Ecteinascidin compound and use thereof

By developing sesquinin compounds with in vitro proliferation inhibitory activity and tumor targeting ability in vivo, the multidrug resistance and toxic side effects of existing anti-cancer drugs have been solved, and a safer and more effective anti-cancer treatment plan is provided.

WO2025168077A1PCT designated stage Publication Date: 2025-08-14DUALITY BIOLOGICS (SUZHOU) CO LTD
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Patent Information

Application Number
PCT/CN2025/076298
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2025-01-24
Filing Date
2025-02-07
Publication Date
2025-08-14

AI Technical Summary

Technical Problem

Existing anti-cancer drugs have problems with multidrug resistance and serious toxic and side effects, and it is necessary to develop sesquinin compounds with better efficacy and lower toxicity.

Method used

It provides a sesquinin compound that has the in vitro proliferation inhibitory activity, in vivo tumor inhibition effect and tumor targeting ability of tumor cells, and has good in vivo safety.

Benefits of technology

It has achieved effective inhibition and targeting ability to tumor cells, while reducing the toxic side effects of the drug, meeting the clinical demand for safer and more effective anti-cancer drugs.

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Abstract

Disclosed in the present invention are an ecteinascidin compound and the use thereof. Provided in the present invention is a compound as represented by formula (I), or a pharmaceutically acceptable salt, an ester, a stereoisomer, a tautomer, a polymorph, a solvate, an isotopically labeled compound, a metabolite or a prodrug thereof. The compounds provided by the present invention have one or more effects selected from the following group: (1) having an inhibitory activity against tumor cell proliferation in vitro; (2) having a tumor inhibition effect in vivo; (3) having an in vivo tumor targeting capability; and (4) having good safety in vivo.
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Description

Echinacea compounds and their applications

[0001] This application claims the benefit of priority to Chinese Patent Application No. 2024101780235 filed on February 8, 2024; Chinese Patent Application No. 2024111028377 filed on August 12, 2024; Chinese Patent Application No. 2024113883016 filed on September 30, 2024; and Chinese Patent Application No. 2025101162270 filed on January 24, 2025. The entire contents of the aforementioned Chinese patent applications are incorporated herein by reference. Technical Field

[0002] The present invention belongs to the field of medical technology, and in particular relates to ecteinascidin compounds and applications thereof. Background Art

[0003] Cancer is a serious malignant disease that threatens human health, claiming over 5 million lives worldwide each year. In recent years, the incidence of tumors has been increasing, with mortality ranking first among all diseases. Chemotherapy is a commonly used and effective cancer treatment in clinical practice. However, due to the multidrug resistance of cancer cells and the severe side effects of existing anticancer drugs, new anticancer drugs with improved efficacy and minimal side effects are urgently needed.

[0004] Et-743 (Trabectedin) is a very effective antitumor agent isolated from the marine tunicate Ecteinascidia turbinata and has been approved by the European Union and the United States for the treatment of advanced soft tissue tumors.

[0005] At present, there is still a need to continue to develop ectocystin compounds with better efficacy and lower toxicity to meet more clinical needs. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to overcome the deficiencies of existing drugs, thereby providing an ectoderma compound and its application. The ectoderma compound of the present invention has one or more effects selected from the following group: (1) having an inhibitory activity on the proliferation of tumor cells in vitro; (2) having an in vivo tumor-suppressing effect; (3) having an in vivo tumor-targeting ability; and (4) having good in vivo safety.

[0007] The present invention provides a compound represented by formula (IA), or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotope-labeled compound, metabolite or prodrug thereof:

[0008] in,

[0009] Q 1 N or CH;

[0010] Q 2 N or CR 11 ;

[0011] R 1 and R 11 are independently hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 Alkyl, -NH-S(O)2-R 1-2 、-C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkyl), -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkyl, -N(R 1-1 )-C(O)R 1-2 、-N(R 1- 1 )-R 1-2 、-OC(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl, -N(R 1-1 )C(O)-C 1-6 Alkylene-R1-2 or -N(R 1- 1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0012] Or, R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution;

[0013] R 2 For hydrogen, deuterium, halogen, -C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -OC(O)-NR 2-1 R 2-2 、-NR 2-1 C(O)-OR 2-2 、-NH-S(O)2-R 2-2 、-N(R 2-1 )C(O)-C 1-6 Alkylene-R 2-2 、-NR 2-1 C(O)NR 2-1 -R 2-2 、-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -N(C 1-6alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -C(O)-R 2-2 or C(O)-NR 2-1 R 2-2 , the C 1- 6 alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted by one or more radicals selected from halogen, -OH, -O-NH-CH3, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0014] R 3 For hydrogen, deuterium, -C 1-6 Alkyl, NHC 1-6 Alkyl, -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-OC(O)-NR 3-1 R 3-2 、-CH2-NR 3-1 C(O)-OR 3-2 、-CH2-NR 3-1 C(O)NR 3-1 -R 3-2 、-CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 Alkyl)2, -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(R 3-1 )C(O)-C 1-6 Alkylene-R 3-2 、-CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl) or -C(O)-R 3-2 , the C 1-6Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -O-NH-CH3, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0015] R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0016] or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH and -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents;

[0017] R 1-1 、R 2-1 、R 3-1 are independently hydrogen, deuterium, C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0018] R 1-2 、R 2-2 、R 3-2 Each independently is C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-12 Cycloalkyl and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more independently selected from halogen, -OH, -SH, -NH2, -O-NH-CH3, -NHC 1-6 Alkyl and -SC1-6 Substitution of alkyl groups;

[0019] Y is -OH or -CN;

[0020] And meet the conditions:

[0021] (1) When R 1 -OH or -OC 1-6 Alkyl, R 11 When it is -OCH3, R 2 、R 3 and R 4 Not simultaneously hydrogen;

[0022] (2) When R 1 -OH, R 11 -OCH3, R 2 and R 3 When it is hydrogen, R 4 is not methyl; and

[0023] (3) When R 1 -OH, R 11 -CH3, R 2 and R 4 When it is hydrogen, R 3 Not ethyl.

[0024] In some embodiments,

[0025] in,

[0026] Q 1 N or CH;

[0027] Q 2 N or CR 11 ;

[0028] R 1 and R 11 are independently hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 Alkyl, -NH-S(O)2-R 1-2 、-C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkyl), -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-R 1-2 、-OC(O)-N(R 1- 1 )R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1- 1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1- 1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl, -N(R 1-1 )C(O)-C 1-6 Alkylene-R 1-2 or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0029] Or, R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution;

[0030] R 2 For hydrogen, deuterium, halogen, -C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -OC(O)-NR 2-1 R 2-2 、-NR 2-1 C(O)-OR 2-2 、-NH-S(O)2-R 2-2 、-N(R 2-1 )C(O)-C 1-6 Alkylene-R 2-2 、-NR 2-1 C(O)NR 2-1 -R 2-2 、-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), or -C(O)-R 2-2 , the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted by one or more radicals selected from halogen, -OH, -O-NH-CH3, -SH, -NH2, -NHC 1- 6-alkyl and -SC 1-6 Substitution of alkyl groups;

[0031] R 3 For hydrogen, deuterium, -C 1-6 Alkyl, -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-OC(O)-NR 3-1 R 3-2 、-CH2-NR 3-1 C(O)-OR 3-2 、-CH2-NR 3-1C(O)NR 3-1 -R 3-2 、-CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 Alkyl)2, -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(R 3-1 )C(O)-C 1-6 Alkylene-R 3-2 、-CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl) or -C(O)-R 3-2 , the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -O-NH-CH3, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0032] R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0033] or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH and -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents;

[0034] R 1-1 、R 2-1 、R 3-1 are independently hydrogen, deuterium, C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0035] R 1-2 、R 2-2 、R 3-2 Each independently is C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-12 Cycloalkyl and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more independently selected from halogen, -OH, -SH, -NH2, -O-NH-CH3, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0036] Y is -OH or -CN;

[0037] And meet the conditions:

[0038] (1) When R 1 -OH or -OC 1-6 Alkyl, R 11 When it is -OCH3, R 2 、R 3 and R 4 Not simultaneously hydrogen;

[0039] (2) When R 1 -OH, R 11 -OCH3, R 2 and R 3 When it is hydrogen, R 4 is not methyl; and

[0040] (3) When R 1 -OH, R 11 -CH3, R 2 and R 4 When it is hydrogen, R 3 Not ethyl.

[0041] In some embodiments, the compound represented by formula (IA) is represented by formula (I):

[0042] in,

[0043] R 1 and R 11 are independently hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 Alkyl, -C 1- 6-alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1- 1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0044] Or, R 1With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution;

[0045] R 1-1 For hydrogen, deuterium, C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0046] R 1-2 C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-12 Cycloalkyl and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more independently selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0047] R 2 For hydrogen, deuterium, halogen, -C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3- 12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0048] R 3 For hydrogen, deuterium, -C 1-6Alkyl, -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 Alkyl)2, -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -CH2-N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3- 12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0049] R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0050] or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH and -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents;

[0051] Y is -OH or -CN;

[0052] And meet the conditions:

[0053] (1) When R 1 -OH or -OC 1-6 Alkyl, R 11 When it is -OCH3, R 2 、R 3 and R 4 Not simultaneously hydrogen;

[0054] (2) When R 1 -OH, R 11 -OCH3, R 2 and R 3 When it is hydrogen, R 4 is not methyl; and

[0055] (3) When R 1 -OH, R 11 -CH3, R 2 and R 4 When it is hydrogen, R 3 Not ethyl.

[0056] In some embodiments, certain groups in the compound of formula (I), or its pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, isotope labels, metabolites or prodrugs are defined as follows. Unmentioned groups are the same as those described in any embodiment of the present application (referred to as "in some embodiments").

[0057] In some embodiments, the compound represented by formula (I) is represented by formula (II):

[0058] in,

[0059] R 1 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 Alkyl, -C 1-6 Alkylene-N(R 1- 1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1- 2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1- 2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0060] R 1-1 For hydrogen, deuterium, C 1-6 Alkyl or halogenated C 1-6 alkyl;

[0061] R 1-2 C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-12 Cycloalkyl and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more independently selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0062] R2 For hydrogen, deuterium, halogen, -C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0063] R 3 For hydrogen, deuterium, C 1-6 Alkyl, -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -CH2-N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0064] R 4 For hydrogen, deuterium, C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0065] or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH and -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents;

[0066] Y is -OH or -CN;

[0067] And meet the conditions:

[0068] When R 1 -OH or -OC 1-6 When alkyl, R 2 、R 3 and R 4 Not hydrogen at the same time.

[0069] In some embodiments, at least one of the following conditions is met:

[0070] (1)R 1 For hydrogen, deuterium, halogen, -CN, -NH2, C 1-6 Alkyl, -NHC 1-6 Alkyl, -NH-S(O)2-R 1-2 、-C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkyl), -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkyl, -N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-R 1-2 、-OC(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1- 1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1- 1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl, -N(R 1-1 )C(O)-C 1-6 Alkylene-R 1-2 or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0071] (2)R 11 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -NHC 1-6 Alkyl, -NH-S(O)2-R 1-2 、-C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12Cycloalkyl, -O-(4- to 12-membered heterocycloalkyl), -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1- 2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、N(R 1-1 )-C 3-12 Cycloalkyl, -N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-R 1-2 、-OC(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl, -N(R 1-1 )C(O)-C 1-6 Alkylene-R 1-2 or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1- 6-alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0072] (3)R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution;

[0073] (4)R 2 For deuterium, halogen, -C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -OC(O)-NR 2-1 R 2-2 、-NR 2-1 C(O)-OR 2-2 、-NH-S(O)2-R 2-2 、-N(R 2-1 )C(O)-C 1-6 Alkylene-R 2-2 、-NR 2-1 C(O)NR 2-1 -R 2-2 、-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -C(O)-R 2-2 or C(O)-N(R 1-1 )R 1-2 , the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted by one or more radicals selected from halogen, -OH, -O-NH-CH3, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0074] (5)R 3 -C 1-6Alkyl, -NHC 1-6 Alkyl, -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-OC(O)-NR 3- 1 R 3-2 、-CH2-NR 3-1 C(O)-OR 3-2 、-CH2-NR 3-1 C(O)NR 3-1 -R 3-2 、-CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 Alkyl)2, -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(R 3-1 )C(O)-C 1-6 Alkylene-R 3-2 、-CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl) or -C(O)-R 3-2 , the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -O-NH-CH3, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0075] Preferably, R 3 NHC 1-6 Alkyl, -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-OC(O)-NR 3-1 R 3-2 、-CH2-NR 3-1 C(O)-OR 3-2 、-CH2-NR 3-1C(O)NR 3-1 -R 3-2 、-CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 Alkyl)2, -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(R 3-1 )C(O)-C 1-6 Alkylene-R 3-2 、-CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl) or -C(O)-R 3- 2 , the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -O-NH-CH3, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0076] (6)R 4 -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1- 6 alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Alkyl is substituted with a substituent; for example -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6Alkyl and -SC 1-6 Substitution of alkyl groups;

[0077] (7)R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH and -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents;

[0078] (8)Q 1 is N; and

[0079] (9)Q 2 is N.

[0080] In some embodiments, the compound represented by formula (I) satisfies at least one of the following conditions:

[0081] (1)R 1 For hydrogen, deuterium, halogen, -CN, -NH2, C 1-6 Alkyl, -C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1- 6-alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0082] (2)R 2 For deuterium, halogen, C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3- 12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0083] (3)R 3 -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-NHC(O)C 3-12Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 Alkyl)2, -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -CH2-N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0084] (4)R 4 C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1- 6 alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Alkyl is substituted with a substituent; for example -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of the alkyl group with a substituent; and

[0085] (5)R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH and -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents;

[0086] (6)R 11 For hydrogen, deuterium, halogen, -CN, -NH2, C 1-6 Alkyl, -C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1- 6-alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6The substituent of the alkylene group -NH2 is substituted.

[0087] In some embodiments, the compounds represented by formula (I) and formula (II) satisfy at least one of the following conditions:

[0088] (1)R 1 For hydrogen, deuterium, halogen, -CN, -NH2, C 1-6 Alkyl, -C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1- 6-alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0089] (2)R 2 For deuterium, halogen, C 1-6Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0090] (3)R 3 -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -CH2-N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0091] (4)R 4 C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1- 6 alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of the alkyl group with a substituent; and

[0092] (5)R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 The substituents are cycloalkylene-OH and -C(O)-(4- to 12-membered heterocycloalkylene)-OH.

[0093] In some embodiments, the compound is not:

[0094] In some embodiments, the compound is not:

[0095] In some embodiments, in formula (I), when R 1 -OH, R 11 -OCH3, R 2 and R 3 When it is hydrogen, R 4 Not for C 1-6 alkyl.

[0096] In some embodiments, in formula (II), when R 1 -OH, R 2 and R 3 When it is hydrogen, R 4 Not for C 1-6 alkyl.

[0097] In some embodiments, in formula (I), when R 1 -OH, R 11 -CH3, R 2 and R 4 When it is hydrogen, R 3 Not for C 1-6 alkyl.

[0098] In some embodiments, when R 1 -OH, R 2 、R 3 and R 4 When it is hydrogen, R 11It is not -OCH2CH2NH2, -OCH2CH2NHCH3, -CH2N(CH3)-C(O)-CH(OH)CH3, or -CH2N(CH3)-C(O)-CH2(OH).

[0099] In some embodiments, when R 1 -OH, R 2 、R 3 and R 4 When it is hydrogen, R 11 Not for-OC 1-6 Alkyl, -C 1-6 Alkylene-N(R 1- 1 )-C(O)R 1-2 Among them, C 1-6 Alkyl substituted -NH2, -NHC 1-6 Alkyl substitution, R 1-1 H or CH3, R 1-2 C 1-6 Alkyl, the C 1-6 The alkyl group is substituted with the substituent -OH.

[0100] In some embodiments, the number of heteroatoms in the 4- to 12-membered heterocycloalkylene and 4- to 12-membered heterocycloalkylene is one or more, and each heteroatom is independently selected from N, O, and S; preferably, the 4- to 12-membered heterocycloalkylene and 4- to 12-membered heterocycloalkylene are 4- to 6-membered heterocycloalkylene and 4- to 6-membered heterocycloalkylene; the number of heteroatoms is one or two, and the heteroatoms are independently selected from N; for example, N-heterocyclobutyl Piperidinyl Piperazinyl or a divalent group thereof.

