Heterocyclic compound and application thereof in medicine

Abstract

The invention relates to a heterocyclic compound and application thereof in medicine, in particular to a compound shown in a general formula (I) or a stereoisomer, a tautomer, a racemate, pharmaceutically acceptable salt, an intermediate and a preparation method of the compound, and application of the compound in preparation of drugs for treating STAT6 related diseases such as cancers, autoimmune diseases or inflammatory diseases.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of medicinal chemistry, and particularly relates to a compound as described in general formula (I) or a stereoisomer, a tautomer, a racemate, a pharmaceutically acceptable salt thereof, and an intermediate and a preparation method thereof, and an application thereof in preparing a drug for treating a disease related to STAT6, such as a cancer, an autoimmune disease or an inflammatory disease. BACKGROUND

[0002] Signal transducer and activator of transcription (STAT) is a kind of important protein responsible for signal transduction and transcription activation, which can transduce extracellular cytokine and growth factor signals into cells. Signal transducer and activator of transcription 6 (STAT 6) is an important protein in the STAT family, which is well known for its specific diagnostic value for solitary fibrous tumor / perivascular cell tumor. STAT6 is composed of about 840 amino acids, participates in physiological processes such as expression of cell surface molecules, Th2 cell differentiation and IgE type transformation, and plays a crucial role in host defense and immune regulation. Abnormal expression of STAT6 can lead to immune disorders and participate in the occurrence and development of diseases. In recent years, STAT6 expression is increased in various cancers such as colon cancer, breast cancer and pancreatic cancer. High expression of STAT interacts with specific DNA binding in the nucleus, thereby regulating the transcription of proliferation, invasion and apoptosis related genes, and promoting the occurrence and development of tumor cells. In addition, STAT6 is a participant in various allergic inflammations, and many chemokines (such as CCL11, CCL17, etc.) are regulated in a STAT6-dependent manner. Therefore, the development of drugs targeting STAT6 has potential application value for cancer and immune diseases. SUMMARY

[0003] The purpose of the present application is to provide a compound as described in general formula (I) or a stereoisomer, a deuterium compound, a solvate, a prodrug, a metabolite, a pharmaceutically acceptable salt or a co-crystal thereof, and an intermediate and a preparation method thereof, and an application thereof in preparing a drug for treating a disease related to STAT6, such as an autoimmune disease or an inflammatory disease.

[0004] The compound of the present application has good pharmacokinetic performance and bioavailability, oral performance and good safety.

[0005] The present application provides a compound represented by general formula (I) or a stereoisomer, a tautomer, a deuterated compound, a solvate, a prodrug, a metabolite, a pharmaceutically acceptable salt or a co-crystal thereof,

[0006]

[0007] In some embodiments, the compound represented by general formula (I) is selected from a compound represented by general formula (II-1) or (II-2),

[0008]

[0009] In some embodiments, ring A is selected from C 3-15 carbocyclyl or 4-15 membered heterocyclyl, said ring A is optionally substituted with 1 to 4 R a ;

[0010] In some embodiments, ring A is selected from phenyl, 5-6 membered heteroaryl, phenyl and 6 membered carbocyclyl, phenyl and 5 membered carbocyclyl, phenyl and 6 membered heterocyclyl, phenyl and 5 membered heterocyclyl, 5 and 5 membered heteroaryl, 5 and 6 membered heteroaryl, 6 and 6 membered heteroaryl or naphthyl, said ring A is optionally substituted with 1 to 4 R a ;

[0011] In some embodiments, ring A is selected from benzothiophenyl, naphthyl, benzopyridinyl, benzopyrimidinyl, benzopyrazinyl, benzopyridazinyl, benzopyrrolyl, benzopyrazolyl, benzimidazolyl, benzothiazolyl, benzothiophenyl, pyridopyridinyl, pyridopyrimidinyl, pyridopyrazinyl, pyridopyridazinyl, pyridopyrrolyl, pyridopyrazolyl, pyridimidazolyl, pyridimidazolyl, said ring A is optionally substituted with 1 to 4 R a ;

[0012] In some embodiments, ring A is selected from benzothiophenyl, naphthyl, benzopyrrolyl, said ring A is optionally substituted with 1 to 4 R a ;

[0013] In some embodiments, ring B2 is selected from 4-15 membered heterocyclyl, said ring B2 is optionally substituted with 1 to 4 R b2 ;

[0014] In some embodiments, is selected from

[0015] In some embodiments, is selected from

[0016] In some embodiments, selected from

[0017] In some embodiments, selected from

[0018] In some embodiments, Z is selected from CH or N;

[0019] In some embodiments, Z is selected from CH;

[0020] In some embodiments, R a each R is independently selected from H, deuterium, halogen, OH, =0, NH2, CN, COOH, CONH2, C1-C6alkyl, C1-C6alkenyl, C1-C6alkynyl, C1-C6alkoxy, carbocyclyl, 3- to 6-membered heterocyclyl, aryl, heteroaryl, wherein said alkyl, alkenyl, alkynyl, alkoxy, carbocyclyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with 1 to 4 R 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3-6 carbocyclyl, 3- to 6-membered heterocyclyl; z substituted;

[0021] In some embodiments, R a each R is independently selected from H, deuterium, halogen, OH, =0, NH2, CN, COOH, CONH2, C1-C6alkyl, C1-C6alkenyl, C1-C6alkynyl, C1-C6alkoxy, carbocyclyl, 3- to 6-membered heterocyclyl, aryl, heteroaryl, wherein said alkyl, alkenyl, alkynyl, alkoxy, carbocyclyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with 1 to 4 R 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 3-6 carbocyclyl, 3- to 6-membered heterocyclyl; z substituted;

[0022] In some embodiments, R a each R is independently selected from H, deuterium, F, Cl, Br, I, OH, =0, NH2, CN, COOH, CONH2, methyl, ethyl, propyl, isopropyl, ethenyl, ethynyl, propynyl, propargyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, wherein said methyl, ethyl, propyl, isopropyl, ethenyl, ethynyl, propynyl, propargyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl is optionally substituted with 1 to 4 R z substituted;

[0023] In some embodiments, R aeach independently selected from H, deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, CH2OH, CH2-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, azetidinyl, or oxetanyl;

[0024] In some embodiments, R A each independently selected from H, deuterium, halogen, OH, =0, NH2, CN, COOH, CONH2, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3-6 carbocyclyl, 3- to 6-membered heterocyclyl, said alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, or heterocyclic group is optionally substituted with 1 to 4 R z substituents;

[0025] In some embodiments, R A each independently selected from H, deuterium, halogen, OH, =0, NH2, CN, COOH, CONH2, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 3-6 carbocyclyl, 3- to 6-membered heterocyclyl, said alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, or heterocyclic group is optionally substituted with 1 to 4 R z substituents;

[0026] In some embodiments, R A each independently selected from H, deuterium, F, Cl, Br, I, OH, =0, NH2, CN, COOH, CONH2, methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, propynyl, propargyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, said methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, propynyl, propargyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl is optionally substituted with 1 to 4 R z substituents;

[0027] In some embodiments, R Aeach independently selected from H, deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, CH2OH, CH2-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, azetidinyl, or oxetanyl;

[0028] In some embodiments, R b1 or R b2 each independently selected from deuterium, halogen, OH, =0, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-6 alkyl, S(O)2C 1-6 alkyl, S(O)2C 3-6 carbocyclyl, S(O)2-3 to 7 membered heterocyclyl, COC 1-6 alkyl, CO-3 to 10 membered heterocyclyl, CO-C 3-10 carbocyclyl, COO-C 1-6 alkylene-C 3-10 carbocyclyl, CO-C 1-6 alkylene-C 3-10 carbocyclyl, C 1-6 alkyl, OC 1-6 alkyl, SC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, NHC 1-6 alkyl, N(C 1-6 alkyl)2, -O-C 3-6 carbocyclyl, -O-3 to 10 membered heterocyclyl, -NH-C 3-10 carbocyclyl, -NH-3 to 10 membered heterocyclyl, -NHCO-C 1-6 alkyl, -CONH-C 1-6 alkyl, -NHCO-C 3-10 carbocyclyl, -CONH-C 3-10 carbocyclyl, -NHCO-3 to 10 membered heterocyclyl, -CONH-3 to 10 membered heterocyclyl, -C 0-4 alkylene-C 3-10 carbocyclyl, -C 0-4 alkylene-3 to 10 membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, carbocyclyl, or heterocyclyl being optionally substituted with one to four R z substituents;

[0029] In some embodiments, R b1 or R b2 each independently selected from deuterium, halogen, OH, =0, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-4alkyl, S(O)2C 1-4 alkyl, S(O)2C 3-6 carbocyclyl, S(O)2-3- to 7-membered heterocyclyl, COC 1-4 alkyl, CO-3- to 10-membered heterocyclyl, CO-C 3-10 carbocyclyl, COO-C 1-4 alkylene-C 3-10 carbocyclyl, CO-C 1-4 alkylene-C 3-10 carbocyclyl, C 1-4 alkyl, OC 1-4 alkyl, SC 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, NHC 1-4 alkyl, N(C 1-4 alkyl)2, -O-C 3-6 carbocyclyl, -O-3- to 10-membered heterocyclyl, -NH-C 3-10 carbocyclyl, -NH-3- to 10-membered heterocyclyl, -NHCO-C 1-4 alkyl, -CONH-C 1-4 alkyl, -NHCO-C 3-10 carbocyclyl, -CONH-C 3-10 carbocyclyl, -NHCO-3- to 10-membered heterocyclyl, -CONH-3- to 10-membered heterocyclyl, -C 0-2 alkylene-C 3-10 carbocyclyl, -C 0-2 alkylene-3- to 10-membered heterocyclyl, which alkyl, alkylene, alkenyl, alkynyl, carbocyclyl or heterocyclyl is optionally substituted by 1 to 4 R z substituents;

[0030] In some embodiments, R b1 or R b2each independently selected from the group consisting of deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, -CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, CO-cyclopropyl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, ethenyl, ethynyl, propynyl, propargyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl)2, N(ethyl)2, N(propyl)2, N(isopropyl)2, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-azetidinyl, -CH2-pyrrolidinyl, -CH2-oxetanyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, said methyl, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, is optionally substituted with 1 to 4 R z ;

[0031] In some embodiments, R b1 is independently selected from H, deuterium, F, Cl, Br, I, OH, CN, NH2, methyl, methoxy, CF3, CHF2, CH2F, CD3, OCD3, cyclopropyl, cyclobutyl, azetidinyl, or oxetanyl;

[0032] In some embodiments, R b2each independently is selected from the group consisting of deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, COOH, CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, CO-CD3, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propargyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl)2, N(ethyl)2, N(propyl)2, N(isopropyl)2, -CO-cyclopropyl, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-azetidinyl, -CH2-pyrrolidinyl, -CH2-oxetanyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl,

[0033] In some embodiments, two R b1 or two R b2 together with the atom to which they are attached form a C 3-10 carbocyclyl or 4-10 membered heterocyclyl, which carbocyclyl or heterocyclyl is optionally substituted with 1 to 4 R z ;

[0034] In some embodiments, two R b1 or two R b2 together with the atom to which they are attached form a C 3-10 carbocyclyl or 4-8 membered heterocyclyl, which carbocyclyl or heterocyclyl is optionally substituted with 1 to 4 R z ;

[0035] In some embodiments, two R b1and the atoms connected thereto form a cyclopropyl or cyclobutyl group, which is optionally substituted with 1 to 4 R z substituted;

[0036] In some embodiments, R 1 is selected from H, deuterium, halogen, OH, =0, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-6 alkyl, S(O)2C 1-6 alkyl, S(O)2C 3-6 carbocyclyl, S(O)2-3- to 7-membered heterocyclyl, COC 1-6 alkyl, C 1-6 alkyl, OC 1-6 alkyl, SC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, NHC 1-6 alkyl, N(C 1-6 alkyl)2, -O-C 3-6 carbocyclyl, -O-3- to 7-membered heterocyclyl, -NH-C 3-6 carbocyclyl, -NH-3- to 7-membered heterocyclyl, -NHCO-C 1-6 alkyl, -CONH-C 1-6 alkyl, -NHCO-C 3-6 carbocyclyl, -CONH-C 3-6 carbocyclyl, -NHCO-3- to 7-membered heterocyclyl, -CONH-3- to 7-membered heterocyclyl, -C 0-4 alkylene-C 3-6 carbocyclyl, -C 0-4 alkylene-3- to 7-membered heterocyclyl, which alkyl, alkylene, alkenyl, alkynyl, carbocyclyl or heterocyclyl is optionally substituted with 1 to 4 R z substituted;

[0037] In some embodiments, R 1 is selected from H, deuterium, halogen, OH, =0, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-4 alkyl, S(O)2C 1-4 alkyl, S(O)2C 3-6 carbocyclyl, S(O)2-3- to 7-membered heterocyclyl, COC 1-4 alkyl, C 1-4 alkyl, OC 1-4 alkyl, SC 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, NHC 1-4 alkyl, N(C 1-4 alkyl)2, -O-C3-6 carbocyclyl, -O-3- to 7-membered heterocyclyl, -NH-C 3-6 carbocyclyl, -NH-3- to 7-membered heterocyclyl, -NHCO-C 1-4 alkyl, -CONH-C 1-4 alkyl, -NHCO-C 3-6 carbocyclyl, -CONH-C 3-6 carbocyclyl, -NHCO-3- to 7-membered heterocyclyl, -CONH-3- to 7-membered heterocyclyl, -C 0-2 alkylene-C 3-6 carbocyclyl, -C 0-2 alkylene-3- to 7-membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, carbocyclyl or heterocyclyl being optionally substituted with 1 to 4 R z substituents;

[0038] In some embodiments, R 1 is selected from the group consisting of H, deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, -CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, methyl, ethyl, propyl, isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -CONH-cyclopropyl, -CONH-cyclobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-azetidinyl, -CH2-pyrrolidinyl, -CH2-oxetanyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, said methyl, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl being optionally substituted with 1 to 4 R z substituents;

[0039] In some embodiments, R 1H, deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, -CONH2, CF3, CHF2, CH2F, CD3, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-azetidinyl, -CH2-pyrrolidinyl, -CH2-oxetanyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl,

[0040] In some embodiments, R 2 or R 3 is selected from H, deuterium, C 1-4 1-4 alkyl, C 3-6 2-10 carbocyclyl, 4-10 membered heterocyclyl, phenyl, naphthyl, or a 5-6 membered heteroaryl ring having 1-4 heteroatoms each independently N, O, or S, said alkyl, carbocyclyl, heterocyclyl, phenyl, naphthyl, or heteroaryl being optionally substituted with 1-4 R z substituents;

[0041] In some embodiments, R 2 or R 3 is selected from H, deuterium, C 1-6 1-4 alkyl, C 3-10 2-10 carbocyclyl, 4-10 membered heterocyclyl, phenyl, naphthyl, or a 5-6 membered heteroaryl ring having 1-4 heteroatoms each independently N, O, or S, said alkyl, carbocyclyl, heterocyclyl, phenyl, naphthyl, or heteroaryl being optionally substituted with 1-4 R z substituents;

[0042] In some embodiments, R 2 or R 3 is selected from H, deuterium, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, said methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl being optionally substituted with 1-4 R z substituents;

[0043] In some embodiments, R 2 or R 3 is selected from H, deuterium, CF3, CHF2, CH2F, CD3, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl;

[0044] In some embodiments, R 1 , R 2 and the atom to which they are attached form a 4-10 membered heterocyclyl, said heterocyclyl being optionally substituted with 1-4 R1a substituted;

[0045] In some embodiments, R 1 , R 2 and the atom to which they are attached form a 4-9 membered heterocyclyl group, which is optionally substituted with 1 to 4 R 1a substituted;

[0046] In some embodiments, or R 1 , R 2 and the atom to which they are attached form a ring which is optionally substituted with 1 to 4 R 1a substituted;

[0047] In some embodiments, is selected from

[0048]

[0049] In some embodiments, R 1a each independently is selected from deuterium, halogen, OH, =0, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-6 alkyl, S(O)2C 1-6 alkyl, S(O)2C 3-10 carbocyclyl, S(O)2-3 to 10 membered heterocyclyl, COC 1-6 alkyl, CO-3 to 10 membered heterocyclyl, CO-C 3-10 carbocyclyl, C 1-6 alkyl, OC 1-6 alkyl, SC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, NHC 1-6 alkyl, N(C 1-6 alkyl)2, -O-C 3-6 carbocyclyl, -O-3 to 10 membered heterocyclyl, -NH-C 3-10 carbocyclyl, -NH-3 to 10 membered heterocyclyl, -NHCO-C 1-6 alkyl, -CONH-C 1-6 alkyl, -NHCO-C 3-10 carbocyclyl, -CONH-C 3-10 carbocyclyl, -NHCO-3 to 10 membered heterocyclyl, -CONH-3 to 10 membered heterocyclyl, -C 0-4 alkylene-C 3-10 carbocyclyl, -C 0-4alkylene-3- to 10-membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, carbocyclyl or heterocyclyl being optionally substituted with 1 to 4 substituents selected from the group consisting of R z substituted;

[0050] In some embodiments, R 1a each independently selected from the group consisting of deuterium, halogen, OH, =0, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-4 alkyl, S(O)2C 1-4 alkyl, S(O)2C 3-10 carbocyclyl, S(O)2-3- to 10-membered heterocyclyl, COC 1-4 alkyl, CO-3- to 10-membered heterocyclyl, CO-C 3-10 carbocyclyl, C 1-4 alkyl, OC 1-4 alkyl, SC 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, NHC 1-4 alkyl, N(C 1-4 alkyl)2, -O-C 3-6 carbocyclyl, -O-3- to 10-membered heterocyclyl, -NH-C 3-10 carbocyclyl, -NH-3- to 10-membered heterocyclyl, -NHCO-C 1-4 alkyl, -CONH-C 1-4 alkyl, -NHCO-C 3-10 carbocyclyl, -CONH-C 3-10 carbocyclyl, -NHCO-3- to 10-membered heterocyclyl, -CONH-3- to 10-membered heterocyclyl, -C 0-2 alkylene-C 3-10 carbocyclyl, -C 0-2 alkylene-3- to 10-membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, carbocyclyl or heterocyclyl being optionally substituted with 1 to 4 substituents selected from the group consisting of R z substituted;

[0051] In some embodiments, R 1aeach independently selected from the group consisting of deuterium, F, CI, Br, I, OH, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, ethenyl, ethynyl, propynyl, propargyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl)2, N(ethyl)2, N(propyl)2, N(isopropyl)2, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, pyridinyl, pyridonyl, -CH2-azetidinyl, -CH2-pyrrolidinyl, -CH2-oxetanyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, -CH2-phenyl, said alkyl, alkylene, alkenyl, alkynyl, carbocyclyl, or heterocyclyl is optionally substituted with 1 to 4 substituents selected from the group consisting of R z substituents;

[0052] In some embodiments, R 1aeach independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, CONH2, SO H2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2- ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, ethenyl, ethynyl, propynyl, propargyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl)2, N(ethyl)2, N(propyl)2, N(isopropyl)2, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, pyridinyl, pyridonyl, -CH2-azetidinyl, -CH2-pyrrolidinyl, -CH2-oxetanyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, -CH2-phenyl,

