclic ring.

[0039] "Heteroaryl" refers to a 4n+2 aromatic ring system (e.g., having 6 or 10 shared π electrons arranged in a ring) having a 5-10 membered monocyclic or bicyclic ring providing a cyclic carbon atom and 1-4 cyclic heteroatoms in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-10 membered heteroaryl"). In heteroaryls containing one or more nitrogen atoms, the linkage can be a carbon or nitrogen atom, provided the valence allows. A heteroaryl bicyclic system may include one or more heteroatoms in one or both rings. "Heteroaryl" includes a ring system in which the aforementioned heteroaryl ring is fused with one or more carbocyclic or heterocyclic groups, wherein the linkage is on the heteroaryl ring, and in such cases, the number of ring members continues to represent the number of ring members in the heteroaryl ring system. "Heteroaryl" also includes ring systems in which the aforementioned heteroaryl ring is fused with one or more aryl groups, wherein the connection point is on the aryl or heteroaryl ring, and in such cases, the number of ring members represents the number of ring members in the fused (aryl / heteroaryl) ring system. A bicyclic heteroaryl group (e.g., indolyl, quinolinyl, carbazolyl, etc.) in which one ring does not contain a heteroatom can have the connection point on either ring, i.e., on the ring with a heteroatom (e.g., 2-indolyl) or the ring without a heteroatom (e.g., 5-indolyl).

[0040] In some embodiments, the heteroaryl group is a 5-10 membered aromatic ring system having a cyclic carbon atom and 1-4 cyclic heteroatoms (present in an aromatic ring system), wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-10 membered heteroaryl”). In some embodiments, the heteroaryl group is a 5-8 membered aromatic ring system having a cyclic carbon atom and 1-4 cyclic heteroatoms (present in an aromatic ring system), wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-8 membered heteroaryl”). In some embodiments, the heteroaryl group is a 5-6 membered aromatic ring system having a cyclic carbon atom and 1-4 cyclic heteroatoms (present in an aromatic ring system), wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-6 membered heteroaryl”). In some embodiments, the 5-6 membered heteroaryl group has 1-3 cyclic heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl group has 1-2 cyclic heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl group has one cyclic heteroatom selected from nitrogen, oxygen, and sulfur. Unless otherwise stated, each heteroaryl group is independently optionally substituted, i.e., unsubstituted (“unsubstituted heteroaryl”) or substituted by one or more substituents (“substituted heteroaryl”). In some embodiments, the heteroaryl group is an unsubstituted 5-14 membered heteroaryl group. In some embodiments, the heteroaryl group is a substituted 5-14 membered heteroaryl group.

[0041] Exemplary 5-membered heteroaryl groups containing one heteroatom include, but are not limited to: pyrroleyl, furanyl, and thiophenyl. Exemplary 5-membered heteroaryl groups containing two heteroatoms include, but are not limited to: imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryl groups containing three heteroatoms include, but are not limited to: triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing four heteroatoms include, but are not limited to: tetrazolyl. Exemplary 6-membered heteroaryl groups containing one heteroatom include, but are not limited to: pyridinyl. Exemplary 6-membered heteroaryl groups containing two heteroatoms include, but are not limited to: pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing three or four heteroatoms each include, but are not limited to: triazinyl and tetraazinyl. Exemplary 7-membered heteroaryl groups containing one heteroatom include, but are not limited to: azirheptatrienyl, oxatrienyl, and thioheptatrienyl. Exemplary 5,6-bicyclic heteroaryl groups include, but are not limited to: indolyl, isoindolyl, indazole, benzotriazolyl, benzothiophene, isobenzothiophene, benzofuranyl, benzoisofuranyl, benzoimidazolyl, benzoxazolyl, benzoisoxazolyl, benzoxadiazolyl, benzothiazolyl, benzoisothiazolyl, benzothiadiazolyl, indazinyl, and purinyl. Exemplary 6,6-bicyclic heteroaryl groups include, but are not limited to: naphthidyl, pteridinyl, quinolinyl, isoquinolinyl, zolinyl, quinoxolinyl, phthalazinyl, and quinazolinyl.

[0042] Representative examples of heteroaryl groups include the following:

[0043] Each Z is selected from carbonyl, N, NR. 65 O and S; R 65 Independently hydrogen, C1-C8 alkyl, C 3- C 10 Cycloalkyl, 4-10 membered heterocyclic, C6-C 10 Aryl and 5-10 heteroaryl compounds.

[0044] "Carbocyclic group" or "carbocyclic ring" refers to a non-aromatic cyclic hydrocarbon group ("C") having 3 to 10 ring carbon atoms and zero heteroatoms in a non-aromatic ring system. 3-10 Carbocyclic group (“CCR”). In some embodiments, the carbocyclic group has 3 to 8 cyclic carbon atoms (“C”). 3-8 Carbocyclic group (“CCR”). In some embodiments, the carbocyclic group has 3 to 6 cyclic carbon atoms (“C”). 3-6 Carbocyclic group (“CCR”). In some embodiments, the carbocyclic group has 3 to 6 cyclic carbon atoms (“C”). 3-6 (Carbocyclic group). In some embodiments, the carbocyclic group has 5 to 10 cyclic carbon atoms (“C”). 5-10 (Carbocyclic group"). An example C 3-6The carbocyclic group includes, but is not limited to: cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), etc. An exemplary C... 3-8 Carbocyclic groups include, but are not limited to, the C groups mentioned above. 3-6 Carbocyclic groups, including cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cyclohepttrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo[2.2.1]heptyl (C7), bicyclo[2.2.2]octyl (C8), etc. Exemplary C 3-10 Carbocyclic groups include, but are not limited to, the C groups mentioned above. 3-8 Carbocyclic groups, as well as cyclononyl (C9), cyclononenyl (C9), and cyclodecyl (C9) groups. 10 ), cyclodecenyl (C 10 ), octahydro-1H-indenyl (C9), decahydronaphthyl (C9) 10 ), spiro[4.5]decyl(C 10 As illustrated in the foregoing examples, in some embodiments, the carbocyclic group is a monocyclic (“monocyclic carbocyclic”) or a carbocyclic group comprising a fused ring system, a bridged ring system, or a spirocyclic system, such as a bicyclic system (“bicyclic carbocyclic”), and may be saturated or partially unsaturated. “Carbocyclic” also includes ring systems in which the aforementioned carbocyclic ring is fused with one or more aryl or heteroaryl groups, wherein the connection point is on the carbocyclic ring, and in such cases, the number of carbons continues to represent the number of carbons in the carbocyclic system. Unless otherwise stated, each of the carbocyclic groups is independently optionally substituted, i.e., unsubstituted (“unsubstituted carbocyclic”) or substituted with one or more substituents (“substituted carbocyclic”). In some embodiments, the carbocyclic group is an unsubstituted C 3-10 Carbocyclic group. In some embodiments, the carbocyclic group is a substituted C 3-10 Carbon cyclic group.

[0045] In some implementations, "carbocyclic group" is a monocyclic saturated carbocyclic group ("C") having 3 to 10 ring carbon atoms. 3-10 cycloalkyl group (“Cycloalkyl”). In some embodiments, the cycloalkyl group has 3 to 8 cyclic carbon atoms (“C”). 3-8 cycloalkyl group (“Cycloalkyl”). In some embodiments, the cycloalkyl group has 3 to 6 cyclic carbon atoms (“C”). 3-6 cycloalkyl group (“Cycloalkyl”). In some embodiments, the cycloalkyl group has 5 to 6 cyclic carbon atoms (“C”). 5-6 cycloalkyl group (“Cycloalkyl”). In some embodiments, the cycloalkyl group has 5 to 10 cyclic carbon atoms (“C”). 5-10 cycloalkyl). C 5-6Examples of cycloalkyl groups include cyclopentyl (C5) and cyclohexyl (C6). 3-6 Examples of cycloalkyl groups include the C10+ mentioned above. 5-6 Cycloalkyl groups, as well as cyclopropyl (C3) and cyclobutyl (C4). 3-8 Examples of cycloalkyl groups include the C10+ mentioned above. 3-6 Cycloalkyl groups, including cycloheptyl (C7) and cyclooctyl (C8). Unless otherwise stated, each cycloalkyl group is independently unsubstituted (“unsubstituted cycloalkyl”) or substituted with one or more substituents (“substituted cycloalkyl”). In some embodiments, the cycloalkyl group is an unsubstituted C7 group. 3-10 Cycloalkyl. In some embodiments, the cycloalkyl group is a substituted C-shaped group. 3-10 Cycloalkyl.

[0046] A "heterocyclic group" or "heterocycle" refers to a non-aromatic ring system consisting of 3 to 10 members, having a ring carbon atom and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon ("3-10 membered heterocyclic groups"). In heterocyclic groups containing one or more nitrogen atoms, the bonding point can be either a carbon or nitrogen atom, provided the valence allows. Heterocyclic groups can be monocyclic ("monocyclic heterocyclic group") or fused ring, bridged ring, or spirocyclic systems, such as bicyclic systems ("bicyclic heterocyclic group"), and can be saturated or partially unsaturated. A bicyclic heterocyclic system can include one or more heteroatoms in one or both rings. "Heterocyclic group" also includes ring systems in which the aforementioned heterocyclic ring is fused with one or more carbocyclic groups, wherein the connection point is on the carbocyclic or heterocyclic ring; or ring systems in which the aforementioned heterocyclic ring is fused with one or more aryl or heteroaryl groups, wherein the connection point is on the heterocyclic ring, and in such cases, the number of ring members continues to represent the number of ring members in the heterocyclic ring system. Unless otherwise stated, each of the heterocyclic groups is independently optionally substituted, i.e., unsubstituted ("unsubstituted heterocyclic group") or substituted by one or more substituents ("substituted heterocyclic group"). In some embodiments, the heterocyclic group is an unsubstituted 3-10 membered heterocyclic group. In some embodiments, the heterocyclic group is a substituted 3-10 membered heterocyclic group.

[0047] In some embodiments, the heterocyclic group is a 5-10 membered non-aromatic ring system having a cyclic carbon atom and 1-4 cyclic heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon (“5-10 membered heterocyclic group”). In some embodiments, the heterocyclic group is a 5-8 membered non-aromatic ring system having a cyclic carbon atom and 1-4 cyclic heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-8 membered heterocyclic group”). In some embodiments, the heterocyclic group is a 5-6 membered non-aromatic ring system having a cyclic carbon atom and 1-4 cyclic heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-6 membered heterocyclic group”). In some embodiments, the 5-6 membered heterocyclic group has 1-3 cyclic heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heterocyclic group has 1-2 cyclic heteroatoms selected from nitrogen, oxygen, and sulfur. In some implementations, the 5-6 membered heterocyclic group has a cyclic heteroatom selected from nitrogen, oxygen, and sulfur.

[0048] Exemplary 3-membered heterocyclic groups containing one heteroatom include, but are not limited to: azircyclopropane, oxacyclopropane, and thiorenyl. Exemplary 4-membered heterocyclic groups containing one heteroatom include, but are not limited to: azircyclobutane, oxacyclobutane, and thiorenyl. Exemplary 5-membered heterocyclic groups containing one heteroatom include, but are not limited to: tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolidinyl, and pyrrolidin-2,5-dione. Exemplary 5-membered heterocyclic groups containing two heteroatoms include, but are not limited to: dioxasulfuranyl, oxasulfuranyl, disulfuranyl, and oxazolidin-2-one. Exemplary 5-membered heterocyclic groups containing three heteroatoms include, but are not limited to: triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclic groups containing one heteroatom include, but are not limited to: piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclic groups containing two heteroatoms include, but are not limited to: piperazineyl, morpholinyl, dithianyl, and dioxane. Exemplary 6-membered heterocyclic groups containing three heteroatoms include, but are not limited to: triazinanyl. Exemplary 7-membered heterocyclic groups containing one heteroatom include, but are not limited to: azirheptanyl, oxetaneheptyl, and thianylheptyl. Exemplary 8-membered heterocyclic groups containing one heteroatom include, but are not limited to: azirheptanyl, oxetaneheptyl, and thianylheptyl. Exemplary 5-membered heterocyclic groups fused with a C6 aryl ring (also referred to herein as 5,6-bicyclic heterocycles) include, but are not limited to: dihydroindolyl, isodihydroindolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, benzoxazolinone, etc. Exemplary 6-membered heterocyclic groups fused with an aryl ring (also referred to herein as 6,6-bicyclic heterocycles) include, but are not limited to: tetrahydroquinolinyl, tetrahydroisoquinolinyl, etc.

[0049] When used to describe a compound or a group present on a compound, "hetero" means that one or more carbon atoms in the compound or group have been replaced by nitrogen, oxygen, or sulfur heteroatoms. "Hetero" can be applied to any of the above-mentioned hydrocarbon groups: for example, alkyl, such as heteroalkyl; cycloalkyl, such as heterocyclic; aryl, such as heteroaryl; cycloalkenyl, such as cycloheterenyl, etc.; having 1 to 5 heteroatoms, especially 1 to 3 heteroatoms.

[0050] "Halogen" or "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br), and iodine (I). In some embodiments, the halogen group is fluorine or chlorine.

[0051] "Halogenated alkyl" refers to an alkyl group in which one or more halogens are substituted. Typical halogenated alkyl groups include, but are not limited to, trifluoromethyl, difluoromethyl, fluoromethyl, chloromethyl, dichloromethyl, dibromoethyl, tribromomethyl, tetrafluoroethyl, etc.

[0052] In this application, the terms “optional” or “optionally” generally refer to an event or environment described subsequently that may but does not have to occur, and the description includes situations in which the event or environment occurs or does not occur. For example, “optionally alkyl-substituted heterocyclic group” means that an alkyl group may but does not have to be present, and the description can include cases where the heterocyclic group is substituted with an alkyl group and cases where the heterocyclic group is not substituted with an alkyl group.