[0101] In some embodiments, the general formula (IA) is a compound shown as follows:

[0102] in,

[0103] Q 1 N or CH;

[0104] Q 2 N or CR 11 ;

[0105] R 1 NHC 1-6 Alkyl, -NH-S(O)2-R 1-2 、-C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12Cycloalkyl, -O-(4- to 12-membered heterocycloalkyl), -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkyl, -N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-R 1-2 、-OC(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1- 1 )R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl, -N(R 1- 1 )C(O)-C 1-6 Alkylene-R 1-2 or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0106] R 11 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 alkyl;

[0107] R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution;

[0108] R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 The alkyl group is substituted with a substituent.

[0109] In some embodiments, the general formula (IA) is a compound shown as follows:

[0110] in,

[0111] Q 1 N or CH;

[0112] R 1 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 alkyl;

[0113] R 11 Independently -NHC 1-6 Alkyl, -NH-S(O)2-R 1-2 、-C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkyl), -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R1-1 )-C(O)R 1-2 、-N(R 1- 1 )-C 3-12 Cycloalkyl, -N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-R 1-2 、-OC(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl, -N(R 1-1 )C(O)-C 1-6 Alkylene-R 1-2 or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0114] R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 The alkyl group is substituted with a substituent.

[0115] In some embodiments, the general formula (IA) is a compound shown as follows:

[0116] in,

[0117] Q 1 N or CH;

[0118] Q 2 N or CR 11 ;

[0119] R 1 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 alkyl;

[0120] R 11 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 alkyl;

[0121] R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution;

[0122] R 2 Halogen, -C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -OC(O)-NR 2-1 R 2-2 、-NR 2-1 C(O)-OR 2-2 、-NH-S(O)2-R 2-2 、-N(R 2-1 )C(O)-C 1-6 Alkylene-R 2-2 、-NR 2-1 C(O)NR 2-1 -R 2-2 、-N(C 1-6 alkyl)C(O)C 3- 12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -C(O)-R 2-2 or C(O)-NR 2-1 R 2-2 , the C 1-6 Alkyl, C 3- 12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted by one or more radicals selected from halogen, -OH, -O-NH-CH3, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0123] R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 The alkyl group is substituted with a substituent.

[0124] In some embodiments, the general formula (IA) is a compound shown as follows:

[0125] in,

[0126] Q 1 N or CH;

[0127] Q 2N or CR 11 ;

[0128] R 1 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 alkyl;

[0129] R 11 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 alkyl;

[0130] R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution;

[0131] R 3 -C 1-6 Alkyl, -NHC 1-6 Alkyl, -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-OC(O)-NR 3-1 R 3- 2 、-CH2-NR 3-1 C(O)-OR 3-2 、-CH2-NR 3-1 C(O)NR 3-1 -R 3-2 、-CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 Alkyl)2, -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(R 3-1 )C(O)-C 1-6 Alkylene-R 3-2 、-CH2-N(C 1-6alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl) or -C(O)-R 3- 2 , the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -O-NH-CH3, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0132] R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0133] or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 The substituents are cycloalkylene-OH and -C(O)-(4- to 12-membered heterocycloalkylene)-OH.

[0134] In some embodiments, the compound represented by formula (IA) or general formula (I) is a compound represented by formula (Ia):

[0135] in,

[0136] R 1 and R 11 are independently hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, halogenated C 1-6 Alkyl, -OC 1-6Alkyl, -O-halogenated C 1-6 Alkyl, -NHC 1-6 Alkyl, -O-halogenated C 1-6 Alkyl or -NH-halogenated C 1-6 alkyl;

[0137] Or, R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution;

[0138] R 2 For hydrogen, deuterium, halogen, C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3- 12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0139] R 3 H or -CH2-NR 3a R 3b ;

[0140] R 3a is hydrogen or C 1-6 Alkyl; the C 1-6 The alkyl group is optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1- 6-alkyl and -SC1-6 Substitution of alkyl groups;

[0141] R 3b For hydrogen, C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1- 6-alkyl and -SC 1-6 Substitution of alkyl groups;

[0142] R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0143] or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH, -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents;

[0144] Y is -OH or -CN;

[0145] The premise is that R 2 and R 3 Cannot be H at the same time.

[0146] In some embodiments, the compound represented by formula (IA), general formula (I), formula (Ia), or formula (II) is a compound represented by formula (IIa):

[0147] in,

[0148] R 1 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, halogenated C 1-6 Alkyl, -OC 1-6 Alkyl, -O-halogenated C 1-6 Alkyl, -NHC 1-6 Alkyl, -O-halogenated C 1-6 Alkyl or -NH-halogenated C 1-6 alkyl;

[0149] R 2 For hydrogen, deuterium, halogen, C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0150] R 3 H or -CH2-NR 3a R 3b ;

[0151] R 3a is hydrogen or C 1-6 Alkyl; the C 1-6 The alkyl group is optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1- 6-alkyl and -SC 1-6 Substitution of alkyl groups;

[0152] R 3b For hydrogen, C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1- 6-alkyl and -SC 1-6 Substitution of alkyl groups;

[0153] R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0154] or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH, -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents;

[0155] Y is -OH or -CN;

[0156] The premise is that R 2 and R 3 Cannot be H at the same time.

[0157] In some embodiments, the compounds of formula (IA), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa) are as follows:

[0158] R 1 It is hydrogen, halogen, -OH, -CN, -NH2, -CH3, -OCH3 or -NHCH3.

[0159] In some embodiments, the compounds of formula (IA), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa) are as follows:

[0160] R 1 It is hydrogen, deuterium, -F, -Cl, -OH, -CH3, -OCH3, -NH2 or -NHCH3.

[0161] In some embodiments, the compounds of formula (IA), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 1 It is H, -CH3, -OH or -OCH3; for example, H, -OH or -OCH3; for example, -OH or -OCH3.

[0162] In some embodiments, the compounds of formula (IA), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa) are as follows:

[0163] R 1 It is hydrogen, halogen, -CN, -CH3, -OCH3 or -NHCH3; for example, H or -OCH3; for example, -OCH3.

[0164] In some embodiments, the compounds of formula (IA), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 1 It is -OH.

[0165] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-1), Formula (IA-3), Formula (IA-4), Formula (I), or Formula (Ia), wherein R 11 It is hydrogen, halogen, -OH, -CN, -NH2, -CH3, -OCH3 or -NHCH3.

[0166] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-1), Formula (IA-3), Formula (IA-4), Formula (I), or Formula (Ia), wherein R 11 It is hydrogen, deuterium, -F, -Cl, -OH, -CH3, -OCH3, -NH2 or -NHCH3.

[0167] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-1), Formula (IA-3), Formula (IA-4), Formula (I), or Formula (Ia), wherein R 11is hydrogen, deuterium or -OCH3.

[0168] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-1), Formula (IA-3), Formula (IA-4), Formula (I), Formula (Ia), R 1 With R 11 Connected, formed with connected carbons The a side is connected to the benzene ring.

[0169] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-1), Formula (IA-3), Formula (IA-4), Formula (I), or Formula (Ia), wherein R 1 and R 11 are independently H, -OH, -CH3, -OCH3, or, R 1 With R 11 Connected, formed with connected carbons The a side is connected to the benzene ring.

[0170] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-3), Formula (I), or Formula (Ia), wherein R 2 -OH, -NH2, -C 1-6 Alkyl, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl or -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, the C 1-6 Alkyl, C 3-12 Each cycloalkyl group is optionally substituted with one or more alkyl groups selected from -OH, -SH, -NH2, -NHCH3 and -SCH3.

[0171] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 2 -OH, -NH2, -C 1-6 Alkyl, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl or -N(C 1-6 alkyl)C(O)C 3-12Cycloalkyl, the C 1-6 Alkyl, C 3-12 Each cycloalkyl group is optionally substituted with one or more alkyl groups selected from -OH, -SH, -NH2, -NHCH3 and -SCH3.

[0172] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 2 -NH2, -NHC(O)C 1-6 Alkyl or -N(C 1-6 alkyl)C(O)C 1-6 Alkyl; the C 1-6 Each alkyl group is optionally substituted with one or more substituents selected from -OH, -SH, -NH2, -NHCH3 and -SCH3.

[0173] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 2 -NH2 or -N(C 1-6 alkyl)C(O)C 1-6 Alkylene-OH.

[0174] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 2 -OC(O)-NR 2-1 R 2-2 、-NR 2-1 C(O)-OR 2-2 、-NH-S(O)2-R 2-2 、-N(R 2-1 )C(O)-C 1-6 Alkylene-R 2-2 、-NR 2-1 C(O)NR 2- 1 -R 2-2 、-C(O)-R 2-2 .

[0175] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 2 -OH, -NH2, -NHCH3, -CH2OH,

[0176] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 2 -OH, -NH2, -NHCH3, -CH2OH,

[0177] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 2 -NH2 or

[0178] In some embodiments, the compound of formula (IA), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 2 For H.

[0179] In some embodiments, the compounds of formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 3a is hydrogen or -C 1-3 alkyl.

[0180] In some embodiments, the compounds of formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 3a It is hydrogen or -CH3.

[0181] In some embodiments, the compounds of formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 3b Hydrogen, -CH3, -C(O)C 1-6 Alkyl or -C(O)C 3-6 Cycloalkyl, the C 1-6 Alkyl or C 3-6 Each cycloalkyl group is optionally substituted with one or more substituents selected from -OH, -SH, -NH2, -NHCH3 and -SCH3.

[0182] In some embodiments, the compounds of formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 3b -C(O)C 1-6 Alkylene-OH.

[0183] In some embodiments, the compounds of formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 3b For hydrogen, -CH3,

[0184] In some embodiments, the compounds of formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 3b for

[0185] In some embodiments, the compound of formula (IA), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 3 For hydrogen.

[0186] In some embodiments, the compounds of formula (IA), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 3 for

[0187] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 4 is hydrogen, deuterium or C 1-6 Alkyl, the C 1-6 The alkyl group is optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 The alkyl group is substituted with a substituent.

[0188] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 4 For hydrogen, deuterium, C 1-6 Alkyl or -C(O)C 1-6 Alkylene-OH.

[0189] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 4 It is hydrogen or -CH3.

[0190] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 4 For hydrogen.

[0191] In some embodiments, the compounds of formula (IA), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 3 With R 4 Together with the atoms to which it is attached, it forms a 5- to 6-membered heterocycloalkyl, wherein each of the 5- to 6-membered heterocycloalkyl groups is optionally substituted with one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substituted with cycloalkylene-OH, -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents.

[0192] In some embodiments, the compounds of formula (IA), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 3 With R 4 The atom to which it is attached together forms a piperazinyl group, wherein each of the piperazinyl groups is optionally substituted with one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substituted with cycloalkylene-OH, -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents.

[0193] In some embodiments, the compounds of formula (IA), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 3 With R 4 Together with the atoms it is connected to, it forms

[0194] In some embodiments, the compounds of formula (IA), formula (IA-4), formula (I), formula (Ia), formula (II), and formula (IIa), wherein R 3 With R 4 Together with the atoms it is connected to, it forms

[0195] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-3), Formula (I), or Formula (Ia) is a compound represented by the structure of Formula (Ia-1).

[0196] Among them, R 1 、R 11 、R 2 、R 4 and Y are as defined in any one of formula (I), formula (Ia), formula (II) and formula (IIa) of the present invention.

[0197] In some embodiments, the compounds represented by formula (IA), formula (IA-3), formula (I), formula (Ia), formula (Ia-1), formula (II), and formula (IIa) are compounds represented by formula (IIa-1), (IIa-4), and (IIa-5).

[0198] Among them, Y and R 2 The definitions are as described in any one of Formula (I), Formula (Ia), Formula (II) and Formula (IIa) of the present invention.

[0199] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-1), (IIa-4), and (IIa-5), wherein,

[0200] R 2 -NH2 or -N(C 1-6 alkyl)C(O)C 1-6 Alkylene-OH.

[0201] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-1), (IIa-4), and (IIa-5), wherein,

[0202] R 2 NHC 1-6 alkyl.

[0203] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-1), (IIa-4), and (IIa-5), wherein,

[0204] R 2 -NH2 or -N(C 1-3 alkyl)C(O)C 1-3Alkylene-OH.

[0205] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-1), (IIa-4), and (IIa-5), wherein,

[0206] R 2 -NH2, -NHCH3,

[0207] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-1), (IIa-4), and (IIa-5), wherein,

[0208] R 2 -NH2 or

[0209] In some embodiments, the compounds of formula (IA), formula (IA-3), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-1), (IIa-4), and (IIa-5), wherein,

[0210] R 2 NHC 1-3 Alkyl; preferably, R 2 It is -NHCH3.

[0211] In some embodiments, the compounds represented by formula (IA), formula (IA-3), formula (I), formula (Ia), formula (Ia-1), formula (II), and formula (IIa) are compounds represented by formula (IIa-1), (IIa-4), and (IIa-5).

[0212] R 2 NH2, -NHC 1-6 Alkyl, -N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl, -N(R 1-1 )C(O)-C 1-6 Alkylene-R 1-2 、-N(R 1-1 )C(O)(4- to 12-membered heterocycloalkyl), -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R1-2 、-N(R 1-1 )-C 3-12 Cycloalkyl, -N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1-1 )R 1-2 、-NH-S(O)2-R 1-2 、-OC(O)-N(R 1-1 )R 1-2 、-OC 1-6 alkyl.

[0213] In some embodiments, the compound represented by formula (IA), formula (IA-4), formula (I), or formula (Ia) is a compound represented by formula (Ia-2).

[0214] Among them, Y, R 1 、R 11 、R 3a 、R 3b and R 4 The definitions are as described in any one of formula (I) and formula (Ia) of the present invention.

[0215] In some embodiments, the compounds represented by formula (IA), formula (IA-4), formula (I), formula (Ia), formula (Ia-2), formula (II), and formula (IIa) are compounds represented by structures represented by formula (IIa-2) and formula (IIa-3).

[0216] Among them, Y, R 3a 、R 3b and R 4 The definitions are as described in any one of formula (I), formula (Ia), formula (Ia-2), formula (II) and formula (IIa) of the present invention.

[0217] In some embodiments, the compounds of formula (IA), formula (IA-4), formula (I), formula (Ia), formula (Ia-2), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3) are as follows:

[0218] R 3a is hydrogen or -CH3;

[0219] R 3b -C(O)C 1-6 Alkylene-OH;

[0220] R 4 is hydrogen or -CH3;

[0221] or, for

[0222] Y is -OH or -CN.

[0223] In some embodiments, the compounds of formula (IA), formula (IA-4), formula (I), formula (Ia), formula (Ia-2), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3), wherein R 3b -C(O)C 1-3 Alkylene-OH.

[0224] In some embodiments, the compounds of formula (IA), formula (IA-4), formula (I), formula (Ia), formula (Ia-2), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3), wherein -CH2-NR 3a R 3b for

[0225] In some embodiments, the compounds represented by formula (IA), formula (IA-4), formula (I), formula (Ia), formula (Ia-1), formula (II), and formula (IIa) are compounds represented by formula (IIa-1), (IIa-4), and (IIa-5).

[0226] R 3 -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, NHC 1-6 Alkyl, -CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-N(R 3-1 )C(O)-C 1-6 Alkylene-R 3-2 、-CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-OC(O)-NR 3-1 R 3-2 、-CH2-NR 3- 1 C(O)NR 3-1 -R 3-2 、C(O)-R 3-2 .

[0227] In some embodiments, the compounds represented by formula (IA), formula (IA-4), formula (I), formula (Ia), formula (Ia-1), formula (II), and formula (IIa) are compounds represented by formula (IIa-1), (IIa-4), and (IIa-5).

[0228] R 3 NHCH3,

[0229] In some embodiments, the compounds represented by formula (IA), formula (IA-4), formula (I), formula (Ia), formula (Ia-1), formula (II), and formula (IIa) are compounds represented by formula (IIa-1), (IIa-4), and (IIa-5).

[0230] R 3 NHCH3,

[0231] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ia), formula (Ia-2), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3), wherein R 4 For hydrogen.

[0232] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ia), formula (Ia-2), formula (II), formula (IIa), and formula (IIa-1) are, wherein, for or a combination thereof.

[0233] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ia), formula (Ia-2), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3), wherein, for or a combination thereof.

[0234] In some embodiments, the compound of formula (IA), (I), (II), (Ia), (IIa) of the present invention is:

[0235] In some embodiments, the compound represented by formula (IA) or formula (I) is a compound represented by formula (Ib).

[0236] in,

[0237] R 1 -NH2, -NHC 1-6 Alkyl, -C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1- 1 )-C 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1- 1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0238] R 11 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 Alkyl, -C1-6 Alkylene-N(R 1- 1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1- 2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1- 2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0239] R 1-1 For hydrogen, deuterium, C 1-6 Alkyl, halogenated C 1-6 alkyl;

[0240] R 1-2 C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl; the C 1-6 Alkyl, C3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0241] R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0242] Y is -OH or -CN.