[0053] In some embodiments, R 4a or R 4b each independently is selected from H, deuterium, halogen, OH, =O, NH2, CN, COOH, CONH2, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3-6 carbocyclyl, 3- to 6-membered heterocyclyl, said alkyl, alkenyl, alkynyl, alkoxy, carbocyclyl, or heterocyclyl optionally substituted with 1 to 4 R z groups;

[0054] In some embodiments, R 4a or R 4b each independently is selected from H, deuterium, halogen, OH, =O, NH2, CN, COOH, CONH2, C 1-4 alkyl, C 2-4alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 3-6 carbocyclyl, 3- to 6-membered heterocyclyl, said alkyl, alkenyl, alkynyl, alkoxy, carbocyclic or heterocyclic group is optionally substituted with 1 to 4 R z substituents;

[0055] In some embodiments, R 4a or R 4b are each independently selected from H, deuterium, F, Cl, Br, I, OH, =0, NH2, CN, COOH, CONH2, CF3, CHF2, CH2F, CD3, OCD3, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, said methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl is optionally substituted with 1 to 4 R z substituents;

[0056] In some embodiments, R 4a or R 4b are each independently selected from H, deuterium, F, Cl, Br, I, OH, =0, NH2, CN, COOH, CONH2, CF3, CHF2, CH2F, CD3, OCD3, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, azetidinyl, oxetanyl;

[0057] In some embodiments, R 5 is selected from

[0058] In some embodiments, R 5a , R 5b , R 5c or R 5d are each independently selected from H, deuterium, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylene-M-C 1-10 alkyl, C 1-6 alkylene-M-C 3-10 carbocyclyl, C 1-6 alkylene-M-3- to 10-membered heterocyclyl, C 3-10 carbocyclyl, 3- to 10-membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, alkoxy, carbocyclic or heterocyclic group is optionally substituted with 1 to 4 R z substituents;

[0059] In some embodiments, R 5a , R 5bR 5c or R 5d each independently is selected from H, deuterium, C 1-4 alkyl, C 1-4 alkoxy, C 1-5 alkylene-M-C 1-8 alkyl, C 1-5 alkylene-M-C 3-6 carbocyclyl, C 1-5 alkylene-M-3- to 7-membered heterocyclyl, C 3-6 carbocyclyl, 3- to 7-membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, alkoxy, carbocyclic or heterocyclic group is optionally substituted with 1 to 4 R z substituents;

[0060] In some embodiments, R 5a , R 5b , R 5c or R 5d each independently is selected from H, deuterium, methyl, ethyl, propyl, isopropyl, methoxy, C 1-4 alkylene-M-C 1-6 alkyl, cyclopropyl, phenyl, pyridyl, said alkyl, alkylene, methyl, ethyl, propyl, isopropyl, methoxy is optionally substituted with 1 to 4 R z substituents;

[0061] In some embodiments, R 5a , R 5b , R 5c or R 5d each independently is selected from H, CF3, CHF2, CH2F, CD3, OCD3, deuterium, methyl, ethyl, propyl, isopropyl, cyclopropyl, phenyl, pyridyl,

[0062] In some embodiments, M is selected from O, S, C(=O), S(=O), S(=O)2, -NR m C(=O)-, -C(=O)NR m -, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -SC(=O)-, -C(=O)S-, -OC(=O)NR m -;

[0063] In some embodiments, M is selected from -OC(=O)-, -C(=O)O-, -OC(=O)O-, -SC(=O)-;

[0064] In some embodiments, R m is selected from H, deuterium, C 1-6 alkyl, C 3-10carbocyclyl, 4- to 10-membered heterocyclyl, said alkyl, carbocyclyl or heterocyclyl optionally substituted with 1 to 4 R z substituted;

[0065] In some embodiments, R m is selected from H, deuterium, C 1-4 alkyl, C 3-6 carbocyclyl, 4- to 7-membered heterocyclyl, said alkyl, carbocyclyl or heterocyclyl optionally substituted with 1 to 4 R z substituted;

[0066] In some embodiments, R m is selected from H, deuterium, methyl, CF3, CHF2, CH2F, CD3, cyclopropyl;

[0067] In some embodiments, R 5c , R 5d and the atom to which they are attached form a 4- to 10-membered heterocyclyl, said heterocyclyl optionally substituted with 1 to 4 R z substituted;

[0068] In some embodiments, R 5c , R 5d and the atom to which they are attached form a 4- to 8-membered heterocyclyl, said heterocyclyl optionally substituted with 1 to 4 R z substituted;

[0069] In some embodiments, R 5c , R 5d and the atom to which they are attached form an azetidinyl, azetidinyl, azetidinyl, piperazinyl, morpholinyl, said azetidinyl, azetidinyl, azetidinyl, piperazinyl, morpholinyl optionally substituted with 1 to 4 R z substituted;

[0070] In some embodiments, R 5 is selected from

[0071] In some embodiments, R z is each independently selected from deuterium, halogen, OH, =0, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-6 alkyl, S(O)2C 1-6 alkyl, S(O)2C 3-10 carbocyclyl, S(O)2-3- to 10-membered heterocyclyl, COC 1-6 alkyl, CO-3- to 10-membered heterocyclyl, CO-C 3-10 carbocyclyl, C 1-6 alkyl, OC 1-6 alkyl, SC 1-6 alkyl, C2-6 alkenyl, C 2-6 alkynyl, NHC 1-6 alkyl, N(C 1-6 alkyl)2, -O-C 3-6 carbocyclyl, -O-3- to 10-membered heterocyclyl, -NH-C 3-10 carbocyclyl, -NH-3- to 10-membered heterocyclyl, -NHCO-C 1-6 alkyl, -CONH-C 1-6 alkyl, -NHCO-C 3-10 carbocyclyl, -CONH-C 3-10 carbocyclyl, -NHCO-3- to 10-membered heterocyclyl, -CONH-3- to 10-membered heterocyclyl, -C 0-4 alkylene-C 3-10 carbocyclyl, -C 0-4 alkylene-3- to 10-membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, carbocyclyl, or heterocyclyl being optionally substituted with one to four substituents selected from the group consisting of deuterium, halogen, =0, CN, OH, NH2, C 1-6 alkyl, C 1-6 alkoxy, C 3-6 carbocyclyl, 3- to 7-membered heterocyclyl;

[0072] In some embodiments, R z each independently selected from the group consisting of deuterium, halogen, OH, =0, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-4 alkyl, S(O)2C 1-4 alkyl, S(O)2C 3-10 carbocyclyl, S(O)2-3- to 10-membered heterocyclyl, COC 1-4 alkyl, CO-3- to 10-membered heterocyclyl, CO-C 3-10 carbocyclyl, C 1-4 alkyl, OC 1-4 alkyl, SC 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, NHC 1-4 alkyl, N(C 1-4 alkyl)2, -O-C 3-6 carbocyclyl, -O-3- to 10-membered heterocyclyl, -NH-C 3-10 carbocyclyl, -NH-3- to 10-membered heterocyclyl, -NHCO-C 1-4 alkyl, -CONH-C 1-4 alkyl, -NHCO-C 3-10 carbocyclyl, -CONH-C 3-10 carbocyclyl, -NHCO-3- to 10-membered heterocyclyl, -CONH-3- to 10-membered heterocyclyl, -C0-2 Alkylene-C 3-10 Carbocyclic group, -C 0-2 Alkylene-3 to 10-membered heterocyclic groups, wherein the alkyl, alkylene, alkenyl, alkynyl, carbocyclic or heterocyclic group is optionally selected from 1 to 4 groups selected from deuterium, halogen, =O, CN, OH, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substituents of carbocyclic groups and 3 to 7-membered heterocyclic groups;

[0073] In some implementation schemes, R z Each is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, -CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propynyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl)2, N( Ethyl)2, N(propyl)2, N(isopropyl)2, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, aziridine, oxaziridine, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -CH2-oxacyclobutyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, wherein the alkyl, alkylene, alkenyl, alkynyl, carbocyclic or heterocyclic group is optionally selected from 1 to 4 groups selected from deuterium, F, Cl, Br, I, =O, CN, OH, NH2, C 1-4 Substituents include alkyl, methoxy, ethoxy, cyclopropyl, and aziridine groups;

[0074] In some implementations, n1 is selected from 0, 1, 2, 3, or 4;

[0075] In some embodiments, n1 is selected from 0, 1, 2, or 3;

[0076] In some embodiments, n2 is selected from 0, 1, 2, 3, or 4;

[0077] In some embodiments, n2 is selected from 0, 1, 2, or 3;

[0078] In some embodiments, n2 is selected from 0, 1, or 2;

[0079] In some embodiments, m is selected from 0, 1, 2, 3, or 4;

[0080] In some embodiments, n3 is selected from 0, 1, 2, or 3;

[0081] In some embodiments, n4 is selected from 0, 1, 2, or 3;

[0082] In some embodiments, n4 is selected from 0, 1, or 2;

[0083] In some embodiments, n5 is selected from 0, 1, 2, or 3;

[0084] In some embodiments, n5 is selected from 0, 1, or 2;

[0085] Optionally,

[0086] 1) R A is not H;

[0087] or 2) two R b1 and the atoms to which they are attached form a C 3-10 carbocyclyl or 4-10 membered heterocyclyl, which carbocyclyl or heterocyclyl is optionally substituted with 1 to 4 R z ;

[0088] or 3) n1 is selected from 2, 3, or 4 and R b1 is not H;

[0089] or 4) at least one ring atom of ring B2 is an oxygen atom;

[0090] or 5) Z is selected from N.

[0091] As a first embodiment of the present application, the aforementioned compound represented by the general formula (I) or a stereoisomer, a tautomer, a racemate, a pharmaceutically acceptable salt thereof,

[0092] Ring A is selected from C 3-15 carbocyclyl or 4-15 membered heterocyclyl, which ring A is optionally substituted with 1 to 4 R a ;

[0093] Ring B2 is selected from 4-15 membered heterocyclyl, which ring B2 is optionally substituted with 1 to 4 R b2substituted;

[0094] Z is selected from CH or N;

[0095] n1 is selected from 0, 1, 2, 3 or 4;

[0096] n2 is selected from 0, 1, 2, 3 or 4;

[0097] m is selected from 0, 1, 2, 3 or 4;

[0098] R a each independently selected from H, deuterium, halogen, OH, =0, NH2, CN, COOH, CONH2, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3-6 carbocyclyl, 3- to 6-membered heterocyclyl, said alkyl, alkenyl, alkynyl, alkoxy, carbocyclic or heterocyclic group being optionally substituted with 1 to 4 R z substituted;

[0099] R A each independently selected from H, deuterium, halogen, OH, =0, NH2, CN, COOH, CONH2, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3-6 carbocyclyl, 3- to 6-membered heterocyclyl, said alkyl, alkenyl, alkynyl, alkoxy, carbocyclic or heterocyclic group being optionally substituted with 1 to 4 R z substituted;

[0100] R b1 or R b2 each independently selected from deuterium, halogen, OH, =0, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-6 alkyl, S(O)2C 1-6 alkyl, S(O)2C 3-6 carbocyclyl, S(O)2-3- to 7-membered heterocyclyl, COC 1-6 alkyl, CO-3- to 10-membered heterocyclyl, CO-C 3-10 carbocyclyl, COO-C 1-6 alkylene-C 3-10 carbocyclyl, CO-C 1-6 alkylene-C 3-10 carbocyclyl, C 1-6 alkyl, OC 1-6 alkyl, SC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, NHC1-6 Alkyl, N(C) 1-6 Alkyl)2, -OC 3-6 Carbocyclic groups, -O-3 to 10-membered heterocyclic groups, -NH-C 3-10 Carbocyclic groups, -NH-3 to 10-membered heterocyclic groups, -NHCO-C 1-6 Alkyl, -CONH-C 1-6 Alkyl, -NHCO-C 3-10 carbonyl group, -CONH-C 3-10 Carbocyclic groups, -NHCO-3 to 10-membered heterocyclic groups, -CONH-3 to 10-membered heterocyclic groups, -C 0-4 Alkylene-C 3-10 Carbocyclic group, -C 0-4 Alkylene-3 to 10-membered heterocyclic group, wherein the alkyl, alkylene, alkenyl, ynyl, carbocyclic or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace;

[0101] Or two Rs b1 Or two Rs b2 Each atom forms a carbon atom with the atoms it is attached to. 3-10 A carbocyclic group or a 4-10 membered heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace;

[0102] R 1 Selected from H, deuterium, halogens, OH, =O, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-6 Alkyl, S(O)2C 1-6 Alkyl, S(O)2C 3-6 Carbocyclic groups, S(O)2-3 to 7-membered heterocyclic groups, COC 1-6 Alkyl, C 1-6 Alkyl, OC 1-6 Alkyl, SC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, NHC 1-6 Alkyl, N(C) 1-6 Alkyl)2, -OC 3-6 Carbocyclic groups, -O-3 to 7-membered heterocyclic groups, -NH-C 3-6 Carbocyclic groups, -NH-3 to 7-membered heterocyclic groups, -NHCO-C 1-6 Alkyl, -CONH-C 1-6 Alkyl, -NHCO-C 3-6 carbonyl group, -CONH-C 3-6 Carbocyclic groups, -NHCO-3 to 7-membered heterocyclic groups, -CONH-3 to 7-membered heterocyclic groups, -C 0-4 Alkylene-C3-6 carbocyclyl, -C 0-4 alkylene-3- to 7-membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, carbocyclyl or heterocyclyl being optionally substituted with 1 to 4 R z substituents;

[0103] R 2 or R 3 is selected from the group consisting of H, deuterium, C 1-6 alkyl, C 3-10 carbocyclyl, 4- to 10-membered heterocyclyl, said alkyl, carbocyclyl or heterocyclyl being optionally substituted with 1 to 4 R z substituents;

[0104] or R 1 , R 2 and the atom to which they are attached form a 4- to 10-membered heterocyclyl, said heterocyclyl being optionally substituted with 1 to 4 R 1a substituents;

[0105] R 1a each independently selected from the group consisting of deuterium, halogen, OH, =0, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-6 alkyl, S(O)2C 1-6 alkyl, S(O)2C 3-10 carbocyclyl, S(O)2-3- to 10-membered heterocyclyl, COC 1-6 alkyl, CO-3- to 10-membered heterocyclyl, CO-C 3-10 carbocyclyl, C 1-6 alkyl, OC 1-6 alkyl, SC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, NHC 1-6 alkyl, N(C 1-6 alkyl)2, -O-C 3-6 carbocyclyl, -O-3- to 10-membered heterocyclyl, -NH-C 3-10 carbocyclyl, -NH-3- to 10-membered heterocyclyl, -NHCO-C 1-6 alkyl, -CONH-C 1-6 alkyl, -NHCO-C 3-10 carbocyclyl, -CONH-C 3-10 carbocyclyl, -NHCO-3- to 10-membered heterocyclyl, -CONH-3- to 10-membered heterocyclyl, -C 0-4 alkylene-C 3-10 carbocyclyl, -C 0-4 alkylene-3- to 10-membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, carbocyclyl or heterocyclyl being optionally substituted with 1 to 4 R z substituents;

[0106] R 4a or R 4b each independently is selected from H, deuterium, halogen, OH, =0, NH2, CN, COOH, CONH2, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3-6 carbocyclyl, 3- to 6-membered heterocyclyl, said alkyl, alkenyl, alkynyl, alkoxy, carbocyclic or heterocyclic group is optionally substituted with 1 to 4 R z substituents;

[0107] R 5 is selected from

[0108] R 5a , R 5b , R 5c or R 5d each independently is selected from H, deuterium, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylene-M-C 1-10 alkyl, C 1-6 alkylene-M-C 3-10 carbocyclyl, C 1-6 alkylene-M-3- to 10-membered heterocyclyl, C 3-10 carbocyclyl, 3- to 10-membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, alkoxy, carbocyclic or heterocyclic group is optionally substituted with 1 to 4 R z substituents;

[0109] M is selected from O, S, C(=0), S(=0), S(=0)2, -NR m C(=0)-, -C(=0)NR m -, -OC(=0)-, -C(=0)0-, -OC(=0)0-, -SC(=0)-, -C(=0)S-, -OC(=0)NR m -;

[0110] R m is selected from H, deuterium, C 1-6 alkyl, C 3-10 carbocyclyl, 4- to 10-membered heterocyclyl, said alkyl, carbocyclyl or heterocyclyl is optionally substituted with 1 to 4 R z substituents;

[0111] or R 5c , R 5d and the atom to which they are attached form a 4- to 10-membered heterocyclyl group, said heterocyclyl group is optionally substituted with 1 to 4 R z substituents;

[0112] R z Each element is independently selected from deuterium, halogens, OH, =O, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, and SOC. 1-6 Alkyl, S(O)2C 1-6 Alkyl, S(O)2C 3-10 Carbocyclic groups, S(O)2-3 to 10-membered heterocyclic groups, COC 1-6 Alkyl, CO-3 to 10-membered heterocyclic groups, CO-C 3-10 carbonyl group, C 1-6 Alkyl, OC 1-6 Alkyl, SC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, NHC 1-6 Alkyl, N(C) 1-6 Alkyl)2, -OC 3-6 Carbocyclic groups, -O-3 to 10-membered heterocyclic groups, -NH-C 3-10 Carbocyclic groups, -NH-3 to 10-membered heterocyclic groups, -NHCO-C 1-6 Alkyl, -CONH-C 1-6 Alkyl, -NHCO-C 3-10 carbonyl group, -CONH-C 3-10 Carbocyclic groups, -NHCO-3 to 10-membered heterocyclic groups, -CONH-3 to 10-membered heterocyclic groups, -C 0-4 Alkylene-C 3-10 Carbocyclic group, -C 0-4 Alkylene-3 to 10-membered heterocyclic groups, wherein the alkyl, alkylene, alkenyl, alkynyl, carbocyclic or heterocyclic group is optionally selected from 1 to 4 groups selected from deuterium, halogen, =O, CN, OH, NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Substituents of carbocyclic groups and 3 to 7-membered heterocyclic groups;

[0113] The condition is that,

[0114] 1)R A Not H;

[0115] Or 2) Two Rs b1 And the atoms bonded to it form C 3-10 A carbocyclic group or a 4-10 membered heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace;

[0116] Or 3) n1 is selected from 2, 3 or 4 and R b1 Not H;

[0117] or 4) at least one ring atom of ring B2is an oxygen atom;

[0118] or 5) Z is selected from N.