[0053] As defined herein, alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl are optionally substituted groups (e.g., "substituted" or "unsubstituted" alkyl, "substituted" or "unsubstituted" alkenyl, "substituted" or "unsubstituted" alkynyl, "substituted" or "unsubstituted" carbocyclic, "substituted" or "unsubstituted" heterocyclic, "substituted" or "unsubstituted" aryl, or "substituted" or "unsubstituted" heteroaryl). Generally, the term "substituted," whether or not preceded by the term "optionally," means that at least one hydrogen atom present on the group (e.g., a carbon or nitrogen atom) is substituted by a permissible substituent, such as a substituent that, upon substitution, produces a stable compound, for example, a compound that does not spontaneously undergo transformation (e.g., by rearrangement, cyclization, elimination, or other reactions). Unless otherwise stated, a "substituted" group has substituents at one or more substituted positions of the group, and when more than one position is substituted in any given structure, the substituents at each position are either the same or different. The term "substituted" includes substitution with all permissible substituents of an organic compound (any substituent described herein that results in the formation of a stable compound). This invention contemplates any and all such combinations to obtain a stable compound. For the purposes of this invention, heteroatoms such as nitrogen may have hydrogen substituents and / or any suitable substituents described herein that satisfy the valence of the heteroatom and result in the formation of a stable moiety.

[0054] Exemplary substituents on carbon atoms include, but are not limited to: halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR aa -ON(R) bb )2、-N(R bb )2、-N(R bb )3 + X - -N(OR) cc )R bb -SH, -SR aa -SSR cc、-C(=O)R aa 、-CO2H、-CHO、-C(OR cc )2、-CO2R aa 、-OC(=O)R aa 、-OCO2R aa 、-C(=O)N(R bb )2、-OC(=O)N(R bb )2、-NR bb C(=O)R aa 、-NR bb CO2R aa 、-NR bb C(=O)N(R bb )2、-C(=NR bb )R aa 、-C(=NR bb )OR aa 、-OC(=NR bb )R aa 、-OC(=NR bb )OR aa 、-C(=NR bb )N(R bb )2、-OC(=NR bb )N(R bb )2、-NR bb C(=NR bb )N(R bb )2、-C(=O)NR bb SO2R aa 、-NR bb SO2R aa 、-SO2N(R bb )2、-SO2R aa 、-SO2OR aa 、-OSO2R aa 、-S(=O)R aa 、-OS(=O)R aa 、-Si(R aa )3、-OSi(R aa )3、-C(=S)N(R bb )2、-C(=O)SR aa 、-C(=S)SR aa 、-SC(=S)SR aa 、-SC(=O)SR aa 、-OC(=O)SR aa 、-SC(=O)OR aa 、-SC(=O)R aa 、-P(=O)2R aa-OP(=O)2R aa -P(=O)(R aa )2、-OP(=O)(R aa )2、-OP(=O)(OR cc )2、-P(=O)2N(R bb )2、-OP(=O)2N(R bb )2、-P(=O)(NR bb )2、-OP(=O)(NR bb )2、-NR bb P(=O)(OR cc )2、-NR bb P(=O)(NR bb )2、-P(R cc )2、-P(R cc )3、-OP(R cc )2、-OP(R cc )3、-B(R aa 2. -B(OR) cc )2、-BR aa (OR cc ), alkyl, haloalkyl, alkenyl, ynyl, carbocyclic, heterocyclic, aryl, and heteroaryl, wherein each alkyl, alkenyl, ynyl, carbocyclic, heterocyclic, aryl, and heteroaryl is independently bounded by 0, 1, 2, 3, 4, or 5 R groups. dd Group substitution; or two hydrogen atoms on the carbon atom are replaced by =O, =S, =NN(R) groups. bb )2、=NNR bb C(=O)R aa =NNR bb C(=O)OR aa =NNR bb S(=O)2R aa =NR bb or = NOR cc Substitute;

[0055] R aa Each of them is independently selected from alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl, or two R aa Groups are combined to form heterocyclic or heteroaryl rings, wherein each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently bounded by 0, 1, 2, 3, 4, or 5 R groups. dd Group substitution;

[0056] R bb Each is independently selected from hydrogen, -OH, -OR aa -N(R) cc )2、-CN、-C(=O)Raa -C(=O)N(R) cc )2、-CO2R aa -SO2R aa -C(=NR) cc OR aa -C(=NR) cc )N(R cc )2、-SO2N(R cc )2、-SO2R cc -SO2OR cc -SOR aa -C(=S)N(R) cc )2、-C(=O)SR cc -C(=S)SR cc -P(=O)2R aa -P(=O)(R aa )2、-P(=O)2N(R cc )2、-P(=O)(NR cc 2. Alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl, or two R bb Groups are combined to form heterocyclic or heteroaryl rings, wherein each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently bounded by 0, 1, 2, 3, 4, or 5 R groups. dd Group substitution;

[0057] R cc Each is independently selected from hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl, or two R cc Groups are combined to form heterocyclic or heteroaryl rings, wherein each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently bounded by 0, 1, 2, 3, 4, or 5 R groups. dd Group substitution;

[0058] R dd Each is independently selected from: halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR ee -ON(R) ff )2、-N(R ff )2、-N(R ff )3 + X - -N(OR) ee )R ff -SH, -SR ee -SSR ee -C(=O)R ee -CO2H, -CO2R ee-OC(=O)R ee -OCO2R ee -C(=O)N(R) ff )2、-OC(=O)N(R ff )2、-NR ff C(=O)R ee -NR ff CO2R ee -NR ff C(=O)N(R ff )2、-C(=NR ff OR ee -OC(=NR) ff )R ee -OC(=NR) ff OR ee -C(=NR) ff )N(R ff )2、-OC(=NR ff )N(R ff )2、-NR ff C(=NR ff )N(R ff )2、-NR ff SO2R ee -SO2N(R) ff )2、-SO2R ee -SO2OR ee -OSO2R ee -S(=O)R ee 、-Si(R ee )3、-OSi(R ee 3. -C(=S)N(R) ff )2、-C(=O)SR ee -C(=S)SR ee -SC(=S)SR ee -P(=O)2R ee -P(=O)(R ee )2、-OP(=O)(R ee )2、-OP(=O)(OR ee 2. Alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently bounded by 0, 1, 2, 3, 4, or 5 R groups. gg Group substitution, or two geminal radicals dd Substituents can combine to form =O or =S;

[0059] R eeEach is independently selected from alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, aryl, heterocyclic, and heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl is independently surrounded by 0, 1, 2, 3, 4, or 5 R groups. gg Group substitution;

[0060] R ff Each is independently selected from hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl, or two R ff The groups combine to form a heterocyclic or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently bounded by 0, 1, 2, 3, 4, or 5 R groups. gg Group substitution;

[0061] R gg Each of these is independently: halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OC 1-6 Alkyl, -ON(C) 1-6 Alkyl)2, -N(C 1-6 Alkyl)2, -N(C 1-6 Alkyl)3 + X - -NH(C 1-6 Alkyl)2 + X - -NH2(C 1-6 alkyl) + X - -NH3 + X - -N(OC) 1-6 Alkyl)(C 1-6 Alkyl), -N(OH)(C 1-6 Alkyl groups, -NH(OH), -SH, -SC 1-6 Alkyl, -SS(C 1-6 Alkyl), -C(=O)(C 1-6 Alkyl group, -CO2H, -CO2(C 1-6 Alkyl), -OC (=O)(C 1-6 Alkyl), -OCO2(C 1-6 Alkyl groups, -C(=O)NH2, -C(=O)N(C 1-6 Alkyl)2、-OC(=O)NH(C 1-6 Alkyl), -NHC(=O)(C 1-6 alkyl), -N(C) 1-6 Alkyl)C(=O)(C 1-6 alkyl), -NHCO2(C 1-6 Alkyl), -NHC(=O)N(C1-6 Alkyl)2、-NHC(=O)NH(C 1-6 Alkyl groups, -NHC(=O)NH2, -C(=NH)O(C 1-6 Alkyl), -OC (=NH)(C 1-6 Alkyl group), -OC (=NH)OC 1-6 Alkyl group, -C(=NH)N(C 1-6 Alkyl)2、-C(=NH)NH(C 1-6 Alkyl groups, -C(=NH)NH2, -OC(=NH)N(C 1-6 Alkyl)2、-OC(NH)NH(C 1-6 Alkyl groups, -OC(NH)NH2, -NHC(NH)N(C 1-6 Alkyl)2, -NHC(=NH)NH2, -NHSO2(C 1-6 alkyl), -SO2N(C 1-6 alkyl)2、-SO2NH(C 1-6 Alkyl groups, -SO2NH2, -SO2C 1-6 Alkyl, -SO2OC 1-6 Alkyl, -OSO2C 1-6 Alkyl, -SOC 1-6 Alkyl, -Si(C) 1-6 Alkyl)3、-OSi(C 1-6 Alkyl)3, -C(=S)N(C 1-6 Alkyl)2、C(=S)NH(C 1-6 Alkyl), C(=S)NH2, -C(=O)S(C 1-6 Alkyl), -C(=S)SC 1-6 Alkyl, -SC (=S)SC 1-6 Alkyl group, -P(=O)2(C 1-6 Alkyl), -P(=O)(C 1-6 Alkyl)2、-OP(=O)(C 1-6 Alkyl)2、-OP(=O)(OC 1-6 Alkyl)2, C 1-6 Alkyl, C 1-6 Haloalkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C7 carbocyclic, C6-C 10 Aryl, C3-C7 heterocyclic, C5-C 10 heteroaryl; or two ethryl groups gg The substituents can combine to form =O or =S; wherein X- is a counterion, and in some embodiments of this application, X... - Selected from F - Cl - ,Br -I - HSO4 - NO3 - HCO3 - and OCl4 - .

[0062] Exemplary substituents on the nitrogen atom include, but are not limited to: hydrogen, -OH, -OR aa -N(R) cc )2、-CN、-C(=O)R aa -C(=O)N(R) cc )2、-CO2R aa -SO2R aa -C(=NR) bb )R aa -C(=NR) cc OR aa -C(=NR) cc )N(R cc )2、-SO2N(R cc )2、-SO2R cc -SO2OR cc -SOR aa -C(=S)N(R) cc )2、-C(=O)SR cc -C(=S)SR cc -P(=O)2R aa -P(=O)(R aa )2、-P(=O)2N(R cc )2、-P(=O)(NR cc 2. Alkyl, haloalkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl, or two R atoms attached to a nitrogen atom. cc The groups combine to form a heterocyclic or heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, and heteroaryl group is independently bounded by 0, 1, 2, 3, 4, or 5 R groups. dd Group substitution, wherein R aa R bb R cc and R dd As described above. In some embodiments, the substituent present on the nitrogen atom is a nitrogen protecting group (also known as an amino protecting group). Nitrogen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, TW Greene and PGMWuts, 3rd edition, John Wiley & Sons, 1999, which are incorporated herein by reference.

[0063] Exemplary substituents on the oxygen atom include, but are not limited to, -R aa -C(=O)SR aa -C(=O)R aa -CO2R aa -C(=O)N(R) bb )2、-C(=NR bb )R aa -C(=NR) bb OR aa -C(=NR) bb )N(R bb )2、-S(=O)R aa -SO2R aa 、-Si(R aa 3. -P(R) cc )2、-P(R cc 3、-P(=O)2R aa -P(=O)(R aa )2、-P(=O)(OR cc )2、-P(=O)2N(R bb )2 and -P(=O)(NR bb )2, where R aa R bb and R cc As defined herein. In some embodiments, the oxygen atom substituent present on the oxygen atom is an oxygen protecting group (also known as a hydroxyl protecting group). Oxygen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, TW Greene and PGMWuts, Third Edition, John Wiley & Sons, 1999, which are incorporated herein by reference.

[0064] Exemplary sulfur substituents include, but are not limited to, -R aa -C(=O)SR aa -C(=O)R aa -CO2R aa -C(=O)N(R) bb )2、-C(=NR bb )R aa -C(=NR) bb OR aa -C(=NR) bb )N(R bb )2、-S(=O)R aa -SO2R aa 、-Si(R aa3. -P(R) cc )2、-P(R cc 3、-P(=O)2R aa -P(=O)(R aa )2、-P(=O)(OR cc )2、-P(=O)2N(R bb )2 and -P(=O)(NR bb )2, where R aa R bb and R cc As defined herein. In some embodiments, the sulfur substituent present on the sulfur atom is a sulfur protecting group (also known as a thiol protecting group). Sulfur protecting groups are those well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, TW Greene and PGM Wuts, 3rd edition, John Wiley & Sons, 1999, which are incorporated herein by reference.

[0065] As used in this article, when the phrase "derived from a group" modifies a substance, it means that the compound of that substance has a group formed by removing any hydrogen atom, and the site where the hydrogen atom is removed is the connection point between that group and the rest of the molecule. For example, glycine (Structural formula: It has hydrogen atoms at three sites: the amino group, the methylene group, and the carboxyl group. Therefore, groups derived from glycine (Gly) include... In a preferred embodiment of this application, "groups derived from natural amino acids and their derivatives" are groups formed by removing a non-carboxyl hydrogen atom from natural amino acids and their derivatives.

[0066] Other definitions

[0067] In this application, the term "comprising" generally means including the explicitly specified features, but does not exclude other elements. The terms "above" and "below" generally refer to situations that include the stated number.

[0068] In this application, the term "about" generally refers to a variation within a range of 0.5% to 10% above or below a specified value, such as a variation within a range of 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10% above or below a specified value.

[0069] "Aprotic solvents," also known as non-proton-transferring solvents, are solvents without protons. These solvents exhibit extremely weak or no tendency for proton self-transfer reactions. Aprotic solvents can be classified as: non-protic nonpolar solvents, such as alkanes (e.g., hexane, heptane, benzene, toluene, diethyl ether, carbon tetrachloride); and non-protic polar solvents, such as amides, ketones, nitriles, dimethyl sulfoxide, pyridine, dichloromethane, N,N-dimethylformamide, acetone, etc.