[0243] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-1), Formula (IA-3), Formula (IA-4), Formula (I), Formula (Ib), wherein R 11 It is hydrogen, halogen, -OH, -CN, -NH2, -CH3, -OCH3 or -NHCH3.

[0244] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-1), Formula (IA-3), Formula (IA-4), Formula (I), Formula (Ib), wherein R 11 It is hydrogen, deuterium, -F, -Cl, -OH, -CH3, -OCH3, -NH2 or -NHCH3.

[0245] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-1), Formula (IA-3), Formula (IA-4), Formula (I), Formula (Ib), wherein R 11 is hydrogen, deuterium or -OCH3.

[0246] In some embodiments, the compound represented by formula (IA), formula (IA-1), formula (I), formula (Ib), and formula (II) is a compound represented by formula (IIb).

[0247] in,

[0248] R 1 -NH2, -C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2、-O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0249] R 1-1 For hydrogen, deuterium, C 1-6 Alkyl, halogenated C 1-6 alkyl;

[0250] R 1-2 C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0251] Y is -OH or -CN.

[0252] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-1), Formula (I), Formula (Ib), Formula (II), or Formula (IIb), wherein:

[0253] R 1 -NH2, -C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution;

[0254] R 1-1 For hydrogen, deuterium, C 1-6 Alkyl, halogenated C 1-6 alkyl;

[0255] R 1-2 C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -O-NHCH3, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups;

[0256] Y is -OH or -CN.

[0257] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-1 is hydrogen, deuterium or C 1-6 alkyl.

[0258] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-1 It is hydrogen, deuterium or -CH3.

[0259] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-1 It is hydrogen or -CH3.

[0260] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-1 is -CH3.

[0261] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-2 C 1-6 Alkyl, C 3-6 Cycloalkyl or 4 to 6 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-6 Cycloalkyl or 4 to 6 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 The alkyl group is substituted with a substituent.

[0262] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-2 C 1-6 Alkyl, C 3-6 Cycloalkyl or 4 to 6 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-6 Cycloalkyl or 4 to 6 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -O-NHCH3, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1- 6 alkyl substituents are substituted.

[0263] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-2 -C 1-6 Alkylene-OH.

[0264] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-2 -C 1-6 Alkylene-O-NHCH3.

[0265] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-2 -CH2OH, -CH(CH3)OH,

[0266] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-2 It is -CH2-O-NHCH3.

[0267] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-2 -C 1-3 Alkylene-OH.

[0268] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-2 -C 1-3 Alkylene-O-NHCH3.

[0269] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1-2 It is -CH2OH or -CH(CH3)OH.

[0270] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 1 -NH2, -C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-O-(4- to 6-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-6 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 6-membered heterocycloalkylene)-C(O)R 1-2 、-(4- to 6-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 6 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-6 Cycloalkyl or -N(R 1-1 )C(O)(4 to 6 membered heterocycloalkyl), said C 1-6 Alkylene, C 3-6 Cycloalkyl, C 3-6 Cycloalkylene, 4 to 6 membered heterocycloalkyl or 4 to 6 membered heterocycloalkylene are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substituted; R 1-1As defined in any one of formula (II) and formula (IIb) of the present invention, R 1-2 As defined in any one of formula (II) and formula (IIb) of the present invention.

[0271] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 1 -NH2, -C 1-6 Alkylene-NH-C(O)R 1-2 、-C 1-6 Alkylene-N(CH3)-C(O)R 1-2 、-O-(4- to 6-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-6 Cycloalkylene-NH-C(O)R 1-2 、-OC 3-6 Cycloalkylene-N(CH3)-C(O)R 1-2 、-NH-C(O)R 1-2 、-N(CH3)-C(O)R 1-2 、-NH-(4 to 6 membered heterocycloalkylene)-C(O)R 1-2 、-N(CH3)-(4 to 6 membered heterocycloalkylene)-C(O)R 1-2 、-NHC(O)C 3- 6-cycloalkyl, -N(CH3)C(O)C 3-6 Cycloalkyl, -NHC(O)(4 to 6 membered heterocycloalkyl) or -N(CH3)C(O)(4 to 6 membered heterocycloalkyl), wherein the C 1-6 Alkylene, C 3-6 Cycloalkyl, C 3-6 Cycloalkylene, 4 to 6 membered heterocycloalkyl or 4 to 6 membered heterocycloalkylene are each optionally substituted by one or more radicals selected from halogen, -OH, -NH2, -NHCH3, -C 1-6 Alkylene-OH substitution; R 1-2 As defined in any one of formula (IIb) of the present invention.

[0272] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 1 -O-(4- to 6-membered heterocycloalkylene)-C(O)R 1-2 、-NH-C(O)R 1-2 or -N(CH3)-C(O)R 1-2 ; R 1-2 As defined in any one of formula (IIb) of the present invention.

[0273] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 1 -NH2, -NHC 1-6 Alkyl, -O-(4- to 6-membered heterocycloalkylene)-C(O)R 1-2 、-NH-C(O)R 1-2 or -N(CH3)-C(O)R 1- 2 ; R 1-2 As defined in any one of formula (IIb) of the present invention.

[0274] In some embodiments, R 1 and R 11 are independently -N(R 1-1 )-R 1-2 、-NH-S(O)2-R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1- 1 )-C(O)-N(R 1-1 )R 1-2 、-OC(O)-N(R 1-1 )R 1-2 .

[0275] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 1 -NH-S(O)2-R 1-2 、-O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-R 1-2 、-OC(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )C(O)-C 1-6 Alkylene-R 1-2 .

[0276] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-1), Formula (I), Formula (Ib), Formula (II), or Formula (IIb), wherein:

[0277] R1 -O-(4- to 6-membered heterocycloalkylene)-C(O)R 1-2 、-NH-C(O)R 1-2 or -N(CH3)-C(O)R 1-2 ;

[0278] R 1-2 -C 1-6 Alkylene-OH;

[0279] Y is -OH or -CN.

[0280] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-1), Formula (I), Formula (Ib), Formula (II), or Formula (IIb), wherein:

[0281] R 1 -O-(4- to 6-membered heterocycloalkylene)-C(O)R 1-2 or -N(CH3)-C(O)R 1-2 ;

[0282] R 1-2 -C 1-6 Alkylene-OH;

[0283] Y is -OH or -CN.

[0284] In some embodiments, the compound represented by the structure of Formula (IA), Formula (IA-1), Formula (I), Formula (Ib), Formula (II), or Formula (IIb), wherein:

[0285] R 1 -NH-C(O)R 1-2 ;

[0286] R 1-2 -C 1-6 Alkylene-O-NHCH3

[0287] Y is -OH or -CN.

[0288] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 1 NH2, NHCH3,

[0289] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows, wherein R 11NH2, NHCH3,

[0290] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 1 for

[0291] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 1 for

[0292] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 1 for

[0293] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 1 for

[0294] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 1 for

[0295] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 1 for

[0296] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 11 for

[0297] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (I), formula (Ib), formula (II), and formula (IIb) are compounds of formula (IA), wherein R 11NH2, NHCH3,

[0298] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), and formula (Ib), wherein R 11 It is hydrogen, halogen, -OH, -CN, -NH2, -CH3, -OCH3 or -NHCH3.

[0299] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), and formula (Ib), wherein R 11 It is hydrogen, deuterium, -F, -Cl, -OH, -CH3, -OCH3, -NH2 or -NHCH3.

[0300] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), and formula (Ib), wherein R 11 is hydrogen, deuterium or -OCH3.

[0301] In some embodiments, the compound represented by formula (IA), formula (IA-1), formula (I), formula (Ib), and formula (II) is a compound represented by formula (IIb).

[0302] Among them, R 1 NH2 or -NHC 1-6 alkyl;

[0303] Y is -OH or -CN.

[0304] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows: 1 NH2 or NHC 1-3 Alkyl; more preferably, R 1 It is NH2 or NHCH3.

[0305] In some embodiments, the compounds of formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), formula (IA-4), formula (I), formula (Ib), formula (II), and formula (IIb) are as follows: 1 For NHC 1-6 Alkyl; More preferably, R1 For NHC 1-3 Alkyl; More preferably, R 1 is NHCH3.

[0306] In some embodiments, the compound of Formula (IA), Formula (IA), (I), Formula (Ib), Formula (II), Formula (IIb) of the present invention is:

[0307] Those skilled in the art will appreciate that the present invention encompasses compounds obtained by any combination of the various embodiments. Embodiments obtained by combining the technical features or preferred technical features in one embodiment with the technical features or preferred technical features in another embodiment are also included within the scope of the present invention.

[0308] In another aspect, the present invention provides a compound having the structure shown below:

[0309] In another aspect, the present invention provides a pharmaceutical composition comprising (a prophylactically or therapeutically effective amount of) a compound as described herein or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotopically labeled, metabolite or prodrug thereof, and one or more pharmaceutically acceptable carriers.

[0310] A further object of the present invention is to provide a method for preparing the pharmaceutical composition of the present invention, which comprises combining the compound of the present invention or a pharmaceutically acceptable form thereof, or a mixture thereof, with one or more pharmaceutically acceptable carriers.

[0311] The pharmaceutically acceptable carrier that can be used in the pharmaceutical composition of the present invention is a pharmaceutically acceptable carrier. Examples of suitable pharmaceutically acceptable carriers are described in Remington's Pharmaceutical Sciences (2005).

[0312] The pharmaceutical composition can be administered in any form, as long as it prevents, alleviates, prevents or cures the symptoms of a human or animal patient. For example, it can be prepared into various suitable dosage forms according to the route of administration.

[0313] In other embodiments, the administration of the compound or pharmaceutical composition of the present invention can be combined with another treatment method. The other treatment method can be selected from, but not limited to: radiation therapy, chemotherapy, immunotherapy, or a combination thereof.

[0314] The present invention also relates to a pharmaceutical preparation comprising a compound of the present invention or a pharmaceutically acceptable form thereof, or a mixture thereof as an active ingredient, or a pharmaceutical composition of the present invention. In some embodiments, the preparation is in the form of a solid preparation, a semi-solid preparation, a liquid preparation, or a gaseous preparation.

[0315] A further object of the present invention is to provide an article of manufacture, for example, in the form of a kit. As used herein, an article of manufacture is intended to include, but is not limited to, a kit and a package. The article of manufacture of the present invention comprises: (a) a first container; (b) a pharmaceutical composition in the first container, wherein the composition comprises: a first therapeutic agent, the first therapeutic agent comprising: a compound of the present invention or a pharmaceutically acceptable form thereof, or a mixture thereof; (c) an optional package insert indicating that the pharmaceutical composition can be used to treat a neoplastic condition (as defined below); and (d) a second container.

[0316] The first container is a container for holding a pharmaceutical composition. This container can be used for preparation, storage, transportation and / or individual / bulk sales. The first container is intended to encompass bottles, jars, vials, flasks, syringes, tubes (e.g., for cream products), or any other container for preparing, holding, storing, or dispensing pharmaceutical products.

[0317] The second container is a container for accommodating the first container and optional package insert. Examples of the second container include, but are not limited to, boxes (e.g., paper or plastic boxes), boxes, cartons, bags (e.g., paper or plastic bags), pouches, and sacks. The package insert can be physically adhered to the outside of the first container via a cable tie, glue, staples, or other adhesion methods, or it can be placed inside the second container without any physical tool for adhering to the first container. Alternatively, the package insert is located outside the second container. When located outside the second container, it is preferred that the package insert is physically adhered via a cable tie, glue, staples, or other adhesion methods. Alternatively, it can abut or contact the outside of the second container without physical adhesion.

[0318] The package insert is a trademark, label, or indicia that lists information about the pharmaceutical composition within the first container. The information listed is typically determined by the regulatory agency (e.g., the U.S. Food and Drug Administration) that governs the region in which the product is to be sold. Preferably, the package insert specifically lists the indications for which the pharmaceutical composition is approved. The package insert can be made of any material from which the information contained therein or thereon can be read. Preferably, the package insert is a printable material (e.g., paper, plastic, cardboard, foil, adhesive paper, or plastic, etc.) onto which the desired information can be formed (e.g., printed or applied).

[0319] In yet another aspect, the present invention provides use of a compound described herein or a pharmaceutically acceptable form thereof, or a pharmaceutical composition of the present invention, in the preparation of a medicament.

[0320] In another aspect, the present invention provides use of a compound described herein or a pharmaceutically acceptable form thereof, or a pharmaceutical composition of the present invention, in the preparation of a medicament for preventing or treating tumors or cancer.

[0321] In another aspect, the present invention provides a method for preventing or treating tumors, comprising administering (a preventively or therapeutically effective amount of) a compound as described herein or a pharmaceutically acceptable form thereof, or a pharmaceutical composition of the present invention to an individual in need thereof.

[0322] In another aspect, the present invention provides a compound as described herein or a pharmaceutically acceptable form thereof (in a prophylactically or therapeutically effective amount), or a pharmaceutical composition of the present invention, for use in preventing or treating tumors or cancer.

[0323] In another aspect, the present invention provides a method for preventing or treating tumors or cancer by combining (a prophylactically or therapeutically effective amount) a compound as described herein or a pharmaceutically acceptable form thereof, or a pharmaceutical composition of the present invention with another treatment method, including but not limited to: radiation therapy, chemotherapy, immunotherapy, or a combination thereof.

[0324] In some embodiments, the tumor or cancer includes, but is not limited to, breast cancer, colorectal cancer, colon cancer, lung cancer, and prostate cancer, as well as bile duct cancer, bone cancer, bladder cancer, head and neck cancer, kidney cancer, liver cancer, gastrointestinal tissue cancer, esophageal cancer, ovarian cancer, pancreatic cancer, skin cancer, testicular cancer, thyroid cancer, uterine cancer, cervical cancer, and vulvar cancer, as well as leukemia (including chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), and chronic myeloid leukemia (CML)), multiple myeloma, and lymphoma.

[0325] In a further preferred embodiment, the compounds of the present invention can be used in combination with chemoradiotherapy or immunotherapy to prevent or treat tumors or cancers.

[0326] The dosage regimen can be adjusted to provide the optimal desired response. For example, when administered as an injectable, a single bolus, bolus, and / or continuous infusion can be administered, among others. For example, several divided doses can be administered over time, or the dose can be proportionally reduced or increased as indicated by the urgency of the therapeutic situation. It should be noted that dosage values ​​can vary depending on the type and severity of the condition to be alleviated and can include single or multiple doses. Generally, the dosage for treatment varies, depending on considerations such as: the age, sex, and general health of the patient to be treated; the frequency of treatment and the nature of the desired effect; the extent of tissue damage; the duration of symptoms; and other variables that can be adjusted by the individual physician. It will be further understood that for any particular individual, the specific dosage regimen should be adjusted over time according to the individual's needs and the professional judgment of the person administering or supervising the administration of the composition. The dosage and administration regimen of the pharmaceutical composition can be readily determined by one of ordinary skill in the clinical field. For example, the composition or compound of the present invention can be administered in divided doses from 4 times a day to once every 3 days, with the dosage amount being, for example, 0.01 to 1000 mg / dose. The required dose may be administered in one or more doses to achieve the desired result.The pharmaceutical composition according to the present invention may also be provided in unit dosage form.

[0327] General Terms and Definitions

[0328] Unless otherwise defined below, all technical and scientific terms used herein are intended to have the same meaning as those commonly understood by those skilled in the art. References to technology used herein are intended to refer to technology commonly understood in the art, including variations of technology or substitutions of equivalent technology that would be apparent to those skilled in the art. While it is believed that the following terms are well understood by those skilled in the art, the following definitions are set forth to better explain the present invention.

[0329] The terms "include," "comprising," "having," "containing," or "involving," and their variations herein, are inclusive or open-ended and do not exclude other unrecited elements or method steps. Those skilled in the art will understand that the above terms, such as "comprising," encompass the meaning of "consisting of."

[0330] The term "about" means within ±10%, preferably within ±5%, and more preferably within ±2% of the stated numerical value.

[0331] Unless otherwise indicated, concentrations are by weight and ratios (including percentages) are by molar amounts.

[0332] The term "one or more" or the similar expression "at least one" may mean, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more.

[0333] When the lower and upper limits of a numerical range are disclosed, any value and any included range falling within the range are specifically disclosed. In particular, each range of values ​​disclosed herein (in the form "about a to b," or equivalently, "approximately a to b," or equivalently, "about a b") should be understood to represent each value and range encompassed within the broader range.

