WO2021057910A1 - Inhibiteur de peptidylarginine déiminase et utilisation associée - Google Patents

Inhibiteur de peptidylarginine déiminase et utilisation associée Download PDF

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WO2021057910A1
WO2021057910A1 PCT/CN2020/117802 CN2020117802W WO2021057910A1 WO 2021057910 A1 WO2021057910 A1 WO 2021057910A1 CN 2020117802 W CN2020117802 W CN 2020117802W WO 2021057910 A1 WO2021057910 A1 WO 2021057910A1
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alkyl
membered
group
amino
alkoxy
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PCT/CN2020/117802
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Chinese (zh)
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吴永谦
李琳
万中晖
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南京药捷安康生物科技有限公司
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Definitions

  • the present invention belongs to the technical field of medicine, and specifically relates to a peptidylarginine deiminase PAD4 inhibitor compound represented by the general formula (I) and each sub-general formula and pharmaceutically acceptable salts, stereoisomers and mutual Tautomers, and their pharmaceutical compositions, pharmaceutical preparations and their uses.
  • the compound involved in the present invention has an inhibitory effect on the peptidylarginine deiminase PAD4, and can be used to treat a variety of diseases, such as rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, and multiple diseases.
  • diseases such as rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, and multiple diseases.
  • PAD4 is a member of the peptidylarginine deiminase (PAD) family. It has a homodimer structure and is a Ca 2+ dependent enzyme. Each monomer contains 5 calcium ion binding sites. It is composed of 663 amino acid residues and has a molecular weight of 74kDa. In the presence of Ca 2+ , the arginine residue in the protein polypeptide is catalyzed to produce citrulline.
  • PAD peptidylarginine deiminase
  • Citrullinated protein often changes its original molecular conformation, which leads to changes in the biochemical activity of the protein, and participates in a variety of physiological and pathological reactions, such as rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, Vasculitis, cancer, etc.
  • Rheumatoid arthritis is a chronic, inflammatory, and systemic autoimmune disease.
  • the main clinical manifestations are joint swelling and pain caused by small joint synovium, followed by cartilage destruction, joint space narrowing, Functional disorders such as joint stiffness and deformity.
  • the worldwide incidence rate is 0.4%-1%, of which there are about 5 million patients with rheumatoid arthritis in China.
  • the disease is more frequent in female population, the ratio of female to male incidence is 3:1, and the age of onset is mainly concentrated in 25-55 years of age.
  • PAD4 inhibitors can also be used to treat multiple sclerosis.
  • histone citrullination is related to the formation of neutrophil extracellular Trap (NET) (innate immune response mechanism), and PAD4 inhibitors can reduce neutrophil activity in a variety of disease pathologies. Therefore, PAD4 inhibitors can be used for tissue damage diseases caused by NET formation. These diseases include, but are not limited to systemic lupus erythematosus, ulcerative colitis, vasculitis, cystic fibrosis and asthma.
  • PAD4 inhibitors can also be used to treat skin diseases caused by the formation of NET.
  • PAD4 inhibitors can also be used to treat cancer, and PAD4 overexpression has been confirmed in many cancers.
  • PAD-targeting inhibitors are in the pre-clinical research stage and are aimed at their catalytic active sites. They are mainly divided into two categories: irreversible inhibitors and reversible inhibitors: The first category is mainly PAD enzyme substrate analogs, namely Mimic peptides are non-selective inhibitors, including halamidines, O-halamidines and tripeptides. The second category is mainly a selective reversible inhibitor of PAD4.
  • WO2014/015905A1 discloses a compound with the following structure (GSK199). GSK199 is currently in the preclinical research stage, and its main indication is rheumatoid arthritis (RA), but its in vitro enzymatic activity has not yet reached the ideal level.
  • PAD4 inhibitors there are fewer varieties of PAD4 inhibitors under development. In order to better meet the huge clinical needs, we aim to develop PAD4 inhibitors with higher activity and better druggability.
  • the purpose of the present invention is to provide a class of peptidylarginine deiminase PAD4 inhibitor compounds and pharmaceutically acceptable salts, stereoisomers and tautomers thereof.
  • the compound of the present invention has good peptide acyl arginine deiminase PAD4 kinase inhibitory activity, and can be used to treat or prevent diseases mediated by peptidyl arginine deiminase PAD4.
  • Y is CR 6 or N
  • R 1 is hydrogen, C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is -L 1 -Cy 1 -(L 3 -Cy 3 ) p -(L 4 -Cy 4 ) q or -L 5 -R a ;
  • R is selected from Or -L 6 -R b ;
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , Carbonyl, sulfonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are independently keys each time they appear, -(CR c R d ) j -(NR c ) k -, -(CR c R d ) j -O-, -(C 2-8 alkenyl) j -, -C(O)-(CR c R d ) j -, -C(O)-(C 2-8 alkynyl) j -, -C(O)-(C 2-8 alkenyl) j -, -C(O)-(NR c ) k -, -(NR c ) k -C(O)-, -C(O)O- (CR c R d ) j -, -S(O) 2 -(CR c R d ) j -;
  • Cy 1 , Cy 2 , Cy 3 , and Cy 4 are independently 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl,
  • Cy 1 , Cy 2 , Cy 3 , Cy 4 can be optionally substituted by one or more hydrogen, halogen, cyano, amino, hydroxyl, carboxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenylcarbonyl, C 2- 8 Alkynylcarbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonylamino substituted, wherein the amino group is unsubstituted or substituted by C 1-6 alkyl, C 1-6 alkyl Carbonyl substitution, the C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkoxycarbonyl group, C 1-6 alkylamino group, C 1-6 alkylcarbonyl group, C 2-8 alkeny
  • R a , R b , R c and R d are independently hydrogen, cyano, amino, carboxy, hydroxy, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1 at each occurrence.
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl groups optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is Or 5-membered heteroaryl
  • n, p, q, j, and k are independently selected from integers from 0 to 5 each time they appear;
  • R is R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R is R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • Y is CR 6 or N
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, -L 1 -Cy 1 , or unsubstituted or substituted Halogen, cyano, amino, hydroxy substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 1 is absent or C 1-6 alkylene, Cy 1 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5-10 membered heteroaryl, Cy 1 can be optionally substituted by hydrogen, halogen, cyano, amino, hydroxyl, C 1-6 alkyl , C 1-6 alkoxy substitution;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylthio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 2 is absent or C 1-6 alkylene, C 1-6 alkylene oxide Group, C 2-6 alkenylene, C 1-6 alkyleneamino, Cy 2 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5- 10-membered heteroaryl,
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group, preferably a 4-7 membered monocyclic group, a 6-11 membered heterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl, (C 1-6 alkyl ) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino , (C 1-6 alkyl) 2 amino, halogenated C
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is Or 5-membered heteroaryl
  • n are each independently an integer of 0-4;
  • R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R 4 is not a C 1-6 alkyl group substituted by a C 1-6 alkyl group or a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N
  • R 1 is hydrogen, C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is -L 1 -Cy 1 -(L 3 -Cy 3 ) p -(L 4 -Cy 4 ) q or -L 5 -R a ;
  • R is selected from Or -L 6 -R b ;
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , Carbonyl, sulfonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are independently keys each time they appear, -(CR c R d ) j -(NR c ) k -, -(CR c R d ) j -O-, -(C 2-8 alkenyl) j -, -C(O)-(CR c R d ) j -, -C(O)-(C 2-8 alkynyl) j -, -C(O)-(C 2-8 alkenyl) j -, -C(O)-(NR c ) k -, -(NR c ) k -C(O)-, -C(O)O- (CR c R d ) j -, -S(O) 2 -(CR c R d ) j -;
  • Cy 1 , Cy 2 , Cy 3 , and Cy 4 are independently 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl,
  • Cy 1 , Cy 2 , Cy 3 , Cy 4 can be optionally substituted by one or more hydrogen, halogen, cyano, amino, hydroxyl, carboxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenylcarbonyl, C 2- 8 Alkynylcarbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonylamino substituted, wherein the amino, C 1-6 alkyl, C 1-6 alkoxy, C 1- 6 Alkoxycarbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenylcarbonyl, C 2-8 alkynylcarbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, aminocarbonyl, C 1-6 alkylsulfonyl,
  • R a , R b , R c and R d are independently hydrogen, cyano, amino, carboxy, hydroxy, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1 at each occurrence. -6 alkoxy C 1-6 alkyl, or unsubstituted or substituted with halogen, cyano, amino, hydroxy, 3-6 membered cycloalkyl, 3-6 membered heterocyclic ring substituted with a C 1-6 alkyl group , C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is Or 5-membered heteroaryl
  • Each occurrence of m, n, p, q, j, and k is independently selected from an integer of 0-5.