[0070] "Acidic conditions" refer to a system with a pH less than 7, usually achieved by adding acid. Acids include organic and inorganic acids. Organic acids include carboxylic acids (R-COOH), sulfonic acids (R-SO3H), sulfinic acids (R-SOOH), and thiocarboxylic acids (R-SH), such as acetic acid, tartaric acid, oxalic acid, malic acid, citric acid, ascorbic acid, benzoic acid, and salicylic acid. Inorganic acids include hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid.

[0071] "Alkaline conditions" refer to a system with a pH greater than 7, usually achieved by adding a base. Bases include organic and inorganic bases. Organic bases include amine compounds and nitrogen-containing heterocyclic compounds, as well as broader organic bases such as alkali metal salts of alcohols (e.g., sodium methoxide, potassium ethoxide, potassium tert-butoxide), alkyl lithium compounds (e.g., butyllithium, phenyllithium), and amino lithium compounds (e.g., diisopropylaminolithium, hexamethyldisilaminolithium). Inorganic bases include lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, barium hydroxide, calcium hydroxide, ammonium hydroxide, potassium carbonate, sodium carbonate, lithium carbonate, cesium carbonate, potassium bicarbonate, sodium bicarbonate, potassium bicarbonate, and cesium bicarbonate.

[0072] As used herein, the term "pharmaceutically acceptable salt" refers to acid or base addition salts of the compounds of the present invention that are suitable for contact with the tissues of a subject within the limits of reliable medical judgment, without producing undue toxicity, irritation, allergic reactions, etc., in proportion to a reasonable benefit / risk ratio, and are effective for their intended use, including (where possible) zwitterionic forms of the compounds of the present invention.

[0073] Pharmaceutically acceptable salts can be sulfates, pyrosulfates, bisulfates, sulfites, nitrates, borates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, etc., prepared from inorganic acids. Representative salts include hydrobromide, hydrochloride, sulfates, bisulfates, nitrates, borates, and phosphates. Salts can also be prepared from organic acids, such as aliphatic monocarboxylic and dicarboxylic acids, phenyl-substituted alkyl acids, hydroxyalkyl acids, alkyl diacids, aromatic acids, and aliphatic and aromatic sulfonic acids. Representative salts include acetates, propionates, valerates, oleates, palmitates, stearates, laurates, caprylates, isobutyrates, oxalates, malonates, succinates, caprylates, sebacic acid salts, fumarates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, naphthates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, maleates, tartrates, methanesulfonates, glucono-p-ethyl, lactobionates, laurylsulfonates, and hydroxyethanesulfonates. Pharmaceutically acceptable salts may include alkali metal and alkaline earth metal-based cations, such as sodium, lithium, potassium, calcium, and magnesium, as well as non-toxic ammonium, quaternary ammonium, and amine cations, including but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, and ethylamine. It also covers salts of amino acids, such as arginine salts, gluconates, galacturons, etc. (see, for example, Berge S. et al., "Pharmaceutical Salts," J. Pharm. Sci., 1977; 66: 1-19, incorporated herein by reference).

[0074] This invention also includes isotopically labeled compounds (isotope variants) that are equivalent to the general formulas or specific compounds described in this application, but in which one or more atoms are replaced by atoms with atomic masses or mass numbers different from those commonly found in nature. Examples of isotopes that can be introduced into the compounds of this invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, respectively, for example... 2 H, 3 H, 13 C 11 C 14 C 15 N、 18 O、 17 O、 31 P, 32 P, 35 S, 18 F and 36Cl. Other isotopes of the present invention containing the aforementioned isotopes and / or other atoms, their prodrugs, and pharmaceutically acceptable salts of said compounds or said prodrugs are all within the scope of this invention. Certain isotope-labeled compounds of the present invention, for example, those incorporating radioactive isotopes (e.g.,...) 3 H and 14 Those in category C) can be used for drug and / or substrate tissue distribution determination. Tritium, i.e. 3 H and carbon-14, i.e. 14 Carbon isotopes are particularly preferred because they are easy to prepare and detect. Additionally, heavier isotopes such as deuterium (i.e.,...) are preferred. 2 H) substitution is preferred in some cases because its higher metabolic stability can provide therapeutic benefits, such as prolonged in vivo half-life or reduced dosage requirements. Isotope-labeled compounds of the present invention and their prodrugs can generally be prepared by replacing non-isotope-labeled reagents with readily available isotope-labeled reagents when performing the processes described below and / or the techniques disclosed in the examples and preparation examples.

[0075] The compounds of this invention comprise one or more asymmetric centers and therefore can exist in a variety of stereoisomeric forms, such as enantiomers and / or diastereomers. For example, the compounds of this invention may be individual enantiomers, diastereomers, or geometric isomers (e.g., cis and trans isomers), or may be in the form of mixtures of stereoisomers, including racemic mixtures and mixtures rich in one or more stereoisomers. The isomers can be separated from the mixture by methods known to those skilled in the art, including chiral high-performance liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers may be prepared by asymmetric synthesis.

[0076] "Tautomers" refer to compounds in which one functional group changes its structure to become another functional group isomer, and can rapidly interconvert to each other, becoming two isomers in dynamic equilibrium. These two isomers are called tautomers.

[0077] The term "solvent" refers to a compound or its salt that is bound to a solvent and formed typically by a solvent decomposition reaction. This physical association may include hydrogen bonding. Common solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, etc. The compounds described herein can be prepared, for example, in crystalline form and can be solvated. Suitable solvates include pharmaceutically acceptable solvates and further include stoichiometric and non-stoichiometric solvates. In some cases, the solvate will be separable, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. "Solvent" includes solvates in solution and separable solvates. Representative solvates include hydrates, ethanolates, and methanolates.

[0078] The term "hydrate" refers to a compound that is bound to water. Typically, it is determined by the ratio of the number of water molecules contained in the hydrate to the number of molecules of the compound in the hydrate. Therefore, a hydrate of a compound can be represented, for example, by the general formula R·xH₂O, where R is the compound and x is a number greater than 0. A given compound can form more than one type of hydrate, including, for example, monohydrates (x is 1), lower hydrates (x is a number greater than 0 and less than 1, e.g., hemihydrates (R·0.5H₂O)), and polyhydrates (x is a number greater than 1, e.g., dihydrates (R·2H₂O) and hexahydrates (R·6H₂O)).

[0079] The compounds of this invention can be in amorphous or crystalline forms (crystalline or polymorphic). Furthermore, the component compounds of this invention can exist in one or more crystalline forms. Therefore, this invention encompasses all amorphous or crystalline forms of the component compounds of this invention within its scope. The term "polymorph" refers to the crystalline form of a compound (or its salts, hydrates, or solvates) with a specific crystal packing arrangement. All polymorphs have the same elemental composition. Different crystalline forms typically have different X-ray diffraction patterns, infrared spectra, melting points, densities, hardness, crystal shapes, photoelectric properties, stability, and solubility. Recrystallization solvents, crystallization rates, storage temperatures, and other factors can lead to the dominance of one crystalline form. Various polymorphs of the compounds can be prepared by crystallization under different conditions.

[0080] Furthermore, prodrugs are also included in the context of this invention. As used herein, the term "prodrug" refers to a compound which is converted in vivo, for example, by hydrolysis in the blood, into its active form having a medical effect. Pharmaceutically acceptable prodrugs are described in T. Higuchi and V. Stella, Prodrugs as Novel Delivery Systems, ACSSymposium Series, Vol. 14; Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987; and D. Fleisher, S. Ramon, and H. Barbra, "Improved oral drug delivery: solubility limitations overcome by the use of prodrugs," Advanced Drug Delivery Reviews (1996) 19(2) 115-130, each of which is incorporated herein by reference.

[0081] A prodrug is any covalently bonded compound of the present invention that, when administered to a subject, releases the parent compound in vivo. Prodrugs are typically prepared by modifying functional groups in a manner that allows the modification to produce the parent compound through conventional procedures or by in vivo cleavage. Prodrugs include, for example, compounds of the present invention in which a hydroxyl, amino, or thiol group is bonded to any group, which, when administered to a subject, can cleave to form a hydroxyl, amino, or thiol group. Thus, representative examples of prodrugs include (but are not limited to) acetate / amide, formate / amide, and benzoate / amide derivatives of formula (I) with hydroxyl, thiol, and amino functional groups. Additionally, in the case of carboxylic acids (-C(O)OH), esters, such as methyl esters, ethyl esters, etc., can be used. The ester itself may be active and / or hydrolyzable under in vivo conditions. Suitable pharmaceutically acceptable in vivo hydrolyzable ester groups include those groups that readily decompose in the body to release the parent acid or its salt.

[0082] In this application, the term "pharmaceutical composition" generally refers to a mixture containing one or more of the compounds described in this application or their physiologically / pharmaceutical-grade salts or prodrugs, along with other chemical components, such as physiologically / pharmaceutical-grade carriers and excipients. Pharmaceutical compositions can facilitate administration to an organism, promote the absorption of the active ingredient, and thereby exert its biological activity. Conventional methods for preparing pharmaceutical compositions are described in the art.

[0083] In this application, the term "pharmaceutically acceptable carrier" generally refers to a carrier for administering therapeutic agents, such as antibodies or peptides, genes, and other therapeutic agents. This term refers to any pharmaceutical carrier that does not itself induce the production of antibodies harmful to the individual receiving the composition and can be administered without causing excessive toxicity. For example, a pharmaceutically acceptable carrier can be distinguished from a nucleic acid vector used in genetic engineering to contain genes. Suitable carriers can be large, slowly metabolized macromolecules, such as proteins, polysaccharides, polylactic acid, polyglycolic acid, polyamino acids, amino acid copolymers, lipid aggregates, and inactivated viral particles. These carriers are well known to those skilled in the art. Pharmaceutically acceptable carriers in therapeutic compositions may include liquids such as water, saline, glycerol, and ethanol. These carriers may also contain excipients such as wetting agents or emulsifiers, pH buffers, etc.

[0084] In this application, the term "effective amount" generally refers to the amount of a therapeutic agent that treats, alleviates, or prevents a target disease or condition, or the amount that exhibits a detectable therapeutic or preventative effect. The precise effective amount for a given subject depends on that subject's body size and health status, the nature and severity of the condition, and the choice of the therapeutic agent and / or combination of therapeutic agents administered. Therefore, it is useless to pre-specify an accurate effective amount. However, for a given condition, the effective amount can be determined using routine laboratory methods, and is readily apparent to a clinician.

[0085] The term "subject" includes both mammals and non-mammals. Examples of mammals include, but are not limited to, any member of the class Mammalia: humans, non-human primates such as chimpanzees and other apes and monkeys; farm animals such as cattle, horses, sheep, goats, and pigs; domesticated animals such as rabbits, dogs, and cats; laboratory animals, including rodents such as rats, mice, and guinea pigs, and including unborn (in utero) mammals. Examples of non-mammals include, but are not limited to, birds and fish.

[0086] The term "subject" includes confirmed subjects, but the "subject" does not need to have any special status in relation to the hospital, clinic, or research facility (such as being a confirmed patient, research participant, etc.).

[0087] As used herein, the term "endogenous substance" refers to a product or intermediate that is already present in the body or is formed during metabolism. In some embodiments of this application, the endogenous substance is selected from amino acids and vitamins.

[0088] As used herein, the term "derivative" refers to another compound formed when a hydrogen atom or group of atoms in a compound is replaced by another atom or group of atoms. For example, -C(=O)OH in a compound is replaced by -CO2R. aa -C(=O)N(R) bb)2、-C(=O)NR bb SO2R aa -C(=O)SR aa Substitution; -C(=O)NH2 is replaced by -C(=O)OH, -CO2Ra a -C(=O)N(R) bb )2、-C(=O)NR bb SO2R aa -C(=O)SR aa The other compounds formed by substitution.

[0089] In this application, the term "amino acid" refers to the basic structural unit that makes up proteins and is the basis for later protein modifications in organisms. There are a total of 20 naturally occurring amino acids. In addition to these basic amino acids, organisms can synthesize derived amino acid types such as hydroxyproline and hydroxylysine. In fireflies, even D-type amino acids are synthesized. Naturally occurring amino acids are generally L-type, but this invention also includes D-type amino acids. The amino acids used in this invention are shown in the table below:

[0090] In this application, the term "vitamin" refers to a class of organic substances essential for maintaining human life. Vitamins can be classified into water-soluble and fat-soluble vitamins based on their solubility. In a preferred embodiment of this application, the vitamins are those that can be prepared into corresponding esters or amide derivatives through a condensation reaction with phenylbutyric acid and its derivatives, such as vitamin A, vitamin E, and vitamin D.

[0091] Vitamin A includes A1 and A2. Vitamin A1 is retinol, and vitamin A2 is 3-dehydroretinol.

[0092] Vitamin E, also known as tocopherol or gestational phenol, is a collective term for fat-soluble vitamins such as α, β, γ and δ-tocopherols and α, β, γ and δ-tocotrienols.

[0093] Vitamin D is a cyclopentane-phenylene oxide compound, a group of molecules with identical A, B, C, and D ring structures but different side chains. The structures of the A, B, C, and D rings are derived from the cyclopentane-phenylene oxide ring structure of steroids. Vitamin D exists in various forms, including D2, D3, D4, D5, D6, and D7, depending on the structure of its side chain. Detailed Implementation Plan

[0094] compound

[0095] In this document, “compound of the present invention” refers to a compound of formula (I) below, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, or a pharmaceutically acceptable salt thereof.

[0096] In one aspect, the present invention provides a compound of formula (I), or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, or a pharmaceutically acceptable salt thereof:

[0097] The variables are defined as described in this paper.

[0098] A

[0099] In one implementation, A is O. In another implementation, A is S.

[0100] B and R #

[0101] In one implementation, B is O. In another implementation, B is S. In yet another implementation, B is NR. # .