[0119] As a second embodiment of the present application, the aforementioned compound represented by the general formula (I) or a stereoisomer, a tautomer, a racemate, a pharmaceutically acceptable salt thereof,

[0120] is selected from

[0121] Y is selected from O, NH or CH2;

[0122] n2is selected from 0, 1, 2 or 3;

[0123] n3is selected from 0, 1, 2 or 3;

[0124] n4is selected from 0, 1, 2 or 3;

[0125] n5is selected from 0, 1, 2 or 3;

[0126] Ring A is selected from phenyl, 5-6 membered heteroaryl, phenyl and 6 membered carbocyclyl, phenyl and 5 membered carbocyclyl, phenyl and 6 membered heterocyclyl, phenyl and 5 membered heterocyclyl, 5 and 5 membered heteroaryl, 5 and 6 membered heteroaryl, 6 and 6 membered heteroaryl or naphthyl, said ring A is optionally substituted with 1 to 4 R a ;

[0127] R a each independently is selected from H, deuterium, halogen, OH, =O, NH2, CN, COOH, CONH2, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 3-6 carbocyclyl, 3 to 6 membered heterocyclyl, said alkyl, alkenyl, alkynyl, alkoxy, carbocyclyl or heterocyclyl is optionally substituted with 1 to 4 R z ;

[0128] R A each independently is selected from H, deuterium, halogen, OH, =O, NH2, CN, COOH, CONH2, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 3-6 carbocyclyl, 3 to 6 membered heterocyclyl, said alkyl, alkenyl, alkynyl, alkoxy, carbocyclyl or heterocyclyl is optionally substituted with 1 to 4 R z ;

[0129] R b1or R b2 each independently selected from the group consisting of deuterium, halogen, OH, =0, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-4 alkyl, S(O)2C 1-4 alkyl, S(O)2C 3-6 carbocyclyl, S(O)2-3- to 7-membered heterocyclyl, COC 1-4 alkyl, CO-3- to 10-membered heterocyclyl, CO-C 3-10 carbocyclyl, COO-C 1-4 alkylene-C 3-10 carbocyclyl, CO-C 1-4 alkylene-C 3-10 carbocyclyl, C 1-4 alkyl, OC 1-4 alkyl, SC 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, NHC 1-4 alkyl, N(C 1-4 alkyl)2, -O-C 3-6 carbocyclyl, -O-3- to 10-membered heterocyclyl, -NH-C 3-10 carbocyclyl, -NH-3- to 10-membered heterocyclyl, -NHCO-C 1-4 alkyl, -CONH-C 1-4 alkyl, -NHCO-C 3-10 carbocyclyl, -CONH-C 3-10 carbocyclyl, -NHCO-3- to 10-membered heterocyclyl, -CONH-3- to 10-membered heterocyclyl, -C 0-2 alkylene-C 3-10 carbocyclyl, -C 0-2 alkylene-3- to 10-membered heterocyclyl, which alkyl, alkylene, alkenyl, alkynyl, carbocyclyl or heterocyclyl is optionally substituted with 1 to 4 R z substituents;

[0130] or two R b1 or two R b2 each and the atom to which they are attached form a C 3-10 carbocyclyl or 4- to 8-membered heterocyclyl, which carbocyclyl or heterocyclyl is optionally substituted with 1 to 4 R z substituents;

[0131] R 1 selected from the group consisting of H, deuterium, halogen, OH, =0, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-4 alkyl, S(O)2C 1-4 alkyl, S(O)2C 3-6carbocyclyl, S(O)2-3- to 7-membered heterocyclyl, COC 1-4 alkyl, C 1-4 alkyl, OC 1-4 alkyl, SC 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, NHC 1-4 alkyl, N(C 1-4 alkyl)2, -O-C 3-6 carbocyclyl, -O-3- to 7-membered heterocyclyl, -NH-C 3-6 carbocyclyl, -NH-3- to 7-membered heterocyclyl, -NHCO-C 1-4 alkyl, -CONH-C 1-4 alkyl, -NHCO-C 3-6 carbocyclyl, -CONH-C 3-6 carbocyclyl, -NHCO-3- to 7-membered heterocyclyl, -CONH-3- to 7-membered heterocyclyl, -C 0-2 alkylene-C 3-6 carbocyclyl, -C 0-2 alkylene-3- to 7-membered heterocyclyl, which alkyl, alkylene, alkenyl, alkynyl, carbocyclyl or heterocyclyl is optionally substituted by 1 to 4 R z substituents;

[0132] R 2 or R 3 is selected from the group consisting of H, deuterium, C 1-4 alkyl, C 3-6 carbocyclyl, 4- to 7-membered heterocyclyl, which alkyl, carbocyclyl or heterocyclyl is optionally substituted by 1 to 4 R z substituents;

[0133] or R 1 , R 2 and the atoms to which they are attached form a 4- to 9-membered heterocyclyl, which heterocyclyl is optionally substituted by 1 to 4 R 1a substituents;

[0134] R 1a each independently is selected from the group consisting of deuterium, halogen, OH, =O, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-4 alkyl, S(O)2C 1-4 alkyl, S(O)2C 3-10 carbocyclyl, S(O)2-3- to 10-membered heterocyclyl, COC 1-4 alkyl, CO-3- to 10-membered heterocyclyl, CO-C 3-10 carbocyclyl, C 1-4 alkyl, OC 1-4 alkyl, SC 1-4 alkyl, C 2-4 alkenyl, C2-4 alkynyl, NHC 1-4 alkyl, N(C 1-4 alkyl)2, -O-C 3-6 carbocyclyl, -O-3- to 10-membered heterocyclyl, -NH-C 3-10 carbocyclyl, -NH-3- to 10-membered heterocyclyl, -NHCO-C 1-4 alkyl, -CONH-C 1-4 alkyl, -NHCO-C 3-10 carbocyclyl, -CONH-C 3-10 carbocyclyl, -NHCO-3- to 10-membered heterocyclyl, -CONH-3- to 10-membered heterocyclyl, -C 0-2 alkylene-C 3-10 carbocyclyl, -C 0-2 alkylene-3- to 10-membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, carbocyclyl or heterocyclyl being optionally substituted with 1 to 4 R z substituents;

[0135] R 4a or R 4b are each independently selected from the group consisting of H, deuterium, halogen, OH, =0, NH2, CN, COOH, CONH2, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, C 3-6 carbocyclyl, 3- to 6-membered heterocyclyl, said alkyl, alkenyl, alkynyl, alkoxy, carbocyclyl or heterocyclyl being optionally substituted with 1 to 4 R z substituents;

[0136] R 5 is selected from the group consisting of

[0137] R 5a , R 5b , R 5c or R 5d are each independently selected from the group consisting of H, deuterium, C 1-4 alkyl, C 1-4 alkoxy, C 1-5 alkylene-M-C 1-8 alkyl, C 1-5 alkylene-M-C 3-6 carbocyclyl, C 1-5 alkylene-M-3- to 7-membered heterocyclyl, C 3-6 carbocyclyl, 3- to 7-membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, alkoxy, carbocyclyl or heterocyclyl being optionally substituted with 1 to 4 R z substituents;

[0138] M is selected from O, S, C(=O), S(=O), S(=O)2, -NR m C(=O)-, -C(=O)NR m -, -OC(=O)-, -C(=O)O-, -OC(=O)O-, -SC(=O)-, -C(=O)S-, -OC(=O)NR m -;

[0139] R m is selected from H, deuterium, C 1-4 alkyl, C 3-6 carbocyclyl, 4- to 7-membered heterocyclyl, said alkyl, carbocyclyl or heterocyclyl being optionally substituted with 1 to 4 R z ;

[0140] or R 5c , R 5d and the atom to which they are attached form a 4- to 8-membered heterocyclyl, said heterocyclyl being optionally substituted with 1 to 4 R z ;

[0141] R z each independently selected from deuterium, halogen, OH, =O, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-4 alkyl, S(O)2C 1-4 alkyl, S(O)2C 3-10 carbocyclyl, S(O)2-3- to 10-membered heterocyclyl, COC 1-4 alkyl, CO-3- to 10-membered heterocyclyl, CO-C 3-10 carbocyclyl, C 1-4 alkyl, OC 1-4 alkyl, SC 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, NHC 1-4 alkyl, N(C 1-4 alkyl)2, -O-C 3-6 carbocyclyl, -O-3- to 10-membered heterocyclyl, -NH-C 3-10 carbocyclyl, -NH-3- to 10-membered heterocyclyl, -NHCO-C 1-4 alkyl, -CONH-C 1-4 alkyl, -NHCO-C 3-10 carbocyclyl, -CONH-C 3-10 carbocyclyl, -NHCO-3- to 10-membered heterocyclyl, -CONH-3- to 10-membered heterocyclyl, -C 0-2 alkylene-C 3-10 carbocyclyl, -C 0-2alkylene-3- to 10-membered heterocyclyl, said alkyl, alkylene, alkenyl, alkynyl, carbocyclyl or heterocyclyl is optionally substituted with 1 to 4 substituents selected from the group consisting of deuterium, halogen, =0, CN, OH, NH2, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 carbocyclyl, 3- to 7-membered heterocyclyl, said alkyl, alkenyl, alkynyl, carbocyclyl or heterocyclyl is optionally substituted with 1 to 4 substituents selected from the group consisting of deuterium, halogen, =0, CN, OH, NH2, C

[0142] The remaining definitions are the same as in the first embodiment of the present application.

[0143] As a third embodiment of the present application, the aforementioned compound represented by the general formula (I) or a stereoisomer, a tautomer, a racemate, a pharmaceutically acceptable salt thereof,

[0144] is selected from the group consisting of

[0145] n2 is selected from 0, 1 or 2; n3 is selected from 0, 1, 2 or 3; n4 is selected from 0, 1 or 2; n5 is selected from 0, 1 or 2;

[0146] ring A is selected from the group consisting of benzothiophenyl, naphthyl, benzopyridinyl, benzopyrimidinyl, benzopyrazinyl, benzopyridazinyl, benzopyrrolyl, benzopyrazolyl, benzimidazolyl, benzothiazolyl, benzothiophenyl, pyridopyridinyl, pyridopyrimidinyl, pyridopyrazinyl, pyridopyridazinyl, pyridopyrrolyl, pyridopyrazolyl, pyridimidazolyl, pyridimidazolyl, said ring A is optionally substituted with 1 to 4 R a substituents;

[0147] R a each independently selected from the group consisting of H, deuterium, F, Cl, Br, I, OH, =0, NH2, CN, COOH, CONH2, methyl, ethyl, propyl, isopropyl, ethenyl, ethynyl, propynyl, propargyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, said methyl, ethyl, propyl, isopropyl, ethenyl, ethynyl, propynyl, propargyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl is optionally substituted with 1 to 4 R z substituents;

[0148] R Aeach independently selected from the group consisting of H, deuterium, F, CI, Br, I, OH, =0, NH2, CN, COOH, CONH2, methyl, ethyl, propyl, isopropyl, ethenyl, ethynyl, propynyl, propargyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, said methyl, ethyl, propyl, isopropyl, ethenyl, ethynyl, propynyl, propargyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl being optionally substituted with 1 to 4 R z substituents;

[0149] R b1 or R b2 each independently selected from the group consisting of deuterium, F, CI, Br, I, OH, CN, NH2, COOH, -CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, CO-cyclopropyl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, ethenyl, ethynyl, propynyl, propargyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl)2, N(ethyl)2, N(propyl)2, N(isopropyl)2, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-azetidinyl, -CH2-pyrrolidinyl, -CH2-oxetanyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, said methyl, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, being optionally substituted with 1 to 4 Rz substituted;

[0150] or two R b1 and the atom to which they are attached form a cyclopropyl or cyclobutyl group, which is optionally substituted with 1 to 4 R z substituted;

[0151] R 1 is selected from the group consisting of H, deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, -CONH2, SO H2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, methyl, ethyl, propyl, isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -CONH-cyclopropyl, -CONH-cyclobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-azetidinyl, -CH2-pyrrolidinyl, -CH2-oxetanyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, which methyl, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl is optionally substituted with 1 to 4 R z substituted;

[0152] R 2 or R 3 is selected from the group consisting of H, deuterium, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, which methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl is optionally substituted with 1 to 4 R z substituted;

[0153] or R 1 , R 2 and the atom to which they are attached form a ring selected from the group consisting of 1a which is optionally substituted with 1 to 4 R

[0154] R 1aeach independently selected from the group consisting of deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, CONH2, SO H2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propargyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl)2, N(ethyl)2, N(propyl)2, N(isopropyl)2, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, pyridyl, pyridonyl, -CH2-azetidinyl, -CH2-pyrrolidinyl, -CH2-oxetanyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, -CH2-phenyl, said alkyl, alkylene, alkenyl, alkynyl, carbocyclyl, or heterocyclyl is optionally substituted with one to four R z ;

[0155] R 4a , R 4b each independently selected from the group consisting of H, deuterium, F, Cl, Br, I, OH, =O, NH2, CN, COOH, CONH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, said methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl is optionally substituted with one to four R z ;

[0156] R 5a , R 5b , R 5c , or R5d Each is independently selected from H, deuterium, methyl, ethyl, propyl, isopropyl, methoxy, C 1-4 Alkylene-MC 1-6 Alkyl, cyclopropyl, phenyl, pyridyl, wherein the alkyl, alkylene, methyl, ethyl, propyl, isopropyl, or methoxy group is optionally marked with 1 to 4 R groups. z replace;

[0157] M is selected from -OC(=O)-, -C(=O)O-, -OC(=O)O-, -SC(=O)-;

[0158] Or R 5c R 5d The atoms bonded to them form azircyclic butyl, azircyclic pentyl, azircyclic hexyl, piperazine, or morpholino groups, wherein the azircyclic butyl, azircyclic pentyl, azircyclic hexyl, piperazine, or morpholino groups are optionally atomized by 1 to 4 R atoms. z replace;

[0159] R z Each is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, -CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propynyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl)2, N( Ethyl)2, N(propyl)2, N(isopropyl)2, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, aziridine, oxaziridine, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -CH2-oxacyclobutyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, wherein the alkyl, alkylene, alkenyl, alkynyl, carbocyclic or heterocyclic group is optionally selected from 1 to 4 groups selected from deuterium, F, Cl, Br, I, =O, CN, OH, NH2, C 1-4 Substituents include alkyl, methoxy, ethoxy, cyclopropyl, and aziridine groups;

[0160] The remaining definitions are the same as those in the first or second embodiment of the present invention.

[0161] As a fourth embodiment of the present invention, the compound represented by the aforementioned general formula (I) or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts thereof...

[0162] Selected from

[0163] R b1 It is independently selected from H, deuterium, F, Cl, Br, I, OH, CN, NH2, methyl, methoxy, CF3, CHF2, CH2F, CD3, OCD3, cyclopropyl, cyclobutyl, aziridine, or oxacyclobutyl;

[0164] R b2Each is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, COOH, CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, CO-CD3, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propynyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl -N(methyl)2, N(ethyl)2, N(propyl)2, N(isopropyl)2, -CO-cyclopropyl, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, aziridine, oxaziridine, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -CH2-oxacyclobutyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl

[0165] R a Each is independently selected from H, deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, CH2OH, CH2-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, aziridine, or oxacyclobutyl;

[0166] R A Each is independently selected from H, deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, CH2OH, CH2-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, aziridine, or oxacyclobutyl;

[0167] R 1Selected from H, deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, -CONH2, CF3, CHF2, CH2F, CD3, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, aziridine, oxadiazinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-aziridine, -CH2-pyrrolidinyl, -CH2-oxadiazinyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl

[0168] R 2 Or R 3 Selected from H, deuterium, CF3, CHF2, CH2F, CD3, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, oxadiazine, tetrahydrofuranyl, piperidinyl, piperazine, morpholinyl;

[0169] Or R 1 R 2 The atoms connected to it are optionally bounded by 1 to 4 R atoms. 1a The following rings are replaced:

[0170] R 1aEach is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propynyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl)2, N(ethyl)2 N(propyl)2, N(isopropyl)2, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, azacyclobutyl, oxacyclobutyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, pyridinyl, pyridoneyl -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -CH2-oxacyclobutyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, -CH2-phenyl

[0171] R 4a Or R 4b Each is independently selected from H, deuterium, F, Cl, Br, I, OH, =O, NH2, CN, COOH, CONH2, CF3, CHF2, CH2F, CD3, OCD3, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, aziridine, and oxacyclobutyl;

[0172] R 5a R 5b R 5c Or R 5d Each is independently selected from H, CF3, CHF2, CH2F, CD3, OCD3, deuterium, methyl, ethyl, propyl, isopropyl, cyclopropyl, phenyl, pyridyl,

[0173] The remaining definitions are the same as those in the first, second, or third embodiments of the present invention.

[0174] As a fifth embodiment of the present invention, the compound represented by the aforementioned general formula (I), or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts, are used.

[0175] Ring A is selected from benzothiophene, naphthyl, benzopyrrole, The ring A is arbitrarily divided by 1 to 4 Rs a replace;

[0176] Selected from

[0177] Selected from

[0178] R 5 Selected from

[0179] The remaining definitions are the same as those in the first, second, third, or fourth embodiments of this invention.

[0180] As a sixth embodiment of the present invention, the compound represented by the aforementioned general formula (I) or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts, wherein the compound represented by general formula (I) is selected from the compounds represented by general formula (II-1) or (II-2),

[0181]

[0182] R A Each is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, CH2OH, CH2-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, aziridine, or oxacyclobutyl;

[0183] R b2Each is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, COOH, CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, CO-CD3, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propynyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl -N(methyl)2, N(ethyl)2, N(propyl)2, N(isopropyl)2, -CO-cyclopropyl, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, aziridine, oxaziridine, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -CH2-oxacyclobutyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl

[0184] Selected from

[0185] n4 or n5 are each independently selected from 0, 1, or 2.

[0186] This invention relates to a compound or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts thereof, wherein the compound is selected from one of the structures in Table E-1.

[0187] This invention relates to a pharmaceutical composition comprising the above-described compound or its stereoisomers, tautomers, racemates, pharmaceutically acceptable salts, and pharmaceutically acceptable carriers.

[0188] This invention relates to the use of the above-mentioned compounds or their stereoisomers, tautomers, racemates, pharmaceutically acceptable salts, or the above-mentioned pharmaceutical compositions in the preparation of drugs that inhibit STAT6.

[0189] This invention relates to the use of the above-mentioned compounds or their stereoisomers, tautomers, racemates, pharmaceutically acceptable salts, or the above-mentioned pharmaceutical compositions in the preparation of medicaments for treating cancer.

[0190] This invention relates to a pharmaceutical composition or pharmaceutical formulation comprising a therapeutically effective amount of the compound of the invention or its stereoisomers, tautomers, racemates, pharmaceutically acceptable salts, and pharmaceutical excipients. The pharmaceutical composition may be in unit dosage form (the amount of the active ingredient in a unit dosage form is also referred to as a "dosage strength").

[0191] The present invention also provides a method for treating diseases in mammals, comprising administering to the mammal a therapeutically effective amount of the compound of the present invention or its stereoisomers, tautomers, racemates, pharmaceutically acceptable salts, or pharmaceutical compositions. In some embodiments, the mammals described in the present invention include humans.