  • Y is CR 6 or N
  • R 1 is hydrogen, C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is -L 1 -Cy 1 -(L 3 -Cy 3 ) p -(L 4 -Cy 4 ) q or -L 5 -R a ;
  • R is selected from Or -L 6 -R b ;
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , Carbonyl, sulfonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are independently keys each time they appear, -(CR c R d ) j -(NR c ) k -, -(CR c R d ) j -O-, -(C 2-8 alkenyl) j -, -C(O)-(CR c R d ) j -, -C(O)-(C 2-8 alkynyl) j -, -C(O)-(C 2-8 alkenyl) j -, -C(O)-(NR c ) k -, -(NR c ) k -C(O)-, -C(O)O- (CR c R d ) j -, -S(O) 2 -(CR c R d ) j -;
  • Cy 1 , Cy 2 , Cy 3 , and Cy 4 are independently 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl,
  • Cy 1 , Cy 2 , Cy 3 , Cy 4 can be optionally substituted by one or more hydrogen, halogen, cyano, amino, hydroxyl, carboxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenylcarbonyl, C 2- 8 Alkynylcarbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonylamino substituted, wherein the amino, C 1-6 alkyl, C 1-6 alkoxy, C 1- 6 Alkoxycarbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenylcarbonyl, C 2-8 alkynylcarbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, aminocarbonyl, C 1-6 alkylsulfonyl,
  • R a , R b , R c and R d are independently hydrogen, cyano, amino, carboxy, hydroxy, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1 at each occurrence.
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is Or 5-membered heteroaryl
  • n, p, q, j, and k are independently selected from integers from 0 to 5 each time they appear;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • Ring B is m is 1, R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 1, R 5 is methyl, R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • a pharmaceutical composition containing one or more compounds of the present invention or pharmaceutically acceptable salts, stereoisomers and tautomers thereof, which may optionally It contains one or more pharmaceutically acceptable carriers and is optionally formulated into any pharmaceutically acceptable dosage form.
  • a compound of the present invention or a pharmaceutically acceptable salt, stereoisomer, and tautomer of the present invention, or a pharmaceutical composition of the present invention for use in the treatment or prevention of diseases .
  • a compound of the present invention or a pharmaceutically acceptable salt, stereoisomer, and tautomer of the present invention, or a pharmaceutical composition of the present invention which is used for the treatment or prevention of Diseases mediated by peptidylarginine deiminase PAD4.
  • a compound of the present invention or a pharmaceutically acceptable salt, stereoisomer and tautomer or a pharmaceutical composition of the present invention for preparing treatment or prevention by peptidyl Use of arginine deiminase PAD4-mediated diseases in medicine.
  • a compound of the present invention or a pharmaceutically acceptable salt, stereoisomer and tautomer or a pharmaceutical composition of the present invention in the treatment or prevention of peptidyl The use of amino acid deiminase PAD4-mediated diseases.
  • a method for treating or preventing a disease mediated by peptidylarginine deiminase PAD4 comprising administering the compound of the present invention to a patient in need thereof or Its pharmaceutically acceptable salts, stereoisomers and tautomers or the pharmaceutical composition of the present invention.
  • the disease mediated by peptidylarginine deiminase PAD4 is selected from rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, multiple sclerosis, cyst Fibrosis, cancer, cutaneous lupus erythematosus, asthma and psoriasis.
  • Y is CR 6 . In another embodiment, Y is N.
  • R 1 is hydrogen
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy. In another embodiment, R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy. In another embodiment, R 2 is C 1-6 alkoxy. In another embodiment, R 2 is methoxy.
  • R 3 is -L 1 -Cy 1 -(L 3 -Cy 3 ) p -(L 4 -Cy 4 ) q . In another embodiment, R 3 is -L 1 -Cy 1 . In another embodiment, R 3 is -L 5 -R a .
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy C 1-6 alkyl, -L 1 -Cy 1 , Or unsubstituted or substituted by halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 1 is absent or C 1-6 alkylene, Cy 1 is 3 -12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5-10 membered heteroaryl, Cy 1 can be optionally hydrogen, halogen, cyano, amino, hydroxyl , C 1-6 alkyl, C 1-6 alkoxy substituted.
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy C 1-6 alkyl, or unsubstituted or substituted C 1-6 alkyl substituted with halogen, cyano, amino, and hydroxy.
  • R 3 is hydrogen, C 1-6 alkyl.
  • R 3 is C 1-6 alkyl.
  • R 3 is methyl.
  • R is In another embodiment, R is In another embodiment, R is -L 6 -R b .
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl, or unsubstituted or substituted by halogen, cyano Group, amino, hydroxy, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino.
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl, or unsubstituted or halogen, Cyano, amino, hydroxy, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl.
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl, or unsubstituted or substituted by cyano , Halogen, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl.
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl, unsubstituted or substituted by cyano, Halogen, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl.
  • R 4 is hydrogen, a cyano membered heterocyclic group, an aryl group, a 5-6 membered heteroaryl substituted C 1-6 alkyl group.
  • R 4 is C 1-6 alkyl substituted with a 3-6 membered group.
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaromatic 6-membered heterocyclyl, aryl, 5 C 1-6 alkyl substituted with -6 membered heteroaryl.
  • R 4 is substituted C 1-6 alkyl.
  • R 4 is hydrogen, or C 1-6 alkyl that is unsubstituted or substituted with halogen, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl.
  • R 4 is C 1-6 alkyl substituted with 3-6 membered cycloalkyl.
  • R 4 is methyl substituted with cyclopropyl or cyclobutyl.
  • R 5 is halogen, cyano, amino, hydroxy, or C 1-6 alkyl, C 1-6 alkoxy that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, 3 -12 membered cycloalkyl.
  • R 5 is -L 2 -Cy 2 .
  • R 5 is halogen, C 1-6 alkoxy, 3-12 membered cycloalkyl, unsubstituted or substituted with halogen C 1-6 alkyl.
  • R 5 is methyl, methoxy, fluoro, bromo, or trifluoromethyl.
  • L 1 is absent or is a C 1-6 alkylene group.
  • L 2 is absent or is C 1-6 alkylene, C 1-6 alkyleneoxy, C 2-6 alkenylene, or C 1-6 alkyleneamino.
  • Cy 1 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclyl, aryl, 5-10 membered heteroaryl, Cy 1 may be optionally Hydrogen, halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy substituted.
  • Cy 1 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclyl, aryl, 5-10 membered heteroaryl, Cy 1 may optionally Substituted by one or more hydrogen, halogen, cyano, amino, hydroxy, carboxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl.