[0334] For example, the statement "C 1-6 " should be understood to include any sub-ranges therein and each point value, such as C 2-5 、C 3-4 、C 1-2 、C 1-3 、C1-4、C 1-5 etc., as well as C1, C2, C3, C4, C5, C6, etc. For example, the expression “C 3-10 ” should also be understood in a similar manner, for example, any sub-ranges and point values ​​contained therein may be included, for example, C 3-9 、C 6-9 、C 6-8 、C 6-7 、C 7-10 、C 7-9 、C 7-8 、C 8-9 etc. and C3, C4, C5, C6, C7, C8, C9, C 10 etc. For another example, the expression "3-10 yuan" should be understood to include any sub-ranges and point values ​​therein, such as 3-4 yuan, 3-5 yuan, 3-6 yuan, 3-7 yuan, 3-8 yuan, 3-9 yuan, 4-5 yuan, 4-6 yuan, 4-7 yuan, 4-8 yuan, 5-7 yuan, 5-8 yuan, 6-7 yuan, etc., as well as 3, 4, 5, 6, 7, 8, 9, 10 yuan, etc. For another example, the expression "5-10 yuan" should also be understood in a similar manner, such as it can include any sub-ranges and point values ​​contained therein, such as 5-6 yuan, 5-7 yuan, 5-8 yuan, 5-9 yuan, 5-10 yuan, 6-7 yuan, 6-8 yuan, 6-9 yuan, 6-10 yuan, 7-8 yuan, etc., as well as 5, 6, 7, 8, 9, 10 yuan, etc.

[0335] In this specification, groups and substituents thereof can be selected by those skilled in the art to provide stable structural moieties and compounds. When substituents are described by conventional chemical formulas written from left to right, the substituents also include chemically equivalent substituents obtained when the structural formula is written from right to left.

[0336] As used herein, the term "alkyl" refers to a saturated straight or branched chain hydrocarbon group, alone or in combination with other groups. 1-6 "Alkyl" refers to a saturated straight or branched chain hydrocarbon group having 1 to 6 carbon atoms (e.g., 1, 2, 3, 4, 5 or 6 carbon atoms).1-6 "Alkyl" is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl or n-hexyl. The alkyl group in the present invention is optionally substituted with one or more substituents described in the present invention.

[0337] In various parts of the present invention, linking substituents are described. When the structure clearly requires a linking group, the Markush variable listed for that group should be understood to be a linking group. For example, if the structure requires a linking group and the Markush group definition for that variable lists "alkyl", it should be understood that the "alkyl" represents the linking alkylene group. For example, in some specific structures, when an alkyl group is clearly shown as a linking group, the alkyl group represents the linking alkylene group, for example, the group "halo-C 1-6 C in "alkyl" 1-6 Alkyl should be understood as C 1-6 Alkylene.

[0338] As used herein, the term "alkylene" refers to a saturated, linear or branched, divalent hydrocarbon group. 1-6 "Alkylene" refers to a saturated straight or branched divalent hydrocarbon group having 1 to 6 carbon atoms. 1-6 Examples of "alkylene" include, but are not limited to, methylene, ethylene, propylene, or butylene. The alkylene group in the present invention is optionally substituted by one or more substituents described in the present invention.

[0339] In this application, the term "cycloalkyl" refers to a saturated or partially saturated, monocyclic or polycyclic (such as bicyclic) non-aromatic hydrocarbon group. For example, "C 3-12 "Cycloalkyl" or "3-12 membered cycloalkyl" refers to a cycloalkyl group having 3-12 ring carbon atoms (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12). Common cycloalkyl groups include, but are not limited to, monocyclic cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclobutene, cyclopentene, cyclohexene, etc.; or bicyclic cycloalkyl groups, including fused rings, bridged rings or spiro rings, such as bicyclo[1.1.1]pentyl, bicyclo[2.2.1]heptyl, bicyclo[3.2.1]octyl, bicyclo[5.2.0]nonyl, decahydronaphthyl, etc.

[0340] In this application, the term "cycloalkylene" refers to a saturated or partially saturated, monocyclic or polycyclic (such as bicyclic) non-aromatic divalent cyclic group. For example, "C 3-12"Cycloalkylene" or "3-12 membered cycloalkylene" refers to a cycloalkylene group having 3-12 ring carbon atoms (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12). Common cycloalkylene groups include, but are not limited to, monocyclic cycloalkylene groups such as cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, cycloheptylene, cyclobutene, cyclopentene, cyclohexene, etc.; or bicyclic cycloalkylene groups including fused, bridged or spiro rings such as bicyclo[1.1.1]pentylene, bicyclo[2.2.1]heptylene, bicyclo[3.2.1]octylene, bicyclo[5.2.0]nonylene, decahydronaphthylene, etc.

[0341] The term "heterocycloalkyl" refers to a saturated or partially saturated non-aromatic cyclic group containing at least one ring member selected from N, O, P and S, wherein the number of heteroatoms is preferably 1, 2, 3 or 4 (e.g., the number of heteroatoms is 1 or 2, and the heteroatoms are independently selected from N). For example, a 3-8-membered, 3-6-membered, 4-12-membered, or 4-6-membered heterocycloalkyl. In addition, the heterocycloalkyl may contain 0, 1, 2 or 3 oxo groups. Specific examples include, but are not limited to, oxiranyl, oxocyclobutane, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, homopiperazinyl, pyrrolidonyl, and the like.

[0342] The term "heterocycloalkylene" refers to a saturated or partially saturated, non-aromatic divalent cyclic group containing at least one ring member selected from N, O, P and S, wherein the number of heteroatoms is preferably 1, 2, 3 or 4 (e.g., the number of heteroatoms is 1 or 2, and the heteroatoms are independently selected from N). For example, a 3-8-membered, 3-6-membered, 4-12-membered, or 4-6-membered heterocycloalkylene group. In addition, the heterocycloalkylene group may contain 0, 1, 2 or 3 oxo groups. Specific examples include, but are not limited to, oxiranylene, oxocyclobutaneylene, pyrrolidinylene, tetrahydrofuranylene, piperidinylene, piperazinylene, tetrahydropyranylene, homopiperazinylene, and pyrrolidonylene.

[0343] In the present application, the term "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

[0344] In this application, the term "hydroxyl" refers to -OH.

[0345] As used herein, the term "cyano" refers to -CN.

[0346] As used herein, the term "nitro" refers to -NO2.

[0347] As used herein, the term "amino" refers to -NH2.

[0348] In the present application, "oxo" refers to C(O), ie, carbonyl.

[0349] In this application, the term "haloalkyl" when used alone or in combination with other groups refers to an alkyl group as described above in which one or more hydrogen atoms are replaced by a halogen. For example, the term "C 1-6 "Haloalkyl" or "halogenated C 1-6 "Alkyl" refers to a C 1-6 Alkyl. It will be understood by those skilled in the art that when there are more than one halogen substituent, the halogens may be the same or different and may be located on the same or different C atoms. Examples of haloalkyl include, for example, -CH2F, -CHF2, -CF3, -CCl3, -C2F5, -C2Cl5, -CH2CF3, -CH2Cl or -CH2CH2CF3. The haloalkyl groups of the present invention are optionally substituted with one or more substituents described herein.

[0350] In this application, the term "alkoxy" when used alone or in combination with other groups means an alkyl group as described above with an oxygen atom attached to the parent molecular moiety. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, n-butoxy, tert-butoxy, pentoxy, and the like.

[0351] The term "independently" as used in this application means that at least two groups (or fragments) with the same or similar value ranges in a structure may have the same or different meanings under specific circumstances. For example, substituent A and substituent B are each independently hydrogen, halogen, hydroxyl, cyano, alkyl or aryl. When substituent A is hydrogen, substituent B can be either hydrogen, or halogen, hydroxyl, cyano, alkyl or aryl. Similarly, when substituent B is hydrogen, substituent A can be either hydrogen, or halogen, hydroxyl, cyano, alkyl or aryl.

[0352] The term "substituted" as used in this application and its other variant forms in this article refer to that one or more (such as 1, 2, 3 or 4) atoms or atomic groups (such as hydrogen atoms) on the specified atom are replaced by other equivalents, provided that the normal valence of the specified atom or atomic group in the current situation is not exceeded and a stable compound can be formed. If a certain atom or atomic group is described as "optionally substituted by...", it can be substituted or unsubstituted. Unless otherwise indicated, the attachment site of a substituent herein can be from any suitable position of a substituent. When the connecting bond in a substituent is shown as a chemical bond between two atoms connected to each other in a ring system, it means that the substituent can be connected to any ring-forming atom in the ring system.

[0353] When any variable (such as R a) appears multiple times in the definition of a compound, the definition of each position of the variable is independent of the definition of the other positions, and their meanings are independent of each other and do not affect each other. Therefore, if a group is replaced by 1, 2 or 3 R a group substituted, that is, the group may be replaced by up to 3 R a Substitution, where a position R a Definition and other positions R a The definitions of are independent of each other. In addition, combinations of substituents and / or variables are permissible only if such combinations result in stable compounds. The term "optionally replaced by one or more R a "Replaced" means not replaced by R a substituted and replaced by one or more R a Replace the two situations. For example, "the C 1-6 The alkyl group is optionally replaced by one or more R a "Substitution" means C 1-6 Alkyl and (with one or more R a Replaced)C 1-6 alkyl.

[0354] When a group is listed without specifying that it has a substituent, such group is only meant to be unsubstituted. For example, when "C 1-6 When "alkyl" is not limited to "substituted or unsubstituted", it only refers to "C 1-6 Alkyl" itself or "unsubstituted C 1-6 alkyl".

[0355] As used herein, the compounds of the present invention may contain one or more chiral centers and exist in different optically active forms. When a compound contains one chiral center, the compound comprises enantiomers. The present invention includes both isomers and mixtures of isomers, such as racemic mixtures. Enantiomers can be resolved by methods known in the art, such as crystallization and chiral chromatography. When the compound of Formula I contains more than one chiral center, diastereomers may exist. The present invention includes resolved optically pure specific isomers and mixtures of diastereomers. Diastereomers can be resolved by methods known in the art, such as crystallization and chiral chromatography.

[0356] The term "stereoisomer" includes conformational isomers and configurational isomers, wherein configurational isomers mainly include cis-trans isomers and optical isomers. The compounds described in the present invention may exist in the form of stereoisomers, and therefore encompass all possible stereoisomeric forms, including but not limited to cis-trans isomers, enantiomers, diastereomers, atropisomers, etc. The compounds described in the present invention may also exist in the form of any combination or any mixture of the aforementioned stereoisomers, such as meso-, racemic-, and equal mixtures of atropisomers, or single enantiomers, single diastereomers, or mixtures thereof, or single atropisomers or mixtures thereof.

[0357] The term "tautomer" refers to functional isomers that result from the rapid shift of an atom between two positions in a molecule.

[0358] Solid lines may be used in this application Solid wedge or virtual wedge The carbon-carbon bonds of the compounds of the present invention are depicted. The use of solid lines to depict bonds to asymmetric carbon atoms is intended to indicate that all possible stereoisomers at that carbon atom are included (e.g., specific enantiomers, racemic mixtures, etc.). The use of solid or dashed wedges to depict bonds to asymmetric carbon atoms is intended to indicate that the indicated stereoisomers exist. When present in a racemic mixture, solid and dashed wedges are used to define relative stereochemistry, not absolute stereochemistry. Unless otherwise indicated, the compounds of the present invention may exist as stereoisomers, which include cis and trans isomers, optical isomers (e.g., R and S enantiomers), diastereomers, geometric isomers, rotational isomers, conformational isomers, atropisomers, and mixtures thereof. The compounds of the present invention may exhibit more than one type of isomerism and consist of mixtures thereof (e.g., racemic mixtures and diastereomeric pairs).

[0359] Wavy lines may be used in this application The bond to the asymmetric carbon atom is depicted to show that the solid wedge at that carbon atom or virtual wedge One of the absolute configurations of the stereoisomers shown.

[0360] In this application, unless otherwise indicated, the structures described herein may also include compounds that differ only in the presence or absence of one or more isotopically enriched atoms. For example, compounds that are identical to the structures described herein except for the replacement of a hydrogen atom by deuterium or tritium, or a carbon atom by carbon-13 or carbon-14, are within the scope of this application.

[0361] The present invention also encompasses all possible crystalline forms or polymorphs of the compounds of the present invention, which may be single polymorphs or mixtures of more than one polymorph in any ratio.

[0362] Unless otherwise stated, "or" or "and" as used herein means "and / or".

[0363] Unless otherwise specified, the specific groups in this article Refers to the connection location; the two are interchangeable.

[0364] The term "pharmaceutically acceptable form" refers to, but is not limited to, pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, isotopically labeled, metabolites, or prodrugs thereof.

[0365] It should also be understood that certain compounds of the present invention may be used therapeutically in free form or, where appropriate, in the form of pharmaceutically acceptable derivatives thereof. In the present invention, pharmaceutically acceptable derivatives include, but are not limited to, pharmaceutically acceptable salts, esters, solvates, metabolites, or prodrugs that, upon administration to a patient in need thereof, are capable of directly or indirectly providing a compound of the present invention or a metabolite thereof. Therefore, when reference is made herein to a "compound of the present invention," such various derivative forms of the compound are also intended to be encompassed.

[0366] Pharmaceutically acceptable salts of the compounds of the present invention include acid addition salts and base addition salts thereof. Suitable acid addition salts are formed from acids that form pharmaceutically acceptable salts. Suitable base addition salts are formed from bases that form pharmaceutically acceptable salts. For a review of suitable salts, see, for example, "Remington's Pharmaceutical Sciences", Mack Publishing Company, Easton, Pa., (2005); and "Handbook of Pharmaceutical Salts: Properties, Selection, and Use", Stahl and Wermuth (Wiley-VCH, Weinheim, Germany, 2002). Methods for preparing pharmaceutically acceptable salts of the compounds of the present invention are known to those skilled in the art.

[0367] As used herein, the term "ester" refers to esters derived from compounds described herein, including physiologically hydrolyzable esters (which can be hydrolyzed under physiological conditions to release the compounds of the invention in the free acid or alcohol form). The compounds of the invention may themselves also be esters.

[0368] The compounds of the present invention may exist in the form of solvates (preferably hydrates), wherein the compounds of the present invention contain a polar solvent as a structural element of the crystal lattice of the compound, in particular water, methanol or ethanol. The amount of polar solvent, in particular water, may be present in a stoichiometric or non-stoichiometric ratio.

[0369] Those skilled in the art will appreciate that, since nitrogen requires an available lone pair of electrons to be oxidized to oxides, not all nitrogen-containing heterocycles are capable of forming nitrogen oxides. Those skilled in the art will recognize nitrogen-containing heterocycles that are capable of forming nitrogen oxides. Those skilled in the art will also recognize that tertiary amines are capable of forming nitrogen oxides. Synthetic methods for preparing nitrogen oxides of heterocycles and tertiary amines are well known to those skilled in the art and include oxidizing heterocycles and tertiary amines with peroxyacids such as Peracetic Acid and Metachloroperbenzoic Acid (mCPBA), hydrogen peroxide, alkyl hydroperoxides such as tert-butyl hydroperoxide, sodium perborate, and dioxirane such as dimethyldioxirane. These methods for preparing nitrogen oxides have been extensively described and reviewed in the literature, see for example: TL Gilchrist, Comprehensive Organic Synthesis, vol. 7, pp 748-750 (AR Katritzky and AJ Boulton, Eds., Academic Press); and GWH Cheeseman and ESGWerstiuk, Advances in Heterocyclic Chemistry, vol. 22, pp 390-392 (AR Katritzky and AJ Boulton, Eds., Academic Press).

[0370] Also included within the scope of the present invention are metabolites of the compounds of the present invention, i.e., substances formed in vivo upon administration of the compounds of the present invention. Metabolites of the compounds can be identified using techniques known in the art, and their activity can be characterized by assays. Such products can be produced, for example, by oxidation, reduction, hydrolysis, amidation, deamidation, esterification, enzymatic hydrolysis, etc. of the administered compound. Thus, the present invention includes metabolites of the compounds of the present invention, including compounds produced by methods that contact the compounds of the present invention with a mammal for a period of time sufficient to produce their metabolites.

[0371] The present invention further includes within its scope prodrugs of the compounds of the present invention, which are certain derivatives of the compounds of the present invention that may themselves have little or no pharmacological activity and can be converted into compounds of the present invention having the desired activity by, for example, hydrolytic cleavage when administered to the body or thereon. Typically, such prodrugs will be functional group derivatives of the compounds that are readily converted into the desired therapeutically active compounds in vivo. Further information on the use of prodrugs can be found in "Pro-drugs as Novel Delivery Systems", Volume 14, ACS Symposium Series (T. Higuchi and V. Stella). Prodrugs of the present invention can be prepared, for example, by replacing appropriate functional groups present in the compounds of the present invention with certain moieties known to those skilled in the art as "pro-moieties" (e.g., as described in "Design of Prodrugs", H. Bundgaard (Elsevier, 1985)).