[0102] In one implementation, R # For H. In another implementation, R # C 1-6 Alkyl group. In another embodiment, R # C 2-6 Alkenyl. In another embodiment, R # C 2-6 Alkyne group. In another embodiment, R # C 3-10 Carbocyclic group. In another embodiment, R # It is a 3-10 membered heterocyclic group. In another embodiment, R # C 6-10 Aryl. In another embodiment, R # It consists of 5-10 heteroaryl compounds.

[0103] R 1

[0104] In one implementation, R 1 H is provided that A and B are not both O at the same time. In another implementation, R 1 C 1-20 Alkyl group. In another embodiment, R 1 C 2-20 Alkenyl. In another embodiment, R 1 C 2-20 Alkyne group. In another embodiment, R1 C 3-10 Carbocyclic group. In another embodiment, R 1 It is a 3-10 membered heterocyclic group. In another embodiment, R 1 C 6-10 Aryl. In another embodiment, R 1 It is a 5-10 membered heteroaryl group. The above groups are optionally substituted by 1, 2, 3, 4 or 5 R's.

[0105] R'

[0106] In one embodiment, each R' is independently a halogen. In another embodiment, each R' is independently -CN. In another embodiment, each R' is independently -NO2. In another embodiment, each R' is independently -N3. In another embodiment, each R' is independently -SO2H. In another embodiment, each R' is independently -SO3H. In another embodiment, each R' is independently -OH. In another embodiment, each R' is independently -OR. a In another implementation, each R' is independently -ON(R b 2. In another implementation, each R' is independently -N(R b 2. In another implementation, each R' is independently -N(R b )3 + X - In another implementation, each R' is independently -N(OR) c )R b In another implementation, each R' is independently -SH. In another implementation, each R' is independently -SR. a In another implementation, each R' is independently -SSR c In another implementation, each R' is independently -C(=O)R a In another embodiment, each R' is independently -CO2H. In another embodiment, each R' is independently -CHO. In another embodiment, each R' is independently -C(OR) c 2. In another implementation, each R' is independently -CO2R a In another implementation, each R' is independently -OC (=O)R. a In another implementation, each R' is independently -OCO2R. a In another implementation, each R' is independently -C(=O)N(R). b2. In another implementation, each R' is independently -OC(=O)N(R b 2. In another implementation, each R' is independently -NR b C(=O)R a In another implementation, each R' is independently -NR. b CO2R a In another implementation, each R' is independently -NR. b C(=O)N(R b 2. In another implementation, each R' is independently -C (=NR) b )R a In another implementation, each R' is independently -C (= NR) b OR a In another implementation, each R' is independently -OC (=NR) b )R a In another implementation, each R' is independently -OC (=NR) b OR a In another implementation, each R' is independently -C (= NR) b )N(R b 2. In another implementation, each R' is independently -OC (=NR) b )N(R b 2. In another implementation, each R' is independently -NR b C(=NR b )N(R b 2. In another implementation, each R' is independently -C(=O)NR b SO2R a In another implementation, each R' is independently -NR. b SO2R a In another implementation, each R' is independently -SO2N(R b 2. In another implementation, each R' is independently -SO2R a In another implementation, each R' is independently -SO2OR a In another implementation, each R' is independently -OSO2R. a In another implementation, each R' is independently -S(=O)R a In another implementation, each R' is independently -OS (=O)R. a In another implementation, each R' is independently -Si(R a3. In another implementation, each R' is independently -OSi(R a 3. In another implementation, each R' is independently -C(=S)N(R) b 2. In another implementation, each R' is independently -C(=O)SR a In another implementation, each R' is independently -C(=S)SR a In another implementation, each R' is independently -SC (=S)SR a In another implementation, each R' is independently -SC (=O)SR a In another implementation, each R' is independently -OC (=O)SR a In another implementation, each R' is independently -SC(=O)OR a In another implementation, each R' is independently -SC(=O)R a In another implementation, each R' is independently -P(=O)2R a In another implementation, each R' is independently -OP(=O)2R a In another implementation, each R' is independently -P (=O)(R a )2. In another implementation, each R' is independently -OP (=O)(R a 2. In another implementation, each R' is independently -OP (=O)(OR) c 2. In another implementation, each R' is independently -P(=O)2N(R b 2. In another implementation, each R' is independently -OP(=O)2N(R b )2. In another implementation, each R' is independently -P (=O)(NR) b )2. In another implementation, each R' is independently -OP (=O)(NR) b 2. In another implementation, each R' is independently -NR b P(=O)(OR c 2. In another implementation, each R' is independently -NR b P(=O)(NR b 2. In another implementation, each R' is independently -P(R c 2. In another implementation, each R' is independently -P(R c 3. In another implementation, each R' is independently -OP(R c2. In another implementation, each R' is independently -OP(R c 3. In another implementation, each R' is independently -B(R a 2. In another implementation, each R' is independently -B(OR c 2. In another implementation, each R' is independently -BR a (OR c In another implementation, each R' is independently C. 1-6 Alkyl group. In another embodiment, each R' is independently C. 1-6 Halogenated alkyl group. In another embodiment, each R' is independently C. 2-6 Alkenyl. In another embodiment, each R' is independently C. 2-6 Alkyne group. In another embodiment, each R' is independently C. 3-10 Carbocyclic group. In another embodiment, each R' is independently a 3-10 membered heterocyclic group. In another embodiment, each R' is independently a C 6-10 Aryl. In another embodiment, each R' is independently a 5-10 membered heteroaryl group. In another embodiment, each R' is independently =0. In another embodiment, each R' is independently =S. In another embodiment, each R' is independently =NN(R b 2. In another implementation, each R' is independently = NNR b C(=O)R a In another implementation, each R' is independently = NNR. b C(=O)OR a In another implementation, each R' is independently = NNR. b S(=O)2R a In another implementation, each R' is independently equal to NR. b In another implementation, each R' is independently = NOR c The C mentioned therein 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups are optionally replaced by 1, 2, 3 or 4 R*.

[0107] In another embodiment, two R' atoms on non-adjacent atoms are connected to form C. 1-6 Alkylene. In another embodiment, two R' atoms on non-adjacent atoms are linked to form C.2-6 Alkenyl group. In another embodiment, two R' atoms on non-adjacent atoms are linked to form C. 2-6 Ethyne group. The above group may optionally be substituted with 1, 2, 3, or 4 R* groups;

[0108] In another embodiment, two R' atoms on adjacent atoms together with the atoms they are connected to form C. 3-8 In another embodiment of the carbocyclic group, the two R's on adjacent atoms together with the atoms they are attached to form a 3-8 membered heterocyclic group. Optionally, the aforementioned group is replaced by 1, 2, 3, or 4 R*s.

[0109] In another embodiment, the two R's on the same carbon atom together with that carbon atom form C. 3-8 A carbocyclic group or a 3-8 membered heterocyclic group. The above groups may optionally be substituted by 1, 2, 3 or 4 R*.

[0110] R*

[0111] In one embodiment, each R* is independently a halogen. In another embodiment, each R* is independently -CN. In another embodiment, each R* is independently -NO2. In another embodiment, each R* is independently -N3. In another embodiment, each R* is independently -SO2H. In another embodiment, each R* is independently -SO3H. In another embodiment, each R* is independently -OH. In another embodiment, each R* is independently -OR. a In another implementation, each R* is independently -ON(R b 2. In another implementation, each R* is independently -N(R b 2. In another implementation, each R* is independently -N(R b )3 + X - In another implementation, each R* is independently -N(OR) c )R b In another implementation, each R* is independently -SH. In another implementation, each R* is independently -SR. a In another implementation, each R* is independently -SSR. c In another implementation, each R* is independently -C(=O)R. a In another embodiment, each R* is independently -CO2H. In another embodiment, each R* is independently -CHO. In another embodiment, each R* is independently -C(OR) c2. In another implementation, each R* is independently -CO2R. a In another implementation, each R* is independently -OC (=O)R. a In another implementation, each R* is independently -OCO2R. a In another implementation, each R* is independently -C(=O)N(R). b 2. In another implementation, each R* is independently -OC(=O)N(R) b 2. In another implementation, each R* is independently -NR. b C(=O)R a In another implementation, each R* is independently -NR. b CO2R a In another implementation, each R* is independently -NR. b C(=O)N(R b 2. In another implementation, each R* is independently -C(=NR) b )R a In another implementation, each R* is independently -C (= NR) b OR a In another implementation, each R* is independently -OC (= NR) b )R a In another implementation, each R* is independently -OC (= NR) b OR a In another implementation, each R* is independently -C (= NR) b )N(R b 2. In another implementation, each R* is independently -OC (=NR) b )N(R b 2. In another implementation, each R* is independently -NR. b C(=NR b )N(R b 2. In another implementation, each R* is independently -C(=O)NR b SO2R a In another implementation, each R* is independently -NR. b SO2R a In another implementation, each R* is independently -SO2N(R b 2. In another implementation, each R* is independently -SO2R. a In another implementation, each R* is independently -SO2OR. aIn another implementation, each R* is independently -OSO2R. a In another implementation, each R* is independently -S(=O)R. a In another implementation, each R* is independently -OS(=O)R. a In another implementation, each R* is independently -Si(R a 3. In another implementation, each R* is independently -OSi(R a 3. In another implementation, each R* is independently -C(=S)N(R) b 2. In another implementation, each R* is independently -C(=O)SR a In another implementation, each R* is independently -C(=S)SR a In another implementation, each R* is independently -SC(=S)SR a In another implementation, each R* is independently -SC(=O)SR a In another implementation, each R* is independently -OC (=O)SR a In another implementation, each R* is independently -SC(=O)OR a In another implementation, each R* is independently -SC(=O)R. a In another implementation, each R* is independently -P(=O)2R a In another implementation, each R* is independently -OP(=O)2R a In another implementation, each R* is independently -P(=O)(R a 2. In another implementation, each R* is independently -OP (=O)(R a 2. In another implementation, each R* is independently -OP (=O)(OR) c 2. In another implementation, each R* is independently -P(=O)2N(R) b 2. In another implementation, each R* is independently -OP(=O)2N(R) b 2. In another implementation, each R* is independently -P (=O)(NR) b 2. In another implementation, each R* is independently -OP (=O)(NR) b 2. In another implementation, each R* is independently -NR. b P(=O)(OR c 2. In another implementation, each R* is independently -NR. bP(=O)(NR b 2. In another implementation, each R* is independently -P(R c 2. In another implementation, each R* is independently -P(R c 3. In another implementation, each R* is independently -OP(R c 2. In another implementation, each R* is independently -OP(R c 3. In another implementation, each R* is independently -B(R a 2. In another implementation, each R* is independently -B(OR c 2. In another implementation, each R* is independently -BR a (OR c In another implementation, each R* is independently C. 1-20 Alkyl group. In another embodiment, each R* is independently C. 1-20 Haloalkyl. In another embodiment, each R* is independently C. 2-20 Alkenyl. In another embodiment, each R* is independently C. 2-20 Alkyne group. In another embodiment, each R* is independently C. 3-10 Carbocyclic group. In another embodiment, each R* is independently a 3-10 membered heterocyclic group. In another embodiment, each R* is independently a C 6-10 Aryl. In another embodiment, each R* is independently a 5-10 membered heteroaryl group. In another embodiment, each R* is independently =0. In another embodiment, each R* is independently =S. In another embodiment, each R* is independently =NN(R b 2. In another implementation, each R* is independently = NNR. b C(=O)R a In another implementation, each R* is independently = NNR. b C(=O)OR a In another implementation, each R* is independently = NNR. b S(=O)2R a In another implementation, each R* is independently equal to NR. b In another implementation, each R* is independently = NOR. c .

[0112] R a R b and R c

[0113] In one implementation scheme, each Ra Independently for C 1-6 Alkyl group. In another embodiment, each R a Independently for C 1-6 Halogenated alkyl groups. In another embodiment, each R a Independently for C 2-6 Alkenyl. In another embodiment, each R a Independently for C 2-6 Alkyne group. In another embodiment, each R a Independently for C 3-10 Carbocyclic group. In another embodiment, each R a Independently, each R is a 3-10 member heterocyclic group. In another embodiment, each R a Independently for C 6-10 Aryl. In another embodiment, each R a Independently, it is a 5-10 member heteroaryl group. In another embodiment, the two R groups... a Groups combine to form 3-10 membered heterocyclic groups or 5-10 membered heteroaryl groups;

[0114] In one implementation scheme, each R b Independently hydrogen. In another embodiment, each R b Independently -OH. In another embodiment, each R b Independently for -OR a In another implementation, each R b Independently -N(R) c 2. In another implementation, each R b Independently for -CN. In another implementation, each R b Independently -C(=O)R a In another implementation, each R b Independently -C(=O)N(R) c )2. In another implementation, each R b Independently for -CO2R a In another implementation, each R b Independently for -SO2R a In another implementation, each R b Independently for -C (=NR) c OR a In another implementation, each R b Independently for -C (=NR) c )N(R c 2. In another implementation, each R b Independently -SO2N(R)c 2. In another implementation, each R b Independently for -SO2R c In another implementation, each R b Independently for -SO2OR c In another implementation, each R b Independently for -SOR a In another implementation, each R b Independently -C(=S)N(R) c 2. In another implementation, each R b Independently -C(=O)SR c In another implementation, each R b Independently -C(=S)SR c In another implementation, each R b Independently -P(=O)2R a In another implementation, each R b Independently -P(=O)(R) a 2. In another implementation, each R b Independently -P(=O)2N(R) c 2. In another implementation, each R b Independently for -P(=O)(NR) c 2. In another implementation, each R b Independently for C 1-6 Alkyl group. In another embodiment, each R b Independently for C 1-6 Halogenated alkyl groups. In another embodiment, each R b Independently for C 2-6 Alkenyl. In another embodiment, each R b Independently for C 2-6 Alkyne group. In another embodiment, each R b Independently for C 3-10 Carbocyclic group. In another embodiment, each R b Independently, each R is a 3-10 member heterocyclic group. In another embodiment, each R b Independently for C 6-10 Aryl. In another embodiment, each R b Independently, it is a 5-10 member heteroaryl group. In another embodiment, the two R groups... b The groups combine to form a 3-10 membered heterocyclic group. In another embodiment, two R groups... b Groups combine to form 5-10 heteroaryl groups.