  • Cy 2 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclyl, aryl, 5-10 membered heteroaryl, Cy 2 can be optionally Hydrogen, halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy substituted.
  • each occurrence of R a , R c , R d is independently hydrogen, cyano, amino, carboxy, hydroxy, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy C 1-6 alkyl, or unsubstituted or substituted with halogen, cyano, amino, hydroxy, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group substituted with a C 1-6 Alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino.
  • R 6 is hydrogen or C 1-6 alkyl.
  • R 7 is hydrogen
  • ring A is a 4-7 membered monoheterocyclic group, a 6-11 membered hexaheterocyclic group, a 7-12 membered spiroheterocyclic group, or a 6-10 membered bridged heterocyclic group.
  • ring A is a 4-7 membered nitrogen-containing monocyclic group, a 6-11 membered nitrogen-containing heterocyclic group, a 7-12 membered nitrogen-containing spiro heterocyclic group, a 6-10 membered nitrogen-containing bridge Heterocyclic group.
  • ring A is a 4-7 membered nitrogen-containing monoheterocyclic group, a 6-10 membered nitrogen-containing bridged heterocyclic group.
  • Ring A is a 6-10 membered bridge heterocyclyl. In another embodiment, Ring A is a 6-10 membered nitrogen-containing bridged heterocyclic group. In another embodiment, Ring A is a 7-membered nitrogen-containing bridged heterocyclic group. In another embodiment, ring A is pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or 7-membered nitrogen-containing bridged heterocyclic group. In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment, ring A is In another embodiment,
  • each R 8 is independently halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein The C 1-6 alkyl group and C 1-6 alkoxy group are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy.
  • each R 8 is independently halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1 -6 alkyl) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl.
  • each R 8 is independently selected from amino group, hydroxyl group, cyano group, carboxyl group, C 1-6 alkyl group, C 1-6 alkoxy group, amino carbonyl group, C 1-6 alkylamino group.
  • each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein, the C 1-6 alkyl group and C 1-6 alkoxy group are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy.
  • each R 8 is independently selected from halogen and amino. In another embodiment, R 8 is halogen or amino. In another embodiment, one R 8 is halogen and the other R 8 is amino. In another embodiment, one R 8 is fluorine and the other R 8 is amino. In another embodiment, R 8 is amino.
  • ring B is a 5-membered heteroaryl group. In another embodiment, ring B is a five-membered sulfur-containing heteroaryl group. In another embodiment, ring B is a five-membered nitrogen-containing heteroaryl group. In another embodiment, ring B is a five-membered oxygen-containing heteroaryl group. In another embodiment, ring B is a five-membered sulfur and nitrogen-containing heteroaryl group. In another embodiment, ring B is a five-membered sulfur and oxaaryl group. In another embodiment, ring B is a five-membered oxygen- and aza-containing heteroaryl group.
  • ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is In another embodiment, ring B is in another embodiment, ring B is
  • m is an integer from 0-4. In another embodiment, m is 0 or 1. In another embodiment, m is zero. In another embodiment, m is 1.
  • n is an integer from 0-4. In another embodiment, n is 1 or 2. In another embodiment, n is 1. In another embodiment, n is an integer from 2-4.
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • Y is CR 6 or N
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, -L 1 -Cy 1 , or unsubstituted or substituted Halogen, cyano, amino, hydroxy substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 1 is absent or C 1-6 alkylene, Cy 1 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5-10 membered heteroaryl, Cy 1 can be optionally substituted by hydrogen, halogen, cyano, amino, hydroxyl, C 1-6 alkyl , C 1-6 alkoxy substitution;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio group, C 1-6 alkylsulfonylamino group, C 1-6 alkylamino group, (C 1-6 alkyl) 2 amino group, L 2 is absent or C 1-6 alkylene group, C 1-6 Alkyleneoxy, C 2-6 alkenylene, C 1-6 alkyleneamino, Cy 2 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl group
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group, preferably a 4-7 membered monocyclic group, a 6-11 membered heterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is Or 5-membered heteroaryl
  • n and n are independently selected from an integer of 0-5 each time they appear;
  • R is R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R is R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, -L 1 -Cy 1 , or unsubstituted or substituted Halogen, cyano, amino, hydroxy substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 1 is absent or C 1-6 alkylene, Cy 1 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5-10 membered heteroaryl, Cy 1 can be optionally substituted by hydrogen, halogen, cyano, amino, hydroxyl, C 1-6 alkyl , C 1-6 alkoxy substitution;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio group, C 1-6 alkylsulfonylamino group, C 1-6 alkylamino group, (C 1-6 alkyl) 2 amino group, L 2 is absent or C 1-6 alkylene group, C 1-6 Alkyleneoxy, C 2-6 alkenylene, C 1-6 alkyleneamino, Cy 2 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl group
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered monoheterocyclic group, a 6-11 membered pentaheterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is a 5-membered heteroaryl group
  • n are each independently an integer of 0-4;
  • R is R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R is R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, or unsubstituted or halogen, cyano, amino, C 1-6 alkyl substituted with hydroxy;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl;
  • R 5 is halogen, cyano, amino, hydroxy, or C 1-6 alkyl, C 1-6 alkoxy, 3-12 membered cycloalkyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy ;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monocyclic group, a 6-11 membered nitrogen-containing heterocyclic group, a 7-12 membered nitrogen-containing spiro heterocyclic group, and a 6-10 membered nitrogen-containing bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is Preferably, ring B is
  • n are each independently an integer of 0-4;
  • R is R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R is R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or cyano, halogen, 3-6 membered Cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl;
  • R 5 is halogen, unsubstituted or substituted C 1-6 alkyl, C 1-6 alkoxy, 3-12 membered cycloalkyl;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monoheterocyclic group and a 6-10 membered nitrogen-containing bridged heterocyclic group;
  • Each R 8 is independently halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, C 1-6 alkyl, halo C 1-6 alkyl, halo C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl group, wherein the C 1-6 alkoxy Group, C 1-6 alkoxy is unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • Ring B is Preferably, ring B is
  • n are each independently an integer of 0-4;
  • R is R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R is R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or cyano, halogen, 3-6 membered Cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl;
  • R 5 is halogen, unsubstituted or substituted C 1-6 alkyl, C 1-6 alkoxy, 3-12 membered cycloalkyl;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monoheterocyclic group and a 6-10 membered nitrogen-containing bridged heterocyclic group;
  • Each R 8 is independently halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino , Amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl;
  • Ring B is Preferably, ring B is
  • n is an integer of 0-4;
  • n 1;
  • R is R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R is R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, unsubstituted or substituted by cyano, halogen, 3-6 membered ring Alkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl; preferably, R 4 is C 1-6 substituted by 3-6 membered cycloalkyl alkyl;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monoheterocyclic group and a 6-10 membered nitrogen-containing bridged heterocyclic group;
  • Each R 8 is independently halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino , Amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl;
  • n is an integer of 0-4;
  • n 1 or 2;
  • R is R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R is R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted by a C 1-6 alkyl group or a 3-6 membered cycloalkyl group.
  • a seventh preferred embodiment of the first aspect of the present invention there is provided a compound or a pharmaceutically acceptable salt, stereoisomer, and tautomer according to any one of the foregoing preferred embodiments,
  • Y is N
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, unsubstituted or substituted by cyano, halogen, 3-6 membered ring Alkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl; preferably, R 4 is C 1-6 substituted by 3-6 membered cycloalkyl alkyl;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monoheterocyclic group, preferably piperidinyl;
  • Each R 8 is independently halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino , Amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl;
  • n is an integer of 0-4;
  • n 1 or 2;
  • R is R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, unsubstituted or substituted by cyano, halogen, 3-6 membered ring Alkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl; preferably, R 4 is C 1-6 substituted by 3-6 membered cycloalkyl alkyl;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monoheterocyclic group, preferably piperidinyl;
  • Each R 8 is independently halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino , Amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl;
  • n is an integer of 0-4;
  • n 1 or 2.