[0192] The term "effective amount" or "therapeutic effective amount" as used in this application means that administering a sufficient amount of the compound disclosed in this application will alleviate, to some extent, one or more symptoms of the disease or condition (e.g., cancer) being treated. In some embodiments, the result is a reduction and / or mitigation of the signs, symptoms, or causes of the disease, or any other desired alteration of the biological system. For example, an "effective amount" for therapeutic use is the amount of the compound disclosed in this application required to provide a clinically significant reduction in disease symptoms.Examples of therapeutically effective doses include, but are not limited to, 1-1500 mg, 1-1000 mg, 1-800 mg, 1-600 mg, 2-600 mg, 3-600 mg, 4-600 mg, 5-600 mg, 6-600 mg, 10-600 mg, 20-600 mg, 25-600 mg, 30-600 mg, 40-600 mg, 50-600 mg, 60-600 mg, 70-600 mg, 75-600 mg, 80-600 mg, 90-600 mg, 100-600 mg, 200-600 mg, 1-500 mg, 2-500 mg, 3-500 mg. g, 4-500mg, 5-500mg, 6-500mg, 10-500mg, 20-500mg, 25-500mg, 30-500mg, 40-500mg, 50-500mg, 60-500mg, 70-500mg, 75-500mg, 80-500mg , 90-500mg, 100-500mg, 125-500mg, 150-500mg, 200-500mg, 250-500mg, 300-500mg, 400-500mg, 5-400mg, 10-400mg, 20-400mg, 25-400mg, 30-400mg, 40-400mg, 50-400mg, 60-400mg, 70-400mg, 75-400mg, 80-400mg, 90-400mg, 100-400mg, 125-400mg, 150-400mg, 200-400mg, 25 0-400mg, 300-400mg, 1-300mg, 2-300mg, 5-300mg, 10-300mg, 20-300mg, 25-300mg, 30-300mg, 40-300mg, 50-300mg, 60-300mg, 70-300mg, 7 5-300mg, 80-300mg, 90-300mg, 100-300mg, 125-300mg, 150-300mg, 200-300mg, 250-300mg, 1-200mg, 2-200mg, 5-200mg, 10-200mg, 20-200 mg, 25-200mg, 30-200mg, 40-200mg, 50-200mg, 60-200mg, 70-200mg, 75-200mg, 80-200mg, 90-200mg, 100-200mg, 125-200mg, 150-200mg;.

[0193] In some embodiments, the pharmaceutical composition includes, but is not limited to, 1-1500 mg, 1-1000 mg, 1-800 mg, 1-600 mg, 20-400 mg, 25-200 mg, 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg. The compounds of the present invention, or their stereoisomers, tautomers, racemates, deuterated derivatives, solvates, prodrugs, metabolites, pharmaceutically acceptable salts, or cocrystals, in doses of g, 100 mg, 110 mg, 120 mg, 125 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, or 300 mg.

[0194] A method for treating a disease in mammals, the method comprising administering to a subject a therapeutically effective amount of the compound of the present invention or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts, preferably 1-1500 mg, wherein the disease is preferably cancer.

[0195] A method for treating a disease in mammals, the method comprising administering a drug, a compound of the present invention or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts thereof, to a subject at a daily dose of 1-1500 mg / day, said daily dose being a single dose or multiple doses, and in some embodiments, the daily dose including but not limited to 10-1500 mg / day, 10-1000 mg / day, 10-800 mg / day, 25-800 mg / day, 50-800 mg / day, etc. 100-800mg / day, 200-800mg / day, 25-400mg / day, 50-400mg / day, 100-400mg / day, 200-400mg / day. In some embodiments, the daily dose includes, but is not limited to, 10mg / day, 20mg / day, 25mg / day, 50mg / day, 100mg / day, 125mg / day, 150mg / day, 200mg / day, 400mg / day, 600mg / day, and 800mg / day.

[0196] This invention relates to a kit that may include a single-dose or multi-dose composition comprising a compound of the present invention or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts thereof, wherein the amount of the compound of the present invention or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts is the same as the amount in the aforementioned pharmaceutical composition.

[0197] The compounds of the present invention also include their deuterated derivatives, solvates, prodrugs, metabolites, and cocrystals.

[0198] In this invention, the amount of the compound of the invention or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts is converted in each case as a free base.

[0199] "Product specification" refers to the weight of the active pharmaceutical ingredient contained in each vial, tablet, or other unit of preparation.

[0200] Unless otherwise stated, the terms used in the specification and claims have the following meanings.

[0201] The carbon, hydrogen, oxygen, sulfur, nitrogen, phosphorus, F, Cl, Br, I, etc. involved in the groups and compounds described in this invention include their isotopic forms. That is, the carbon, hydrogen, oxygen, sulfur, or nitrogen involved in the groups and compounds described in this invention may optionally be further replaced by one or more of their corresponding isotopes, wherein the isotopes of carbon include 11 C 12 C 13 C and 14 C, the isotopes of hydrogen include protium (H), deuterium (D, also called heavy hydrogen), and tritium (T, also called superheavy hydrogen), and the isotopes of oxygen include 15 O、 16 O、 17 O and 18 O, isotopes of sulfur include 32 S, 33 S, 34 S, 35 S and 36 S, nitrogen isotopes include 13 N、 14 N and 15 N, isotopes of fluorine include 17 F, 18 F and 19 F, isotopes of chlorine include 35 Cl、 36 Cl and 37 Cl, isotopes of bromine include 79 Br and 81 Br, an isotope of iodine, includes 123 I, 125 I, phosphorus isotopes include 31 P, 32 P.

[0202] “CN” refers to cyano.

[0203] "Halogen" refers to F, Cl, Br or I.

[0204] "Halogen-substituted" refers to substitution with F, Cl, Br, or I, including but not limited to 1 to 10 substituents selected from F, Cl, Br, or I, 1 to 6 substituents selected from F, Cl, Br, or I, and 1 to 4 substituents selected from F, Cl, Br, or I. "Halogen-substituted" is abbreviated as "halogenated".

[0205] "alkyl" refers to a substituted or unsubstituted straight-chain or branched saturated aliphatic hydrocarbon group, including but not limited to alkyl groups with 1 to 20 carbon atoms, alkyl groups with 1 to 8 carbon atoms, alkyl groups with 1 to 6 carbon atoms, and alkyl groups with 1 to 4 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, neobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, and their various branched isomers; the alkyl group can be monovalent, divalent, trivalent, or tetravalent.

[0206] "Alkylene" refers to substituted or unsubstituted straight-chain and branched divalent saturated hydrocarbon groups, including -(CH2). v - (v is an integer from 1 to 10), alkylene examples include, but are not limited to, methylene, ethylene, propylene, and butylene.

[0207] "Cycloalkyl" refers to a substituted or unsubstituted saturated carbocyclic hydrocarbon group, typically having 3 to 12 carbon atoms. Cycloalkyl groups can be monocyclic, fused, bridged, or spirocyclic. Non-limiting examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclobutyl-cyclobutyl, cyclobutyl-spirobutyl, adamantane, etc. Cycloalkyl groups can be monovalent, divalent, trivalent, or tetravalent.

[0208] "Heterocyclic alkyl" refers to a substituted or unsubstituted saturated cyclic hydrocarbon group containing heteroatoms, including but not limited to 3 to 12 atoms or 3 to 8 atoms, containing 1 to 3 heteroatoms selected from N, O, S, or Se. The C, N, and S atoms on the ring of the heterocyclic alkyl group can be oxidized to various oxidation states. Heterocyclic alkyl groups can be monocyclic, fused, bridged, or spirocyclic. Heterocyclic alkyl groups can be attached to heteroatoms or carbon atoms. Non-limiting examples include epoxyethyl, aziridinepropyl, oxacyclobutyl, aziridinebutyl, tetrahydrofuranyl, tetrahydro-2H-pyranyl, dioxopentyl, dioxohexyl, pyrrolylalkyl, piperidinyl, imidazoalkyl, oxazolidinyl, oxazinylalkyl, morpholinyl, hexahydropyrimidinyl, piperazineyl, etc. Heterocyclic alkyl groups can be monovalent, divalent, trivalent, or tetravalent.

[0209] "Alkenyl" refers to a substituted or unsubstituted straight-chain and branched unsaturated hydrocarbon group having at least one, typically one, two, or three, carbon-carbon double bonds. The main chain has, but is not limited to, 2 to 10, 2 to 6, or 2 to 4 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl, allyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 2... -Methyl-3-butenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 1-octenyl, 3-octenyl, 1-nonenyl, 3-nonenyl, 1-decenyl, 4-decenyl, 1,3-butadiene, 1,3-pentadiene, 1,4-pentadiene, and 1,4-hexadiene, etc.; the alkenyl group can be monovalent, divalent, trivalent, or tetravalent.

[0210] "Alynyl" refers to a substituted or unsubstituted straight-chain and branched unsaturated hydrocarbon group having at least one, typically one, two, or three, carbon-carbon triple bonds. The main chain comprises 2 to 10 carbon atoms, including but not limited to having 2 to 6 carbon atoms on the main chain, or 2 to 4 carbon atoms on the main chain. Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, and 4-pentynyl. The alkynyl group can be monovalent, divalent, trivalent, or tetravalent.

[0211] "Alkoxy" refers to a substituted or unsubstituted -O-alkyl group. Non-limiting examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, n-hexoxy, cyclopropoxy, and cyclobutoxy.

[0212] "Carbocyclic group" or "carbocyclic ring" refers to a substituted or unsubstituted aromatic or non-aromatic ring. The aromatic or non-aromatic ring can be a 3- to 8-membered monocyclic ring, a 4- to 12-membered bicyclic ring, a 10- to 15-membered tricyclic ring, or a 12- to 18-membered quaternary system. The carbocyclic group can be attached to an aromatic or non-aromatic ring, and the ring can be optionally a monocyclic, fused, bridged, or spirocyclic ring. Non-limiting examples include cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, 1-cyclopentyl-1-enyl, 1-cyclopentyl-2-enyl, 1-cyclopentyl-3-enyl, cyclohexyl, 1-cyclohexyl-2-enyl, 1-cyclohexyl-3-enyl, cyclohexenyl, benzene ring, naphthalene ring, etc. "Carbocyclic group" or "carbon ring" can be monovalent, divalent, trivalent or tetravalent.

[0213] "Heterocyclic group" or "heterocyclic" refers to a substituted or unsubstituted aromatic or non-aromatic ring. The aromatic or non-aromatic ring can be a 3- to 8-membered monocyclic ring, a 4- to 12-membered bicyclic ring, a 10- to 15-membered tricyclic ring, or a 12- to 18-membered quaternary system, and contains one or more (including but not limited to 2, 3, 4 or 5) heteroatoms selected from N, O, S or Se. The C, N, S or Se selectively substituted in the ring of the heterocyclic group can be oxidized to various oxidation states. The heterocyclic group can be attached to a heteroatom or a carbon atom, and can be attached to an aromatic ring or a non-aromatic ring. The heterocyclic group is optionally a monocyclic, bridged, fused, or spirocyclic ring. Non-limiting examples include epoxyethyl, aziridinepropyl, oxacyclobutyl, aziridinebutyl, 1,3-dioxopentyl, 1,4-dioxopentyl, 1,3-dioxahexane, aziridineheptyl, pyridinyl, furanyl, thiophene, pyranyl, N-alkylpyrroleyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazolyl, piperidinyl, morpholinyl, thiomorpholinyl, 1,3-dithioyl, dihydrofuranyl, dihydropyranyl, dithiapentylcycloyl. Tetrahydrofuranyl, tetrahydropyrrolyl, tetrahydroimidazolyl, tetrahydrothiazolyl, tetrahydropyranyl, benzimidazolyl, benzopyridyl, pyrrolopyridyl, benzodihydrofuranyl, pyrrolyl, pyrazolyl, thiazolyl, oxazolyl, pyrazinyl, indazolyl, benzothiophene, benzofuranyl, benzopyrrolyl, benzimidazolyl, benzothiazolyl, benzooxazolyl, benzopyridyl, benzopyrimidinyl, benzopyrazinyl, piperazinyl, azabicyclo[3.2.1]octyl, azabicyclo[5.2.0]nonyl, oxatricyclo[5.3.1.1]dodecyl, azaadamantyl, oxaspiro[3.3]heptyl,

[0214] "Heterocyclic group" or "heterocyclic" can be monovalent, divalent, trivalent or tetravalent.

[0215] A "spirocyclic" or "spirocyclic group" refers to a polycyclic group in which substituted or unsubstituted rings share a single atom (called a spiro atom). The number of ring atoms in a spirocyclic system includes, but is not limited to, 5 to 20, 6 to 14, 6 to 12, or 6 to 10. One or more rings may contain zero or more (including but not limited to 1, 2, 3, or 4) double bonds, and optionally, may contain 0 to 5 double bonds selected from N, O, or S (=O). n heteroatoms (n is 0, 1 or 2).

[0216] "Spirocyclic" or "spirocyclic group" can be monovalent, divalent, trivalent or tetravalent.

[0217] "Circular fused" or "circular fused group" refers to a polycyclic group in which each ring in a system shares a pair of adjacent atoms with other rings in the system. One or more rings may contain zero or more (including but not limited to 1, 2, 3 or 4) double bonds and may be substituted or unsubstituted. Each ring in a circular fused system may contain 0 to 5 heteroatoms or groups containing heteroatoms (including but not limited to those selected from N, S (=O)). n Or O, where n is 0, 1, or 2). The number of ring atoms in a cyclic system includes, but is not limited to, 5 to 20, 5 to 14, 5 to 12, and 5 to 10. Non-limiting examples include: "Cyclone" or "cyclone base" can be monovalent, divalent, trivalent, or tetravalent.

[0218] A “bridged ring” or “bridged ring group” refers to a substituted or unsubstituted polycyclic group containing any two atoms that are not directly connected, and may contain zero or more double bonds. Any ring in a bridged ring system may contain 0 to 5 groups selected from heteroatoms or containing heteroatoms (including but not limited to N, S(=O)n, or O, where n is 0, 1, or 2). The number of ring atoms includes, but is not limited to, 5 to 20, 5 to 14, 5 to 12, or 5 to 10. Non-limiting examples include… Cubicane, adamantane. "Bridged ring" or "bridged ring group" can be monovalent, divalent, trivalent, or tetravalent.

[0219] "Aryl" or "aromatic ring" refers to a substituted or unsubstituted aromatic hydrocarbon group having a monocyclic or fused ring, wherein the number of ring atoms in the aromatic ring includes, but is not limited to, 6 to 18, 6 to 12, or 6 to 10 carbon atoms. The aryl ring can be fused to a saturated or unsaturated carbon ring, wherein the ring connected to the parent structure is the aryl ring. Non-limiting embodiments include benzene rings, naphthalene rings, etc. The "aryl" or "aryl ring" can be monovalent, divalent, trivalent, or tetravalent. When it is divalent, trivalent, or tetravalent, the linking site is located on the aryl ring.

[0220] "Heteroaryl" or "heteroary ring" refers to a substituted or unsubstituted aromatic hydrocarbon group containing 1 to 5 heteroatoms or a group containing heteroatoms (including but not limited to N, O, S(=O)n or Se(=O)n, where n is 0, 1, or 2). The number of ring atoms in the heteroaryl ring includes, but is not limited to, 5 to 15, 5 to 10, or 5 to 6. The atoms C, N, and S on the ring may be optionally oxidized (i.e., C(=O), NO, S(=O)n, Se(=O)n, where n is 1 or 2). Non-limiting examples of heteroaryl groups include, but are not limited to, pyridyl, furanyl, thiophenyl, selenyl, pyridyl, pyranyl, N-alkylpyrrolithyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazoleyl, benzopyrazolyl, benzimidazoleyl, benzopyridyl, pyrrolopyridyl, pyridinoneyl, etc. The heteroaryl ring can be fused to a saturated or unsaturated carbon ring or heterocycle, wherein the ring connected to the parent structure is an aryl ring. Non-limiting embodiments include... The heteroaryl groups mentioned in this article are defined in accordance with this definition. Heteroaryl groups can be monovalent, divalent, trivalent, or tetravalent. When divalent, trivalent, or tetravalent, the linkage site is located on an aromatic ring.

[0221] "Substituted" or "substituted" means substituted by one or more (including but not limited to 2, 3, 4, or 5) substituents, including but not limited to H, F, Cl, Br, I, alkyl, cycloalkyl, alkoxy, haloalkyl, thiol, hydroxyl, nitro, mercapto, amino, cyano, isocyano, aryl, heteroaryl, heterocyclic, bridged cyclic, spirocyclic, fused cyclic, hydroxyalkyl, =O, carbonyl, aldehyde, carboxylic acid, formate, and -(CH2). m -C(=O)-R a -O-(CH2) m -C(=O)-R a -(CH2) m -C(=O)-NR b R c -(CH2) m S(=O) n R a -(CH2) m -Alkenyl-R a OR d Or -(CH2) m -alkynyl-R a (where m and n are 0, 1, or 2), arylthio, thiocarbonyl, silyl, or -NR b R c Groups, wherein R b With R c Independently selected from H, hydroxyl, amino, carbonyl, alkyl, alkoxy, cycloalkyl, heterocyclic, aryl, heteroaryl, sulfonyl, trifluoromethanesulfonyl, Rb With R c It can form five- or six-membered cycloalkyl or heterocyclic groups, R a With R d Each group is independently selected from aryl, heteroaryl, alkyl, alkoxy, cycloalkyl, heterocyclic, carbonyl, ester, bridged cyclic, spirocyclic, or fused cyclic groups.

[0222] "1 to X substituents selected from..." means substituted by 1, 2, 3...X substituents selected from..., where X is any integer between 1 and 10. For example, "1 to 4 R..." k "Replace" refers to being replaced by 1, 2, 3, or 4 Rs. k Substitution. For example, "1 to 5 substituents selected from ..." means that the ring is substituted by 1, 2, 3, 4 or 5 substituents selected from .... For example, "the heterobridged ring is optionally substituted by 1 to 4 substituents selected from H or F" means that the heterobridged ring is optionally substituted by 1, 2, 3 or 4 substituents selected from H or F.

[0223] XY-membered rings (where X and Y are integers, and 3 ≤ X < Y, X < Y ≤ 20, selected from any integer between 4 and 20) include rings of the X, X+1, X+2, X+3, X+4…Y-membered types. These rings include heterocyclic rings, carbocyclic rings, aromatic rings, aryl groups, heteroaryl groups, cycloalkyl groups, heteromonocyclic rings, heterofused rings, heterospirocyclic rings, or heterobridged rings. For example, "4-7-membered heteromonocyclic rings" refers to heteromonocyclic rings of 4, 5, 6, or 7 members, and "5-10-membered heterofused rings" refers to heterofused rings of 5, 6, 7, 8, 9, or 10 members.

[0224] C x-y Carbocyclic rings (including aryl, cycloalkyl, monocyclic, spirocyclic, fused, or bridged carbocyclic rings) include C x C x+1 C x+2 C x+3 C x+4 …C y A ring of elements (x is an integer, and 3 ≤ x < y, where y is any integer between 4 and 20), for example, C. 3-6 "Cycloalkyl" refers to C3, C4, C5, or C6 cycloalkyl groups.

[0225] When a functional group has one or more connectable sites, any one or more of these sites can be linked to other functional groups via chemical bonds. When the chemical bond connection is non-directional and a hydrogen atom is present at the connectable site, the number of hydrogen atoms at that site decreases accordingly with the number of bonds being formed, resulting in a functional group with a corresponding valence. For example... This indicates that any connectable site on the piperidinyl group can be linked to other groups via a single chemical bond, including at least... These four connection methods, even if an H atom is drawn on -N-, This also includes For example This indicates that the R group on the piperidinyl group can be located on C or N, and at least includes [missing information]. For example, the general formula segment is: When X is selected from CH2 or NH, it means that the R group on the general formula fragment can be located on C or X. When X is selected from CH2, the general formula fragment can be... When X is selected from NH, the general formula fragment can be:

[0226] When the listed linking groups do not specify their linking direction, the linking direction includes the direction of the reading order from left to right and from right to left. For example, when ALB is selected from -MW-, it includes AMWB and AWMB.