[0115] In one implementation scheme, each R c Independently hydrogen. In another embodiment, each R c Independently for C 1-6 Alkyl group. In another embodiment, each R c Independently for C 1-6 Halogenated alkyl groups. In another embodiment, each R c Independently for C 2-6 Alkenyl. In another embodiment, each R c Independently for C 2-6 Alkyne group. In another embodiment, each R c Independently for C 3- 10 Carbocyclic group. In another embodiment, each R c Independently, each R is a 3-10 member heterocyclic group. In another embodiment, each R c Independently for C 6-10 Aryl. In another embodiment, each R c Independently, it is a 5-10 member heteroaryl group. In another embodiment, the two R groups... c The groups combine to form a 3-10 membered heterocyclic group. In another embodiment, two R groups... c Groups combine to form 5-10 heteroaryl groups.

[0116] X -

[0117] In one implementation, X- is F-. In another implementation, X - For Cl - In another implementation, X - For Br - In another implementation, X - I- is used. In another embodiment, X- is HSO4. - In another implementation, X - NO3 - In another implementation, X - HCO3 - In another implementation, X - For OCl4 - .

[0118] In one implementation scheme These are groups derived from natural amino acids and their derivatives, optionally substituted with 1, 2, 3, 4, or 5 R's. In one specific embodiment, for In another specific implementation plan, for In another specific implementation plan, for In another specific implementation plan, for In another specific implementation plan, for In another specific implementation plan, for In another specific implementation plan, for In another specific implementation plan, for

[0119] Preparation methods of compounds

[0120] This invention also provides a method for preparing the compound that inhibits the progression of myopia, or its pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate, wherein phenylbutyric acid is synthesized from Michaelis acid and phenylacetaldehyde, and the corresponding ester or amide derivative is prepared by condensation reaction. Additionally, the corresponding thiocarbonyl compound is obtained using Lawesson's reagent. Wherein B is O, N, or S.

[0121] Pharmaceutical Composition

[0122] In one aspect, the present invention provides a pharmaceutical composition comprising an ophthalmologically active compound of formula I as claimed in claim 1, or a pharmaceutically acceptable salt, isotope variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate as an active ingredient, and pharmaceutically acceptable excipients, carriers, diluents, etc.

[0123] Pharmaceutical compositions containing the compounds of the present invention can be prepared by conventional methods, for example, as described in Remington: The Science and Practice of Pharmacy, 19th ED., 1995. The compositions can be conventional ophthalmic compositions such as solutions or suspensions. They may contain suitable solid or liquid carriers, or be formed into injectable solutions or suspensions in suitable sterile media. The compositions may contain 0.001%-20%, preferably 0.1%-10% by weight of the active compound, with the balance being pharmaceutically acceptable carriers, excipients, diluents, solvents, etc.

[0124] The ophthalmic compositions used include eye drops, suspensions, ointments, gels, emulsions, injections, intraocular implants, sustained-release formulations, and creams for use on the skin around the eyes. The ophthalmic compositions comprise a compound of formula I and one or more components selected from the group consisting of: surfactants, buffers, antioxidants or stabilizers, osmotic pressure regulators, viscosity regulators, pH regulators, preservatives, carriers, excipients, media, and water.

[0125] The present invention provides the following specific technical solutions;

[0126] Technical Solution 1. A compound of formula (I), or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, or a pharmaceutically acceptable salt thereof:

[0127] in,

[0128] A is either O or S;

[0129] B is O, S, or NR. # ;R # Selected from H, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups;

[0130] R 1 Selected from H, C 1-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, wherein the above groups are optionally substituted by 1, 2, 3, 4 or 5 R's; provided that when A is O and B is O, R's are substituted by 1, 2, 3, 4 or 5 R's. 1 Not H;

[0131] or, These are groups derived from endogenous substances and their derivatives, which are optionally replaced by 1, 2, 3, 4 or 5 R's;

[0132] Each R' is independently selected from halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR a -ON(R) b )2、-N(R b )2、-N(R b )3 + X - -N(OR) c )R b、-SH、-SR a 、-SSR c 、-C(=O)R a 、-CO2H、-CHO、-C(OR c )2、-CO2R a 、-OC(=O)R a 、-OCO2R a 、-C(=O)N(R b )2、-OC(=O)N(R b )2、-NR b C(=O)R a 、-NR b CO2R a 、-NR b C(=O)N(R b )2、-C(=NR b )R a 、-C(=NR b )OR a 、-OC(=NR b )R a 、-OC(=NR b )OR a 、-C(=NR b )N(R b )2、-OC(=NR b )N(R b )2、-NR b C(=NR b )N(R b )2、-C(=O)NR b SO2R a 、-NR b SO2R a 、-SO2N(R b )2、-SO2R a 、-SO2OR a 、-OSO2R a 、-S(=O)R a 、-OS(=O)R a 、-Si(R a )3、-OSi(R a )3、-C(=S)N(R b )2、-C(=O)SR a 、-C(=S)SR a 、-SC(=S)SR a 、-SC(=O)SR a 、-OC(=O)SR a 、-SC(=O)OR a-SC(=O)R a -P(=O)2R a -OP(=O)2R a -P(=O)(R a )2、-OP(=O)(R a )2、-OP(=O)(OR c )2、-P(=O)2N(R b )2、-OP(=O)2N(R b )2、-P(=O)(NR b )2、-OP(=O)(NR b )2、-NR b P(=O)(OR c )2、-NR b P(=O)(NR b )2、-P(R c )2、-P(R c )3、-OP(R c )2、-OP(R c )3、-B(R a 2. -B(OR) c )2、-BR a (OR c C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, =O, =S, =NN(R) b )2、=NNR b C(=O)R a =NNR b C(=O)OR a =NNR b S(=O)2R a =NR b and = NOR c Wherein C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups may be optionally replaced by 1, 2, 3 or 4 R*s;

[0133] And / or, two R' atoms on non-adjacent atoms are connected to form C. 1-6 Alkylene, C2-6 imide or C 2-6 The ynyl group, wherein the above group is optionally substituted by 1, 2, 3 or 4 R*;

[0134] And / or, two R's on adjacent atoms together with the atoms they are connected to form C. 3-8 A carbocyclic group or a 3-8 membered heterocyclic group, wherein the above groups are optionally substituted by 1, 2, 3 or 4 R*;

[0135] And / or, two R's on the same carbon atom together with that carbon atom form C. 3-8 A carbocyclic group or a 3-8 membered heterocyclic group, wherein the above groups are optionally substituted by 1, 2, 3 or 4 R*;

[0136] Each R* is independently selected from halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR a -ON(R) b )2、-N(R b )2、-N(R b )3 + X - -N(OR) c )R b -SH, -SR a -SSR c -C(=O)R a -CO2H, -CHO, -C(OR) c )2、-CO2R a -OC(=O)R a -OCO2R a -C(=O)N(R) b )2、-OC(=O)N(R b )2、-NR b C(=O)R a -NR b CO2R a -NR b C(=O)N(R b )2、-C(=NR b )R a -C(=NR) b OR a -OC(=NR) b )R a -OC(=NR) b OR a -C(=NR) b )N(R b )2、-OC(=NR b )N(R b)2, -NR b C(=NR b )N(R b )2, -C(=O)NR b SO2R a , -NR b SO2R a , -SO2N(R b )2, -SO2R a , -SO2OR a , -OSO2R a , -S(=O)R a , -OS(=O)R a , -Si(R a )3, -OSi(R a )3, -C(=S)N(R b )2, -C(=O)SR a , -C(=S)SR a , -SC(=S)SR a , -SC(=O)SR a , -OC(=O)SR a , -SC(=O)OR a , -SC(=O)R a , -P(=O)2R a , -OP(=O)2R a , -P(=O)(R a )2, -OP(=O)(R a )2, -OP(=O)(OR c )2, -P(=O)2N(R b )2, -OP(=O)2N(R b )2, -P(=O)(NR b )2, -OP(=O)(NR b )2, -NR b P(=O)(OR c )2, -NR b P(=O)(NR b )2, -P(R c )2, -P(R c )3, -OP(R[[ID=7"]] c )2, -OP(R c )3, -B(R a [[ID="]] c )2, -BR a (OR c ), C 1-20 alkyl, C 1-20 haloalkyl, C 2-20 alkenyl, C​2-20 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, =O, =S, =NN(R) b )2、=NNR b C(=O)R a =NNR b C(=O)OR a =NNR b S(=O)2R a =NR b and = NOR c ;

[0137] Each R a Selected independently from C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl and 5-10 heteroaryl, or two R a Groups combine to form 3-10 membered heterocyclic groups or 5-10 membered heteroaryl groups;

[0138] Each R b Independently selected from hydrogen, -OH, -OR a -N(R) c )2、-CN、-C(=O)R a -C(=O)N(R) c )2、-CO2R a -SO2R a -C(=NR) c OR a -C(=NR) c )N(R c )2、-SO2N(R c )2、-SO2R c -SO2OR c -SOR a -C(=S)N(R) c )2、-C(=O)SR c -C(=S)SR c -P(=O)2R a -P(=O)(R a )2、-P(=O)2N(R c )2、-P(=O)(NR c 2. C 1-6 Alkyl, C 1-6 Haloalkyl, C2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl and 5-10 heteroaryl, or two R b Groups combine to form 3-10 membered heterocyclic groups or 5-10 membered heteroaryl groups;

[0139] Each R c Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl and 5-10 heteroaryl, or two R c Groups combine to form 3-10 membered heterocyclic groups or 5-10 membered heteroaryl groups;

[0140] X - Selected from F - Cl - ,Br - I - HSO4 - NO3 - HCO3 - and OCl4 - .

[0141] 2. The compound described in technical solution 1, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein A is O.

[0142] 3. The compound described in technical solution 1 or 2, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein B is O, S or NH.

[0143] 4. The compound of any one of technical solutions 1-3, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein R 1 Selected from C 1-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, wherein the above groups are optionally substituted by 1, 2, 3, 4 or 5 R's;

[0144] Preferably, R 1Selected from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl and 5-10 heteroaryl groups, wherein the above groups are optionally substituted by 1, 2, 3, 4 or 5 R's;

[0145] More preferably, R 1 Selected from C 2-4 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne and phenyl, wherein the above groups are optionally substituted by 1, 2, 3, 4 or 5 R's.

[0146] 5. The compound of any one of technical solutions 1-4, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein each R' is independently selected from halogens, -CN, -NO2, -SO2H, -OH, -OR a -N(R) b )2、-SH、-SR a -C(=O)R a -CO2H, -CHO, -C(OR) c )2、-CO2R a -OC(=O)R a -OCO2R a -C(=O)N(R) b )2、-OC(=O)N(R b )2、-NR b C(=O)R a -NR b CO2R a -NR b C(=O)N(R b )2、-C(=O)NR b SO2R a -NR b SO2R a -SO2N(R) b )2、-SO2R a -SO2OR a -OSO2R a -S(=O)R a -OS(=O)R a -C(=S)N(R) b )2、-C(=O)SR a -C(=S)SR a -SC(=S)SR a -SC(=O)SR a-OC(=O)SR a -SC(=O)OR a -SC(=O)R a C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl, 5-10 heteroaryl, =O and =S, wherein the C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups may be optionally replaced by 1, 2, 3 or 4 R*s;

[0147] And / or, two R's on adjacent atoms together with the atoms they are connected to form C. 3-8 Carbocyclic group, 3-8 membered heterocyclic group, wherein the above groups are optionally substituted by 1, 2, 3 or 4 R*;

[0148] And / or, two R's on the same carbon atom together with that carbon atom form C. 3-8 Carbocyclic group, 3-8 membered heterocyclic group, wherein the above groups are optionally substituted by 1, 2, 3 or 4 R*;

[0149] Each R* is independently selected from halogens, C 1-20 Alkyl, C 1-20 Haloalkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-10 Carbocyclic group and C 6- 10 Aryl.

[0150] 6. The compound of any one of technical solutions 1-5, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein each R' is independently selected from halogens, -CN, -OH, -CO2H, -NR. b C(=O)R a C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl and 5-10 heteroaryl groups;

[0151] And / or, two R's on adjacent atoms together with the atoms they are connected to form C. 3-8Carbocyclic groups, 3-8 membered heterocyclic groups, which are optionally substituted by 1, 2, 3 or 4 R* groups;

[0152] Each R* is independently selected from C 1-20 alkyl;

[0153] Each R a Selected independently from C 1-6 alkyl;

[0154] Each R b Independently selected from hydrogen and C 1-6 alkyl.

[0155] 7. The compound described in technical solution 1, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein, The group is derived from an endogenous substance and its derivatives, which is optionally replaced by 1, 2, 3, 4 or 5 R's, said endogenous substance being selected from amino acids and vitamins.

[0156] 8. The compound described in technical solution 7, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein, The group is derived from natural amino acids and their derivatives, and is optionally replaced by 1, 2, 3, 4 or 5 R' groups, wherein the natural amino acid is selected from:

[0157] Alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro), phenylalanine (Phe), tryptophan (Trp), methionine (Met), glycine (Gly), serine (Ser), threonine (Thr), cysteine ​​(Cys), tyrosine (Tyr), asparagine (Asn), glutamine (Gln), lysine (Lys), arginine (Arg), histidine (His), aspartic acid (Asp), and glutamic acid (Glu).