  • ring A is pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 7-membered nitrogen-containing bridged heterocyclic group;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 Alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • n is an integer of 2-4.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, or C 1-6 alkyl which is unsubstituted or substituted by halogen, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group;
  • R 5 is halogen, unsubstituted or substituted C 1-6 alkyl, C 1-6 alkoxy, 3-12 membered cycloalkyl;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is piperidinyl
  • Each R 8 is independently selected from amino, hydroxy, cyano, carboxy, C 1-6 alkyl, C 1-6 alkoxy, amino carbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1 -6 alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • Ring B is Preferably, ring B is
  • n 0 or 1
  • n is an integer of 2-4.
  • Y is CR 6 or N;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 Alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • Y is CR 6 or N;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 Alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • Y is CR 6 or N;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 The alkyl group and C 1-6 alkoxy group are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy.
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is -L 5 -R a ;
  • L 5 is a bond, -(CR c R d ) j -(NR c ) k -;
  • R a , R c , and R d are independently hydrogen, cyano, amino, carboxyl, hydroxyl, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy at each occurrence.
  • R 6 is hydrogen, C 1-6 alkyl
  • R 7 is hydrogen, C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group, preferably a 4-7 membered monocyclic group, a 6-11 membered heterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Ring B is a 5-membered heteroaryl group, preferably, ring B is More preferably, ring B is
  • n, j, and k are independently selected from integers from 0 to 5 each time they appear;
  • R is R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R is R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • R is R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is -L 1 -Cy 1 ;
  • R is selected from
  • L 1 is a bond, -(CR c R d ) j -(NR c ) k -, -(CR c R d ) j -O-, -(C 2-8 alkenyl) j -, -C(O) -(CR c R d ) j -, -C(O)-(C 2-8 alkynyl) j -, -C(O)-(C 2-8 alkenyl) j -, -C(O)- (NR c ) k -, -(NR c ) k -C(O)-, -C(O)O-(CR c R d ) j -, -S(O) 2 -(CR c R d ) j -;
  • Cy 1 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12
  • Cy 1 can be optionally substituted by one or more hydrogen, halogen, cyano, amino, hydroxy, carboxy, C 1-6 alkyl, C 1-6 alkane Oxy, C 1-6 alkoxycarbonyl substitution;
  • R 6 is hydrogen, C 1-6 alkyl
  • R 7 is hydrogen, C 1-6 alkyl
  • Ring A is a 4-7 membered monoheterocyclic group, a 6-11 membered pentaheterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Ring B is a 5-membered heteroaryl group, preferably, ring B is
  • n, j, and k are independently selected from an integer of 0-5 each time they appear.
  • Ring A is a 6-10 membered heterocyclic group
  • Y is N
  • R 1 is hydrogen
  • R 2 is C 1-6 alkoxy
  • R 3 is C 1-6 alkyl
  • R 4 is C 1-6 alkyl substituted by 3-6 membered cycloalkyl
  • R 7 is hydrogen
  • n 1 or 2
  • R 8 is halogen or amino
  • the compound represented by general formula (I) and each sub-general formula or pharmaceutically acceptable salts, stereoisomers and tautomers thereof further satisfy the following condition:
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • Y is CR 6 or N
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, -L 1 -Cy 1 , or unsubstituted or substituted Halogen, cyano, amino, hydroxy substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 1 is absent or C 1-6 alkylene, Cy 1 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5-10 membered heteroaryl, Cy 1 can be optionally substituted by hydrogen, halogen, cyano, amino, hydroxyl, C 1-6 alkyl , C 1-6 alkoxy substitution;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylthio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 2 is absent or C 1-6 alkylene, C 1-6 alkylene oxide Group, C 2-6 alkenylene, C 1-6 alkyleneamino, Cy 2 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5- 10-membered heteroaryl,
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group, preferably a 4-7 membered monocyclic group, a 6-11 membered heterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl, (C 1-6 alkyl ) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino , (C 1-6 alkyl) 2 amino, halogenated C
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is Or 5-membered heteroaryl
  • n are each independently an integer of 0-4;
  • R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R 4 is not a C 1-6 alkyl group substituted by a C 1-6 alkyl group or a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, -L 1 -Cy 1 , or unsubstituted or substituted Halogen, cyano, amino, hydroxy substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 1 is absent or C 1-6 alkylene, Cy 1 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5-10 membered heteroaryl, Cy 1 can be optionally substituted by hydrogen, halogen, cyano, amino, hydroxyl, C 1-6 alkyl , C 1-6 alkoxy substitution;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylthio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 2 is absent or C 1-6 alkylene, C 1-6 alkylene oxide Group, C 2-6 alkenylene, C 1-6 alkyleneamino, Cy 2 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5- 10-membered heteroaryl,
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered monoheterocyclic group, a 6-11 membered pentaheterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl, (C 1-6 alkyl ) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino , (C 1-6 alkyl) 2 amino, halogenated C
  • the membered heterocyclic group is substituted with a 5-6 membered heteroaryl group that is unsubstituted or optionally substituted by a substituent;
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is a 5-membered heteroaryl group
  • n are each independently an integer of 0-4;
  • R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R 4 is not a C 1-6 alkyl group substituted by a C 1-6 alkyl group or a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, or unsubstituted or halogen, cyano, amino, C 1-6 alkyl substituted with hydroxy;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl;
  • R 5 is halogen, cyano, amino, hydroxy, or C 1-6 alkyl, C 1-6 alkoxy that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monocyclic group, a 6-11 membered nitrogen-containing heterocyclic group, a 7-12 membered nitrogen-containing spiro heterocyclic group, and a 6-10 membered nitrogen-containing bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl, (C 1-6 alkyl ) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino , (C 1-6 alkyl) 2 amino, halogenated C
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • n are each independently an integer of 0-4;
  • R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R 4 is not a C 1-6 alkyl group substituted by a C 1-6 alkyl group or a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or cyano, halogen, 3-6 membered Cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl;
  • R 5 is halogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monocyclic group
  • Each R 8 is independently halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, C 1-6 alkyl, halo C 1-6 alkyl, halo C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl group, wherein the C 1-6 alkoxy Group, C 1-6 alkoxy is unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • n are each independently an integer of 0-4;
  • R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • R 4 is not a C 1-6 alkyl group substituted by a C 1-6 alkyl group or a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or cyano, halogen, 3-6 membered Cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl;
  • R 5 is halogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monoheterocyclic group, preferably piperidinyl;
  • Each R 8 is independently halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino , Amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl;
  • n is an integer of 0-4;
  • n 1;
  • R 4 is a C 1-6 alkyl group substituted by a 3-6 membered heterocyclic group, an aryl group, or a 5-6 membered heteroaryl group;
  • R 4 is a C 1-6 alkyl group substituted by halogen, a 3-6 membered heterocyclic group, an aryl group, or a 5-6 membered heteroaryl group.
  • Ring A is pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 Alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • n is an integer of 2-4.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, or C 1-6 alkyl which is unsubstituted or substituted by halogen, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group;
  • R 5 is halogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is piperidinyl
  • Each R 8 is independently selected from amino, hydroxy, cyano, carboxy, C 1-6 alkyl, C 1-6 alkoxy, amino carbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1 -6 alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • n 0 or 1
  • n is an integer of 2-4.