[0227] "Optional" or "optionally" means that the event or environment described below may but does not have to occur, and the description includes the possibility or possibility that the event or environment may or may not occur. For example, "optionally substituted F alkyl" means that the alkyl group may but does not have to be substituted with F, and the description includes the case where the alkyl group is substituted with F and the case where the alkyl group is not substituted with F.

[0228] "Pharmaceutically acceptable salt" or "its pharmaceutically acceptable salt" means that the compound of the present invention retains the bioavailability and properties of a free acid or a free base, and that the free acid is obtained by reacting with a non-toxic inorganic or organic base, and the free base is obtained by reacting with a non-toxic inorganic or organic acid.

[0229] "Pharmaceutical composition" refers to a mixture of one or more compounds described in this invention, or stereoisomers, tautomers, deuterated compounds, solvates, prodrugs, metabolites, pharmaceutically acceptable salts or cocrystals, and other chemical components, wherein "other chemical components" refers to pharmaceutically acceptable carriers, excipients, and / or one or more other therapeutic agents.

[0230] "Product specification" refers to the weight of the active pharmaceutical ingredient contained in each vial, tablet, or other unit of preparation.

[0231] "Carrier" refers to a material that does not cause significant stimulation to an organism and does not eliminate the biological activity and properties of the compound given.

[0232] "Prodrug" refers to a compound of the present invention that can be metabolized in vivo and converted into a biologically active compound. The prodrug of the present invention is prepared by modifying the amino or carboxyl groups in the compound of the present invention. This modification can be performed through conventional procedures or removed in vivo to obtain the parent compound. When the prodrug of the present invention is administered to a mammalian individual, the prodrug is cleaved to form free amino or carboxyl groups.

[0233] "Co-crystal" refers to a crystal formed by the bonding of an active pharmaceutical ingredient (API) and a co-crystal form (CCF) through hydrogen bonds or other non-covalent bonds. Both API and CCF are solids at room temperature in their pure states, and a fixed stoichiometric ratio exists between the components. Co-crystal is a multi-component crystal, encompassing both binary co-crystals formed between two neutral solids and multi-component co-crystals formed between a neutral solid and a salt or solvate.

[0234] "Animals" refers to mammals, such as humans, companion animals, zoo animals, and livestock, with humans, horses, or dogs being preferred.

[0235] "Stereoisomers" refer to isomers that are produced by different spatial arrangements of atoms in a molecule, including cis-trans isomers, enantiomers, diastereomers, and conformational isomers.

[0236] "Tautomers" refer to functional group isomers that are produced by the rapid movement of an atom in two positions within a molecule, such as keto-enol isomers and amide-imine alcohol isomers.

[0237] IC 50 "It refers to the concentration of a drug or inhibitor required to inhibit a specified biological process (or a component of that process, such as an enzyme, receptor, or cell) by half."

[0238] Synthesis Method 1:

[0239]

[0240] The compound of general formula (Z-1) and the compound of general formula (Z-2) are coupled together to give the compound of general formula (Z-3);

[0241] The general formula compound (Z-3) is deprotected to give the general formula compound (Z-4);

[0242] The compound of general formula (Z-5) and the compound of general formula (Z-6) undergo a condensation reaction to give the compound of general formula (Z-7);

[0243] The general formula compound (Z-7) is deprotected to give the general formula compound (Z-8);

[0244] The compound of general formula (Z-8) and the compound of general formula (Z-4) undergo a condensation reaction to give the compound of general formula (Ia);

[0245] R m1 Each is independently selected from groups such as Boc, Cbz, PMB, Fmoc, and Trt;

[0246] R m2Each is independently selected from groups such as Me, Et, tBu, and Bn;

[0247] R m3 Each is independently selected from groups such as Br, I, and OTf;

[0248] R m4 Each is independently selected from groups such as Br, I, OTf, and TMS;

[0249] The definitions of the remaining groups are the same as those of compounds of general formula (I). Detailed Implementation

[0250] The following embodiments illustrate the technical solution of the present invention in detail, but the scope of protection of the present invention includes, but is not limited to, these embodiments.

[0251] The structure of the compound was determined by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). NMR shifts (δ) were expressed in 10⁻¹⁰ increments. -6 The unit (ppm) is given. NMR measurements were performed using a Bruker Avance III 400 and Bruker Avance 300 NMR spectrometer. The solvents used were deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), and deuterated methanol (CD3OD). The internal standard was tetramethylsilane (TMS).

[0252] MS determination was performed using (Agilent 6120B (ESI) and Agilent 6120B (APCI));

[0253] HPLC determinations were performed using an Agilent 1260DAD high-performance liquid chromatograph (Zorbax SB-C18 100×4.6mm, 3.5μM).

[0254] Thin-layer chromatography silica gel plates used were from Yantai Huanghai HSGF. 254 Or Qingdao GF 254 Silica gel plates: The silica gel plates used in thin-layer chromatography (TLC) have a diameter of 0.15mm-0.20mm, while those used for TLC separation and purification of products have a diameter of 0.4mm-0.5mm.

[0255] Column chromatography typically uses Yantai Huanghai silica gel 200-300 mesh silica gel as the carrier;

[0256] The starting materials of this invention can be synthesized using or according to methods known in the art, or can be purchased from companies such as Titan Technology, Anaiji Chemical, Shanghai Demo, Chengdu Kelong Chemical, Shaoyuan Chemical Technology, and Bailingwei Technology.

[0257] Example 1: Preparation of Compound 1

[0258]

[0259] Step 1: Preparation of chiral isomer 1 and chiral isomer 2

[0260] 1a (synthesis method see WO2023133336) was chirally resolved under the following conditions:

[0261] 1. Instrument: SFC Prep 150AP; Column: Daicel OJ column (19mm×250mm).

[0262] 2. Dissolve the sample in methanol and filter it through a 0.45μm filter to prepare a sample solution.

[0263] 3. Preparative chromatographic conditions: a. The mobile phase consists of system A and system B: mobile phase A: CO2; mobile phase B: isopropanol; b. Isocratic elution, mobile phase B content is 10%; c. Flow rate is 40 mL / min.

[0264] The conditions for chiral analysis are as follows:

[0265] 1. Instrument: Shimadzu 20A; Column: Chiralcel OJ column.

[0266] 2. Analytical chromatographic conditions: a. The mobile phase consists of system A and system B: Mobile phase A: n-hexane; Mobile phase B: ethanol; b. Isocratic elution, with mobile phase B containing 15%; c. Flow rate: 1 mL / min.

[0267] Peak elution time: chiral isomer 1: 8.34 min, chiral isomer 2: 10.92 min.

[0268] Chiral isomers 1 and 2 of compound 1a are one of the isomers of structure 1a-1 or 1a-2, respectively.

[0269] Step 2: Preparation of 1b

[0270] Chiral isomer 2 (2.0 g, 7.62 mmol) of 1a was dissolved in 40 mL of acetonitrile, and 1-chloroethyl chloroformate (3.27 g, 22.87 mmol) and N,N-diisopropylethylamine (0.98 g, 7.58 mmol) were added separately. The mixture was heated to 70 °C and reacted for 12 h. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in 50 mL of methanol and reacted at 70 °C for 3 h. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and 50 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was extracted with dichloromethane (50 mL × 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (dichloromethane / methanol (v / v) = 1:0-10:1) to obtain crude product 1b (0.7 g).

[0271] LCMSm / z = 173.1 [M+1] +

[0272] Compound 1b is one of the isomers of structure 1b-1 or 1b-2.

[0273] Step 3: Preparation of 1c

[0274] 1A (0.1 g, 0.31 mmol) (synthetic method referred to WO2023133336), the above crude product 1b (0.053 g), 2-chloro-1-methylpyridine iodide (0.087 g, 0.34 mmol), and triethylamine (0.094 g, 0.93 mmol) were dissolved in 2 mL of dichloromethane and reacted at room temperature for 16 h. The reaction solution was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 1:0-1:8) to give 1c (0.1 g, yield: 67%).

[0275] Compound 1c is one of the isomers of structure 1c-1 or 1c-2.

[0276] Step 4: Preparation of 1 day

[0277] 1c (0.1 g, 0.21 mmol) was dissolved in 2 mL of dichloromethane and 1 mL of trifluoroacetic acid and reacted at room temperature for 3 h. 50 mL of dichloromethane and 20 mL of saturated sodium bicarbonate aqueous solution were added to the reaction mixture. The mixture was separated, and the aqueous phase was extracted with dichloromethane (20 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give crude product 1d (70 mg).

[0278] Compound 1d is one of the isomers of structure 1d-1 or 1d-2.

[0279] Step 5: Preparation of 1f

[0280] 1e (5.0 g, 18.85 mmol) (synthetic method according to CN109721536) was dissolved in 50 mL of dichloromethane and 50 mL of methanol, and 10% palladium on carbon (2.0 g) was added. The mixture was reacted at room temperature for 12 h under a hydrogen balloon atmosphere. The reaction system was filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 1:0-1:1) to give 1f (4.0 g, yield: 90%).

[0281] LCMSm / z = 236.1 [M+1] +

[0282] Step 6: Preparation of 1g

[0283] 1 f (4.0 g, 17.0 mmol) was dissolved in 40 mL of 70% sulfuric acid solution, cooled to 0 °C, and 5 mL of sodium nitrite (1.76 g, 25.5 mmol) aqueous solution was slowly added dropwise. After reacting at 0 °C for 30 min, potassium iodide (5.64 g, 34.0 mmol) was added, and the reaction was carried out at 0 °C for 30 min, followed by reaction at room temperature for 2 h. 50 mL of saturated sodium bisulfite aqueous solution and 200 mL of water were added to the reaction system. The aqueous phase was extracted with ethyl acetate (100 mL × 3), and the organic phase was washed with 100 mL of saturated brine. The mixture was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 1:0-10:1) to obtain 1 g (0.6 g, yield: 10%).

[0284] Step 7: Preparation over 1 hour

[0285] 1 g (0.6 g, 1.73 mmol) was dissolved in 5 mL of tetrahydrofuran and 5 mL of water, and lithium hydroxide monohydrate (0.36 g, 8.58 mmol) was added. The reaction was carried out at room temperature for 16 h. 50 mL of water was added to the reaction system, and the pH was adjusted to 2 with 2 mol / L hydrochloric acid aqueous solution. The mixture was extracted with ethyl acetate (50 mL × 3), and the organic phase was dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to give crude product 1 h (0.5 g).

[0286] Step 8: Preparation of 1i

[0287] The crude product 1h (0.5 g), benzyl bromide (0.32 g, 1.87 mmol), and potassium carbonate (0.43 g, 3.1 mmol) were dissolved in 10 mL of DMF and reacted at room temperature for 16 h. 50 mL of water was added to the reaction mixture, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phase was washed with saturated brine (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 1:0-10:1) to give 1i (0.6 g, two-step yield from 1 g of compound: 85%).

[0288] Step 9: Preparation of 1j

[0289] To anhydrous tetrahydrofuran (86 mL), zinc powder (2.26 g, 34.57 mmol) and 1,2-dibromoethane (0.32 g, 1.70 mmol) were added, and the mixture was reacted at 50 °C for 15 min. The reaction solution was cooled to room temperature, and TMSCl (0.22 g, 2.0 mmol) was added. The mixture was then sonicated at room temperature for 15 min, followed by the dropwise addition of diethyl (bromodifluoromethyl)phosphonate (9.23 g, 34.57 mmol), and the reaction was continued at 50 °C for 1 h. The reaction solution was cooled to room temperature to obtain a 1J-1 solution. In another reaction flask, 1i (0.6 g, 1.47 mmol), cuprous bromide (0.41 g, 2.86 mmol), and 5 mL of dry DMF were added. Under nitrogen protection, the above 1J-1 solution (20 mL) was added, and the mixture was reacted at room temperature for 16 h. The reaction solution was poured into 50 mL of water, filtered, and the filtrate was extracted with ethyl acetate (50 mL × 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was subjected to Pre-HPLC (instrument and preparative column: Glison GX-281 preparative HPLC, Sunfire C18 column, 5 μm, inner diameter × length = 30 mm × 150 mm). Preparation method: The crude product was dissolved in methanol and filtered through a 0.45 μm filter membrane to prepare the sample solution. Mobile phase system: acetonitrile / water (containing 0.1% TFA). Gradient elution method: Acetonitrile was used to elute 95% of the product with a 50% gradient (elution time 18 min), and the product was lyophilized to obtain compound 1j (0.14 g, yield: 20%).

[0290] LCMSm / z = 469.1 [M+1] +

[0291] Step 10: Preparation of 1k

[0292] Dissolve 1J (0.14 g, 0.3 mmol) in 9 mL of methanol and 1 mL of dichloromethane, add 10% palladium hydroxide on carbon (0.5 g), and react at room temperature for 5 h under a hydrogen balloon atmosphere. Filter the reaction system, concentrate the filtrate under reduced pressure to obtain crude product 1K (0.11 g).

[0293] LCMSm / z = 379.0 [M+1] +

[0294] Step 11: 1L Preparation

[0295] The crude product 1k (57 mg), crude product 1d (57 mg), 2-chloro-1-methylpyridine iodide (77 mg, 0.30 mmol), and triethylamine (46 mg, 0.45 mmol) were dissolved in 2 mL of dichloromethane and reacted at room temperature for 16 h. The reaction solution was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 1:0-1:8) to give 1 L (0.08 g, yield: two-step yield from compound 1j: 70%).

[0296] LCMSm / z = 741.3[M+1] +

[0297] Compound 1l is one of the isomers of structure 1l-1 or 1l-2.

[0298] Step 12: Preparation of Compound 1

[0299] 1 L (80 mg, 0.11 mmol) was dissolved in 2 mL of acetonitrile, and 1 mL of TMSOTf was added dropwise. The reaction was carried out at room temperature for 12 h. 5 mL of methanol was added to the reaction system, and the mixture was concentrated under reduced pressure. The crude product was then passed through Pre-HPLC (instrument and preparative column: Shimadzu LC-20AP preparative HPLC, column type C18). Preparation method: The crude product was dissolved in acetonitrile and filtered through a 0.45 μm filter membrane to prepare the sample solution. Mobile phase: Acetonitrile / water (containing 0.1% TFA). Gradient elution method: Acetonitrile was used to elute 60% of the product with a 30% gradient (elution time 18 min), and the solution was lyophilized to obtain compound 1 (40 mg, yield: 53%).

[0300] 1 H NMR (400MHz, CD3OD) δ8.13–8.03(m,2H),7.83–7.75(m,1H),7.47–7.26(m,5H),5.10–4.95(m,1H),4.70–4.55(m,1H),4.50–4. 35(m,1H),4.24–4.15(m,1H),4.15–3.55(m,4H),3.52–3.35(m,1H),2.73–2.62(m,3H),2.45–2.15(m,2H),2.14–1.55(m,10H).

[0301] LCMSm / z = 685.3 [M+1] +

[0302] Compound 1 is one of the isomers of compound 1-1 or 1-2.

[0303] Example 3: Preparation of Compound 3

[0304]

[0305] Step 1: Preparation of 3b

[0306] 3a (2.0 g, 5.71 mmol) (synthetic method referred to WO2023164680) was dissolved in 15 mL of tetrahydrofuran and 15 mL of water, and lithium hydroxide (0.82 g, 34.24 mmol) was added. The reaction was carried out at room temperature for 16 h. 100 mL of water was added to the reaction system, and the pH was adjusted to 2 with 2 mol / L hydrochloric acid. The mixture was extracted with ethyl acetate (100 mL × 3), and the organic phase was dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain crude product 3b (2.0 g).

[0307] Step 2: Preparation of 3C

[0308] The crude product 3b (2.0 g), benzyl bromide (1.06 g, 6.20 mmol), and potassium carbonate (1.72 g, 12.45 mmol) were dissolved in 20 mL of DMF and reacted at room temperature for 16 h. 100 mL of water was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phase was washed with saturated brine (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 1:0-10:1) to give 3c (1.3 g, two-step yield from 3a: 55%).

[0309] Compound 3 was obtained from compounds 3c and 1d using the synthesis method described in Example 1.

[0310] 1 H NMR (400MHz, CD3OD) δ8.15–8.07(m,2H),7.83–7.75(m,1H),7.46–7.27(m,5H),5.07–4.98(m,1H),4.68–4.60(m,1H),4.48–4.39(m,1H),4.23–4. 15(m,1H),4.15–3.87(m,2H),3.83–3.57(m,2H),3.50–3.38(m,1H),2.4 0–2.18(m,2H),2.12–1.91(m,6H),1.91–1.74(m,2H),1.74–1.57(m,2H).

[0311] LCMSm / z = 689.3 [M+1] +

[0312] Compound 3 is one of the isomers of compound 3-1 or 3-2.

[0313] The following compounds were obtained by synthesizing according to the methods described in other embodiments:

[0314]

[0315] Example 5: Preparation of Compound 5

[0316]

[0317] Step 1: Preparation of 5b

[0318] 5a (5 g, 20.16 mmol) was dissolved in 50 mL of DMF, and ethyl mercaptoacetate (2.42 g, 20.14 mmol) and potassium carbonate (5.57 g, 40.30 mmol) were added separately. The reaction mixture was reacted at 80 °C for 19 h. The reaction solution was cooled to room temperature, and 100 mL of ethyl acetate and 100 mL of water were added. The mixture was separated, and the organic phase was dried over anhydrous sodium sulfate. The solution was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1-5:1) to give 5b (5.2 g, yield: 78%).

[0319] Step 2: Preparation of 5C

[0320] 5b (2.3 g, 6.97 mmol) was dissolved in a mixture of 50 mL toluene and 10 mL water. Cyclopropylboronic acid (0.96 g, 11.18 mmol), tricyclohexylphosphine (0.39 g, 1.39 mmol), palladium acetate (0.16 g, 0.71 mmol), and potassium phosphate (4.44 g, 20.92 mmol) were added, and the mixture was purged with nitrogen three times. The reaction was carried out at 90 °C for 19 h. The reaction solution was cooled to room temperature, and 100 mL of ethyl acetate and 100 mL of water were added. The mixture was separated, and the organic phase was dried over anhydrous sodium sulfate. The solution was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1-3:1) to give 5c (1.8 g, yield: 89%).

[0321] Step 3: Preparation of 5D

[0322] 5c (0.9 g, 3.09 mmol) was dissolved in 20 mL of tetrahydrofuran, and zinc powder (2.02 g, 30.9 mmol) and ammonium chloride (1.65 g, 30.85 mmol) were added separately. The mixture was reacted at 80 °C for 1 h. The reaction solution was cooled to room temperature, and 50 mL of ethyl acetate and 50 mL of water were added. The mixture was separated, and the organic phase was dried over anhydrous sodium sulfate. The solution was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1-2:1) to give 5d (0.75 g, yield: 93%).

[0323] Step 4: Preparation of 5e

[0324] 5d (0.15 g, 0.57 mmol) was dissolved in 3 mL of acetonitrile, and isoamyl nitrite (0.10 g, 0.85 mmol), potassium iodide (0.14 g, 0.84 mmol), and cuprous iodide (0.16 g, 0.84 mmol) were added, respectively. The mixture was reacted at 50 °C for 1 h. The reaction solution was cooled to room temperature, and 10 mL of ethyl acetate and 10 mL of water were added. The mixture was filtered, and the filtrate was collected. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1-5:1) to give 5e (0.09 g, yield: 42%).