[0372] The present invention also encompasses compounds of the present invention that contain protecting groups. During any process for preparing the compounds of the present invention, it may be necessary and / or desirable to protect sensitive or reactive groups on any of the molecules involved, thereby forming a chemically protected form of the compounds of the present invention. This can be achieved using conventional protecting groups, for example, those described in TW Greene & P.G.M. Wuts, Protective Groups in Organic Synthesis, John Wiley & Sons, 2006, which references are incorporated herein by reference. Protecting groups can be removed at an appropriate subsequent stage using methods known in the art.

[0373] The present invention also encompasses methods for preparing the compounds described herein. It should be understood that the compounds of the present invention can be synthesized using the methods described below, as well as synthetic methods known in the art of synthetic organic chemistry or variations thereof known to those skilled in the art. Preferred methods include, but are not limited to, those described below. The reaction can be carried out in a solvent or solvent mixture that is appropriate for the reagents and materials used and suitable for the transformation to be achieved.

[0374] The terms "active ingredient," "therapeutic agent," "active substance," or "active agent" refer to a chemical entity that is effective in treating one or more symptoms of a target disorder or condition.

[0375] As used herein, the term "effective amount" (e.g., "therapeutically effective amount" or "prophylactically effective amount") refers to an amount of active ingredient that, after administration, will achieve the desired effect to some extent, such as alleviating one or more symptoms of the condition being treated or preventing the appearance of the condition or its symptoms.

[0376] As used herein, unless otherwise indicated, the terms "treat," ...

[0377] As used herein, "subject" includes humans and non-human animals. Exemplary human subjects include human subjects suffering from diseases (e.g., the diseases described herein) (referred to as patients) or normal individuals. "Non-human animals" herein include all vertebrates, such as non-mammals (e.g., birds, amphibians, reptiles) and mammals, such as non-human primates, livestock and / or domesticated animals (e.g., sheep, dogs, cats, cows, pigs, etc.).

[0378] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

[0379] The reagents and raw materials used in the present invention are commercially available.

[0380] The positive progress of the present invention is that the novel highly active ecteinascidin derivatives provided by the present invention can achieve at least one of the following technical effects: (1) high inhibitory activity against tumor cells; (2) excellent physicochemical properties (such as solubility, physical and / or chemical stability); (3) excellent safety (lower toxicity and / or fewer side effects, wider therapeutic window), etc. DETAILED DESCRIPTION

[0381] The present invention includes all combinations of the described specific embodiments. Further embodiments of the present invention and the full scope of applicability will become apparent from the detailed description provided below. However, it should be understood that although the detailed description and specific examples indicate preferred embodiments of the present invention, these descriptions and examples are provided by way of illustration only, because various changes and modifications within the spirit and scope of the present invention will become apparent to those skilled in the art from this detailed description. For all purposes, all publications, patents and patent applications cited herein, including citations, will be incorporated herein by reference in their entirety. The present invention is further illustrated below by way of example, but the present invention is not limited to the scope of the described embodiments. The experimental methods for which specific conditions are not specified in the following examples are selected according to conventional methods and conditions, or according to the product specifications.

[0382] Mass spectrometry (MS) was measured using an Agilent (ESI) mass spectrometer, manufactured by Agilent, model: Agilent 6120B.

[0383] Preparative high performance liquid chromatography (HPLC) was performed using a Shimadzu LC-8A preparative liquid chromatograph (YMC, ODS, 250 × 20 mm column).

[0384] Thin layer chromatography purification was performed using GF 254 (0.4-0.5 nm) silica gel plates produced in Yantai.

[0385] The reaction is monitored by thin layer chromatography (TLC) or liquid chromatography-mass spectrometry (LC-MS). The developing solvent systems used include, but are not limited to, dichloromethane and methanol systems, n-hexane and ethyl acetate systems, and petroleum ether and ethyl acetate systems. The volume ratio of the solvents is adjusted according to the polarity of the compounds or by adding triethylamine.

[0386] Column chromatography generally uses Qingdao Ocean 200-300 mesh silica gel as the stationary phase. Eluent systems include, but are not limited to, dichloromethane and methanol systems and n-hexane and ethyl acetate systems. The volume ratio of the solvents is adjusted according to the polarity of the compound, and a small amount of triethylamine can also be added for adjustment.

[0387] Unless otherwise specified in the examples, the reaction temperature is room temperature (20°C to 30°C).

[0388] Unless otherwise specified, the reagents used in the examples were purchased from Acros Organics, Aldrich Chemical Company, Nanjing Yaoshi Technology, Anaiji, or Shanghai Shuya Pharmaceutical Technology.

[0389] The above embodiments do not limit the solutions of the present application in any way. In addition to those described herein, various modifications of the present invention will be apparent to those skilled in the art based on the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. Each reference cited in this application (including all patents, patent applications, journal articles, books and any other disclosures) is incorporated by reference in its entirety.

[0390] In the conventional synthesis methods, preparation examples, examples, and intermediate synthesis examples, starting materials were commercially available and purchased from Shanghai Leyan, Shanghai Shaoyuan, Bid Biotech, Aladdin Reagents, and others. The key starting material M24 and the reference compound trabectedin were both purchased from Zhejiang Zhongke Chuangyue. The meanings of the abbreviations are shown in the table below.

[0391] Synthesis of intermediates:

[0392] Intermediate Preparation Example 1: Preparation of Compound Int7

[0393] Step 1: Preparation of compound Int7-2

[0394] Compound Int7-1 (5.0 g, 32.7 mmol) was dissolved in anhydrous methanol (80 mL), and a 30% aqueous solution of methylamine (6.8 g, 65.4 mmol) was added. After stirring for 30 minutes, trimethylsilyl cyanide (4.9 g, 49.3 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. The reaction was monitored for completion by LCMS. The reaction solution was concentrated under reduced pressure, and the residue was extracted with saturated sodium bicarbonate and DCM. After stirring, the layers were separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford Int7-2 (4.12 g, 64% yield).

[0395] Step 2: Preparation of compound Int7-3

[0396] Compound Int7-2 (1.36 g, 7.08 mmol) was dissolved in THF (40 mL), and DIEA (1.37 g, 10.62 mol) and (Boc)2O (3.2 g, 17 mmol) were added. The reaction was stirred at room temperature for 16 h. The reaction solution was cooled to room temperature and concentrated under reduced pressure. The residue was purified by column chromatography to afford Int7-3 (1.2 g, 58% yield).

[0397] MS m / z(ESI):293.1[M+H] +

[0398] 1 H NMR (400MHz, CDCl3) δ7.28 (dd, J=8.5, 2.4Hz, 1H), 7.15 (d, J=2.4Hz, 1H), 6.98 (d ,J=8.5Hz,1H),6.40(brs,1H),3.86(s,3H),2.73(s,3H),1.52(d,J=16.5Hz,9H).

[0399] Step 3: Preparation of compound Int7

[0400] Compound Int7-3 (0.5 g, 1.28 mmol) was dissolved in a mixture of EtOH (40 mL) and aqueous ammonia (30%, 10 mL). RanyNi (100 mg) was added, and the mixture was replaced with hydrogen three times. The pressure was then increased to 1.5 MPa and the reaction was continued at 50°C for 16 h. LCMS monitored the reaction for completion. The reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography to afford Int7 (0.26 g, 69% yield).

[0401] Intermediate Preparation Example 2:

[0402] Step 1: Preparation of compound Int1-2

[0403] Int1-1 (450.0 mg, 2.13 mmol) was dissolved in MeOH (10 mL), 10% Pd / C (50 mg) was added, and the mixture was replaced with hydrogen. The mixture was stirred under hydrogen at 20°C for 2 hours. The resulting mixture was filtered through Celite and concentrated to dryness to afford Int1-2 (385 mg crude) as a colorless oil, which was used in the next reaction.

[0404] Step 2: Preparation of Compound Int1-3

[0405] Int1-2 (385 mg, 2.13 mmol) was dissolved in THF (10 mL), and saturated NaHCO3 (3 mL) and Boc2O (928.68 mg, 4.26 mmol) were added, followed by stirring at 20°C overnight. The resulting mixture was adjusted to pH 5-6 with 1N HCl and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to afford compound Int1-3 (280.0 mg, 47% yield).

[0406] Step 3: Preparation of Compound Int1-4

[0407] Int1-3 (270.0 mg, 0.96 mmol) was dissolved in DCM (10 mL) and DMF (1 drop), cooled to 0°C, and oxalyl chloride (243.7 mg, 1.92 mmol) was added under nitrogen. After addition, the mixture was naturally warmed to room temperature and reacted for 30 minutes. The mixed solution was cooled to 0°C, and aqueous ammonia was slowly added to adjust the pH to approximately 8. The mixture was then extracted with ethyl acetate, separated, and the organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to obtain compound Int1-4 (230.0 mg, 85.48% yield).

[0408] Step 4: Preparation of Compound Int1

[0409] Int1-4 (230.0 mg, 0.82 mmol) was dissolved in THF (5 mL), followed by the addition of BH3 / THF (6 mL, 1 N), and the mixture was heated to 70°C and stirred for 2 hours. The reaction solution was then cooled to 0°C, and methanol was slowly added dropwise to quench the reaction. HCl / MeOH solution was then added, and the mixture was heated to 70°C and stirred for 2 hours. The reaction solution was cooled to 40°C and concentrated under reduced pressure. The residue was purified by reverse-phase HPLC to afford compound Int1 (70.0 mg, 51.33% yield).

[0410] Intermediate Preparation Example 3: Preparation of Compound Int2

[0411] Refer to the method of steps 3 to 4 of intermediate preparation example 2 to synthesize intermediate Int2

[0412] Intermediate Preparation Example 4: Preparation of Compound Int3

[0413] Refer to the method of steps 3 to 4 of intermediate preparation example 2 to synthesize intermediate Int3

[0414] Intermediate Preparation Example 5: Preparation of Compound Int4

[0415] Refer to the method of steps 3 to 4 of intermediate preparation example 2 to synthesize intermediate Int4

[0416] Intermediate Preparation Example 6: Preparation of Compound Int5

[0417] Refer to the method of steps 3 to 4 of intermediate preparation example 2 to synthesize intermediate Int5

[0418] Intermediate Preparation Example 7: Preparation of Compound Int6

[0419] Step 1: Preparation of compound Int6-2

[0420] To a solution of compound Int6-1 (1.0 g, 6.6 mmol) in DCM (30 mL) at 0°C, zinc iodide (1.1 g, 3.3 mmol) and TMSCN (1.9 g, 19.8 mmol) were added, and the mixture was stirred at 0°C for 1 hour. The reaction was monitored for completion by TLC. The supernatant was concentrated, and the residue was purified by column chromatography to afford compound Int6-2 (1.17 g, 99% yield).

[0421] Step 2: Preparation of compound Int6-3

[0422] To a solution of compound Int6-2 (1.17 g, 6.57 mmol) in THF (10 mL) at 0°C was added a solution of borane in tetrahydrofuran (20 mL, 20.00 mmol, 1 M). The reaction was stirred at 70°C for 2 hours. The temperature was lowered to 0°C, and methanol (100 mL) was slowly added to quench the reaction. The reaction solution was concentrated, and the residue was purified by column chromatography to afford compound Int6-3 (1.19 g, 99% yield).

[0423] Step 3: Preparation of compound Int6-4

[0424] To a solution of compound Int6-3 (1.19 g, 6.53 mmol) in tetrahydrofuran (10 mL) was added saturated aqueous sodium bicarbonate (10 mL) and Boc2O (2.85 g, 13.06 mmol) at 25°C, and the mixture was stirred at 25°C for 10 minutes. The reaction mixture was concentrated under reduced pressure to remove THF, and then ethyl acetate and water were added. The layers were separated, and the organic phase was concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound Int6-4 (1.5 g, yield 81%).

[0425] Step 4: Preparation of compound Int6-5

[0426] To a solution of compound Int6-4 (1.3 g, 4.61 mmol) in MeOH / H2O (40 mL / 8 mL) at 25°C, iron powder (2.6 g, 46.05 mmol) and ammonium chloride (2.5 g, 46.05 mmol) were added, and the mixture was stirred at 80°C for 4 hours. After completion of the reaction, the mixture was filtered, the filtrate was concentrated to dryness, and the residue was purified by column chromatography to afford compound Int6-5 (1 g, 86% yield).

[0427] Step 5: Preparation of compound Int6

[0428] To a solution of compound Int6-5 (900.00 mg, 3.57 mmol) in dichloromethane (3 mL) was added a solution of dioxane hydrochloride (3 mL, 12.00 mmol, 4 M) at 25°C, and the mixture was stirred at 25°C for 1 hour. The reaction solution was concentrated and purified by reverse-phase HPLC to afford Int6 (300.0 mg, 55% yield).

[0429] MS m / z(ESI):152.9[M+H] + .

[0430] Intermediate Preparation Example 8: Preparation of Compound Int7

[0431] Step 1: Preparation of compound Int7-2

[0432] To a solution of compound Int7-1 (600.00 mg, 2.53 mmol) in ethanol (6 mL) was added 37% aqueous formaldehyde (10 drops) and sodium cyanoborohydride (317.90 mg, 5.06 mmol) at 30°C, and the mixture was stirred at 30°C for 30 minutes. The reaction solution was concentrated to dryness, and the residue was purified by reverse-phase HPLC to afford compound Int7-2 (150.0 mg, 23% yield).

[0433] Step 1: Preparation of compound Int7

[0434] To a solution of compound Int7-2 (150.00 mg, 0.60 mmol) in dichloromethane (2 mL) was added a solution of hydrochloric acid in dioxane (1.5 mL, 6.00 mmol, 4 M) at 30°C, and the mixture was stirred at 30°C for 60 minutes. The reaction solution was concentrated to dryness, and the residue was purified by reverse-phase HPLC to afford compound Int7 (80.0 mg, 88% yield).

[0435] Example 1: Synthesis of Compound 53 and Compound 45

[0436] Step 1: Preparation of compound 53-1

[0437] Compound M24 (100 mg, 0.16 mmol) and compound Int7 (0.80 mmol) were dissolved in anhydrous ethanol (5 mL), and acetic acid (120 mg, 2.00 mmol) was added. The mixture was stirred at 60°C overnight. After completion of the reaction as monitored by LCMS, the temperature was cooled to room temperature, and the reaction solution was concentrated under reduced pressure. The residue was added with ethyl acetate and saturated aqueous sodium bicarbonate solution, stirred, and separated. The organic phase was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by Pre-TLC to afford compound 53-1 (112 mg, 78% yield).

[0438] Step 2: Preparation of compound 53

[0439] Compound 53-1 (112 mg, 0.12 mmol) was dissolved in DCM (2 mL) and added to TFA (0.5 mL). The reaction was allowed to react at room temperature for 2 h. LCMS monitored the reaction for completion. The reaction solution was concentrated to dryness under reduced pressure, adjusted to pH 8 with saturated sodium bicarbonate solution, and extracted three times with DCM. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford crude product 53 (90 mg, 93% yield). This was further purified by reverse-phase HPLC to afford compound 53 (70 mg, 72% yield).

[0440] MS m / z(ESI):800.1[M+H] + .

[0441] 1H NMR(400MHz,DMSO-d6)δ9.38(s,1H),8.95–8.65(m,1H),8.50(s,1H),8.43–8.10(m,1H),6.85–6.65(m,1H) ,6.55–6.35(m,2H),6.23–6.11(m,2H),5.95–5.15(brs,4H),5.06(t,J=12.2Hz,1H),4.53(s,2H),4.30–4.0 5(m,3H),4.01–3.88(m,1H),3.68–3.60(m,3H),3.60–3.50(m,3H),3.50–3.24(m,2H),3.24–3.03(m,1H),3. 01–2.61(m,3H),2.43(t,J=5.3Hz,2H),2.29(s,2H),2.24(s,2H),2.14–2.05(m,3H),1.97(d,J=6.8Hz,3H).

[0442] Step 3: Preparation of compound 45

[0443] Compound 53 (60.0 mg, 0.075 mmol) was dissolved in DMF (1.5 mL), and glycolic acid (5.7 mg, 0.075 mol), HATU (28.7 mg, 0.075 mmol), and DIEA (11.6 mg, 0.090 mmol) were added sequentially. The mixture was stirred at room temperature for 2 h, and the reaction was monitored for completion by LCMS. Ethyl acetate and saturated aqueous sodium bicarbonate solution were added, stirred, and the layers separated. The organic phase was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by preparative HPLC to afford compound 45 (50 mg, 64% yield).