  • Y is CR 6 or N;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 The alkyl group and C 1-6 alkoxy group are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy.
  • Y is CR 6 or N;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 Alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • R 4 is not C 1-6 alkyl, halogen-substituted C 1-6 alkyl, or 3-6 membered cycloalkyl substituted C 1-6 alkyl.
  • Y is CR 6 or N;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 The alkyl group and C 1-6 alkoxy group are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy.
  • Y is CR 6 or N
  • R 1 is hydrogen, C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is -L 1 -Cy 1 -(L 3 -Cy 3 ) p -(L 4 -Cy 4 ) q or -L 5 -R a ;
  • R is selected from Or -L 6 -R b ;
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , Carbonyl, sulfonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are independently keys each time they appear, -(CR c R d ) j -(NR c ) k -, -(CR c R d ) j -O-, -(C 2-8 alkenyl) j -, -C(O)-(CR c R d ) j -, -C(O)-(C 2-8 alkynyl) j -, -C(O)-(C 2-8 alkenyl) j -, -C(O)-(NR c ) k -, -(NR c ) k -C(O)-, -C(O)O- (CR c R d ) j -, -S(O) 2 -(CR c R d ) j -;
  • Cy 1 , Cy 2 , Cy 3 , and Cy 4 are independently 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl,
  • Cy 1 , Cy 2 , Cy 3 , Cy 4 can be optionally substituted by one or more hydrogen, halogen, cyano, amino, hydroxyl, carboxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenylcarbonyl, C 2- 8 Alkynylcarbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonylamino substituted, wherein the amino, C 1-6 alkyl, C 1-6 alkoxy, C 1- 6 Alkoxycarbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenylcarbonyl, C 2-8 alkynylcarbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, aminocarbonyl, C 1-6 alkylsulfonyl,
  • R a , R b , R c and R d are independently hydrogen, cyano, amino, carboxy, hydroxy, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1 at each occurrence. -6 alkoxy C 1-6 alkyl, or unsubstituted or substituted with halogen, cyano, amino, hydroxy, 3-6 membered cycloalkyl, 3-6 membered heterocyclic ring substituted with a C 1-6 alkyl group , C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl groups optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is Or 5-membered heteroaryl
  • Each occurrence of m, n, p, q, j, and k is independently selected from an integer of 0-5.
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • Y is CR 6 or N
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, -L 1 -Cy 1 , or unsubstituted or substituted Halogen, cyano, amino, hydroxy substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 1 is absent or C 1-6 alkylene, Cy 1 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5-10 membered heteroaryl, Cy 1 can be optionally substituted by hydrogen, halogen, cyano, amino, hydroxyl, C 1-6 alkyl , C 1-6 alkoxy substitution;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio group, C 1-6 alkylsulfonylamino group, C 1-6 alkylamino group, (C 1-6 alkyl) 2 amino group, L 2 is absent or C 1-6 alkylene group, C 1-6 Alkyleneoxy, C 2-6 alkenylene, C 1-6 alkyleneamino, Cy 2 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl group
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group, preferably a 4-7 membered monocyclic group, a 6-11 membered heterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is Or 5-membered heteroaryl
  • n is independently selected from an integer of 0-5.
  • Y is CR 6 or N
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, -L 1 -Cy 1 , or unsubstituted or substituted Halogen, cyano, amino, hydroxy substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 1 is absent or C 1-6 alkylene, Cy 1 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5-10 membered heteroaryl, Cy 1 can be optionally substituted by hydrogen, halogen, cyano, amino, hydroxyl, C 1-6 alkyl , C 1-6 alkoxy substitution;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl, C 2-8 unsubstituted or substituted by halogen, cyano, amino, or hydroxy 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio group, C 1-6 alkylsulfonylamino group, C 1-6 alkylamino group, (C 1-6 alkyl) 2 amino group, L 2 is absent or C 1-6 alkylene group, C 1-6 Alkyleneoxy, C 2-6 alkenylene, C 1-6 alkyleneamino, Cy 2 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl group
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered monoheterocyclic group, a 6-11 membered pentaheterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is a 5-membered heteroaryl group
  • n are each independently an integer of 0-4.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, or unsubstituted or halogen, cyano, amino, C 1-6 alkyl substituted with hydroxy;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl;
  • R 5 is halogen, cyano, amino, hydroxy, or C 1-6 alkyl, C 1-6 alkoxy that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monocyclic group, a 6-11 membered nitrogen-containing heterocyclic group, a 7-12 membered nitrogen-containing spiro heterocyclic group, and a 6-10 membered nitrogen-containing bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • n are each independently an integer of 0-4.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or cyano, halogen, 3-6 membered Cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl;
  • R 5 is halogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monocyclic group
  • Each R 8 is independently halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, C 1-6 alkyl, halo C 1-6 alkyl, halo C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl group, wherein the C 1-6 alkoxy Group, C 1-6 alkoxy is unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • n are each independently an integer of 0-4.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or cyano, halogen, 3-6 membered Cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl;
  • R 5 is halogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monoheterocyclic group, preferably piperidinyl;
  • Each R 8 is independently halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino , Amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl;
  • n is an integer of 0-4;
  • n 1.
  • Y is CR 4 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl, or cyano, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl Substituted C 1-6 alkyl; preferably, R 4 is a C 1-6 alkyl substituted by a 3-6 membered heterocyclic group;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monoheterocyclic group, preferably piperidinyl;
  • Each R 8 is independently halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino , Amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl;
  • n is an integer of 0-4;
  • n 1.
  • Y is N
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl, or cyano, halogen, 3-6 membered heterocyclyl, Aryl, C 1-6 alkyl substituted by 5-6 membered heteroaryl; preferably, R 4 is C 1-6 alkyl substituted by halogen;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monoheterocyclic group, preferably piperidinyl;
  • Each R 8 is independently halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino , Amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl;
  • n is an integer of 0-4;
  • n 1.
  • Ring A is pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 Alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • n is an integer of 2-4.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, or C 1-6 alkyl which is unsubstituted or substituted by halogen, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group;
  • R 5 is halogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is piperidinyl
  • Each R 8 is independently selected from amino, hydroxy, cyano, carboxy, C 1-6 alkyl, C 1-6 alkoxy, amino carbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1 -6 alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • n 0 or 1
  • n is an integer of 2-4.
  • Y is CR 6 or N;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 The alkyl group and C 1-6 alkoxy group are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy.
  • Y is CR 6 or N;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 Alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • R 4 is not C 1-6 alkyl, halogen-substituted C 1-6 alkyl, or 3-6 membered cycloalkyl substituted C 1-6 alkyl.
  • Y is CR 6 or N;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 The alkyl group and C 1-6 alkoxy group are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy.
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • Y is CR 6 or N
  • R 1 is hydrogen, C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is -L 5 -R a ;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , Carbonyl, sulfonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • L 2 and L 5 are independently keys each time they appear, -(CR c R d ) j -(NR c ) k -, -(CR c R d ) j -O-, -(C 2-8 Alkenyl) j -, -C(O)-(CR c R d ) j -, -C(O)-(C 2-8alkynyl ) j -, -C(O)-(C 2-8alkene Base) j -, -C(O)-(NR c ) k -, -(NR c ) k -C(O)-, -C(O)O-(CR c R d ) j -, -S( O) 2 -(CR c R d ) j -;
  • Cy 2 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5-10 membered heteroaryl, Cy 2 can be any
  • R a , R c , R d are independently hydrogen, cyano, amino, carboxyl, hydroxyl, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy at each occurrence.