[0325] Step 5: Preparation of 5f

[0326] 5e (0.7 g, 1.88 mmol) was dissolved in 1 mL of tetrahydrofuran and 1 mL of water, and lithium hydroxide monohydrate (0.39 g, 9.29 mmol) was added. The reaction mixture was allowed to react at room temperature for 16 h. 10 mL of water was added to the reaction mixture, and the pH was adjusted to 2 with 2 mol / L hydrochloric acid. The mixture was extracted with ethyl acetate (100 mL × 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give crude 5f (0.65 g).

[0327] Step 6: Preparation of 5g

[0328] The crude product 5f (0.44 g) was dissolved in 5 mL of tetrahydrofuran, and tert-butyltrichloroacetylimine (0.70 g, 3.20 mmol) was added. Boron trifluoride diethyl ether (45 mg, 0.32 mmol) was added at 0 °C, and the reaction was carried out at room temperature for 19 h. 10 mL of ethyl acetate and 10 mL of saturated sodium bicarbonate aqueous solution were added to the reaction solution, the mixture was separated, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1-5:1) to give 5 g (0.38 g, two-step yield from compound 5e: 75%).

[0329] Step 7: Preparation over 5 hours

[0330] Under nitrogen protection, the above-mentioned 1J-1 solution (7 mL) and cuprous bromide (0.39 g, 2.72 mmol) were added to a reaction flask, and the reaction was carried out at room temperature for 30 min to obtain a 5H-1 solution. In another reaction flask, 5 g (0.55 g, 1.37 mmol) was dissolved in 5 mL of dry DMAc, and the above-mentioned 5H-1 solution was added. The reaction was carried out at 50 °C for 16 h. The reaction solution was cooled to room temperature, 10 mL of saturated ammonium chloride aqueous solution was added, and the mixture was extracted with ethyl acetate (30 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1-2:1) to obtain 5 h (0.154 g, yield: 24%).

[0331] LCMSm / z = 461.2[M+1] +

[0332] Step 8: Preparation of 5i

[0333] Dissolve 5h (0.152 g, 0.33 mmol) in 2 mL of dichloromethane, add 1 mL of trifluoroacetic acid, and react at room temperature for 2 h. Concentrate the reaction system under reduced pressure to obtain crude product 5i (0.11 g).

[0334] Step 9: Preparation of 5B

[0335] 5A (0.6 g, 1.62 mmol) (synthetic method referred to WO2021188696), the above crude product 1b (0.34 g), 2-chloro-1-methylpyridine iodide (0.83 g, 3.25 mmol), and triethylamine (0.49 g, 4.84 mmol) were dissolved in 3 mL of dichloromethane and reacted at room temperature for 16 h. The reaction solution was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 10:1-1:8) to give 5B (0.35 g, yield: 41%).

[0336] Compound 5B is one of the isomers of structure 5B-1 or 5B-2.

[0337] Compound 5 was obtained from compounds 5B and 5i using the synthesis method described in Example 1.

[0338] 1 H NMR (400MHz, CD3OD) δ8.15–8.00(m,2H),7.52–7.26(m,5H),7.21–7.08(m ,1H),6.27–6.13(m,1H),5.16–4.96(m,1H),4.75–4.60(m,1H),4.52–4.2 8(m,1H),4.25–3.72(m,6H),3.69–3.51(m,3H),3.51–3.39(m,1H),2.48– 2.34(m,1H),2.33–2.10(m,5H),2.08–1.81(m,7H).LCMSm / z=754.4[M+1] +

[0339] Compound 5 is one of the isomers of compound 5-1 or 5-2. The following compounds were obtained by synthesis according to other examples:

[0340]

[0341] Example 9: Preparation of Compound 9

[0342]

[0343] Step 1: Preparation of 9b

[0344] 9a (5.0 g, 22.62 mmol) was dissolved in 5 mL of DMF, and potassium carbonate (4.69 g, 33.94 mmol) was added. The mixture was cooled to 0 °C in an ice-water bath, and ethyl mercaptoacetate (3.26 g, 27.13 mmol) was slowly added. The reaction mixture was allowed to react at room temperature for 12 h. 50 mL of ethyl acetate was added to the reaction mixture, and the organic phase was washed with saturated brine (50 mL × 3), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / dichloromethane (v / v) = 1:0-1:1) to give 9b (2.0 g, yield: 29%).

[0345] Step 2: Preparation of 9c

[0346] Under nitrogen protection, 9b (2.0 g, 6.6 mmol) was dissolved in 20 mL of 1,4-dioxane, and cuprous iodide (0.25 g, 1.31 mmol), N,N'-dimethylethylenediamine (0.12 g, 1.36 mmol), and potassium iodide (2.19 g, 13.19 mmol) were added, respectively. The reaction was carried out at 110 °C for 16 h. The reaction solution was cooled to room temperature, 100 mL of water was added, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phase was washed with 100 mL of saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / dichloromethane (v / v) = 1:0-1:1) to give 9c (2.0 g, yield: 87%).

[0347] Compound 9 was obtained from compounds 9c and 1d using the synthesis method described in Example 3.

[0348] 1 H NMR (400MHz, CD3OD) δ8.24–8.17(m,1H),8.02–7.97(m,1H),7.47–7.26(m,6H),5.08–5.00(m,1H),4.70–4.58(m,1H),4.49–4.39(m,1H),4.23–4. 15(m,1H),4.14–3.88(m,2H),3.83–3.56(m,2H),3.51–3.37(m,1H),2.4 1–2.17(m,2H),2.13–1.92(m,6H),1.92–1.74(m,2H),1.74–1.56(m,2H).

[0349] LCMSm / z = 689.2 [M+1] +

[0350] Compound 9 is one of the isomers of compound 9-1 or 9-2.

[0351] The following compounds were obtained by synthesizing according to the methods described in other embodiments:

[0352]

[0353]

[0354] Example 11: Preparation of Compound 11

[0355]

[0356] Compound 11 was obtained from compounds 5C and 3e using the synthesis method described in Example 5.

[0357] 1 H NMR (400MHz, CD3OD) δ8.21–7.28(m,8H),5.11–4.90(m,1H),4.72–4.60(m,1H),4.33–3. 93(m,6H),3.84–3.65(m,2H),3.57–3.37(m,3H),2.45–2.34(m,3H),2.29–1.87(m,6H).

[0358] LCMSm / z = 732.1 [M+1] +

[0359] Compound 11 is one of the isomers of compound 11-1 or 11-2.

[0360] The following compounds were obtained by synthesizing according to the methods described in other embodiments:

[0361]

[0362]

[0363] Example 15: Preparation of Compound 15

[0364]

[0365] Step 1: Preparation of 15a

[0366] 5b (5.0 g, 15.14 mmol), methyl fluorosulfonyl difluoroacetate (5.82 g, 30.3 mmol), and CuI (2.88 g, 15.12 mmol) were dissolved in 50 mL of DMF and reacted at 80 °C for 4 h under a nitrogen atmosphere. The reaction solution was cooled to room temperature, and 200 mL of saturated sodium bicarbonate aqueous solution was added. The mixture was extracted with ethyl acetate (100 mL × 3), and the organic phase was washed with saturated brine (100 mL × 2). The solution was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 1:0-1:1) to give 15a (3.5 g, yield: 72%).

[0367] Compound 15 was obtained from compounds 5C and 15a using the synthesis methods described in Examples 1 and 5.

[0368] 1 H NMR (400MHz, CD3OD) δ8.58–8.48(m,1H),8.47–8.38(m,1H),8.24–8.16(m,1H),7.49–7.25(m,5H),5.19–4.97(m,1H),4.76–4. 61(m,1H),4.52–4.30(m,1H),4.24–3.73(m,6H),3.69–3.37(m,4H),2.49–2.35(m,1H),2.33–2.14(m,4H),2.11–1.78(m,4H).

[0369] LCMSm / z = 782.0 [M+1] +

[0370] Compound 15 is one of the isomers of compound 15-1 or 15-2.

[0371] The following compounds were obtained by synthesizing according to the methods described in other embodiments:

[0372]

[0373] Example 17: Preparation of Compound 17

[0374]

[0375] Step 1: Preparation of 17a

[0376] 5a (6 g, 24.19 mmol) was dissolved in 50 mL of DMSO, and tert-butyl mercaptoacetate (3.59 g, 24.22 mmol) and potassium carbonate (6.68 g, 48.34 mmol) were added separately. The reaction mixture was reacted at 80 °C for 19 h. The reaction solution was cooled to room temperature, and 100 mL of ethyl acetate and 100 mL of water were added. The mixture was separated, and the organic phase was dried over anhydrous sodium sulfate. The solution was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / dichloromethane (v / v) = 10:1-1:1) to give 17a (8.1 g, yield: 93%).

[0377] Step 2: Preparation of 17b

[0378] 17a (4.1 g, 11.45 mmol) was dissolved in a mixture of 50 mL ethanol and 6 mL water. Iron powder (6.39 g, 114.1 mmol) and ammonium chloride (6.13 g, 114.6 mmol) were added separately, and the mixture was reacted at 70 °C for 19 h. The reaction solution was cooled to room temperature, filtered, and 50 mL ethyl acetate and 30 mL water were added to the filtrate. The mixture was separated, and the organic phase was dried over anhydrous sodium sulfate. The solution was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / dichloromethane (v / v) = 1:0-3:7) to give 17b (2.7 g, yield: 72%).

[0379] Step 3: Preparation of 17c

[0380] 17b (2.7 g, 8.23 ​​mmol) was dissolved in 30 mL of acetonitrile, and isoamyl nitrite (1.45 g, 12.38 mmol), potassium iodide (2.05 g, 12.35 mmol), and cuprous iodide (2.35 g, 12.34 mmol) were added, respectively. The mixture was reacted at 50 °C for 2 h. The reaction solution was cooled to room temperature, and 50 mL of ethyl acetate and 30 mL of water were added. The mixture was filtered, and the filtrate was collected. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / dichloromethane (v / v) = 10:1-1:1) to give 17c (2.5 g, yield: 69%).

[0381] Compound 17 was obtained from compounds 5C and 17c using the synthesis method described in Example 5.

[0382] 1H NMR (400MHz, CD3OD) δ8.36–8.28(m,1H),8.27–8.19(m,1H),8.14–8.06(m,1H),7.49–7.27(m,5H),5.15–4.98(m,1H),4.75–4.62(m,1H) ,4.50–4.31(m,1H),4.23–4.05(m,2H),4.05–3.72(m,4H),3.68–3.39(m,4H),2.48–2.35(m,1H),2.32–2.13(m,4H),2.10–1.79(m,4H).

[0383] LCMSm / z = 790.0 [M-1] -

[0384] Compound 17 is one of the isomers of compound 17-1 or 17-2.

[0385] The following compounds were obtained by synthesizing according to the methods described in other embodiments:

[0386]

[0387] Example 19: Preparation of Compound 19

[0388]

[0389] Step 1: Preparation of 19b

[0390] 19a (2.0 g, 5.86 mmol) (synthetic method referred to WO2007130626) was dissolved in 20 mL of dichloromethane, and triethylamine (1.78 g, 17.59 mmol) was added. Cyclopropylformyl chloride (0.61 g, 5.84 mmol) was added dropwise at 0 °C, and the reaction was carried out at room temperature for 3 h. 20 mL of saturated sodium bicarbonate aqueous solution and 20 mL of dichloromethane were added to the reaction system, the mixture was separated, the organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 5:1-1:1) to give 19b (2.3 g, yield: 96%).

[0391] Step 2: Preparation of 19c

[0392] 19b (2.3 g, 5.62 mmol) was dissolved in 20 mL of tetrahydrofuran and 20 mL of water, and lithium hydroxide monohydrate (2.37 g, 56.48 mmol) was added. The reaction mixture was reacted at room temperature for 16 h. The pH of the reaction solution was adjusted to 2 with 1 mol / L hydrochloric acid, and 50 mL of dichloromethane and 5 mL of methanol were added. The mixture was separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude 19c (2.0 g).

[0393] LCMSm / z = 396.1 [M+1] +

[0394] Compound 19 was obtained from compounds 19c, 1b and 3e using the synthesis method described in Example 5.

[0395] 1 H NMR(400MHz,CD3OD)δ8.21–7.96(m,2H),7.90–7.63(m,1H),7.53–7.17(m,5H) ,5.13–4.66(m,2H),4.50–3.37(m,11H),2.55–1.76(m,7H),1.13–0.75(m,4H).

[0396] LCMSm / z = 758.1 [M+1] +

[0397] Compound 19 is one of the isomers of compound 19-1 or 19-2.

[0398] Example 20: Preparation of Compound 20

[0399]

[0400] Step 1: Preparation of 20a

[0401] 19a (0.43 g, 1.26 mmol) (synthetic method referred to WO2007130626) was dissolved in 20 mL of dichloromethane, and DIPEA (0.24 g, 1.86 mmol) and 2,2-difluoroethyl trifluoromethanesulfonate (0.40 g, 1.87 mmol) were added separately. The reaction was carried out at room temperature for 1 h. 20 mL of water and 20 mL of dichloromethane were added to the reaction solution, and the mixture was separated. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 5:1-1:1) to obtain 20a (0.5 g, yield: 98%).

[0402] LCMSm / z = 406.4 [M+1] +

[0403] Step 2: Preparation of 20b

[0404] Dissolve 20a (0.45 g, 1.11 mmol) in 5 mL of tetrahydrofuran and 5 mL of water, add lithium hydroxide monohydrate (0.47 g, 11.2 mmol), and react at room temperature for 16 h. Adjust the pH of the reaction solution to 2 with 1 mol / L hydrochloric acid, add 30 mL of dichloromethane and 3 mL of methanol, separate the liquids, dry the organic phase with anhydrous sodium sulfate, concentrate under reduced pressure, and give crude product 20b (0.39 g).

[0405] LCMSm / z = 392.2[M+1] +

[0406] Compound 20 was obtained from 20b, 1b and 3e as raw materials, using the synthesis method described in Example 5.

[0407] 1 H NMR (400MHz, CD3OD) δ8.19–8.02(m,2H),7.83–7.68(m,1H),7.54–7.26(m,5H),6.52–5.99(m,1H) ,5.46–5.12(m,1H),4.96–4.73(m,1H),4.69–4.53(m,1H),4.27–3.30(m,12H),2.66–1.77(m,6H).

[0408] LCMSm / z = 753.9 [M+1] +

[0409] Compound 20 is one of the isomers of compound 20-1 or 20-2.

[0410] The following compounds were obtained by synthesizing according to the methods described in other embodiments:

[0411]

[0412]

[0413] Example 23: Preparation of compound 23

[0414]

[0415] Step 1: Preparation of 23a

[0416] 3d (2.5 g, 5.29 mmol) was dissolved in 50 mL of acetonitrile, and TMSOTf (11.76 g, 52.9 mmol) was added at room temperature. The reaction mixture was reacted at 40 °C for 4 h. The reaction system was cooled to room temperature, 10 mL of methanol was added, and the mixture was concentrated under reduced pressure. The crude product was then subjected to Pre-HPLC (instrument and preparative column: CAS-05-Semi-Prep-S preparative HPLC, column type C18, 5 μm, inner diameter × length = 19 mm × 250 mm). Preparation method: The acetonitrile solution of the crude product was filtered through a 0.45 μm filter membrane to prepare the sample solution. Mobile phase system: water (containing 0.1% TFA) / acetonitrile. Gradient elution method: Acetonitrile was eluted from 25% to 55% (elution time 9.5 min), and the solution was lyophilized to obtain 23a (893 mg, yield: 41%).

[0417] Step 2: Preparation of 23b

[0418] Dissolve 23a (262 mg, 0.63 mmol) in a mixture of deionized water (4 mL) and THF (2 mL), then add Amberlite IR 120 resin (Na... + (1.5 g). After stirring at room temperature for 1 h, filter and collect the filtrate. Dissolve AgNO3 (420 mg, 2.47 mmol) in 2 mL of deionized water, and add the resulting solution dropwise to the above filtrate. Stir at room temperature for 1 h. Filter the reaction system, collect the filter cake, wash with water (2 mL × 3), dry the filter cake under reduced pressure, and add 10 mL of anhydrous toluene and methyl iodide 2-methylpropionate (463 mg, 1.91 mmol) to the filter cake in sequence. React at room temperature for 12 h. Separate and purify the reaction solution by silica gel column chromatography (petroleum ether / ethyl acetate (v / v) = 1:0-1:1) to obtain 23b (0.2 g, yield: 49%).

[0419] Step 3: Preparation of 23c

[0420] 23b (0.2 g, 0.31 mmol) was dissolved in 10 mL of methanol, and 10% palladium hydroxide on carbon (0.2 g) was added. The mixture was reacted at room temperature for 3 h under a hydrogen balloon atmosphere. The reaction system was filtered, and the filtrate was concentrated under reduced pressure to obtain crude 23c (0.16 g).

[0421] Step 4: Preparation of Compound 23

[0422] The crude compounds 23c (40 mg), 5C (30 mg, 0.071 mmol), 2-chloro-1-methylpyridine iodide (37 mg, 0.14 mmol), and triethylamine (15 mg, 0.15 mmol) were dissolved in 5 mL of dichloromethane and reacted at room temperature for 5 min. The reaction solution was adjusted to pH 7 with glacial acetic acid, concentrated under reduced pressure, and the obtained crude product was subjected to Pre-HPLC (instrument and preparative column: CAS-05-Semi-Prep-S preparative HPLC, column type C18, 5 μm, inner diameter × length = 19 mm × 250 mm). Preparation method: The acetonitrile solution of the crude product was filtered through a 0.45 μm filter membrane to prepare the sample solution. Mobile phase system: water (containing 0.1% TFA) / acetonitrile. Gradient elution method: Acetonitrile was eluted from 45% to 67% (elution time 9.5 min), and lyophilized to obtain compound 23 (45 mg, yield: 66%).

[0423] 1H NMR (400MHz, DMSO-d6) δ8.22–8.02(m,2H),7.95–7.80(m,1H),7.59–7.27(m,5H),5.92–5.70(m,4H),5.20–5. 06(m,1H),5.06–4.60(m,3H),4.51–4.39(m,1H),4.25–3.40(m,10H),2.62–1.87(m,9H),1.45–1.21(m,12H).

[0424] LCMSm / z = 964.5 [M+1] +

[0425] Compound 23 is one of the isomers of compound 23-1 or 23-2.

[0426] Example 24: Preparation of trifluoroacetate of compound 24

[0427]

[0428] Step 1: Preparation of 24a

[0429] 24A (0.2 g, 0.56 mmol) (synthetic method referred to WO2020198435), crude product 1b (0.2 g), 2-chloro-1-methylpyridine iodide (0.29 g, 1.14 mmol), and triethylamine (0.17 g, 1.68 mmol) were dissolved in 3 mL of dichloromethane and reacted at room temperature for 16 h. The reaction solution was concentrated under reduced pressure, and the crude product was passed through Pre-HPLC (instrument and preparative column: Waters 2767 preparative HPLC, preparative column model SunFire@Prep C18, 5 μm, inner diameter × length = 19 mm × 250 mm). Preparation method: The DMSO solution of the crude product was filtered through a 0.45 μm filter membrane to prepare the sample solution. Mobile phase system: water (containing 0.1% TFA) / acetonitrile. Gradient elution method: Acetonitrile was eluted from 80% by a 20% gradient (elution time 15 min), and lyophilized to obtain 24a (0.1 g, yield: 35%).