[0444] MS m / z(ESI):858.3[M+H] + .

[0445] The compound was further purified by Pre-TLC using a developing solvent (DCM:MeOH = 10:1) to obtain two compounds. Peak 1 had a retention time of 1.557 min on LCMS, and Peak 2 had a retention time of 1.543 min on LCMS. Characterization is as follows:

[0446] Peak 1:

[0447] MS m / z(ESI):858.3[M+H] + .

[0448] 1H NMR (400MHz, DMSO) δ9.21 (s, 1H), 8.75 (s, 1H), 6.51–6.29 (m, 3H), 6.16 (d, J = 9.1Hz, 2H) ,5.14(s,1H),5.04(d,J=11.6Hz,1H),4.54–4.42(m,3H),4.21–4.16(m,1H),4.13–4.08 (m,1H),4.07–4.01(m,2H),3.62(s,3H),3.52(s,3H),2.83–2.67(m,4H),2.47–2.30(m, 3H),2.36–2.29(m,3H),2.22–2.16(m,3H),2.04(s,3H),1.98(s,3H),1.28–1.20(m,6H).

[0449] Peak 2:

[0450] MS m / z(ESI):858.3[M+H] + .

[0451] 1 H NMR(400MHz,DMSO-d6)δ9.26(s,1H),8.79(s,1H),6.50–6.40(m,1H),6.40–6.23(m,2H),6.20– 6.10(m,2H),5.40–5.25(m,1H),5.10–5.00(m,1H),4.70–4.60(m,1H),4.53–4.43(m,1H),4.24 –4.19(m,2H),4.15–4.08(m,3H),3.63(s,3H),3.21–3.13(d,J=4.4Hz,3H),2.82–2.64(m,4H), 2.34–2.28(m,3H),2.25–2.16(m,3H),2.08–2.03(m,3H),2.01–1.96(m,3H),1.29–1.21(m,6H).

[0452] Example 2: Synthesis of Compound 46

[0453] Compound 45 (30 mg, 0.034 mmol) was dissolved in ACN (3 mL) and water (2 mL), and silver nitrate (143 mg, 0.840 mmol) was added. The mixture was stirred at room temperature in the dark for 12 hours. After completion of the reaction as monitored by LCMS, saturated aqueous sodium bicarbonate solution was added, stirred, and the layers separated. The organic phase was retained, and the aqueous phase was extracted once with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by preparative HPLC to afford compound 46 (5 mg, 17% yield).

[0454] MS m / z(ESI):849.4[M+H] + .

[0455] 1 H NMR (400MHz, CDCl3) δ6.67-6.29(m,3H),6.08-5.91(m,2H),5.84-5.80(m,1H),5.63-5.50(m ,1H),5.40-5.30(m,1H),5.20-5.04(m,1H),4.88-4.84(m,1H),4.60-4.45(m,2H),4.45-4.0 0(m,5H),3.79(d,J=3.6Hz,3H),3.75-3.70(m,1H),3.67-3.62(m,3H),3.58-3.15(m,3H),3. 00-2.78(m,3H),2.60-2.58(m,1H),2.49-2.45(m,2H),2.38-2.20(m,9H),2.10-2.00(m,4H).

[0456] Example 3: Synthesis of Compound 55

[0457] Compound Int1 (50.0 mg, 0.29 mmol) and NaOAc (200 mg, 2.46 mmol) were added separately to a solution of compound M24 (90.0 mg, 0.14 mmol) in acetic acid (3.0 mL) at room temperature. The reaction mixture was heated to 65°C and stirred for 3 h. The resulting mixture was then concentrated, and the residue was purified by reverse-phase HPLC to afford compound 55 (75 mg, 69% yield).

[0458] MS m / z(ESI):770.2[M+H] + .

[0459] 1H NMR (400MHz, DMSO-d6) δ8.69(s,1H),6.43(s,1H),6.20(s,1H),6.17(s,1H),6.15(s,1H),6.14(s,1H),5.02(d,J=11.6H z,1H),4.61(s,2H),4.47(d,J=2.8Hz,2H),4.18(d,J=3.6Hz,1H),4.09(s,1H),4.00(dd,J=2.0,11.2Hz,1H),3.63(s,3H ),3.47(s,3H),3.38-3.34(m,1H),3.32-3.26(m,1H),2.99-2.93(m,1H),2.83-2.75(m,2H),2.71-2.67(m,1H),2.40-2. 32(m,2H),2.29(s,3H),2.24(s,1H),2.20(s,3H),2.10(d,J=14.4Hz,1H),2.04(s,3H),1.97(s,3H),1.79-1.68(m,1H).

[0460] Example 4: Synthesis of Compound 59

[0461] Step 1: Preparation of compound 59-1

[0462] To a solution of compound 53-1 (80.0 mg, 0.09 mmol) in DMF (12 mL) were added Cs2CO3 (57.9 mg, 0.18 mmol) and iodomethane (25.2 mg, 0.18 mmol) at room temperature. The reaction mixture was stirred at room temperature for 1 minute. Ethyl acetate and saturated aqueous sodium bicarbonate were added, stirred, and the layers separated. The organic phase was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography to afford compound 59-1 (30.0 mg, 37% yield).

[0463] Step 2: Preparation of compound 59-2

[0464] To a solution of compound 59-1 (30.0 mg, 0.03 mmol) in DCM (1 mL) was added HCl / dioxane (4 mmol, 1 mL, 4 M) at room temperature. The reaction mixture was stirred at room temperature for half an hour. After concentration, the residue was purified by column chromatography to afford compound 59-2 (20.0 mg, 74% yield).

[0465] Step 3: Preparation of compounds 59R and 59S

[0466] To a solution of compound 59-2 (20.0 mg, 0.03 mmol) in DMF (4 mL) were added glycolic acid (13.1 mg, 0.17 mmol), HATU (31.9 mg, 0.08 mmol), HOAT (31.9 mg, 0.24 mmol), and TMP (38.3 mg, 0.32 mmol) at room temperature. The reaction mixture was stirred at room temperature for 1 hour. LCMS confirmed the reaction was complete. Ethyl acetate and saturated aqueous ammonium chloride were added, stirred, and the mixture was separated. The organic phase was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by Pre-TLC using a developing solvent (DCM:MeOH = 10:1) to obtain two compounds. The retention time of peak 1 on LCMS was 1.649 min, and the retention time of peak 2 on LCMS was 1.622 min. Characterization is as follows:

[0467] Peak 1: 6 mg, yield 30%

[0468] MS m / z(ESI):872.2[M+H] +

[0469] 1 H NMR (400MHz, DMSO-d6) δ8.74 (s, 1H), 6.74-6.30 (m, 3H), 6.15 (d, J = 9.5Hz, 2H), 5.44-4.90 (m, 2H), 4.40-4.34 (m, 3H), 4.22-4.05 (m, 5H), 3.68-3. 57(m,6H),3.51(s,3H),3.28-3.27(m,3H),3.00-2.62(m,3H),2.42(d,J= 3.1Hz, 3H), 2.32 (d, J = 2.3Hz, 3H), 2.22-2.18 (m, 4H), 2.12-1.87 (m, 8H).

[0470] Peak 2: 6 mg, yield 30%

[0471] MS m / z(ESI):872.2[M+H] +

[0472] 1H NMR (400MHz, DMSO-d6) δ8.74 (d, J=6.3Hz, 1H), 6.49-6.29 (m, 3H), 6.14 (d, J= 4.1Hz,2H),5.40-5.27(m,1H),5.05(d,J=11.4Hz,1H),4.67-4.42(m,3H),4. 30-4.03(m,5H),3.63(t,J=2.4Hz,6H),3.49(s,3H),3.27(d,J=12.1Hz,3H), 2.86-2.65(m,3H),2.42-2.28(m,6H),2.22-2.18(m,4H),2.06-1.94(m,8H).

[0473] Example 5: Synthesis of Compound 61

[0474] To a solution of compound 45 (25.0 mg, 0.006 mmol) in ethanol (1 mL) was added 37% formic acid (4 drops) and NaBH3CN (20.0 mg, 0.32 mmol) at room temperature. The reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was purified by reverse-phase HPLC to afford compound 51 (10.0 mg, 40% yield).

[0475] MS m / z(ESI):872.8[M+H] +

[0476] 1 H NMR(400MHz,DMSO-d6)δ9.15(d,J=14.0Hz,1H),8.71(d,J=10.2Hz,1H),6.4 5-6.19(m,3H),6.11(d,J=9.7Hz,2H),5.39-4.78(m,2H),4.68-4.43(m,2H), 4.36-3.98(m,4H),3.79-3.54(m,4H),3.52-3.34(m,4H),3.30-3.20(m,3H), 2.87-2.80(m,2H),2.40-2.28(m,7H),2.22-2.06(m,6H),2.01-1.98(m,8H).

[0477] Example 6: Synthesis of Compound 89

[0478] Compound 89 was synthesized by referring to the method of step 2 to step 3 of Example 1.

[0479] MS m / z(ESI):858.2[M+H] + .

[0480] Example 7: Synthesis of Compound 91

[0481] Compound 91 was synthesized by referring to the method of step 2 to step 3 of Example 1

[0482] MS m / z(ESI):858.2[M+H] + .

[0483] Example 8: Synthesis of Compound 81

[0484] Compound 81 was synthesized by referring to the method of step 2 to step 3 of Example 1.

[0485] MS m / z(ESI):828.2[M+H] + .

[0486] 1 H NMR (400MHz, DMSO-d6) δ9.32(s,1H),8.73(s,1H),7.67(t,J=6.0Hz,1H),6.83(d,J=8.0Hz,1H),6.48-6.39(m,2H),6.34(d,J=2.4Hz,1H),6. 25(s,1H),6.16(s,1H),5.56(t,J=5.6Hz,1H),5.09(d,J=11.2Hz,1H),4.54-4.50(m,1H),4.43(d,J=2.4Hz,1H),4.19(d,J=4.0Hz,1H),4.14 -4.12(m,1H),4.08-4.05(m,1H),3.85(d,J=3.6Hz,2H),3.65-3.64(m,3H),3.40(d,J=10.4Hz,1H),3.22(d,J=4.4Hz,1H),3.15-3.08(m,1H) ,2.89-2.77(m,2H),2.72–2.64(m,1H),2.58-2.54(m,1H),2.38-2.33 (m,1H),2.29(s,3H),2.15(s,3H),1.97(d,J=6.4Hz,6H),1.80(s,1H).

[0487] Example 9: Synthesis of Compound 83

[0488] Compound 83 was synthesized by referring to the method of step 2 to step 3 of Example 1.

[0489] MS m / z(ESI):828.2[M+H] + .

[0490] 1 H NMR (400MHz, DMSO-d6) δ9.34(s,1H),8.73(s,1H),7.47(t,J=4.0Hz,1H),6.68(d,J=8.8Hz,1H),6.49(s,1H),6.45(dd,J=8.8,2.4Hz,1H),6 .34(d,J=2.4Hz,1H),6.26(s,1H),6.15(s,1H),5.54(t,J=5.6Hz,1H),5.05(d,J=11.2Hz,1H),4.55-4.51(m,1H),4.46(d,J=2.4Hz,1H),4.1 9(d,J=4.0Hz,1H),4.10(s,1H),4.04-3.94(m,1H),3.85(d,J=5.2Hz,2H),3.63(s,3H),3.50-3.45(m,1H),3.42-3.38(m,1H),3.21(d,J=4. 8Hz,1H),2.91-2.75(m,3H),2.39-2.28(m,3H),2.29(s,3H),2.22-2.14(m,4H),2.02(d,J=7.6Hz,6H),1.97(s,1H),1.70(d,J=14.4Hz,1H).

[0491] Example 9: Synthesis of Compound 93

[0492] Step 1: Preparation of compound 74

[0493] M24 (45.0 mg, 72.4 μmol) and compound 74-1 (45.0 mg, 330.4 μmol) were dissolved in acetic acid (2 mL), and NaOAc (80 mg, 975.3 μmol) was added. The mixture was stirred at 65°C for 1 hour. LCMS confirmed the reaction was complete, and the product was concentrated under reduced pressure. The residue was purified by reverse-phase HPLC to afford compound 74 (39.8 mg, 74.25% yield).

[0494] MS m / z(ESI):740.7[M+H] + .

[0495] 1H NMR(400MHz,DMSO-d6)δ8.73(s,1H),6.55(d,J=8.5Hz,1H),6.44(s,1H),6.25(s,1H),6.21(dd,J=8 .5,2.3Hz,1H),6.15-6.12(m,2H),5.04(d,J=11.3Hz,1H),4.91(s,2H),4.44(d,J=2.6Hz,2H),4.19 (d,J=3.6Hz,1H),4.05(s,1H),3.94(d,J=9.8Hz,1H),3.63(s,3H),3.24-3.06(m,2H),2.78(d,J=5. 0Hz,2H),2.69-2.57(m,1H),2.45-2.31(m,3H),2.28(s,3H),2.22(s,3H),2.03(s,3H),1.98(s,4H).

[0496] Step 2: Preparation of compound 93-1

[0497] Compound 74 (30.0 mg, 0.041 mmol) was dissolved in DMF (1 mL), and tert-butyloxycarbonylaminooxyacetic acid (7.8 mg, 0.041 mol), HATU (15.7 mg, 0.041 mmol), and DIEA (11.6 mg, 0.090 mmol) were added sequentially. The mixture was stirred at room temperature for 2 h, and the reaction was monitored for completion by LCMS. Ethyl acetate and saturated aqueous sodium bicarbonate were added, stirred, and the layers separated. The organic phase was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography to afford compound 93-1 (26.5 mg, 70% yield).

[0498] Step 3: Preparation of compound 93

[0499] Compound 93-1 (26.5 mg, 0.028 mmol) was dissolved in DCM (2 mL) and added to TFA (0.5 mL). The reaction was allowed to react at room temperature for 2 h. LCMS monitored the reaction for completion. The reaction solution was concentrated to dryness under reduced pressure, adjusted to pH 8 with saturated sodium bicarbonate solution, and extracted three times with DCM. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. Reverse-phase HPLC was used to prepare and purify compound 93 (3.4 mg, 15% yield). MS m / z (ESI): 827.2 [M+H] + .

[0500] 1H NMR (400MHz, DMSO-d6) δ9.55(s,1H),8.76(s,1H),7.32(s,1H),7.27(d,J=8.7Hz,1H),6.90-6.80(m,2H),6.46(s,1H),6.27(s, 1H),6.17(s,1H),5.06(d,J=11.3Hz,1H),4.46(d,J=2.5Hz,1H),4.20(d,J=4.0Hz,1H),4.08(d,J=9.1Hz,3H),4.01(d,J=10.2H z,1H),3.63(s,3H),3.22(d,J=3.7Hz,1H),3.16-3.11(m,1H),2.79(d,J=4.7Hz,2H),2.69-2.65(m,1H),2.56(d,J=6.4Hz,4H), 2.43(d,J=14.8Hz,2H),2.36–2.31(m,1H),2.28(s,3H),2.23(s,3H),2.04(s,3H),1.99(s,3H),1.77-1.67(s,1H),1.23(s,4H).

[0501] Example 10: Synthesis of Compound 94

[0502] Compound 94 was synthesized by referring to the method of Step 2 to Step 3 of Example 9.

[0503] MS m / z(ESI):857.2[M+H] + .

[0504] 1 H NMR(400MHz,DMSO-d6)δ9.18(s,1H),8.91(s,1H),7.90(s,1H),6.52(s,1H),6.32(s,1H),6.22(s,1 H),6.19(s,1H),5.18(d,J=10.4Hz,1H),4.66-4.57(m,2H),4.25-4.19(m,6H),3.65(s,4H),3.62(s, 4H),3.46(d,J=8.0Hz,1H),3.35(d,J=4.8Hz,2H),3.14(s,1H),2.90-2.84(m,1H),2.76(s,1H),2.6 9-2.66(m,1H),2.62(s,3H),2.43-2.36(s,2H),2.31(s,3H),2.25(s,3H),2.01(s,3H),1.98(s,3H).

[0505] Example 11: Synthesis of Compound 216 and Compound 217

[0506] Step 1: Preparation of compound 216

[0507] To a solution of M24 (50.00 mg, 0.08 mmol) and compound Int6 (39.17 mg, 0.26 mmol) in acetic acid (5 mL) was added sodium acetate (98.96 mg, 1.21 mmol) at 20°C, and the mixture was stirred at 65°C for 2 hours. The reaction mixture was concentrated and purified by reverse-phase HPLC to afford compound 216 (27.0 mg, 45% yield).