[0158] 9. The compound described in technical solution 8, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein, These are groups derived from natural amino acids and their derivatives, optionally surrounded by 1, 2, 3, or 4 R groups. A * Replaces, where,

[0159] The natural amino acids are selected from: alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro), phenylalanine (Phe), tryptophan (Trp), methionine (Met), glycine (Gly), serine (Ser), threonine (Thr), cysteine ​​(Cys), tyrosine (Tyr), asparagine (Asn), glutamine (Gln), lysine (Lys), arginine (Arg), histidine (His), aspartic acid (Asp), and glutamic acid (Glu);

[0160] Each R A *Independently selected from halogens, -CN, -NO2, -SO2H, -OH, -OR a -N(R) b )2、-SH、-SR a -C(=O)R a -CO2H, -CHO, -C(OR) c )2、-CO2R a -OC(=O)R a -OCO2R a -C(=O)N(R) b )2、-OC(=O)N(R b )2、-NR b C(=O)R a -NR b CO2R a -NR b C(=O)N(R b )2、-C(=O)NR b SO2R a -NR b SO2R a -SO2N(R) b )2、-SO2R a -SO2OR a -OSO2R a -S(=O)R a -OS(=O)R a -C(=S)N(R) b )2、-C(=O)SR a -C(=S)SR a -SC(=S)SR a -SC(=O)SR a -OC(=O)SR a -SC(=O)OR a -SC(=O)R a C 1-6 Alkyl, C1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl, 5-10 heteroaryl, =O and =S; preferably, -C(=O)R a More preferably, -C(=O)CH3.

[0161] 10. The compound described in technical solution 8 or 9, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein the linkage of the group derived from natural amino acids and their derivatives is on the side chain of the amino acid; preferably, the amino acid is selected from tryptophan (Trp), serine (Ser), threonine (Thr), cysteine ​​(Cys), tyrosine (Tyr), lysine (Lys) and histidine (His), more preferably serine (Ser), threonine (Thr), cysteine ​​(Cys) and tyrosine (Tyr), more preferably serine (Ser), threonine (Thr) and cysteine ​​(Cys), and most preferably cysteine ​​(Cys).

[0162] 11. The compound described in technical solution 8 or 9, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein the group derived from natural amino acids and their derivatives is attached to the amino group on the main chain.

[0163] 12. The compound of any one of technical solutions 8-11, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein the derivative of the natural amino acid is a compound formed by the following derivatization of the natural amino acid:

[0164] -C(=O)OH is reacted with -C(=O)OR a -C(=O)N(R) b )2、-C(=O)NR b SO2R a -C(=O)SR a Substitute;

[0165] And / or, -C(=O)NH2 is replaced by -C(=O)OH, -C(=O)OR a -C(=O)N(R) b )2、-C(=O)NR b SO2R a -C(=O)SR a Substitute;

[0166] R a and R b As defined in technical solution 1.

[0167] 13. The compound described in technical solution 7 or 8, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein, for

[0168] 14. The compound described in technical solution 7, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein, The group is a group derived from vitamin A and its derivatives, a group derived from vitamin E and its derivatives, or a group derived from vitamin D and its derivatives, which may optionally be replaced by 1, 2, 3, 4 or 5 R's.

[0169] 15. The compound described in technical solution 14, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein, for

[0170] 16. The compound described in technical solution 1, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein the compound is selected from...

[0171] 17. A pharmaceutical composition comprising any one of the compounds described in claims 1-16, or isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates thereof, or pharmaceutically acceptable salts thereof, and pharmaceutically acceptable excipients.

[0172] 18. Use of any compound, or isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, or pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 17, in the preparation of a medicament for inhibiting the progression of myopia.

[0173] 19. The compound of any one of claims 1-16, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, or the pharmaceutical composition of claim 17, for inhibiting the progression of myopia.

[0174] 20. A method for inhibiting myopia progression in a subject, comprising administering to the subject any of the compounds described in any of technical solutions 1-16, or isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates thereof, or pharmaceutically acceptable salts thereof, or the pharmaceutical composition described in technical solution 17.

[0175] Example

[0176] To make the technical solution of this application clearer and more explicit, the following embodiments are provided for further detailed explanation. These embodiments are only used to illustrate specific implementation methods of this application so that those skilled in the art can understand it, but are not intended to limit the scope of protection of this application. In the specific embodiments of this application, technical means or methods not specifically described are conventional technical means or methods in the art. Unless otherwise specified, the materials and reagents used in the embodiments are commercially available.

[0177] target compound 1 ¹H NMR was performed using a Bruker ARX-300 NMR spectrometer with DMSO-d6 and TMS internal standard. Mass spectrometry was performed using an Agilent 1100 quadrupole liquid chromatography-mass spectrometry system or a Bruker MicroTOF-Q high-resolution mass spectrometer. All raw materials and solvents were commercially available chemically pure or analytically pure.

[0178] intermediate

[0179] Synthesis of phenylbutyric acid

[0180] At room temperature, phenylacetaldehyde (30.00 g, 0.25 mol), Michaelis-Menten acid (43.24 g, 0.30 mol), and triethylamine (50.60 g, 0.50 mol) were added to N,N-dimethylformamide (100 mL). The mixture was stirred at room temperature for 0.5 hours. Formic acid (115.08 g, 2.50 mmol) was slowly added to the reaction mixture. The mixture was stirred at 100 °C for 10 hours. The reaction mixture was cooled to room temperature and diluted with dilute hydrochloric acid (2N, 500 mL). It was extracted with dichloromethane (2 x 200 mL). The organic phase was washed with saturated aqueous sodium hydroxide solution. The aqueous phase was adjusted to pH 2 with concentrated hydrochloric acid and extracted with ethyl acetate (2 x 300 mL). The organic layer was washed with brine (2 x 300 mL) and finally dried with anhydrous sodium sulfate (Na₂SO₄). The solution was filtered and concentrated to obtain phenylbutyric acid (28 g, 68% yield) as a yellow oil. It can be used in the next step without further purification. 1H NMR (400MHz, DMSO-d6) δ12.10(s,1H),7.31-7.25(m,2H),7.21-7.16(m,3H),2.58(dd,J=8.6,6.8Hz,2H),2.21(t,J=7.3Hz,2H),1.79(p,J=7.5Hz,2H).

[0181] Synthesis of phenylbutyryl chloride

[0182] At room temperature, phthalic acid (2.00 g, 12.20 mmol) was added to dichloromethane (20 mL). Thionyl chloride (10 mL) was slowly added dropwise. The mixture was stirred at room temperature for 3 hours. After the reaction was complete, the reaction mixture was concentrated to give phenylbutyryl chloride (2.10 g, 94% yield) as a brown oil. This product can be used in the next step without purification.

[0183] Example 1. Synthesis of ethyl 4-phenylbutyrate (1)

[0184] At room temperature, phenylbutyric acid (5.00 g, 30.45 mmol) was added to anhydrous ethanol (50 mL). Sulfuric acid (2.99 g, 30.45 mmol) was slowly added. The mixture was stirred at room temperature for 5 hours. After the reaction was complete, the mixture was concentrated and added to a saturated aqueous solution of sodium bicarbonate (NaHCO3) (100 mL). The aqueous phase was extracted with ethyl acetate (2 x 200 mL), the organic layer was washed with brine (200 mL), dried over anhydrous sodium sulfate (Na2SO4), filtered, and concentrated. Column chromatography yielded ethyl 4-phenylbutyrate (2.10 g, 36% yield) as a colorless oily liquid. 1 H NMR (400MHz, DMSO-d6) δ7.31-7.25(m,2H),7.18(m,J=6.9,2.0Hz,3H),4.05(q,J=7.1Hz,2H),2 .58(t,J=8.5,6.8Hz,2H), 2.28(t,J=7.4Hz,2H), 1.82(p,J=7.4Hz,2H), 1.17(t,J=7.1Hz,3H). HRMS(EI)m / z:193.12[M+H] + .

[0185] Example 2. Synthesis of 4-phenylbutyrylglycine (2)

[0186] Glycine (0.66 g, 8.76 mmol) was added to a mixture of acetone (12 mL) and sodium hydroxide aqueous solution (2 M, 12 mL) at room temperature. The mixture was cooled to 0 °C under a nitrogen atmosphere. Phenyloyl chloride (2 g, 10.95 mmol) was slowly added dropwise at 0 °C. After the addition was complete, the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the pH was adjusted to 2 with hydrochloric acid aqueous solution (2 N). The aqueous phase was extracted with dichloromethane (2 x 200 mL). The organic layer was washed with brine (200 mL), dried over anhydrous sodium sulfate (Na₂SO₄), filtered, and concentrated. Column chromatography yielded 4-phenylbutyrylglycine (0.50 g, 21% yield) as a yellow solid. 1 H NMR (400MHz, DMSO-d6) δ12.49(s,1H),8.13(t,J=6.0Hz,1H),7.28(m,J=7.5Hz,2H),7.23-7.12(m,3H),3.74(d,J =14.1,5.9Hz,2H),2.57(t,J=7.7Hz,2H),2.14(t,J=7.4Hz,2H),1.79(p,J=7.6Hz,2H); MS(EI)m / z:222.07[M+H] + 244.05 [M+Na] + .

[0187] Example 3. Synthesis of 2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-yl 4-phenylbutyrate (3)

[0188] Phthalic acid (4.00 g, 23 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (6.28 g, 36 mmol), N,N-dimethyl-4-pyridinylamine (0.40 g), α-tocopherol (9.44 g, 23 mmol), and 60 mL of dichloromethane were added to a 100 mL three-necked flask and stirred at room temperature for 4 hours. 40 mL of water was added to the reaction mixture, and the mixture was stirred, retaining the organic layer. The organic layer was washed once with dilute hydrochloric acid (2N, 100 mL), once with 100 mL of water, and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated to obtain the product. 1H NMR (400MHz, DMSO-d6) δ7.42-7.16(m,5H),2.66(dt,J=23.8,7.5Hz,4H),2.54(d,J=7.0Hz,2H),2.08-1.83(m,12H),1.78-1.72(m,2H),1.52-1.47 (m,2H),1.37(d,J=8.0Hz,4H),1.22(d,J=22.7Hz,10H),1.11(q,J=7.8Hz,4H),1.04(s,3H),0.82(dd,J=9.8,6.5Hz,12H).MS(EI)m / z:615.52[M+K] + .

[0189] Example 4. Synthesis of N-acetyl-S-(4-phenylbutyryl)-D-cysteine ​​(4)

[0190] At room temperature, N-acetyl-L-cysteine ​​(4.1 g, 25 mmol) was added to 50 mL of N,N-dimethylformamide, followed by potassium carbonate solid (5.2 g, 37.5 mmol). Then, phenylbutyryl chloride (6.8 g, 37.5 mmol) was added dropwise to the system. The mixture was stirred at room temperature for 3 h until the solution turned dark brown and gas was generated. After the reaction was complete, the system was transferred to water and extracted twice with 100 mL of dichloromethane, washed once with 200 mL of water and once with 100 mL of saturated salt. The organic phases were separated and dried. The solvent was then rotary evaporated to obtain the crude product. The crude product was purified by silica gel column chromatography using a 10:1 dichloromethane:methanol mixture to obtain 6.1 g of the target product, N-acetyl-S-(4-phenylbutyryl)-D-cysteine, with a yield of approximately 80%. 1 HNMR(400MHz,DMSO-d6)δ7.44-7.39(m,1H),7.28(d,J=7.2Hz,2H),7.22-7.14(m,3H),3.64(s,1H),3.59(s,2 H),3.35(s,3H),2.64-2.54(m,2H),2.31(dd,J=15.1,7.7Hz,2H),1.89-1.72(m,2H).MS(EI)m / z:307.99[MH] - .

[0191] Example 5. Synthesis of ethyl thio-4-phenylbutyrate (5)

[0192] Ethyl 4-phenylbutyrate (5 g, 26.01 mmol) was added to xylene (25 mL) at room temperature. Lawesson's reagent (12.62 g, 31.21 mmol) was added. The mixture was refluxed for 3 h. After cooling to room temperature, the precipitate was removed by filtration, and the mixture was concentrated. Column chromatography yielded a yellow oily liquid containing 1.08 g of ethyl 4-thiophenylbutyrate, in a yield of 20%. 1 H NMR (400MHz, DMSO-d6) δ7.24-7.19(m,5H),3.58(q,J=6.8Hz,2H),2.63(t,J=7.5,6.7Hz,2H),1.50-1.46(m,4H),1.23(t,J=7.3Hz,3H). HRMS(EI)m / z:209.09[M+H] + .

[0193] Example 6. Synthesis of allyl phenylbutyrate (6)

[0194] At room temperature, phenylbutyric acid (5.00 g, 30.45 mmol) was added to allyl alcohol (50 mL). Sulfuric acid (2.99 g, 30.45 mmol) was slowly added. The mixture was stirred at room temperature for 5 hours. After the reaction was complete, the mixture was concentrated and added to a saturated aqueous solution of sodium bicarbonate (NaHCO3) (100 mL). The aqueous phase was extracted with ethyl acetate (2 x 200 mL), the organic layer was washed with brine (200 mL), dried over anhydrous sodium sulfate (Na2SO4), filtered, and concentrated. Column chromatography yielded an oily liquid of allyl phenylbutyrate (2.66 g, 43% yield). 1 H NMR(400MHz,DMSO-d6)δ7.24-7.19(m,5H),6.05(m,1H),5.31-5.34(m,2H),4.69(q,J =8.5, 6.8Hz, 2H), 2.63 (t, J = 7.1Hz, 2H), 2.32 (t, J = 7.2Hz, 2H), 1.81 (t, J = 7.1Hz, 2H). MS(EI)m / z:205.32[M+H] + .

[0195] Example 7. Butylene phenylbutyrate (7)

[0196] At room temperature, phenylbutyric acid (5.00 g, 30.45 mmol) was added to acetylacetonate (50 mL). Sulfuric acid (2.99 g, 30.45 mmol) was slowly added. The mixture was stirred at room temperature for 5 hours. After the reaction was complete, the mixture was concentrated and added to a saturated aqueous solution of sodium bicarbonate (NaHCO3) (100 mL). The aqueous phase was extracted with ethyl acetate (2 x 200 mL), the organic layer was washed with brine (200 mL), dried over anhydrous sodium sulfate (Na2SO4), filtered, and concentrated. Column chromatography yielded acetylacetonate (2.24 g, 34.6% yield) as an oily liquid. 1 H NMR (400MHz, DMSO-d6) δ7.24-7.19(m,5H),4.25(t,J=6.8Hz,2H),3.06(t,J=7. 3Hz, 1H), .2.63 (t, J = 7.1Hz, 2H), 2.32 (t, J = 7.2Hz, 2H), 1.81 (t, J = 7.1Hz, 2H). MS(EI)m / z:217.51[M+H] + .