  • R 6 is hydrogen, C 1-6 alkyl
  • R 7 is hydrogen, C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group, preferably a 4-7 membered monocyclic group, a 6-11 membered heterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl groups optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is a 5-membered heteroaryl group, preferably, ring B is
  • n, j, and k are independently selected from an integer of 0-5 each time they appear.
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • Y is CR 6 or N
  • R 1 is hydrogen, C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is -L 1 -Cy 1 -(L 3 -Cy 3 ) p -(L 4 -Cy 4 ) q ;
  • R is selected from
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , Carbonyl, sulfonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • L 1 , L 2 , L 3 , and L 4 are independently keys each time they appear, -(CR c R d ) j -(NR c ) k -, -(CR c R d ) j -O-, -(C 2-8alkenyl ) j -, -C(O)-(CR c R d ) j -, -C(O)-(C 2-8alkynyl ) j -, -C(O)- (C 2-8 alkenyl) j -, -C(O)-(NR c ) k -, -(NR c ) k -C(O)-, -C(O)O-(CR c R d ) j -, -S(O) 2 -(CR c R d ) j -;
  • Cy 1 , Cy 2 , Cy 3 , and Cy 4 are independently 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 each time they appear
  • Cy 1 , Cy 2 , Cy 3 and Cy 4 may optionally be substituted by one or more hydrogen, halogen, cyano, amino, hydroxyl, carboxyl, C 1- 6 alkyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenyl carbonyl, C 2-8 alkynyl Carbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonylamino substituted, wherein the amino, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy Carbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenylcarbonyl, C 2-8 alkynylcarbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl, C 1-6 alkylsulfonyl, C 1-6 al
  • R c and R d is independently hydrogen, cyano, amino, carboxy, hydroxy, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy C 1 -6 alkyl, or unsubstituted or substituted by halogen, cyano, amino, hydroxy, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkyl, C 1-6 alkyl Carbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 Amino;
  • R 6 is hydrogen, C 1-6 alkyl
  • R 7 is hydrogen, C 1-6 alkyl
  • Ring A is a 4-7 membered monoheterocyclic group, a 6-11 membered pentaheterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is a 5-membered heteroaryl group, preferably, ring B is
  • Each occurrence of m, n, p, q, j, and k is independently selected from an integer of 0-5.
  • Ring A is a 6-10 membered heterocyclic group
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy.
  • Y is CR 6 or N
  • R 1 is hydrogen, C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is -L 1 -Cy 1 -(L 3 -Cy 3 ) p -(L 4 -Cy 4 ) q or -L 5 -R a ;
  • R is selected from Or -L 6 -R b ;
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , Carbonyl, sulfonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • L 1 , L 2 , L 3 , L 4 , L 5 , and L 6 are independently keys each time they appear, -(CR c R d ) j -(NR c ) k -, -(CR c R d ) j -O-, -(C 2-8 alkenyl) j -, -C(O)-(CR c R d ) j -, -C(O)-(C 2-8 alkynyl) j -, -C(O)-(C 2-8 alkenyl) j -, -C(O)-(NR c ) k -, -(NR c ) k -C(O)-, -C(O)O- (CR c R d ) j -, -S(O) 2 -(CR c R d ) j -;
  • Cy 1 , Cy 2 , Cy 3 , and Cy 4 are independently 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl,
  • Cy 1 , Cy 2 , Cy 3 , Cy 4 can be optionally substituted by one or more hydrogen, halogen, cyano, amino, hydroxyl, carboxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenylcarbonyl, C 2- 8 Alkynylcarbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonylamino substituted, wherein the amino, C 1-6 alkyl, C 1-6 alkoxy, C 1- 6 Alkoxycarbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenylcarbonyl, C 2-8 alkynylcarbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, aminocarbonyl, C 1-6 alkylsulfonyl,
  • R a , R b , R c and R d are independently hydrogen, cyano, amino, carboxy, hydroxy, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1 at each occurrence.
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is Or 5-membered heteroaryl
  • n, p, q, j, and k are independently selected from integers from 0 to 5 each time they appear;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • Ring B is m is 1, R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 1, R 5 is methyl, R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • Y is CR 6 or N
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, -L 1 -Cy 1 , or unsubstituted or substituted Halogen, cyano, amino, hydroxy substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 1 is absent or C 1-6 alkylene, Cy 1 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5-10 membered heteroaryl, Cy 1 can be optionally substituted by hydrogen, halogen, cyano, amino, hydroxyl, C 1-6 alkyl , C 1-6 alkoxy substitution;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio group, C 1-6 alkylsulfonylamino group, C 1-6 alkylamino group, (C 1-6 alkyl) 2 amino group, L 2 is absent or C 1-6 alkylene group, C 1-6 Alkyleneoxy, C 2-6 alkenylene, C 1-6 alkyleneamino, Cy 2 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl group
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group, preferably a 4-7 membered monocyclic group, a 6-11 membered heterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is Or 5-membered heteroaryl
  • n and n are independently selected from an integer of 0-5 each time they appear;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • Ring B is m is 1, R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 1, R 5 is methyl, R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, 3-6 membered cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, -L 1 -Cy 1 , or unsubstituted or substituted Halogen, cyano, amino, hydroxy substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, L 1 is absent or C 1-6 alkylene, Cy 1 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5-10 membered heteroaryl, Cy 1 can be optionally substituted by hydrogen, halogen, cyano, amino, hydroxyl, C 1-6 alkyl , C 1-6 alkoxy substitution;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio group, C 1-6 alkylsulfonylamino group, C 1-6 alkylamino group, (C 1-6 alkyl) 2 amino group, L 2 is absent or C 1-6 alkylene group, C 1-6 Alkyleneoxy, C 2-6 alkenylene, C 1-6 alkyleneamino, Cy 2 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl group
  • R 6 is hydrogen, C 1-6 alkyl or 3-6 membered cycloalkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered monoheterocyclic group, a 6-11 membered pentaheterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is a 5-membered heteroaryl group
  • n are each independently an integer of 0-4;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • Ring B is m is 1, R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 1, R 5 is methyl, R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, or halogenated C 1-6 alkoxy;
  • R 3 is hydrogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, or unsubstituted or halogen, cyano, amino, C 1-6 alkyl substituted with hydroxy;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl;
  • R 5 is halogen, cyano, amino, hydroxy, or C 1-6 alkyl, C 1-6 alkoxy that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monocyclic group, a 6-11 membered nitrogen-containing heterocyclic group, a 7-12 membered nitrogen-containing spiro heterocyclic group, and a 6-10 membered nitrogen-containing bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • n are each independently an integer of 0-4;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • Ring B is m is 1, R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 1, R 5 is methyl, R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or cyano, halogen, 3-6 membered Cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl;
  • R 5 is halogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monocyclic group
  • Each R 8 is independently halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino, C 1-6 alkyl, halo C 1-6 alkyl, halo C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl group, wherein the C 1-6 alkoxy Group, C 1-6 alkoxy is unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • n are each independently an integer of 0-4;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • Ring B is m is 1, R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 1, R 5 is methyl, R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or cyano, halogen, 3-6 membered Cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl;
  • R 5 is halogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monoheterocyclic group, preferably piperidinyl;
  • Each R 8 is independently halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino , Amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl;
  • n is an integer of 0-4;
  • n 1;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • Ring B is m is 1, R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 1, R 5 is methyl, R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl, or cyano, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl Substituted C 1-6 alkyl; preferably, R 4 is a C 1-6 alkyl substituted by a 3-6 membered heterocyclic group;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monoheterocyclic group, preferably piperidinyl;
  • Each R 8 is independently halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino , Amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl;
  • n is an integer of 0-4;
  • n 1.