[0508] MS m / z(ESI):756.3[M+H] + .

[0509] 1 H NMR (400MHz, DMSO-d6) δ8.74 (d, J = 5.6Hz, 1H), 6.71-6.38 (m, 3H), 6.32-6.22 (m, 2H), 6.15 (s, 1H), 5.13-4.57 (m, 4H), 4. 45-4.42(m,2H),4.19-3.93(m,4H),3.63(d,J=5.9Hz,3H),3.23-2.92(m,3H),2.85-2.60(m,3H),2.39-2.23(m,8H),2.09 -1.90(m,7H).

[0510] Step 2: Preparation of compound 217

[0511] Compound 217 was synthesized according to the method of Step 3 of Example 9.

[0512] MS m / z(ESI):814.3[M+H] + .

[0513] 1H NMR (400MHz, DMSO-d6) δ9.58(d,J=4.2Hz,1H),8.77(d,J=5.2Hz,1H),7.71(d,J=37.1Hz,1H),7.35(d,J=8.6Hz,1H),7. 21(s,1H),6.83(dd,J=20.0,9.4Hz,1H),6.47(d,J=6.3Hz,1H),6.27(d,J=2.3Hz,1H),6.17(s,1H),5.68-5.52(m,1H),5 .39-5.20(m,1H),5.13-5.04(m,1H),4.46(d,J=9.7Hz,2H),4.27-4.18(m,2H),4.12-3.97(m,2H),3.93(d,J=5.9Hz,2H) ,3.64(d,J=6.5Hz,3H),3.09-2.97(m,2H),2.83-2.75(m,3H),2.70-2.65(m,1H),2.34-2.21(m,7H),2.07-1.94(m,8H).

[0514] Example 12: Synthesis of Compound 39

[0515] Compound 39 was synthesized by referring to the method of Step 2 to Step 3 of Example 9.

[0516] MS m / z(ESI):812.0[M+H] + .

[0517] 1 H NMR(400MHz,DMSO-d6)δ8.78(s,1H),7.11-6.84(m,3H),6.47(s,1H),6.25(s,1H), 6.16(s,1H),5.08(d,J=11.4Hz,1H),4.54(t,J=5.7Hz,1H),4.48(s,2H),4.21(d,J= 3.6Hz,1H),4.11-3.97(m,2H),3.80-3.63(m,5H),3.23-3.16(m,4H),3.07(s,3H), 2.79-2.67(m,4H),2.33-2.28(m,4H),2.23(s,3H),2.09-2.04(m,5H),2.00(s,3H).

[0518] Effect Test Example 1: In vitro proliferation inhibition test of compounds on OVCAR-3, BT474 and LOVO tumor cells

[0519] Purpose of the test

[0520] In order to detect the inhibitory activity of drug compounds on the proliferation of OVCAR-3, BT474 and LOVO tumor cells in vitro, cells were treated with different concentrations of compounds in vitro and cultured for 6 days. Luminescent Cell Viability Assay (Promega, Catalog No. G7558) was used to detect cell proliferation. 50 The in vitro activity of the compound was evaluated.

[0521] Experimental method (taking OVCAR3 as an example)

[0522] 1. Cell culture: OVCAR-3 cells were cultured in RPMI-1640 medium supplemented with 10% FBS.

[0523] 2. Cell preparation: Take OVCAR-3 cells in the logarithmic growth phase, wash once with PBS, add 2-3 ml of trypsin to digest for 2-3 minutes, wait until the cells are completely digested, add 10-15 ml of cell culture medium to elute the digested cells, centrifuge at 1000 rpm for 5 minutes, discard the supernatant, and then add 10-20 ml of cell culture medium to resuspend the cells to make a single cell suspension.

[0524] 3. Cell plating: Mix the OVCAR-3 single cell suspension and adjust the viable cell density to 6x10 4 After adjusting the density, the cell suspension was mixed and added to a 96-well cell culture plate at 50 μl / well. The culture plate was cultured in an incubator for 18 hours (37°C, 5% CO2).

[0525] 4. Compound Preparation: Dissolve the compound in DMSO and prepare a stock solution with an initial concentration of 10 mM. For small molecule compounds, a total of 9 concentrations are prepared, with a maximum concentration of 1 uM, and 3-fold dilution.

[0526] 5. Sample addition: Add different concentrations of the test sample to the culture plate, with two replicates for each sample. Incubate the culture plate in an incubator for 6 days (37°C, 5% CO2).

[0527] 6. Color development: Take out the 96-well cell culture plate, add 50ul CTG reagent to each well, and incubate at room temperature for 10 minutes.

[0528] 7. Plate reading operation: Take out the 96-well cell culture plate, place it in a microplate reader, and measure the chemiluminescence using the microplate reader.

[0529] Data analysis: Microsoft Excel and Graphpad Prism 9 were used to process and analyze the data.

[0530] Table 1 IC values ​​of the compounds in this application for inhibition of cell proliferation in vitro 50 value

[0531] Conclusion: The results show that the compounds in the present application have strong proliferation inhibitory activity on OVCAR-3, BT474, and LOVO cells, and the activity is not weaker than or better than the control compound trabectedin.

[0532] Effect Test Example 2: Toxicology Study of Different Compounds by Intravenous Injection in SD Rats

[0533] Purpose of the experiment

[0534] Sprague-Dawley rats were given a single intravenous injection of the three test articles to observe the acute toxic reactions of the three test articles in SD rats, so as to compare the toxic effects of the three test articles and provide data support for subsequent safety evaluation.

[0535] dose:

[0536] Under the conditions of this experiment, SD rats were intravenously administered with 0.3 mg / kg of trabectinine, 2.4 mg / kg of compound 45, 2.4 mg / kg of compound 55, and 1.2 mg / kg of compound 55, respectively.

[0537] Phenomena: On the second day of dosing in the G1 group, male rats showed perianal filth due to loose stools. Female rats also showed erect piloerection, arched backs, decreased activity, and red discharge around the eyes and nose. All animals in the G1 group died on the second day of dosing. Clinical pathology revealed decreased white blood cell count (WBC), platinum lipoprotein (PLT), lysozyme (LYMP), mononuclear lipoprotein (MONO), and urethral ejaculation (RET). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamic glutathione (GGT), bilirubin (DBIL), and tertiary bilirubin (TBIL), while potassium and chlorine levels were decreased. Autopsy revealed yellowing of multiple tissues (including the inner skin, thymus, gastrointestinal tract, and uterus). Female rats also showed hepatomegaly, suggesting possible hepatotoxicity of trabentinine. Autopsy revealed intestinal bleeding, perianal filth, and thin stomach walls. Male rats also showed punctate protrusions on the intestinal surface. The thymus and spleen were smaller. Female rats also showed hemorrhagic puncta in the lungs and patchy gray plaques on the heart.

[0538] After administration, the G3 group showed decreased white blood cell counts, platinum lipoprotein (PLT), lymphocytes (LYMP), mononuclear oxidase (MONO), and urethral respiration (RET). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamic glutathione (GGT), bilirubin (DBIL), and tertiary pulmonary edema (TBIL), while potassium and chlorine levels decreased. Autopsies of the animals revealed yellowing of multiple tissues (including the inner skin, thymus, gastrointestinal tract, and uterus). Female animals also showed liver enlargement, suggesting that compound 55 may be toxic to the liver. Seven days after administration, euthanasia of the animals revealed intestinal bleeding, perianal filth, and thin stomach walls. Male animals also showed punctate protrusions on the intestinal surface. The thymus and spleen were smaller. Female animals also showed hemorrhagic puncta in the lungs and patchy gray spots on the heart.

[0539] The G2 and G4 groups were well tolerated, with no significant changes in body weight and food intake.

[0540] Conclusion: At 0.3 mg / kg, trabectinine was intolerant to both male and female SD rats. Compound 45 was well tolerated at 2.4 mg / kg and exhibited significantly better toxicity than trabectinine. Compound 55 was well tolerated at 1.2 mg / kg and exhibited significantly better toxicity than trabectinine.

[0541] The above embodiments do not limit the solutions of the present application in any way. In addition to those described herein, various modifications of the present invention will be apparent to those skilled in the art based on the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. Each reference cited in this application (including all patents, patent applications, journal articles, books and any other disclosures) is incorporated by reference in its entirety.

Claims

1. A compound of formula (IA), or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotope-labeled substance, metabolite or prodrug thereof: in, Q 1 N or CH; Q 2 N or CR 11 ; R 1 and R 11 are independently hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 Alkyl, -NH-S(O)2-R 1-2 、-C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkyl), -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkyl, -N(R 1-1 )-C(O)R 1-2 、-N(R 1- 1 )-R 1-2 、-OC(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl, -N(R 1-1 )C(O)-C 1-6 Alkylene-R 1-2 or -N(R 1- 1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution; Or, R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution; R 2 For hydrogen, deuterium, halogen, -C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -OC(O)-NR 2-1 R 2-2 、-NR 2-1 C(O)-OR 2-2 、-NH-S(O)2-R 2-2 、-N(R 2-1 )C(O)-C 1-6 Alkylene-R 2-2 、-NR 2-1 C(O)NR 2-1 -R 2-2 、-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -C(O)-R 2-2 or C(O)-NR 2-1 R 2-2 , the C 1- 6 alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -O-NH-CH3, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 3 For hydrogen, deuterium, -C 1-6 Alkyl, NHC 1-6 Alkyl, -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-OC(O)-NR 3-1 R 3-2 、-CH2-NR 3-1 C(O)-OR 3-2 、-CH2-NR 3-1 C(O)NR 3-1 -R 3-2 、-CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 Alkyl)2, -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(R 3-1 )C(O)-C 1-6 Alkylene-R 3-2 、-CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl) or -C(O)-R 3-2 , the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -O-NH-CH3, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH and -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents; R 1-1 、R 2-1 、R 3-1 are independently hydrogen, deuterium, C 1-6 Alkyl or halogenated C 1-6 alkyl; R 1-2 、R 2-2 、R 3-2 Each independently is C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-12 Cycloalkyl and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more independently selected from halogen, -OH, -SH, -NH2, -O-NH-CH3, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; Y is -OH or -CN.

2. The compound according to claim 1 or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotope-labeled substance, metabolite or prodrug thereof, wherein: The compound represented by formula (IA) is a compound having the structure represented by formula (I): in, R 1 and R 11 are independently hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 Alkyl, -C 1- 6-alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1- 1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution; Or, R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution; R 1-1 For hydrogen, deuterium, C 1-6 Alkyl or halogenated C 1-6 alkyl; R 1-2 C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-12 Cycloalkyl and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more independently selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 2 For hydrogen, deuterium, halogen, -C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3- 12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 3 For hydrogen, deuterium, -C 1-6 Alkyl, -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 Alkyl)2, -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -CH2-N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3- 12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH and -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents; Y is -OH or -CN; And meet the conditions: (1) When R 1 -OH or -OC 1-6 Alkyl, R 11 When it is -OCH3, R 2 、R 3 and R 4 Not simultaneously hydrogen; (2) When R 1 -OH, R 11 -OCH3, R 2 and R 3 When it is hydrogen, R 4 is not methyl; and (3) When R 1 -OH, R 11 -CH3, R 2 and R 4 When it is hydrogen, R 3 Not ethyl.

3. The compound according to claim 2 or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotope-labeled substance, metabolite or prodrug thereof, wherein: The compound satisfies at least one of the following conditions: (1)R 1 For hydrogen, deuterium, halogen, -CN, -NH2, C 1-6 Alkyl, -NHC 1-6 Alkyl, -NH-S(O)2-R 1-2 、-C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkyl), -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkyl, -N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-R 1-2 、-OC(O)-N(R 1- 1 )R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1- 1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1- 1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl, -N(R 1-1 )C(O)-C 1-6 Alkylene-R 1-2 or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution; (2)R 2 For deuterium, halogen, -C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -OC(O)-NR 2-1 R 2-2 、-NR 2-1 C(O)-OR 2-2 、-NH-S(O)2-R 2-2 、-N(R 2-1 )C(O)-C 1-6 Alkylene-R 2-2 、-NR 2-1 C(O)NR 2-1 -R 2-2 、-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -C(O)-R 2-2 or C(O)-N(R 1-1 )R 1-2 , the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -O-NH-CH3, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; (3)R 3 -C 1-6 Alkyl, -NHC 1-6 Alkyl, -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-OC(O)-NR 3- 1 R 3-2 、-CH2-NR 3-1 C(O)-OR 3-2 、-CH2-NR 3-1 C(O)NR 3-1 -R 3-2 、-CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 Alkyl)2, -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(R 3-1 )C(O)-C 1-6 Alkylene-R 3-2 、-CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl) or -C(O)-R 3-2 , the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -O-NH-CH3, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; (4)R 4 -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1- 6 alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 The alkyl group is substituted with a substituent; preferably -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; (5)R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH and -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents; (6)R 11 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -NHC 1-6 Alkyl, -NH-S(O)2-R 1-2 、-C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkyl), -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1- 2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、N(R 1-1 )-C 3-12 Cycloalkyl, -N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-R 1-2 、-OC(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl, -N(R 1-1 )C(O)-C 1-6 Alkylene-R 1-2 or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1- 6-alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution; (7) In formula (IA) and formula (I), when R 1 -OH, R 11 -OCH3, R 2 and R 3 When it is hydrogen, R 4 Not for C 1-6 alkyl; (8) In formula (IA) and formula (II), when R 1 -OH, R 2 and R 3 When it is hydrogen, R 4 Not for C 1-6 alkyl; (9) In formula (IA) and formula (I), when R 1 -OH, R 11 -CH3, R 2 and R 4 When it is hydrogen, R 3 Not for C 1-6 alkyl; (10) When R 1 -OH, R 2 、R 3 and R 4 When it is hydrogen, R 11 Not -OCH2CH2NH2, -O CH2CH2NHCH3, -CH2N(CH3)-C(O)-CH(OH)CH3, -CH2N(CH3)-C(O)-CH2(OH); (11)Q 1 is N; and (11)Q 2 is N.