[0197] Example 8. 2-Bromoethyl-4-phenylbutyrate (8)

[0198] At room temperature, phenylbutyric acid (5.00 g, 30.45 mmol) was added to 2-bromoethanol (50 mL). Sulfuric acid (2.99 g, 30.45 mmol) was slowly added. The mixture was stirred at room temperature for 5 hours. After the reaction was complete, the mixture was concentrated and added to a saturated aqueous solution of sodium bicarbonate (NaHCO3) (100 mL). The aqueous phase was extracted with ethyl acetate (2 x 200 mL), the organic layer was washed with brine (200 mL), dried over anhydrous sodium sulfate (Na2SO4), filtered, and concentrated. Column chromatography yielded an oily liquid of 2-bromoethyl-4-phenylbutyrate (3.16 g, 38.9% yield). 1 H NMR (400MHz, DMSO-d6) δ7.22-7.17(m,5H),4.58(t,J=6.9Hz,2H),3.65(t,J=7. 3Hz, 2H), .2.66 (t, J = 7.1Hz, 2H), 2.30 (t, J = 7.2Hz, 2H), 1.83 (t, J = 7.1Hz, 2H). MS(EI)m / z:272.30[M+H] + .

[0199] Example 9. 2-Cyanoethyl-4-phenylbutyrate (9)

[0200] Phthalic acid (4.00 g, 23 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (6.28 g, 36 mmol), N,N-dimethyl-4-pyridinamide (0.40 g), 2-cyanoethanol (1.63 g, 23 mmol), and 60 mL of dichloromethane were added to a 100 mL three-necked flask and stirred at room temperature for 4 hours. 40 mL of water was added to the reaction mixture, and the mixture was stirred, retaining the organic layer. The organic layer was washed once with dilute hydrochloric acid (2N, 100 mL), once with 100 mL of water, and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated to obtain the product in 47% yield. 1 H NMR(400MHz,DMSO-d6)δ7.24-7.19(m,5H),4.45(t,J=6.9Hz,2H),2.63-2.69 (m,4H),.2.66(t,J=7.1Hz,2H),2.30(t,J=7.0Hz,2H),1.83(t,J=6.7Hz,2H). MS(EI)m / z:218.20[M+H] + .

[0201] Example 10. Phenyl 4-phenylbutyrate (10)

[0202] Phenol (0.80 g, 8.76 mmol) was added to a mixture of acetone (12 mL) and sodium hydroxide aqueous solution (2 M, 12 mL) at room temperature. The mixture was cooled to 0 °C under a nitrogen atmosphere. Phenylacetyl chloride (2 g, 10.95 mmol) was slowly added dropwise at 0 °C. After the addition was complete, the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the pH was adjusted to 2 with hydrochloric acid aqueous solution (2 N). The aqueous phase was extracted with dichloromethane (2 x 200 mL). The organic layer was washed with brine (200 mL), dried over anhydrous sodium sulfate (Na₂SO₄), and concentrated by filtration. Column chromatography yielded phenyl 4-phenylbutyrate (0.80 g, 38% yield) as an oily liquid. 1 H NMR (400MHz, DMSO-d6) δ7.45-7.37(m,3H),7.22-7.17(m,5H),7.08(d,J=6.9 Hz, 2H), 2.66 (t, J = 7.0 Hz, 2H), 2.30 (t, J = 6.9 Hz, 2H), 1.83 (t, J = 7.1 Hz, 2H). MS(EI)m / z:241.62[M+H] + .

[0203] Example 11. Pyridine-3-methyl-4-phenylbutyrate (11)

[0204] At room temperature, phenylbutyric acid (5.00 g, 30.45 mmol) was added to 3-pyridinemethanol (30 mL). Sulfuric acid (2.99 g, 30.45 mmol) was slowly added. The mixture was stirred at room temperature for 5 hours. After the reaction was complete, the mixture was concentrated and added to a saturated aqueous solution of sodium bicarbonate (NaHCO3) (50 mL). The aqueous phase was extracted with ethyl acetate (2 x 100 mL), the organic layer was washed with brine (100 mL), dried over anhydrous sodium sulfate (Na2SO4), filtered, and concentrated. Column chromatography yielded an oily liquid of pyridine-3-methyl-4-phenylbutyrate (3.22 g, 41.2% yield). 1 H NMR (400MHz, DMSO-d6) δ8.54(s,1H),8.33(d,J=6.1Hz,1H),7.88(d,J=6.4Hz,1H),7.37(t,J=6.7Hz,1H ),7.22-7.17(m,5H),5.05(s,2H),2.63(t,J=7.1Hz,2H),2.30(t,J=7.2Hz,2H),1.83(t,J=7.1Hz,2H). MS(EI)m / z:256.38[M+H] + .

[0205] Example 12. (2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexyl-1-en-1-yl)non-2,4,6,8-tetraen-1-yl p-phenylbutyrate (12)

[0206] Phthalic acid (4.00 g, 23 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (6.28 g, 36 mmol), N,N-dimethyl-4-pyridinamide (0.40 g), vitamin A (4.18 g, 23 mmol), and 60 mL of dichloromethane were added to a 100 mL three-necked flask and stirred at room temperature for 4 hours. 40 mL of water was added to the reaction mixture, and the mixture was stirred, retaining the organic layer. The organic layer was washed once with dilute hydrochloric acid (2N, 100 mL), once with 100 mL of water, and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated to obtain the product. 1H NMR(400MHz,DMSO-d6)δ7.42-7.19(m,5H),6.51(s,4H),2.54(d,J=7.0Hz,2H), 2.08-1.83(m,12H),1.78-1.72(m,2H),1.52-1.47(m,2H),6.23(s,1H),5.63(t ,J=7.5,6.8Hz,1H),4.69(d,J=6.9Hz,2H),2.63(t,J=7.7Hz,2H),2.32(t,J=7. 4Hz,2H),2.12(s,3H)1.96-1.53(m,11H).1.01(s,6H)MS(EI)m / z:433.71[M+H] + .

[0207] Example 13. (4-Phenylacetyl)-D-valine (13)

[0208] At room temperature, valine (0.42 g, 8.76 mmol) was added to a mixture of acetone (12 mL) and sodium hydroxide aqueous solution (2 M, 12 mL). The mixture was cooled to 0 °C under a nitrogen atmosphere. Phenylenoyl chloride (2 g, 10.95 mmol) was slowly added dropwise at 0 °C. After the addition was complete, the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the pH was adjusted to 2 with hydrochloric acid aqueous solution (2 N). The aqueous phase was extracted with dichloromethane (2 x 200 mL). The organic layer was washed with brine (200 mL), dried over anhydrous sodium sulfate (Na₂SO₄), filtered, and concentrated. Column chromatography yielded 0.60 g of (4-phenylbutyryl)-D-valine as a yellow solid. 1 H NMR (400MHz, DMSO-d6) δ8.32 (s, 1H), 7.23-7.12 (m, 3H), 4.25 (d, J = 6.1Hz, 1H), 2.63 (t,J=7.7Hz,2H),2.05-1.70(t,J=7.4Hz,5H),0.98(s,6H); MS(EI)m / z:264.43[M+H] + .

[0209] Example 14. (4-Phenylacetyl)-D-Aspartic Acid (14)

[0210] Aspartic acid (0.37 g, 8.76 mmol) was added to a mixture of acetone (12 mL) and sodium hydroxide aqueous solution (2 M, 12 mL) at room temperature. The mixture was cooled to 0 °C under a nitrogen atmosphere. Phenylenoyl chloride (2 g, 10.95 mmol) was slowly added dropwise at 0 °C. After the addition was complete, the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the pH was adjusted to 2 with hydrochloric acid aqueous solution (2 N). The aqueous phase was extracted with dichloromethane (2 x 200 mL). The organic layer was washed with brine (200 mL), dried over anhydrous sodium sulfate (Na₂SO₄), and concentrated by filtration. Column chromatography yielded 0.48 g of solid 2-(4-phenylbutyramide)malonic acid. 1 H NMR(400MHz,DMSO-d6)δ13.82(s,2H),8.65(s,1H),7.23-7.12(m,5H),5.15(s,1H),2. 90-2.57(m,4H),2.28(t,J=7.7Hz,2H),1.70(t,J=7.6Hz,2H); MS(EI)m / z:279.36[M+H] + .

[0211] Example 15. (4-Phenylacetyl)-D-phenylpropionic acid (15)

[0212] Phenylalanine (0.3 g, 8.76 mmol) was added to a mixture of acetone (12 mL) and sodium hydroxide aqueous solution (2 M, 12 mL) at room temperature. The mixture was cooled to 0 °C under a nitrogen atmosphere. Phenylacetyl chloride (2 g, 10.95 mmol) was slowly added dropwise at 0 °C. After the addition was complete, the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the pH was adjusted to 2 with hydrochloric acid aqueous solution (2 N). The aqueous phase was extracted with dichloromethane (2 x 200 mL). The organic layer was washed with brine (200 mL), dried over anhydrous sodium sulfate (Na₂SO₄), filtered, and concentrated. Column chromatography yielded 0.66 g of (4-phenylbutyryl)-D-phenylpropionic acid solid. 1 H NMR (400MHz, DMSO-d6) δ12.89(s,1H),8.35(s,1H),7.24-7.14(m,10H),4.72(t,J=14.1,5.9Hz,1H),3.12- 2.87(m,2H),2.63(t,J=7.4Hz,2H),2.05(t,J=7.4Hz,2H),1.70(t,J=7.6Hz,2H); MS(EI)m / z:312.34[M+H] + .

[0213] Example 16. (4-Phenylacetyl)-D-Serine (16)

[0214] At room temperature, D-serine (0.47 g, 8.76 mmol) was added to a mixture of acetone (12 mL) and sodium hydroxide aqueous solution (2 M, 12 mL). The mixture was cooled to 0 °C under a nitrogen atmosphere. Phenylenoyl chloride (2 g, 10.95 mmol) was slowly added dropwise at 0 °C. After the addition was complete, the mixture was stirred at room temperature for 2 hours. After the reaction was complete, the pH was adjusted to 2 with hydrochloric acid aqueous solution (2 N). The aqueous phase was extracted with dichloromethane (2 x 200 mL). The organic layer was washed with brine (200 mL), dried over anhydrous sodium sulfate (Na₂SO₄), filtered, and concentrated. Column chromatography yielded 0.52 g of (4-phenylbutyryl)-D-serine solid. 1 H NMR(400MHz,DMSO-d6)δ12.39(s,1H),8.23(s,1H),7.23-7.12(m,5H),4.94(s,1H),4.14-3.89(m, 2H),2.60(t,J=7.7Hz,2H),2.39(t,J=7.4Hz,2H),1.76(p,J=7.6Hz,2H); MS(EI)m / z:252.42[M+H] + .

[0215] Measurement Example 1. Study on changes in refractive power and axial length of the compound

[0216] Compounds (1)-(16) and atropine sulfate were prepared into eye drops, with water as the solvent and sodium hydrogen phosphate as the buffer salt, and the pH was adjusted to 7. The concentration of atropine sulfate was 2%, and the other compounds were prepared to the same concentration of 0.25%.

[0217] The drugs were administered via eye drops once daily. A blank control group (without any treatment, receiving the same amount of water each time) and a model group (after visual deprivation in the right eye, receiving the same amount of excipient solution each time) were used to measure the refractive error and axial length of the experimental animals before and 21 days after drug administration (corresponding compound formulation) using the corresponding detection methods.

[0218] The final calculation of the difference in axial length between the experimental and control eyes was given as the mean ± SD value for each group of animals. Measurement methods: Refractive error: detected by a strip retinoscope; Axial length change: detected by anterior segment OCT. Experimental instruments: Strip retinoscope: YZ24; Anterior segment OCT: CASIA2

[0219] Experimental results showed that, compared with the model group, compounds (1)-(16) all had a certain inhibitory effect on changes in refractive power and axial elongation in guinea pigs. However, due to the poor water solubility of some compounds, the prepared eye drops exhibited stratification (compounds (1), (3), (5)-(12)). Although the solution was shaken before administration, uneven concentrations still existed. Therefore, a new formulation was prepared, and tylosap was added to the above formulation to ensure uniform mixing of the compounds with water. The concentration remained at 0.25%. The solution was administered again according to the above experimental method, and the results are shown in the table below:

[0220] Table 1. Difference between the refractive power of the experimental eye and the refractive power before drug administration (D, mean ± SD), where N is the number of experimental animals.

[0221] Table 2 Comparison of axial length differences between experimental and control eyes before modeling and 21 days after drug administration (mm, mean ± SD), where N is the number of experimental animals.

[0222] Experimental results showed that, compared with the model group, compounds (1)-(16) all had a certain inhibitory effect on changes in guinea pig refractive power. In the experiment on inhibiting guinea pig axial elongation, compared with the model group, compounds (1)-(16) all had a certain inhibitory effect on guinea pig axial elongation. In addition, the above experimental results showed that using 0.25% of the compounds of this application had a good effect on myopia prevention or delaying myopia progression, and its effect was basically equivalent to that of 2% atropine, with higher bioavailability.