[0430] LCMSm / z = 510.3[M+1] +

[0431] Compound 24a is one of the isomers of structure 24a-1 or 24a-2.

[0432] The trifluoroacetate of compound 24 was obtained from 24a and 3e using the synthesis method described in Example 3.

[0433] 1H NMR (400MHz, CD3OD) δ8.24–8.13(m,1H),8.11–8.01(m,1H),7.80–7.68(m,1H),7.51–7.29(m,5H),5.67–5.50(m,1H) ,5.05–4.70(m,2H),4.25–3.35(m,12H),2.77–2.57(m,1H),2.42–2.19(m,2H),2.12–1.81(m,3H),1.58–1.40(m,3H).

[0434] LCMSm / z = 718.4 [M+1] +

[0435] Compound 24 is one of the isomers of compound 24-1 or 24-2.

[0436] The following compounds were obtained by synthesizing according to the methods described in other embodiments:

[0437]

[0438]

[0439] Biological test cases

[0440] 1. STAT6 enzyme activity assay

[0441] The inhibitory effect of the compounds on STAT6 enzyme activity was tested using the TR-FRET method. The enzyme and substrate were prepared in reaction buffer (50 mM NaCl, 10 mM HEPES, pH 7.5, 1 mM EDTA, 0.01% Triton-X100, and 2 mM DTT). STAT6 (ICE, Cat: E2309T-H18H) and the fluorescent peptide 5-FAM-ApYKPFQDLI-NH2 (synthesized from Nanjing Peptide Industry) were added to the reaction buffer and gently mixed. The final concentrations of STAT6 and the fluorescent peptide in the reaction mixture were 12.5 nM and 500 nM, respectively. The positive reference SI-109 was started at 100 μM, diluted 2-fold, and used in 10 concentrations. 0.1 μL of the compound in 100% DMSO was delivered to a 384-well plate (Corning, 4514) using an acoustic liquid delivery system (Echo 655); 2.5 μL of STAT6 enzyme solution was transferred to the 384-well plate and centrifuged at 1000 rpm for 1 min, then incubated at 25°C for 10 min; 2.5 μL of substrate solution was transferred to the 384-well plate and centrifuged at 1000 rpm for 1 min; 5 μL of His-Tb solution was transferred to the 384-well plate and centrifuged at 1000 rpm for 1 min, then incubated at 25°C for 60 min; finally, the TR-FRET (337 nm / 520 nm / 490 nm) signal values ​​were read using a BMG PHERAstar FSX. Subsequently, a four-parameter IC50 regression curve was fitted using GraphPad Prism 8 software. 50 Value. The inhibition rate is calculated according to Equation 1, where Ratio sample Ratio represents the compound well read value. max Ratio is the solvent control well reading. min For the blank control wells without enzyme, the IC was calculated using GraphPad Prism software by performing curve fitting using log(inhibitor) vs. response -- Variable slope (four parameters). 50 value.

[0442] Inhibition%=100%×(Ratio max -Ratio sample ) / (Ratio max -Ratio min (Equation 1)

[0443] Table 1 IC50 of STAT6 enzyme activity 50 value

[0444] Compound No. IC 50 (nM) Compound No. IC 50 (nM) Compound 3 <100 Compound 13 <100 Compound 4 <100 Compound 14 <100 Compound 9 <100 Compound 19 <100 Compound 10 <100 Compound 21 <100 Compound 11 <100 Compound 22 <100 Compound 12 <100

[0445] Conclusion: The compounds of the present invention, such as the compounds in the examples, exhibit good inhibitory activity against STAT6 enzyme.

[0446] 2. STAT6-reporter cell experiments

[0447] The HEK293-STAT6-Luc2P reporter cell line was cultured in complete growth DMEM medium containing 10% fetal bovine serum. The cell density was approximately 80%-90% at the time of the experiment. HEK293-STAT6-Luc2P reporter cells were isolated from the culture flasks using 0.25% Trypsin-EDTA (1X) (Gibco, 25200-072), collected by centrifugation at 1000 rpm for 5 minutes, and a cell suspension was prepared in DMEM medium containing 10% fetal bovine serum. 10,000 cells / well / 40 μL were seeded into 384-well plates and incubated overnight at 37°C and 5% CO2. The compound stock solution in DMSO was diluted, and 40 nanoliters of the dilution were transferred to 384-well plates using an Echo. The plates were incubated at 37°C and 5% CO2 for 0.5 hours. Add 40 nanoliters of human interleukin-4 protein (ACRO, IL4-H4218) to each well of a 384-well cell culture plate to a final concentration of 5 nanograms / mL, and incubate at 37°C and 5% carbon dioxide for 24 hours. Add 20 microliters of Bright-Lite luciferase assay reagent (Vazyme, DD1204-03) to each well of the cell culture plate. Immediately read the luminescence value on a BMG.

[0448] Data analysis methods:

[0449]

[0450] Negative control, DMSO control group mean data values

[0451] Positive control, unstimulated group mean data value

[0452] Compound treatment sample group data values

[0453] Fit curves and calculate IC using a four-parameter model in Graphpad Prism software. 50 Value, absolute IC 50 The numerical value represents the compound concentration at which the inhibition rate reaches 50%.

[0454] Conclusion: The compounds of the present invention, such as the compounds in the examples, have good inhibitory activity against STAT6reporter cells.

[0455] 3. Pharmacokinetic assay in mice

[0456] 3.1 Experimental animals: Male Balb / c mice, 18–25 g, 6 mice / compound. Purchased from Beijing Huafukang Biotechnology Co., Ltd.

[0457] 3.2 Experimental Design: On the day of the experiment, 6 ICR mice were randomly divided into groups according to their body weight. They were fasted for 12-14 hours before administration but allowed free access to water, and were fed 4 hours after administration.

[0458] Table 2. Dosage information for mouse pharmacokinetic tests

[0459]

[0460] Note: Intravenous administration solvent: 5% DMA + 5% Solutol + 90% (saline); Gavage administration solvent: PO: 5% DMSO + 95% (20% SBE-β-CD)

[0461] Blood samples of 0.06 mL were collected via the orbital cavity before and after isoflurane anesthesia, placed in EDTAK2 centrifuge tubes, and centrifuged at 5000 rpm for 10 min at 4°C to collect plasma. Blood collection time points for both the intravenous and gavage groups were 0, 5, 15, 30 min, 1, 2, 4, 7, and 24 h. All samples were stored at -60°C before analysis and quantitative analysis was performed using LC-MS / MS.

[0462] Conclusion: The compounds of the present invention, such as the compounds in the examples, have good oral absorption in mice.

[0463] 4. Rat pharmacokinetic test

[0464] Experimental objective: This experiment aimed to evaluate the pharmacokinetic characteristics of the test substance in rats by administering a single dose of the test substance intravenously and by gavage to SD rats, measuring the concentration of the test substance in rat plasma, and administering it intravenously and by gavage.

[0465] Experimental animals: Male SD rats, 160–180g, 6–8 weeks old, 6 rats / compound. Purchased from Chengdu Dashuo Experimental Animal Co., Ltd.

[0466] Experimental method: On the day of the experiment, 6 SD rats were randomly divided into groups according to their body weight. They were fasted for 12-14 hours before administration but allowed free access to water. They were fed 4 hours after administration.

[0467] Table 3. Dosage information for rat pharmacokinetic tests

[0468]

[0469] *Dosage is calculated based on free base.

[0470] Sampling: Blood samples of 0.06 mL were collected via the orbital cavity before and after isoflurane anesthesia and placed in EDTAK2 centrifuge tubes. The plasma was collected by centrifugation at 5000 rpm and 4°C for 10 min.

[0471] Plasma collection time points for IV&PO groups: 0, 5 min, 15 min, 30 min, 1, 2, 4, 6, 8, 24 h.

[0472] All samples were stored at -60℃ before analysis and testing. Quantitative analysis of the samples was performed using LC-MS / MS.

[0473] Conclusion: The compounds of the present invention, such as the compounds in the examples, have good oral absorption in rats.

[0474] 5. Pharmacokinetics of Beagle Dogs

[0475] Experimental animals: Male beagles, weighing approximately 8-10 kg, 6 per compound, purchased from Beijing Mars Biotechnology Co., Ltd.

[0476] Experimental method: On the day of the experiment, 6 beagle dogs were randomly divided into groups according to their weight. They were fasted for 14-18 hours before administration but allowed free access to water. They were fed 4 hours after administration.

[0477] Table 4. Dosing information for beagle pharmacokinetic studies

[0478]

[0479] Note: Intravenous administration solvent: 5% DMA + 5% Solutol + 90% Saline;

[0480] Oral (oral) administration solvent: 5% DMSO + 95% (20% SBE-β-CD);

[0481] *Dosage is calculated based on free base.

[0482] Blood samples (1 ml) were collected via jugular or limb veins before and after drug administration and placed in EDTAK2 centrifuge tubes. Plasma was collected by centrifugation at 5000 rpm and 4°C for 10 min. Blood collection time points for both the intravenous and gavage groups were: 0, 5, 15, 30 min, 1, 2, 4, 6, 8, 10, 12, 24, and 48 h. All samples were stored at -80°C before analysis and quantitative analysis was performed using LC-MS / MS.

[0483] Conclusion: The compounds of the present invention, such as the compounds in the examples, have good oral absorption in dogs.

[0484] 6. Pharmacokinetics in monkeys

[0485] Experimental animals: Male cynomolgus monkeys, 3–5 kg, 3–6 years old, 4 animals / compound. Purchased from Suzhou Xishan Biotechnology Co., Ltd.

[0486] Experimental method: On the day of the experiment, four monkeys were randomly divided into groups according to their body weight. They were fasted for 14-18 hours before administration but allowed free access to water. They were fed 4 hours after administration.

[0487] Table 5. Dosing information for pharmacokinetic studies in monkeys

[0488]

[0489] Note: Intravenous administration solvent: 5% DMA + 5% Solutol + 90% Saline;

[0490] Oral (oral) administration solvent: 5% DMSO + 95% (20% SBE-β-CD);

[0491] *Dosage is calculated based on free base.

[0492] Blood samples of 1.0 mL were collected via the jugular vein before and after drug administration and placed in EDTAK2 centrifuge tubes. Plasma was collected by centrifugation at 5000 rpm and 4°C for 10 min. Blood collection time points for both the intravenous and gavage groups were: 0, 5, 15, 30 min, 1, 2, 4, 6, 8, 10, 12, 24, and 48 h. Before analysis, all samples were stored at -60°C and quantitatively analyzed using LC-MS / MS.

[0493] Conclusion: The compounds of the present invention, such as the compounds in the examples, have good oral absorption in monkeys.

Claims

1. A compound or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts, wherein the compound is selected from compounds represented by general formula (I), wherein, Ring A is selected from C 3-15 A carbocyclic or 4-15 membered heterocyclic group, wherein ring A is optionally divided by 1 to 4 R groups. a replace; Ring B2 is selected from 4-15 member heterocyclic rings, wherein ring B2 is optionally divided by 1 to 4 R... b2 replace; Z is selected from CH or N; n1 is selected from 0, 1, 2, 3 or 4; n2 is selected from 0, 1, 2, 3 or 4; m is selected from 0, 1, 2, 3 or 4; R a Each element is independently selected from H, deuterium, halogen, OH, =O, NH2, CN, COOH, CONH2, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-6 Carbocyclic or 3- to 6-membered heterocyclic groups, wherein the alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; R A Each element is independently selected from H, deuterium, halogen, OH, =O, NH2, CN, COOH, CONH2, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-6 Carbocyclic or 3- to 6-membered heterocyclic groups, wherein the alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; R b1 Or R b2 Each is independently selected from deuterium, halogens, OH, =O, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, and SOC. 1-6 Alkyl, S(O)2C 1-6 Alkyl, S(O)2C 3-6 Carbocyclic groups, S(O)2-3 to 7-membered heterocyclic groups, COC 1-6 Alkyl, CO-3 to 10-membered heterocyclic groups, CO-C 3-10 Carbocyclic group, COO-C 1-6 Alkylene-C 3-10 Carbocyclic group, CO-C 1-6 Alkylene-C 3-10 carbonyl group, C 1-6 Alkyl, OC 1-6 Alkyl, SC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, NHC 1-6 Alkyl, N(C) 1-6 Alkyl)2, -OC 3-6 Carbocyclic groups, -O-3 to 10-membered heterocyclic groups, -NH-C 3-10 Carbocyclic groups, -NH-3 to 10-membered heterocyclic groups, -NHCO-C 1-6 Alkyl, -CONH-C 1-6 Alkyl, -NHCO-C 3-10 carbonyl group, -CONH-C 3-10 Carbocyclic groups, -NHCO-3 to 10-membered heterocyclic groups, -CONH-3 to 10-membered heterocyclic groups, -C 0-4 Alkylene-C 3-10 Carbocyclic group, -C 0-4 Alkylene-3 to 10-membered heterocyclic group, wherein the alkyl, alkylene, alkenyl, ynyl, carbocyclic or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; Or two Rs b1 Or two Rs b2 Each atom forms a carbon atom with the atoms it is attached to. 3-10 A carbocyclic group or a 4-10 membered heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; R 1 Selected from H, deuterium, halogens, OH, =O, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-6 Alkyl, S(O)2C 1-6 Alkyl, S(O)2C 3-6 Carbocyclic groups, S(O)2-3 to 7-membered heterocyclic groups, COC 1-6 Alkyl, C 1-6 Alkyl, OC 1-6 Alkyl, SC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, NHC 1-6 Alkyl, N(C) 1-6 Alkyl)2, -OC 3-6 Carbocyclic groups, -O-3 to 7-membered heterocyclic groups, -NH-C 3-6 Carbocyclic groups, -NH-3 to 7-membered heterocyclic groups, -NHCO-C 1-6 Alkyl, -CONH-C 1-6 Alkyl, -NHCO-C 3-6 carbonyl group, -CONH-C 3-6 Carbocyclic groups, -NHCO-3 to 7-membered heterocyclic groups, -CONH-3 to 7-membered heterocyclic groups, -C 0-4 Alkylene-C 3-6 Carbocyclic group, -C 0-4 Alkylene-3 to 7-membered heterocyclic group, wherein the alkylene, alkenyl, ynyl, carbocyclic or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; R 2 Or R 3 Selected from H, deuterium, C 1-6 Alkyl, C 3-10 Carbocyclic, 4- to 10-membered heterocyclic, wherein the alkyl, carbocyclic or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; Or R 1 R 2 The atoms bonded to it form 4-10 membered heterocyclic groups, wherein the heterocyclic group is optionally surrounded by 1 to 4 R atoms. 1a replace; R 1a Each element is independently selected from deuterium, halogens, OH, =O, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, and SOC. 1-6 Alkyl, S(O)2C 1-6 Alkyl, S(O)2C 3-10 Carbocyclic groups, S(O)2-3 to 10-membered heterocyclic groups, COC 1-6 Alkyl, CO-3 to 10-membered heterocyclic groups, CO-C 3-10 carbonyl group, C 1-6 Alkyl, OC 1-6 Alkyl, SC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, NHC 1-6 Alkyl, N(C) 1-6 Alkyl)2, -OC 3-6 Carbocyclic groups, -O-3 to 10-membered heterocyclic groups, -NH-C 3-10 Carbocyclic groups, -NH-3 to 10-membered heterocyclic groups, -NHCO-C 1-6 Alkyl, -CONH-C 1-6 Alkyl, -NHCO-C 3-10 carbonyl group, -CONH-C 3-10 Carbocyclic groups, -NHCO-3 to 10-membered heterocyclic groups, -CONH-3 to 10-membered heterocyclic groups, -C 0-4 Alkylene-C 3-10 Carbocyclic group, -C 0-4 Alkylene-3 to 10-membered heterocyclic group, wherein the alkyl, alkylene, alkenyl, ynyl, carbocyclic or heterocyclic group is optionally selected from 1 to 4 R groups. z replace; R 4a Or R 4b Each element is independently selected from H, deuterium, halogen, OH, =O, NH2, CN, COOH, CONH2, and C. 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Alkoxy, C 3-6 Carbocyclic or 3- to 6-membered heterocyclic groups, wherein the alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; R 5 Selected from R 5a R 5b R 5c Or R 5d Each is independently selected from H, deuterium, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylene-MC 1-10 Alkyl, C 1-6 Alkylene-MC 3-10 carbonyl group, C 1-6 Alkylene-M-3 to 10-membered heterocyclic groups, C 3-10 Carbocyclic, 3 to 10-membered heterocyclic, wherein the alkyl, alkylene, alkenyl, alkoxy, carbocyclic or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; M is selected from O, S, C(=O), S(=O), S(=O)2, -NR m C(=O)-, -C(=O)NR m -, -OC(=O)-, -C(=O)O-, -OC(=O)O- -SC(=O)-、-C(=O)S-、-OC(=O)NR m -; R m Selected from H, deuterium, C 1-6 Alkyl, C 3-10 Carbocyclic, 4- to 10-membered heterocyclic, wherein the alkyl, carbocyclic or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; Or R 5c R 5d The atoms bonded to it form 4-10 membered heterocyclic groups, wherein the heterocyclic group is optionally surrounded by 1 to 4 R atoms. z replace; R z Each element is independently selected from deuterium, halogens, OH, =O, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, and SOC. 1-6 Alkyl, S(O)2C 1-6 Alkyl, S(O)2C 3-10 Carbocyclic groups, S(O)2-3 to 10-membered heterocyclic groups, COC 1-6 Alkyl, CO-3 to 10-membered heterocyclic groups, CO-C 3-10 carbonyl group, C 1-6 Alkyl, OC 1-6 Alkyl, SC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, NHC 1-6 Alkyl, N(C) 1-6 Alkyl)2, -OC 3-6 Carbocyclic groups, -O-3 to 10-membered heterocyclic groups, -NH-C 3-10 Carbocyclic groups, -NH-3 to 10-membered heterocyclic groups, -NHCO-C 1-6 Alkyl, -CONH-C 1-6 Alkyl, -NHCO-C 3-10 carbonyl group, -CONH-C 3-10 Carbocyclic groups, -NHCO-3 to 10-membered heterocyclic groups, -CONH-3 to 10-membered heterocyclic groups, -C 0-4 Alkylene-C 3-10 Carbocyclic group, -C 0-4 Alkylene-3 to 10-membered heterocyclic groups, wherein the alkyl, alkylene, alkenyl, alkynyl, carbocyclic or heterocyclic group is optionally selected from 1 to 4 groups selected from deuterium, halogen, =O, CN, OH, NH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Substituents of carbocyclic groups and 3 to 7-membered heterocyclic groups; The condition is that, 1)R A Not H; Or 2) Two Rs b1 And the atoms bonded to it form C 3-10 A carbocyclic group or a 4-10 membered heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; Or 3) n1 is selected from 2, 3 or 4 and R b1 Not H; Or 4) At least one of the atoms on ring B2 is an oxygen atom; Or 5) Z is selected from N.