4. The compound according to claim 2 or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotope-labeled substance, metabolite or prodrug thereof, wherein: The compound represented by formula (IA) is a compound represented by formula (IA), formula (IA-1), formula (IA-2), formula (IA-3), and formula (IA-4): in, Q 1 N or CH; Q 2 N or CR 11 ; R 1 NHC 1-6 Alkyl, -NH-S(O)2-R 1-2 、-C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkyl), -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkyl, -N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-R 1-2 、-OC(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1- 1 )R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl, -N(R 1- 1 )C(O)-C 1-6 Alkylene-R 1-2 or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution; R 11 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 alkyl; R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution; R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; in, Q 1 N or CH; R 1 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 alkyl; R 11 Independently -NHC 1-6 Alkyl, -NH-S(O)2-R 1-2 、-C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkyl), -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1- 1 )-C 3-12 Cycloalkyl, -N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-R 1-2 、-OC(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-C(O)-OR 1-2 、-N(R 1-1 )-C(O)-N(R 1-1 )R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl, -N(R 1-1 )C(O)-C 1-6 Alkylene-R 1-2 or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution; R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; in, Q 1 N or CH; Q 2 N or CR 11 ; R 1 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 alkyl; R 11 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 alkyl; R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution; R 2 Halogen, -C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -OC(O)-NR 2-1 R 2-2 、-NR 2- 1 C(O)-OR 2-2 、-NH-S(O)2-R 2-2 、-N(R 2-1 )C(O)-C 1-6 Alkylene-R 2-2 、-NR 2-1 C(O)NR 2-1 -R 2-2 、-N(C 1-6 alkyl)C(O)C 3- 12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -C(O)-R 2-2 or C(O)-NR 2-1 R 2-2 , the C 1-6 Alkyl, C 3- 12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -O-NH-CH3, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; in, Q 1 N or CH; Q 2 N or CR 11 ; R 1 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 alkyl; R 11 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 alkyl; R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution; R 3 -C 1-6 Alkyl, -NHC 1-6 Alkyl, -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-OC(O)-NR 3-1 R 3- 2 、-CH2-NR 3-1 C(O)-OR 3-2 、-CH2-NR 3-1 C(O)NR 3-1 -R 3-2 、-CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 Alkyl)2, -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(R 3-1 )C(O)-C 1-6 Alkylene-R 3-2 、-CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, -CH2-N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl) or -C(O)-R 3- 2 , the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -O-NH-CH3, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 The substituents are substituted by cycloalkylene-OH and -C(O)-(4 to 12-membered heterocycloalkylene)-OH; preferably, the compound represented by formula (I) is a compound represented by the structure of formula (II), formula (Ia), formula (IIa), formula (Ib), or formula (IIb): in, R 1 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 Alkyl, -C 1-6 Alkylene-N(R 1- 1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1- 2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1- 2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution; R 1-1 For hydrogen, deuterium, C 1-6 Alkyl or halogenated C 1-6 alkyl; R 1-2 C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-12 Cycloalkyl and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more independently selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 2 For hydrogen, deuterium, halogen, -C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 3 For hydrogen, deuterium, C 1-6 Alkyl, -CH2-NHC 1-6 Alkyl, -CH2-NHC(O)C 1-6 Alkyl, -CH2-NHC(O)C 3-12 Cycloalkyl, -CH2-NHC(O)(4 to 12 membered heterocycloalkyl), -CH2-N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -CH2-N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -CH2-N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 4 For hydrogen, deuterium, C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 The cycloalkyl and 4 to 12 membered heterocycloalkyl groups are each optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH and -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents; Y is -OH or -CN; And meet the conditions: When R 1 -OH or -OC 1-6 When alkyl, R 2 、R 3 and R 4 Not simultaneously hydrogen; in, R 1 and R 11 are independently hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, halogenated C 1-6 Alkyl, -OC 1-6 Alkyl, -O-halogenated C 1-6 Alkyl, -NHC 1-6 Alkyl, -O-halogenated C 1-6 Alkyl or -NH-halogenated C 1-6 alkyl; Or, R 1 With R 11 Together with the atoms to which they are attached, they form a 5- to 6-membered cycloalkyl or a 5- to 6-membered heterocycloalkyl; the cycloalkyl or heterocycloalkyl groups are each optionally substituted with one or more halogens, -C 1-6 Alkyl substituent substitution; R 2 For hydrogen, deuterium, halogen, C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3- 12 Cycloalkyl, -N(C 1-6 alkyl)C(O)(4- to 12-membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 3 H or -CH2-NR 3a R 3b ; R 3a is hydrogen or C 1-6 Alkyl; the C 1-6 The alkyl group is optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1- 6-alkyl and -SC 1-6 Substitution of alkyl groups; R 3b For hydrogen, C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1- 6-alkyl and -SC 1-6 Substitution of alkyl groups; R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH, -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents; Y is -OH or -CN; The premise is that R 2 and R 3 Cannot be H at the same time; in, R 1 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, halogenated C 1-6 Alkyl, -OC 1-6 Alkyl, -O-halogenated C 1-6 Alkyl, -NHC 1-6 Alkyl, -O-halogenated C 1-6 Alkyl or -NH-halogenated C 1-6 alkyl; R 2 For hydrogen, deuterium, halogen, C 1-6 Alkyl, -OH, -NH2, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -NHC(O)C 3-12 Cycloalkyl, -NHC(O)(4 to 12 membered heterocycloalkyl), -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl or -N(C 1-6 alkyl)C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 3 H or -CH2-NR 3a R 3b ; R 3a is hydrogen or C 1-6 Alkyl; the C 1-6 The alkyl group is optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1- 6-alkyl and -SC 1-6 Substitution of alkyl groups; R 3b For hydrogen, C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1- 6-alkyl and -SC 1-6 Substitution of alkyl groups; R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; or R 3 With R 4 The atoms to which it is attached together form a 5-12 membered heterocycloalkyl group; each of the 5-12 membered heterocycloalkyl groups is optionally substituted by one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkyl-OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH, -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents; Y is -OH or -CN; The premise is that R 2 and R 3 Cannot be H at the same time; in, R 1 -NH2, -NHC 1-6 Alkyl, -C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1- 1 )-C 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1- 1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution; R 11 For hydrogen, deuterium, halogen, -OH, -CN, -NH2, C 1-6 Alkyl, -OC 1-6 Alkyl, -NHC 1-6 Alkyl, -C 1-6 Alkylene-N(R 1- 1 )-C(O)R 1-2 、-OC 3-12 Cycloalkyl, -O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1- 2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-3 )-C(O)R 1- 2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene and 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution; R 1-1 For hydrogen, deuterium, C 1-6 Alkyl, halogenated C 1-6 alkyl; R 1-2 C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; R 4 For hydrogen, deuterium, -C 1-6 Alkyl, -C(O)C 1-6 Alkyl, -C(O)C 3-12 Cycloalkyl or -C(O)(4 to 12 membered heterocycloalkyl), the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; Y is -OH or -CN; in, R 1 -NH2, -C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-O-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-N(R 1-1 )-C 3-12 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-(4- to 12-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 12 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-12 Cycloalkyl or -N(R 1-1 )C(O)(4 to 12 membered heterocycloalkyl), said C 1-6 Alkyl, C 1-6 Alkylene, C 3-12 Cycloalkyl, C 3-12 Cycloalkylene, 4 to 12 membered heterocycloalkylene or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution; R 1-1 For hydrogen, deuterium, C 1-6 Alkyl, halogenated C 1-6 alkyl; R 1-2 C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-12 Cycloalkyl or 4 to 12 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; Y is -OH or -CN.

5. The compound according to any one of claims 2 to 4, or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotope-labeled substance, metabolite or prodrug thereof, characterized in that: The compounds represented by formula (IA) and formula (I) are compounds represented by formula (II), formula (Ia), formula (II), and formula (IIa), and the compounds represented by formula (Ia-1), formula (Ia-2), formula (IIa-1), formula (IIa-2), formula (IIa-3), formula (IIa-4), and formula (IIa-5). in, Y, R 1 、R 11 、R 3a 、R 3b 、R 4 and R 2 As defined in any one of claims 1 to 3; Preferably, among the compounds represented by formula (Ia), formula (Ia-2), formula (IIa), formula (IIa-2), and formula (IIa-3), R 3a is hydrogen or -CH3; R 3b -C(O)C 1-6 Alkylene-OH; R 4 is hydrogen or -CH3; or, for Y is -OH or -CN.

6. The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotope-labeled substance, metabolite or prodrug thereof, characterized in that: It meets at least one of the following conditions: (1) The number of heteroatoms in the 4- to 12-membered heterocycloalkylene group and the 4- to 12-membered heterocycloalkyl group is one or more, and each heteroatom is independently selected from N, O, and S; Preferably, the 4- to 12-membered heterocycloalkylene group and ...6-membered heterocycloalkylene group and the 4- to 6-membered heterocycloalkylene group are 4- to 6-membered heterocycloalkylene groups and 4- to 6-membered heterocycloalkyl groups; the number of heteroatoms is one or two, and the heteroatoms are independently selected from N; (2) In the compounds represented by formula (IA), formula (I), formula (Ia), formula (II), and formula (IIa), R 1 is hydrogen, halogen, -OH, -CN, -NH2, -CH3, -OCH3 or -NHCH3; Preferably, R 1 is hydrogen, deuterium, -F, -Cl, -OH, -CH3, -OCH3, -NH2 or -NHCH3; (3) In the compounds represented by formula (IA), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-1), formula (IIa-4), and formula (IIa-5), R 2 -OH, -NH2, -C 1-6 Alkyl, -NHC 1-6 Alkyl, -NHC(O)C 1-6 Alkyl, -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl or -N(C 1-6 alkyl)C(O)C 3-12 Cycloalkyl, the C 1-6 Alkyl, C 3- 12 The cycloalkyl groups are each optionally substituted with one or more alkyl groups selected from -OH, -SH, -NH2, -NHCH3 and -SCH3; Preferably, R 2 -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -N(C 1-6 alkyl)C(O)C 1-6 Alkyl, or -N(C 1-6 alkyl)C(O)C 1- 6-alkylene-OH; More preferably, R 2 -NH2, -NHC 1-3 Alkyl or -N(C 1-3 alkyl)C(O)C 1-3 Alkylene-OH; (3) In the compounds represented by formula (IA), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3), R 3a is hydrogen or -C 1-3 alkyl; Preferably, R 3a is hydrogen or -CH3; (4) In the compounds represented by formula (IA), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3), R 3b Hydrogen, -CH3, -C(O)C 1-6 Alkyl or -C(O)C 3-6 Cycloalkyl, the C 1-6 Alkyl or C 3-6 Each cycloalkyl group is optionally substituted with one or more substituents selected from -OH, -SH, -NH2, -NHCH3 and -SCH3; Preferably, R 3b -C(O)C 1-6 Alkylene-OH; More preferably, R 3b -C(O)C 1-3 Alkylene-OH; (5) In the compounds represented by formula (IA), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3), R 4 is hydrogen, deuterium or C 1-6 Alkyl, the C 1-6 The alkyl group is optionally substituted with one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; Preferably, R 4 For hydrogen, deuterium, C 1-6 Alkyl or -C(O)C 1-6 Alkylene-OH; (6) In the compounds represented by formula (IA), formula (I), formula (Ia), formula (II), and formula (IIa), R 3 With R 4 Together with the atoms to which it is attached, it forms a 5- to 6-membered heterocycloalkyl, wherein each of the 5- to 6-membered heterocycloalkyl groups is optionally substituted with one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1-6 Alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH, -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents; Preferably, R 3 With R 4 The atoms to which it is attached together form a piperazinyl group, wherein each of the piperazinyl groups is optionally substituted with one or more halogen, oxo, -OH, -CN, -NH2, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, -C 1-6 Alkyl, -C 1-6 Alkylene -OH, -C(O)C 1- 6-alkylene-OH, -C(O)-C 3-12 Substitution with cycloalkylene-OH, -C(O)-(4- to 12-membered heterocycloalkylene)-OH substituents; (7) In the compounds represented by formula (I), formula (Ib), formula (II), and formula (IIb), R 1-1 is hydrogen, deuterium or C 1-6 alkyl; Preferably, R 1-1 is hydrogen, deuterium or -CH3; More preferably, R 1-1 is hydrogen or -CH3; (8) In the compounds represented by formula (IA), formula (I), formula (Ib), formula (II), and formula (IIb), R 1-2 C 1-6 Alkyl, C 3-6 Cycloalkyl or 4 to 6 membered heterocycloalkyl; the C 1-6 Alkyl, C 3-6 Cycloalkyl or 4 to 6 membered heterocycloalkyl are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl and -SC 1-6 Substitution of alkyl groups; Preferably, R 1-2 -C 1-6 Alkylene-OH; More preferably, R 1-2 -C 1-3 Alkylene-OH; (9) In the compounds represented by formula (IA), formula (I), formula (Ib), formula (II), and formula (IIb), R 1 -NH2, -NHC 1-6 Alkyl, -C 1-6 Alkylene-N(R 1-1 )-C(O)R 1-2 、-O-(4- to 6-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-6 Cycloalkylene-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-(4- to 6-membered heterocycloalkylene)-C(O)R 1-2 、-(4- to 6-membered heterocycloalkylene)-C(O)R 1-2 、-(4 to 6 membered heterocycloalkylene)-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )-C(O)R 1-2 、-N(R 1-1 )C(O)C 3-6 Cycloalkyl or -N(R 1-1 )C(O)(4 to 6 membered heterocycloalkyl), said C 1-6 Alkylene, C 3-6 Cycloalkyl, C 3-6 Cycloalkylene, 4 to 6 membered heterocycloalkyl or 4 to 6 membered heterocycloalkylene are each optionally substituted by one or more radicals selected from halogen, -OH, -SH, -NH2, -NHC 1-6 Alkyl, -SC 1-6 Alkyl, -C 1-6 Alkylene-OH, -C 1-6 Alkylene -SH, -C 1-6 Alkylene-S(C 1-6 alkyl) and -C 1-6 Alkylene-NH2 substituent substitution; Preferably, R 1 -NH2, -NHC 1-6 Alkyl, -C 1-6 Alkylene-NH-C(O)R 1-2 、-C 1-6 Alkylene-N(CH3)-C(O)R 1-2 、-O-(4- to 6-membered heterocycloalkylene)-C(O)R 1-2 、-OC 3-6 Cycloalkylene-NH-C(O)R 1-2 、-OC 3-6 Cycloalkylene-N(CH3)-C(O)R 1-2 、-NH-C(O)R 1-2 、-N(CH3)-C(O)R 1-2 、-NH-(4 to 6 membered heterocycloalkylene)-C(O)R 1-2 、-N(CH3)-(4 to 6 membered heterocycloalkylene)-C(O)R 1-2 、-NHC(O)C 3-6 Cycloalkyl, -N(CH3)C(O)C 3-6 Cycloalkyl, -NHC(O)(4 to 6 membered heterocycloalkyl) or -N(CH3)C(O)(4 to 6 membered heterocycloalkyl), wherein the C 1-6 Alkylene, C 3-6 Cycloalkyl, C 3-6 Cycloalkylene, 4 to 6 membered heterocycloalkyl or 4 to 6 membered heterocycloalkylene are each optionally substituted by one or more radicals selected from halogen, -OH, -NH2, -NHCH3, -C 1-6 Alkylene-OH substituted; More preferably, R 1 NH2, NHCH3, -O-(4 to 6 membered heterocycloalkylene)-C(O)R 1-2 、-NH-C(O)R 1-2 or -N(CH3)-C(O)R 1-2 ; (10) Compounds having structures represented by formula (IA), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-1), formula (IIa-4), and formula (IIa-5), wherein: for or a combination thereof; (11) Compounds having structures represented by formula (IA), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3), wherein: for or a combination thereof; (12) Compounds represented by formula (IA), formula (I), and formula (Ia), wherein R 11 is hydrogen, halogen, -OH, -CN, -NH2, -CH3, -OCH3 or -NHCH3; preferably, hydrogen, deuterium or -OCH3; (13) Compounds represented by formula (IA), formula (I), and formula (Ia), R 1 With R 11 Connected, formed with connected carbons The a side is connected to the benzene ring.

7. The compound according to claim 2 or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotope-labeled substance, metabolite or prodrug thereof, wherein: It meets at least one of the following conditions: (1) In the compounds represented by formula (IA), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-1), formula (IIa-4), and formula (IIa-5), R 2 For H, -OH, -NH2, -NHCH3, -CH2OH, Preferably, in the compounds represented by formula (IA), formula (I), formula (Ia), formula (IIa), formula (IIa-1), formula (IIa-4), and formula (IIa-5), R 2 -NH2, -NHCH3 or (2) In the compounds represented by formula (IA), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3), R 3a is hydrogen; (3) In the compounds represented by formula (IA), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3), R 3b For hydrogen, -CH3, Preferably, R 3b for (4) In the compounds represented by formula (IA), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3), -CH2-NR 3a R 3b for (5) In the compounds represented by formula (IA), formula (I), formula (Ia), formula (Ia-1), formula (II), formula (IIa), formula (IIa-2), and formula (IIa-3), R 4 is hydrogen or -CH3; Preferably, R 4 is hydrogen; (6) In the compounds represented by formula (IA), formula (I), formula (Ia), formula (II), and formula (IIa), R 3 With R 4 Together with the atoms it is connected to, it forms Preferably, R 3 With R 4 Together with the atoms it is connected to, it forms (7) In the compounds represented by formula (IA), formula (I), formula (Ib), formula (II), and formula (IIb), R 1-1 is -CH3; (8) In the compounds represented by formula (IA), formula (II), and formula (IIb), R 1-2 -CH2OH, -CH(CH3)OH, Preferably, R 1-2 is -CH2OH or -CH(CH3)OH; (9) In the compounds represented by formula (IA), formula (I), formula (Ib), formula (II), and formula (IIb), R 1 and R 11 are independently NH2, NHCH3, Preferably, R 1 NH2, NHCH3, (10) In the compounds represented by formula (IA), formula (I), formula (Ib), formula (II), and formula (IIb), R 3 NHCH3, 8. The compound according to claim 1 or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotope-labeled substance, metabolite or prodrug thereof, wherein: The compound is any of the following structures:

9. A compound having the structure shown below:

10. A pharmaceutical composition, characterized in that It comprises the compound according to any one of claims 1 to 8 or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotope label, metabolite or prodrug thereof, and one or more pharmaceutically acceptable carriers.

11. Use of a substance A in the preparation of a medicament for preventing or treating tumors or cancers, characterized in that: The substance A is a compound according to any one of claims 1 to 8 or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, polymorph, solvate, isotope-labeled substance, metabolite or prodrug thereof, or the pharmaceutical composition according to claim 10; The tumor or cancer is preferably breast cancer, colorectal cancer, colon cancer, lung cancer, prostate cancer, bile duct cancer, bone cancer, bladder cancer, head and neck cancer, kidney cancer, liver cancer, gastrointestinal tissue cancer, esophageal cancer, ovarian cancer, pancreatic cancer, skin cancer, testicular cancer, thyroid cancer, uterine cancer, cervical cancer, vulvar cancer, leukemia, multiple myeloma and lymphoma; The leukemia is preferably chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL) and chronic myeloid leukemia (CML).

Citation Information

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