  • Y is N
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, 5-6 membered heteroaryl, or cyano, halogen, 3-6 membered heterocyclyl, Aryl, C 1-6 alkyl substituted by 5-6 membered heteroaryl; preferably, R 4 is C 1-6 alkyl substituted by halogen;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is a 4-7 membered nitrogen-containing monoheterocyclic group, preferably piperidinyl;
  • Each R 8 is independently halogen, cyano, amino, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino , Amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl;
  • n is an integer of 0-4;
  • n 1.
  • Ring A is pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 Alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • n is an integer of 2-4.
  • Y is CR 6 or N;
  • R 1 is hydrogen or C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is hydrogen, C 1-6 alkyl
  • R 4 is hydrogen, or C 1-6 alkyl which is unsubstituted or substituted by halogen, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group;
  • R 5 is halogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 6 is hydrogen or C 1-6 alkyl
  • R 7 is hydrogen or C 1-6 alkyl
  • Ring A is piperidinyl
  • Each R 8 is independently selected from amino, hydroxy, cyano, carboxy, C 1-6 alkyl, C 1-6 alkoxy, amino carbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1 -6 alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • n 0 or 1
  • n is an integer of 2-4.
  • Y is CR 6 or N;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 The alkyl group and C 1-6 alkoxy group are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy.
  • Y is CR 6 or N;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 Alkyl and C 1-6 alkoxy are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy;
  • R 4 is not C 1-6 alkyl, halogen-substituted C 1-6 alkyl, or 3-6 membered cycloalkyl substituted C 1-6 alkyl.
  • Y is CR 6 or N;
  • Each R 8 is independently selected from halogen, cyano, amino, carboxy, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 alkyl ) 2 amino, amino C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, aminocarbonyl, C 1-6 alkylaminocarbonyl, wherein the C 1-6 The alkyl group and C 1-6 alkoxy group are unsubstituted or substituted with one or more groups independently selected from cyano, amino, carboxy, and hydroxy.
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • Y is CR 6 or N
  • R 1 is hydrogen, C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is -L 5 -R a ;
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogenated, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , Carbonyl, sulfonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • L 2 and L 5 are independently keys each time they appear, -(CR c R d ) j -(NR c ) k -, -(CR c R d ) j -O-, -(C 2-8 Alkenyl) j -, -C(O)-(CR c R d ) j -, -C(O)-(C 2-8alkynyl ) j -, -C(O)-(C 2-8alkene Base) j -, -C(O)-(NR c ) k -, -(NR c ) k -C(O)-, -C(O)O-(CR c R d ) j -, -S( O) 2 -(CR c R d ) j -;
  • Cy 2 is 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 membered heterocyclic group, aryl, 5-10 membered heteroaryl, Cy 2 can be any
  • R a , R c , R d are independently hydrogen, cyano, amino, carboxyl, hydroxyl, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy at each occurrence.
  • R 6 is hydrogen, C 1-6 alkyl
  • R 7 is hydrogen, C 1-6 alkyl
  • Ring A is a 3-12 membered heterocyclic group, preferably a 4-7 membered monocyclic group, a 6-11 membered heterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is a 5-membered heteroaryl group, preferably, ring B is
  • n, j, and k are independently selected from integers from 0 to 5 each time they appear;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not C 1-6 alkyl, halogen substituted C 1-6 alkyl, 3-6 membered cycloalkyl substituted C 1-6 alkyl;
  • Ring B is m is 1, R 5 is methyl, methoxy, fluorine, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 0, R 3 is methyl, and ring A is When R 4 is not a C 1-6 alkyl group or a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group;
  • Ring B is m is 1, R 5 is methyl, R 3 is methyl, and ring A is When, R 4 is not a C 1-6 alkyl group substituted with a 3-6 membered cycloalkyl group.
  • X 1 , X 2 , X 3 , and X 4 are each independently selected from C, CR 4 , C(R 4 ) 2 , N or NR 4 ;
  • Y is CR 6 or N
  • R 1 is hydrogen, C 1-6 alkyl
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy
  • R 3 is -L 1 -Cy 1 -(L 3 -Cy 3 ) p -(L 4 -Cy 4 ) q ;
  • R is selected from
  • R 4 is hydrogen, cyano, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl, or unsubstituted or halogen, cyano, amino, hydroxyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, aryl, 5-6 membered heteroaryl substituted C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl , Carbonyl, sulfonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • L 1 , L 2 , L 3 , and L 4 are independently keys each time they appear, -(CR c R d ) j -(NR c ) k -, -(CR c R d ) j -O-, -(C 2-8alkenyl ) j -, -C(O)-(CR c R d ) j -, -C(O)-(C 2-8alkynyl ) j -, -C(O)- (C 2-8 alkenyl) j -, -C(O)-(NR c ) k -, -(NR c ) k -C(O)-, -C(O)O-(CR c R d ) j -, -S(O) 2 -(CR c R d ) j -;
  • Cy 1 , Cy 2 , Cy 3 , and Cy 4 are independently 3-12 membered cycloalkyl, 3-12 membered cycloalkenyl, 3-12 each time they appear
  • Cy 1 , Cy 2 , Cy 3 and Cy 4 may be optionally substituted by one or more hydrogen, halogen, cyano, amino, hydroxyl, carboxyl, C 1- 6 alkyl, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenyl carbonyl, C 2-8 alkynyl Carbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonylamino substituted, wherein the amino, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy Carbonyl, C 1-6 alkylamino, C 1-6 alkylcarbonyl, C 2-8 alkenylcarbonyl, C 2-8 alkynylcarbonyl, aminocarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl, C 1-6 alkylsulfonyl, C 1-6 al
  • R c and R d is independently hydrogen, cyano, amino, carboxy, hydroxy, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy C 1 -6 alkyl, or unsubstituted or substituted by halogen, cyano, amino, hydroxy, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkyl, C 1-6 alkyl Carbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylamino, (C 1-6 alkyl) 2 Amino;
  • R 6 is hydrogen, C 1-6 alkyl
  • R 7 is hydrogen, C 1-6 alkyl
  • Ring A is a 4-7 membered monoheterocyclic group, a 6-11 membered pentaheterocyclic group, a 7-12 membered spiro heterocyclic group, and a 6-10 membered bridged heterocyclic group;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy;
  • Ring B is a 5-membered heteroaryl group, preferably, ring B is
  • Each occurrence of m, n, p, q, j, and k is independently selected from an integer of 0-5.
  • Ring A is a 6-10 membered heterocyclic group
  • R 5 is halogen, cyano, amino, hydroxy, -L 2 -Cy 2 , or C 1-6 alkyl, C 2-8 alkenyl that is unsubstituted or substituted by halogen, cyano, amino, or hydroxy, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxy, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkyl Thio, C 1-6 alkylsulfonylamino, C 1-6 alkylamino, (C 1-6 alkyl) 2 amino;
  • Each R 8 is independently hydroxyl, amino, carboxy, cyano, nitro, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylamino, (C 1-6 Alkyl) 2 amino, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, C 2-8 alkenyl, C 2-8 alkynyl, C 1-6 alkylsulfonyl, C 1 -6 alkylthio, C 1-6 alkoxycarbonyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclic group, C 1-6 alkylcarbonyl, aminocarbonyl, C 1-6 alkylaminocarbonyl , (C 1-6 alkyl) 2 aminocarbonyl, 3-6-membered heterocyclyl group and a 5-6 membered heteroaryl - group, wherein said C 1-6 alkyl, C 1-6 alkoxy, , C 1-6 alkylamino, (C 1-6 al
  • substituents of the above-mentioned 3-6 membered heterocyclic group optionally substituted by substituents and 5-6 membered heteroaryl group optionally substituted by substituents are selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C 1-6 alkyl and C 1-6 alkoxy.