[0223] The above embodiments are only for illustrating the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. They should not be construed as limiting the scope of protection of the present invention. All equivalent changes or modifications made in accordance with the spirit and essence of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A compound of formula (I), or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, or a pharmaceutically acceptable salt thereof: in, A is either O or S; B is O, S, or NR. # ;R # Selected from H, C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6- 10 Aryl and 5-10 heteroaryl groups; R 1 Selected from H, C 1-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, wherein the above groups are optionally substituted by 1, 2, 3, 4 or 5 R's; provided that when A is O and B is O, R's are substituted by 1, 2, 3, 4 or 5 R's. 1 Not H; or, These are groups derived from endogenous substances and their derivatives, which are optionally replaced by 1, 2, 3, 4 or 5 R's; Each R’ is independently selected from halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR a , -ON(R b )2, -N(R b )2, -N(R b )3 + X - , -N(OR c )R b , -SH, -SR a , -SSR c , -C(=O)R a , -CO2H, -CHO, -C(OR c )2, -CO2R a , -OC(=O)R a , -OCO2R a , -C(=O)N(R b )2, -OC(=O)N(R b )2, -NR b C(=O)R a , -NR b CO2R a , -NR b C(=O)N(R b )2, -C(=NR b )R a , -C(=NR b )OR a , -OC(=NR b )R a , -OC(=NR b )OR a , -C(=NR b )N(R b )2, -OC(=NR b )N(R b )2, -NR b C(=NR b )N(R b )2, -C(=O)NR b SO2R a , -NR b SO2R a , -SO2N(R b )2, -SO2R a , -SO2OR a , -OSO2R a , -S(=O)R a , -OS(=O)R a , -Si(R a )3, -OSi(R a 3. -C(=S)N(R) b )2、-C(=O)SR a -C(=S)SR a -SC(=S)SR a -SC(=O)SR a -OC(=O)SR a -SC(=O)OR a -SC(=O)R a -P(=O)2R a -OP(=O)2R a -P(=O)(R a )2、-OP(=O)(R a )2、-OP(=O)(OR c )2、-P(=O)2N(R b )2、-OP(=O)2N(R b )2、-P(=O)(NR b )2、-OP(=O)(NR b )2、-NR b P(=O)(OR c )2、-NR b P(=O)(NR b )2、-P(R c )2、-P(R c )3、-OP(R c )2、-OP(R c )3、-B(R a 2. -B(OR) c )2、-BR a (OR c C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, =O, =S, =NN(R) b )2、=NNR b C(=O)R a =NNR b C(=O)OR a =NNR b S(=O)2R a =NR b and = NOR c Wherein C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups may be optionally replaced by 1, 2, 3 or 4 R*s; And / or, two R' atoms on non-adjacent atoms are connected to form C. 1-6 Alkylene, C 2-6 imide or C 2-6 The ynyl group, wherein the above group is optionally substituted by 1, 2, 3 or 4 R*; And / or, two R's on adjacent atoms together with the atoms they are connected to form C. 3-8 A carbocyclic group or a 3-8 membered heterocyclic group, wherein the above groups are optionally substituted by 1, 2, 3 or 4 R*; And / or, two R's on the same carbon atom together with that carbon atom form C. 3-8 A carbocyclic group or a 3-8 membered heterocyclic group, wherein the above groups are optionally substituted by 1, 2, 3 or 4 R*; Each R* is independently selected from halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR a 、-ON(R b )2、-N(R b )2、-N(R b )3 + X - 、-N(OR c )R b 、-SH、-SR a 、-SSR c 、-C(=O)R a 、-CO2H、-CHO、-C(OR c )2、-CO2R a 、-OC(=O)R a 、-OCO2R a 、-C(=O)N(R b )2、-OC(=O)N(R b )2、-NR b C(=O)R a 、-NR b CO2R a 、-NR b C(=O)N(R b )2、-C(=NR b )R a 、-C(=NR b )OR a 、-OC(=NR b )R a 、-OC(=NR b )OR a 、-C(=NR b )N(R b )2、-OC(=NR b )N(R b )2、-NR b C(=NR b )N(R b )2、-C(=O)NR b SO2R a 、-NR b SO2R a 、-SO2N(R b )2、-SO2R a 、-SO2OR a 、-OSO2R a 、-S(=O)R a 、-OS(=O)R a 、-Si(R a )3、-OSi(R a 3. -C(=S)N(R) b )2、-C(=O)SR a -C(=S)SR a -SC(=S)SR a -SC(=O)SR a -OC(=O)SR a -SC(=O)OR a -SC(=O)R a -P(=O)2R a -OP(=O)2R a -P(=O)(R a )2、-OP(=O)(R a )2、-OP(=O)(OR c )2、-P(=O)2N(R b )2、-OP(=O)2N(R b )2、-P(=O)(NR b )2、-OP(=O)(NR b )2、-NR b P(=O)(OR c )2、-NR b P(=O)(NR b )2、-P(R c )2、-P(R c )3、-OP(R c )2、-OP(R c )3、-B(R a 2. -B(OR) c )2、-BR a (OR c C 1-20 Alkyl, C 1-20 Haloalkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl, 5-10 heteroaryl, =O, =S, =NN(R) b )2、=NNR b C(=O)R a =NNR b C(=O)OR a =NNR b S(=O)2R a =NR b and = NOR c ; Each R a Selected independently from C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl and 5-10 heteroaryl, or two R a Groups combine to form 3-10 membered heterocyclic groups or 5-10 membered heteroaryl groups; Each R b Independently selected from hydrogen, -OH, -OR a -N(R) c )2、-CN、-C(=O)R a -C(=O)N(R) c )2、-CO2R a -SO2R a -C(=NR) c OR a -C(=NR) c )N(R c )2、-SO2N(R c )2、-SO2R c -SO2OR c -SOR a -C(=S)N(R) c )2、-C(=O)SR c -C(=S)SR c -P(=O)2R a -P(=O)(R a )2、-P(=O)2N(R c )2、-P(=O)(NR c 2. C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl and 5-10 heteroaryl, or two R b Groups combine to form 3-10 membered heterocyclic groups or 5-10 membered heteroaryl groups; Each R c Independently selected from hydrogen and C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl and 5-10 heteroaryl, or two R c Groups combine to form 3-10 membered heterocyclic groups or 5-10 membered heteroaryl groups; X - Selected from F - Cl - ,Br - I - HSO4 - NO3 - HCO3 - and OCl4 - .

2. The compound of claim 1, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein, A is O.

3. The compound of claim 1 or 2, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate thereof, or a pharmaceutically acceptable salt thereof, wherein, B can be O, S, or NH.

4. The compound of any one of claims 1-3, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate thereof, or a pharmaceutically acceptable salt thereof, wherein, R 1 Selected from C 1-20 Alkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups, wherein the above groups are optionally substituted by 1, 2, 3, 4 or 5 R's; Preferably, R 1 Selected from C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl and 5-10 heteroaryl groups, wherein the above groups are optionally substituted by 1, 2, 3, 4 or 5 R's; More preferably, R 1 Selected from C 2-4 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne and phenyl, wherein the above groups are optionally substituted by 1, 2, 3, 4 or 5 R's.

5. The compound of any one of claims 1-4, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate thereof, or a pharmaceutically acceptable salt thereof, wherein, Each R' is independently selected from halogen, -CN, -NO2, -SO2H, -OH, -OR a -N(R) b )2、-SH、-SR a -C(=O)R a -CO2H, -CHO, -C(OR) c )2、-CO2R a -OC(=O)R a -OCO2R a -C(=O)N(R) b )2、-OC(=O)N(R b )2、-NR b C(=O)R a -NR b CO2R a -NR b C(=O)N(R b )2、-C(=O)NR b SO2R a -NR b SO2R a -SO2N(R) b )2、-SO2R a -SO2OR a -OSO2R a -S(=O)R a -OS(=O)R a -C(=S)N(R) b )2、-C(=O)SR a -C(=S)SR a -SC(=S)SR a -SC(=O)SR a -OC(=O)SR a -SC(=O)OR a -SC(=O)R a C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl, 5-10 heteroaryl, =O and =S, wherein the C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 Aryl and 5-10 heteroaryl groups may be optionally replaced by 1, 2, 3 or 4 R*s; And / or, two R's on adjacent atoms together with the atoms they are connected to form C. 3-8 Carbocyclic group, 3-8 membered heterocyclic group, wherein the above groups are optionally substituted by 1, 2, 3 or 4 R*; And / or, two R's on the same carbon atom together with that carbon atom form C. 3-8 Carbocyclic group, 3-8 membered heterocyclic group, wherein the above groups are optionally substituted by 1, 2, 3 or 4 R*; Each R* is independently selected from halogens, C 1-20 Alkyl, C 1-20 Haloalkyl, C 2-20 alkenyl, C 2-20 alkynyl group, C 3-10 Carbocyclic group and C 6-10 Aryl.

6. The compound of any one of claims 1-5, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate thereof, or a pharmaceutically acceptable salt thereof, wherein, Each R' is independently selected from halogen, -CN, -OH, -CO2H, -NR. b C(=O)R a C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 6-10 Aryl and 5-10 heteroaryl groups; And / or, two R's on adjacent atoms together with the atoms they are connected to form C. 3-8 Carbocyclic groups, 3-8 membered heterocyclic groups, which are optionally substituted by 1, 2, 3 or 4 R* groups; Each R* is independently selected from C 1-20 alkyl; Each R a Selected independently from C 1-6 alkyl; Each R b Independently selected from hydrogen and C 1-6 alkyl.

7. The compound of claim 1, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein, The group is derived from an endogenous substance and its derivatives, which is optionally replaced by 1, 2, 3, 4 or 5 R's, said endogenous substance being selected from amino acids and vitamins.

8. The compound of claim 7, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate thereof, or a pharmaceutically acceptable salt thereof, wherein, The group is derived from natural amino acids and their derivatives, and is optionally replaced by 1, 2, 3, 4 or 5 R' groups, wherein the natural amino acid is selected from: Alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro), phenylalanine (Phe), tryptophan (Trp), methionine (Met), glycine (Gly), serine (Ser), threonine (Thr), cysteine ​​(Cys), tyrosine (Tyr), asparagine (Asn), glutamine (Gln), lysine (Lys), arginine (Arg), histidine (His), aspartic acid (Asp), and glutamic acid (Glu).

9. The compound of claim 8, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate thereof, or a pharmaceutically acceptable salt thereof, wherein, These are groups derived from natural amino acids and their derivatives, optionally surrounded by 1, 2, 3, or 4 R groups. A * Replaces, where, The natural amino acids are selected from: alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro), phenylalanine (Phe), tryptophan (Trp), methionine (Met), glycine (Gly), serine (Ser), threonine (Thr), cysteine ​​(Cys), tyrosine (Tyr), asparagine (Asn), glutamine (Gln), lysine (Lys), arginine (Arg), histidine (His), aspartic acid (Asp), and glutamic acid (Glu); Each R A *Independently selected from halogens, -CN, -NO2, -SO2H, -OH, -OR a -N(R) b )2、-SH、-SR a -C(=O)R a -CO2H, -CHO, -C(OR) c )2、-CO2R a -OC(=O)R a -OCO2R a -C(=O)N(R) b )2、-OC(=O)N(R b )2、-NR b C(=O)R a -NR b CO2R a -NR b C(=O)N(R b )2、-C(=O)NR b SO2R a -NR b SO2R a -SO2N(R) b )2、-SO2R a -SO2OR a -OSO2R a -S(=O)R a -OS(=O)R a -C(=S)N(R) b )2、-C(=O)SR a -C(=S)SR a -SC(=S)SR a -SC(=O)SR a -OC(=O)SR a -SC(=O)OR a -SC(=O)R a C 1-6 Alkyl, C 1-6 Haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-10 Carbocyclic groups, 3-10 membered heterocyclic groups, C 6-10 aryl, 5-10 heteroaryl, =O and =S; preferably, -C(=O)R a More preferably, -C(=O)CH3.

10. The compound of claim 8 or 9, or its isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates, or pharmaceutically acceptable salts thereof, wherein the group derived from a natural amino acid and its derivatives is attached at the side chain of the amino acid; preferably, the amino acid is selected from tryptophan (Trp), serine (Ser), threonine (Thr), cysteine ​​(Cys), tyrosine (Tyr), lysine (Lys), and histidine (His), more preferably serine (Ser), threonine (Thr), cysteine ​​(Cys), and tyrosine (Tyr), more preferably serine (Ser), threonine (Thr), and cysteine ​​(Cys), and most preferably cysteine ​​(Cys).

11. The compound of claim 8 or 9, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, or a pharmaceutically acceptable salt thereof, wherein the group derived from a natural amino acid and its derivatives is attached to the amino group on the main chain.

12. The compound of any one of claims 8-11, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate thereof, or a pharmaceutically acceptable salt thereof, wherein the derivative of the natural amino acid is a compound formed by the following derivatization of the natural amino acid: -C(=O)OH is reacted with -C(=O)OR a -C(=O)N(R) b )2、-C(=O)NR b SO2R a -C(=O)SR a Substitute; And / or, -C(=O)NH2 is replaced by -C(=O)OH, -C(=O)OR a -C(=O)N(R) b )2、-C(=O)NR b SO2R a -C(=O)SR a Substitute; R a and R b As defined in claim 1.

13. The compound of claim 7 or 8, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate thereof, or a pharmaceutically acceptable salt thereof, wherein, for 14. The compound of claim 7, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate thereof, or a pharmaceutically acceptable salt thereof, wherein, The group is a group derived from vitamin A and its derivatives, a group derived from vitamin E and its derivatives, or a group derived from vitamin D and its derivatives, which may optionally be replaced by 1, 2, 3, 4 or 5 R's.

15. The compound of claim 14, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate thereof, or a pharmaceutically acceptable salt thereof, wherein, for 16. The compound of claim 1, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate, or solvate thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from...

17. A pharmaceutical composition comprising the compound of any one of claims 1-16, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

18. Use of any compound of claims 1-16, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 17, in the preparation of a medicament for inhibiting the progression of myopia.

19. The compound of any one of claims 1-16, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 17, for inhibiting the progression of myopia.

20. A method for inhibiting myopia progression in a subject, comprising administering to the subject a compound of any one of claims 1-16, or an isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 17.

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