2. The compound according to claim 1, or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts, wherein, Selected from Y is selected from O, NH, or CH2; n2 is selected from 0, 1, 2, or 3; n3 is selected from 0, 1, 2, or 3; n4 is selected from 0, 1, 2, or 3; n5 is selected from 0, 1, 2, or 3; Ring A is selected from phenyl, 5-6-membered heteroaryl, phenyl-6-membered carbon cycloyl, phenyl-5-membered carbon cycloyl, phenyl-6-membered heteroaryl, phenyl-5-membered heteroaryl, 5-5-membered heteroaryl, and 5-6-membered heteroaryl. 6-membered heteroaryl or naphthyl, wherein ring A is optionally surrounded by 1 to 4 R groups. a replace; R a Each element is independently selected from H, deuterium, halogen, OH, =O, NH2, CN, COOH, CONH2, and C. 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy, C 3-6 Carbocyclic or 3- to 6-membered heterocyclic groups, wherein the alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; R A Each element is independently selected from H, deuterium, halogen, OH, =O, NH2, CN, COOH, CONH2, and C. 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy, C 3-6 Carbocyclic or 3- to 6-membered heterocyclic groups, wherein the alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; R b1 Or R b2 Each is independently selected from deuterium, halogens, OH, =O, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, and SOC. 1-4 Alkyl, S(O)2C 1-4 Alkyl, S(O)2C 3-6 Carbocyclic groups, S(O)2-3 to 7-membered heterocyclic groups, COC 1-4 Alkyl, CO-3 to 10-membered heterocyclic groups, CO-C 3-10 Carbocyclic group, COO-C 1-4 Alkylene-C 3-10 Carbocyclic group, CO-C 1-4 Alkylene-C 3-10 carbonyl group, C 1-4 Alkyl, OC 1-4 Alkyl, SC 1-4 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, NHC 1-4 Alkyl, N(C) 1-4 Alkyl)2, -OC 3-6 Carbocyclic groups, -O-3 to 10-membered heterocyclic groups, -NH-C 3-10 Carbocyclic groups, -NH-3 to 10-membered heterocyclic groups, -NHCO-C 1-4 Alkyl, -CONH-C 1-4 Alkyl, -NHCO-C 3-10 carbonyl group, -CONH-C 3-10 Carbocyclic groups, -NHCO-3 to 10-membered heterocyclic groups, -CONH-3 to 10-membered heterocyclic groups, -C 0-2 Alkylene-C 3-10 Carbocyclic group, -C 0-2 Alkylene-3 to 10-membered heterocyclic group, wherein the alkyl, alkylene, alkenyl, ynyl, carbocyclic or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; Or two Rs b1 Or two Rs b2 Each atom forms a carbon atom with the atoms it is attached to. 3-10 A carbocyclic group or a 4-8 membered heterocyclic group, wherein the carbocyclic group or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; R 1 Selected from H, deuterium, halogens, OH, =O, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SOC 1-4 Alkyl, S(O)2C 1-4 Alkyl, S(O)2C 3-6 Carbocyclic groups, S(O)2-3 to 7-membered heterocyclic groups, COC 1-4 Alkyl, C 1-4 Alkyl, OC 1-4 Alkyl, SC 1-4 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, NHC 1-4 Alkyl, N(C) 1-4 Alkyl)2, -OC 3-6 Carbocyclic groups, -O-3 to 7-membered heterocyclic groups, -NH-C 3-6 Carbocyclic groups, -NH-3 to 7-membered heterocyclic groups, -NHCO-C 1-4 Alkyl, -CONH-C 1-4 Alkyl, -NHCO-C 3-6 carbonyl group, -CONH-C 3-6 Carbocyclic groups, -NHCO-3 to 7-membered heterocyclic groups, -CONH-3 to 7-membered heterocyclic groups, -C 0-2 Alkylene-C 3-6 Carbocyclic group, -C 0-2 Alkylene-3 to 7-membered heterocyclic group, wherein the alkylene, alkenyl, ynyl, carbocyclic or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; R 2 Or R 3 Selected from H, deuterium, C 1-4 Alkyl, C 3-6 Carbocyclic, 4- to 7-membered heterocyclic, wherein the alkyl, carbocyclic or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; Or R 1 R 2 The atoms bonded to it form 4-9 membered heterocyclic groups, wherein the heterocyclic group is optionally surrounded by 1 to 4 R atoms. 1a replace; R 1a Each element is independently selected from deuterium, halogens, OH, =O, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, and SOC. 1-4 Alkyl, S(O)2C 1-4 Alkyl, S(O)2C 3-10 Carbocyclic groups, S(O)2-3 to 10-membered heterocyclic groups, COC 1-4 Alkyl, CO-3 to 10-membered heterocyclic groups, CO-C 3-10 carbonyl group, C 1-4 Alkyl, OC 1-4 Alkyl, SC 1-4 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, NHC 1-4 Alkyl, N(C) 1-4 Alkyl)2, -OC 3-6 Carbocyclic groups, -O-3 to 10-membered heterocyclic groups, -NH-C 3-10 Carbocyclic groups, -NH-3 to 10-membered heterocyclic groups, -NHCO-C 1-4 Alkyl, -CONH-C 1-4 Alkyl, -NHCO-C 3-10 carbonyl group, -CONH-C 3-10 Carbocyclic groups, -NHCO-3 to 10-membered heterocyclic groups, -CONH-3 to 10-membered heterocyclic groups, -C 0-2 Alkylene-C 3-10 Carbocyclic group, -C 0-2 Alkylene-3 to 10-membered heterocyclic group, wherein the alkyl, alkylene, alkenyl, ynyl, carbocyclic or heterocyclic group is optionally selected from 1 to 4 R groups. z replace; R 4a Or R 4b Each element is independently selected from H, deuterium, halogen, OH, =O, NH2, CN, COOH, CONH2, and C. 1-4 Alkyl, C 2-4 alkenyl, C 2-4 alkynyl group, C 1-4 Alkoxy, C 3-6 Carbocyclic or 3- to 6-membered heterocyclic groups, wherein the alkyl, alkenyl, alkynyl, alkoxy, carbocyclic, or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; R 5 Selected from R 5a R 5b R 5c Or R 5d Each is independently selected from H, deuterium, and C. 1-4 Alkyl, C 1-4 Alkoxy, C 1-5 Alkylene-MC 1-8 Alkyl, C 1-5 Alkylene-MC 3-6 carbonyl group, C 1-5 alkylene-M-3 to 7-membered heterocyclic groups, C 3-6 Carbocyclic, 3- to 7-membered heterocyclic, wherein the alkyl, alkylene, alkenyl, alkoxy, carbocyclic or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; M is selected from O, S, C(=O), S(=O), S(=O)2, -NR m C(=O)-, -C(=O)NR m -, -OC(=O)-, -C(=O)O-, -OC(=O)O- -SC(=O)-、-C(=O)S-、-OC(=O)NR m -; R m Selected from H, deuterium, C 1-4 Alkyl, C 3-6 Carbocyclic, 4- to 7-membered heterocyclic, wherein the alkyl, carbocyclic or heterocyclic group is optionally surrounded by 1 to 4 R groups. z replace; Or R 5c R 5d The atoms bonded to it form 4-8 membered heterocyclic groups, wherein the heterocyclic group is optionally surrounded by 1 to 4 R atoms. z replace; R z Each element is independently selected from deuterium, halogens, OH, =O, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, and SOC. 1-4 Alkyl, S(O)2C 1-4 Alkyl, S(O)2C 3-10 Carbocyclic groups, S(O)2-3 to 10-membered heterocyclic groups, COC 1-4 Alkyl, CO-3 to 10-membered heterocyclic groups, CO-C 3-10 carbonyl group, C 1-4 Alkyl, OC 1-4 Alkyl, SC 1-4 Alkyl, C 2-4 alkenyl, C 2-4 Alkyne group, NHC 1-4 Alkyl, N(C) 1-4 Alkyl)2, -OC 3-6 Carbocyclic groups, -O-3 to 10-membered heterocyclic groups, -NH-C 3-10 Carbocyclic groups, -NH-3 to 10-membered heterocyclic groups, -NHCO-C 1-4 Alkyl, -CONH-C 1-4 Alkyl, -NHCO-C 3-10 carbonyl group, -CONH-C 3-10 Carbocyclic groups, -NHCO-3 to 10-membered heterocyclic groups, -CONH-3 to 10-membered heterocyclic groups, -C 0-2 Alkylene-C 3-10 Carbocyclic group, -C 0-2 Alkylene-3 to 10-membered heterocyclic groups, wherein the alkyl, alkylene, alkenyl, alkynyl, carbocyclic or heterocyclic group is optionally selected from 1 to 4 groups selected from deuterium, halogen, =O, CN, OH, NH2, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substituents of carbocyclic groups and 3 to 7-membered heterocyclic groups.

3. The compound according to claim 2, or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts, wherein, Selected from n2 is selected from 0, 1, or 2; n3 is selected from 0, 1, 2, or 3; n4 is selected from 0, 1, or 2; n5 is selected from 0, 1, or 2; Ring A is selected from benzothiophene, naphthyl, benzopyridyl, benzopyrimidinyl, benzopyrazinyl, benzopyridazinyl, benzopyrroleyl, benzopyrazolyl, benzoimidazolyl, benzothiazolyl, benzothiophene, pyridinopyridyl, pyridinopyrimidinyl, pyridinopyrazinyl, pyridinopyrroleyl, pyridinopyrazolyl, pyridinoimidazolyl, pyridinoimidazolyl, pyridinoimidazolyl. The ring A is arbitrarily divided by 1 to 4 Rs a replace; R a Each of the following groups is independently selected from H, deuterium, F, Cl, Br, I, OH, =O, NH2, CN, COOH, CONH2, methyl, ethyl, propyl, isopropyl, vinyl, ynyl, propynyl, propynyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, oxacyclobutyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, wherein the methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, propynyl, propynyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, oxacyclobutyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl is optionally surrounded by 1 to 4 R. z replace; R A Each of the following groups is independently selected from H, deuterium, F, Cl, Br, I, OH, =O, NH2, CN, COOH, CONH2, methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, propynyl, propargyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, oxacyclobutyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, wherein the methyl, ethyl, propyl, isopropyl, vinyl, ethynyl, propynyl, propargyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, oxacyclobutyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl is optionally surrounded by 1 to 4 R. z replace; R b1 Or R b2 Each is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, -CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, CO-cyclopropyl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propynyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl) 2. N(ethyl)2, N(propyl)2, N(isopropyl)2, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, aziridine, oxaziridine, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -CH2-oxacyclobutyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl The methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, aziridine, oxacyclobutyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, etc. Choose from 1 to 4 Rs z replace; Or two Rs b1 The atoms bonded to it form a cyclopropyl or cyclobutyl group, wherein the cyclopropyl or cyclobutyl group is optionally bonded by 1 to 4 R atoms. z replace; R 1 Selected from H, deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, -CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, methyl, ethyl, propyl, isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -CONH-cyclopropyl, -CONH-cyclobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclo Hexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, aziridine, oxadiazine, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-aziridine, -CH2-pyrrolidinyl, -CH2-oxadiazine, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, wherein the methyl, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, aziridine, oxadiazine, tetrahydrofuranyl, piperidinyl, piperazinyl, or morpholinyl group is optionally surrounded by 1 to 4 R groups. z replace; R 2 Or R 3 The group is selected from H, deuterium, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, oxacyclobutyl, tetrahydrofuranyl, piperidinyl, piperazinyl, and morpholinyl, wherein the methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, oxacyclobutyl, tetrahydrofuranyl, piperidinyl, piperazinyl, and morpholinyl groups are optionally surrounded by 1 to 4 R groups. z replace; Or R 1 R 2 The atoms connected to it are optionally bounded by 1 to 4 R atoms. 1a The following rings are replaced: R 1a Each is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propynyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl)2, N(ethyl)2 N(propyl)2, N(isopropyl)2, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, azacyclobutyl, oxacyclobutyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, pyridinyl, pyridoneyl -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -CH2-oxacyclobutyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, -CH2-phenyl The alkyl, alkylene, alkenyl, ynyl, carbocyclic, or heterocyclic groups are optionally selected from 1 to 4 R groups. z replace; R 4a Or R 4b Each of the following groups is independently selected from H, deuterium, F, Cl, Br, I, OH, =O, NH2, CN, COOH, CONH2, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, oxacyclobutyl, tetrahydrofuranyl, piperidinyl, piperazinyl, and morpholinyl, wherein the methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, oxacyclobutyl, tetrahydrofuranyl, piperidinyl, piperazinyl, and morpholinyl groups are optionally prefixed with 1 to 4 R groups. z replace; R 5a R 5b R 5c Or R 5d Each is independently selected from H, deuterium, methyl, ethyl, propyl, isopropyl, methoxy, C 1-4 Alkylene-MC 1-6 Alkyl, cyclopropyl, phenyl, pyridyl, wherein the alkyl, alkylene, methyl, ethyl, propyl, isopropyl, or methoxy group is optionally marked with 1 to 4 R groups. z replace; M is selected from -OC(=O)-, -C(=O)O-, -OC(=O)O-, -SC(=O)-; Or R 5c R 5d The atoms bonded to them form azircyclic butyl, azircyclic pentyl, azircyclic hexyl, piperazine, or morpholino groups, wherein the azircyclic butyl, azircyclic pentyl, azircyclic hexyl, piperazine, or morpholino groups are optionally atomized by 1 to 4 R atoms. z replace; R z Each is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, -CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propynyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl)2, N( Ethyl)2, N(propyl)2, N(isopropyl)2, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, aziridine, oxaziridine, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -CH2-oxacyclobutyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, wherein the alkyl, alkylene, alkenyl, alkynyl, carbocyclic or heterocyclic group is optionally selected from 1 to 4 groups selected from deuterium, F, Cl, Br, I, =O, CN, OH, NH2, C 1-4 It is substituted by alkyl, methoxy, ethoxy, cyclopropyl, or aziridine substituents.

4. The compound according to claim 3, or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts, wherein, Selected from R b1 It is independently selected from H, deuterium, F, Cl, Br, I, OH, CN, NH2, methyl, methoxy, CF3, CHF2, CH2F, CD3, OCD3, cyclopropyl, cyclobutyl, aziridine, or oxacyclobutyl; R b2 Each is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, COOH, CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, CO-CD3, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propynyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl -N(methyl)2, N(ethyl)2, N(propyl)2, N(isopropyl)2, -CO-cyclopropyl, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, aziridine, oxaziridine, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -CH2-oxacyclobutyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl R a Each is independently selected from H, deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, CH2OH, CH2-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, aziridine, or oxacyclobutyl; R A Each is independently selected from H, deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, CH2OH, CH2-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, aziridine, or oxacyclobutyl; R 1 Selected from H, deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, -CONH2, CF3, CHF2, CH2F, CD3, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, aziridine, oxadiazinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, -CH2-aziridine, -CH2-pyrrolidinyl, -CH2-oxadiazinyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl R 2 Or R 3 Selected from H, deuterium, CF3, CHF2, CH2F, CD3, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, aziridine, oxadiazine, tetrahydrofuranyl, piperidinyl, piperazine, morpholinyl; Or R 1 R 2 The atoms connected to it are optionally bounded by 1 to 4 R atoms. 1a The following rings are replaced: R 1a Each is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, COOH, CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propynyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl, N(methyl)2, N(ethyl)2 N(propyl)2, N(isopropyl)2, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, azacyclobutyl, oxacyclobutyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, pyridinyl, pyridoneyl -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -CH2-oxacyclobutyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl, -CH2-phenyl R 4a Or R 4b Each is independently selected from H, deuterium, F, Cl, Br, I, OH, =O, NH2, CN, COOH, CONH2, CF3, CHF2, CH2F, CD3, OCD3, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, cyclopropyl, cyclobutyl, aziridine, and oxacyclobutyl; R 5a R 5b R 5c Or R 5d Each is independently selected from H, CF3, CHF2, CH2F, CD3, OCD3, deuterium, methyl, ethyl, propyl, isopropyl, cyclopropyl, phenyl, pyridyl, 5. The compound according to claim 4, or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts, wherein, Ring A is selected from benzothiophene, naphthyl, benzopyrrole, The ring A is arbitrarily divided by 1 to 4 Rs a replace; Selected from Selected from R 5 Selected from 6. The compound according to claim 5, or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts, wherein, The compounds represented by general formula (I) are selected from the compounds represented by general formula (II-1) or (II-2). R A Each is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, CH2OH, CH2-cyclopropyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, cyclopropyl, cyclobutyl, aziridine, or oxacyclobutyl; R b2 Each is independently selected from deuterium, F, Cl, Br, I, OH, CN, NH2, CF3, CHF2, CH2F, CD3, OCD3, COOH, CONH2, SONH2, S(O)2NH2, SO-methyl, SO-ethyl, SO-propyl, SO-isopropyl, S(O)2-methyl, S(O)2-ethyl, S(O)2-propyl, S(O)2-isopropyl, S(O)2-cyclopropyl, S(O)2-cyclobutyl, CO-methyl, CO-CD3, methyl, ethyl, propyl, isopropyl, O-methyl, O-ethyl, O-propyl, O-isopropyl, S-methyl, S-ethyl, S-propyl, S-isopropyl, vinyl, ethynyl, propynyl, propynyl, NH-methyl, NH-ethyl, NH-propyl, NH-isopropyl -N(methyl)2, N(ethyl)2, N(propyl)2, N(isopropyl)2, -CO-cyclopropyl, -NHCO-methyl, -NHCO-ethyl, -NHCO-propyl, -NHCO-isopropyl, -CONH-methyl, -CONH-ethyl, -CONH-propyl, -CONH-isopropyl, -NHCO-cyclopropyl, -CONH-cyclopropyl, -NHCO-cyclobutyl, -CONH-cyclobutyl, -O-cyclopropyl, -O-piperazinyl, -NH-cyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -CH2-phenyl, aziridine, oxaziridine, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl -CH2-azacyclobutyl, -CH2-pyrrolidinyl, -CH2-oxacyclobutyl, -CH2-tetrahydrofuranyl, -CH2-piperidinyl, -CH2-piperazinyl, -CH2-morpholinyl Selected from n4 or n5 are each independently selected from 0, 1, or 2.

7. The compound according to claim 1, or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts, wherein the compound is selected from one of the structures in Table E-1. Table E-1 8. A pharmaceutical composition comprising the compound of any one of claims 1-7 or its stereoisomers, tautomers, racemates, pharmaceutically acceptable salts, and a pharmaceutically acceptable carrier, preferably, the pharmaceutical composition containing 1-1500 mg of the compound of any one of claims 1-7 or its stereoisomers, tautomers, racemates, or pharmaceutically acceptable salts.

9. The use of the compound according to any one of claims 1-7, or its stereoisomers, tautomers, racemates, pharmaceutically acceptable salts, or the composition of claim 8, in the preparation of a medicament for treating diseases related to STAT6 activity or expression levels.

10. The use of the compound or its stereoisomer, tautomer, racemate, pharmaceutically acceptable salt, or the pharmaceutical composition of claim 8 in the preparation of a medicament for treating cancer, autoimmune diseases, or inflammatory diseases.

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