  • the disease mediated by peptidylarginine deiminase PAD4 is selected from rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, multiple sclerosis, cyst Fibrosis, cancer, cutaneous lupus erythematosus, asthma and psoriasis.
  • a pharmaceutical composition containing one or more compounds of the present invention or pharmaceutically acceptable salts, stereoisomers and tautomers thereof, which may optionally It contains one or more pharmaceutically acceptable carriers and is optionally formulated into any pharmaceutically acceptable dosage form.
  • the pharmaceutical carrier of the present invention can be one or more solid or liquid carriers suitable for human use.
  • the pharmaceutical carrier preferably has sufficient purity and sufficiently low toxicity, and is compatible with the active ingredient of the present invention without significantly reducing the efficacy of the active ingredient.
  • the pharmaceutical carrier can be selected from fillers, binders, disintegrants, lubricants, aqueous solvents or non-aqueous solvents, and the like.
  • the pharmaceutical composition of the present invention can be optionally formulated into any pharmaceutically acceptable dosage form, and administered to the needs in any suitable way of administration, such as oral, parenteral, rectal or pulmonary administration.
  • administration such as oral, parenteral, rectal or pulmonary administration.
  • the patient or subject of this treatment When used for oral administration, it can be made into tablets, capsules, pills, granules, etc.
  • parenteral administration When used for parenteral administration, it can be made into injection, sterile powder for injection, etc.
  • rectal administration it can be made into suppositories and the like.
  • pulmonary administration it can be made into aerosols, sprays and powder mists.
  • a compound of the present invention or a pharmaceutically acceptable salt, stereoisomer, and tautomer of the present invention, or a pharmaceutical composition of the present invention for use in the treatment or prevention of diseases .
  • a compound of the present invention or a pharmaceutically acceptable salt, stereoisomer, and tautomer of the present invention, or a pharmaceutical composition of the present invention which is used for the treatment or prevention of Peptidyl arginine deiminase PAD4 mediated diseases (including diseases caused by abnormal expression of peptidyl arginine deiminase PAD4), such as rheumatoid arthritis, vasculitis, systemic lupus erythematosus, Ulcerative colitis, multiple sclerosis, cystic fibrosis, cancer, cutaneous lupus erythematosus, asthma, and psoriasis.
  • Peptidyl arginine deiminase PAD4 mediated diseases including diseases caused by abnormal expression of peptidyl arginine deiminase PAD4
  • diseases including diseases caused by abnormal expression of peptidyl arginine deiminase PAD4
  • diseases such as r
  • a compound of the present invention or a pharmaceutically acceptable salt, stereoisomer and tautomer or a pharmaceutical composition of the present invention for preparing treatment or prevention by peptidyl
  • arginine deiminase PAD4-mediated diseases including diseases caused by abnormal expression of peptidyl arginine deiminase PAD4
  • diseases including diseases caused by abnormal expression of peptidyl arginine deiminase PAD4
  • diseases including diseases caused by abnormal expression of peptidyl arginine deiminase PAD4
  • medicine such as rheumatoid arthritis and vasculitis , Systemic lupus erythematosus, ulcerative colitis, multiple sclerosis, cystic fibrosis, cancer, cutaneous lupus erythematosus, asthma and psoriasis.
  • a compound of the present invention or a pharmaceutically acceptable salt, stereoisomer and tautomer or a pharmaceutical composition of the present invention in the treatment or prevention of peptidyl Use in diseases mediated by amino acid deiminase PAD4 (including diseases caused by the abnormal expression of peptidyl arginine deiminase PAD4), such as rheumatoid arthritis, vasculitis, systemic Lupus erythematosus, ulcerative colitis, multiple sclerosis, cystic fibrosis, cancer, cutaneous lupus erythematosus, asthma, and psoriasis.
  • diseases mediated by amino acid deiminase PAD4 including diseases caused by the abnormal expression of peptidyl arginine deiminase PAD4
  • diseases mediated by amino acid deiminase PAD4 including diseases caused by the abnormal expression of peptidyl arginine deiminase PAD4
  • a treatment or prevention of diseases mediated by peptidylarginine deiminase PAD4 (including those caused by abnormal expression of peptidylarginine deiminase PAD4).
  • Diseases such as rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, multiple sclerosis, cystic fibrosis, cancer, cutaneous lupus erythematosus, asthma and psoriasis Disease
  • the method includes administering the compound of the present invention or a pharmaceutically acceptable salt, stereoisomer and tautomer of the present invention or the pharmaceutical composition of the present invention to a patient in need thereof.
  • the patient is preferably a mammal, more preferably a human.
  • halogen in the present invention refers to fluorine, chlorine, bromine, iodine, etc., preferably fluorine atom and chlorine atom.
  • halo in the present invention means that one or more hydrogen atoms in the substituent are replaced by one or more identical or different halogen atoms.
  • Halogen is as defined above.
  • the "cyano group” in the present invention refers to a -CN group.
  • amino group in the present invention refers to the -NH 2 group.
  • hydroxyl group in the present invention refers to the -OH group.
  • the "thio group” in the present invention refers to the -S- group.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Rheumatology (AREA)
  • Pulmonology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un inhibiteur de peptidylarginine déiminase et une utilisation associée. En particulier, la présente invention concerne un composé inhibiteur de peptidylarginine déiminase PAD4 représenté par la formule (I) et diverses sous-formules, un sel, un stéréoisomère, un tautomère pharmaceutiquement acceptables de celui-ci, ainsi qu'une composition pharmaceutique, une préparation pharmaceutique et une utilisation associées. Chaque variable dans la formule générale est telle que définie dans la description. Le composé selon la présente invention a un effet inhibiteur sur la peptidylarginine déiminase PAD4 et peut être utilisé pour traiter diverses maladies telles que la polyarthrite rhumatoïde, la vascularite, le lupus érythémateux systémique, la rectocolite hémorragique, la sclérose en plaques, la fibrose kystique, le cancer, le lupus érythémateux cutané, l'asthme et le psoriasis.
PCT/CN2020/117802 2019-09-27 2020-09-25 Inhibiteur de peptidylarginine déiminase et utilisation associée WO2021057910A1 (fr)

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US11878965B2 (en) 2020-12-22 2024-01-23 Gilead Sciences, Inc. Inhibitors of peptidylarginine deiminases
US11976083B2 (en) 2020-04-30 2024-05-07 Gilead Sciences, Inc. Inhibitors of peptidylarginine deiminases

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CN114853748A (zh) * 2022-05-06 2022-08-05 武汉工程大学 一种含三氟甲烷异噁唑啉类衍生物、其制备方法和应用

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WO2014015905A1 (fr) * 2012-07-26 2014-01-30 Glaxo Group Limited 2-(azaindol-2-yl)benzimidazoles utilisés comme inhibiteurs de pad4
WO2016185279A1 (fr) * 2015-05-21 2016-11-24 Glaxosmithkline Intellectual Property Development Limited Dérivés de benzoimidazole en tant qu'inhibiteurs de pad4
WO2017100594A1 (fr) * 2015-12-09 2017-06-15 Padlock Therapeutics, Inc. Inhibiteurs bicycliques de pad4
WO2019161803A1 (fr) * 2018-02-26 2019-08-29 南京药捷安康生物科技有限公司 Inhibiteur de peptidylarginine déiminase et son utilisation

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ES2770102T3 (es) * 2016-02-23 2020-06-30 Padlock Therapeutics Inc Inhibidores de heteroarilo de PAD4
DK3697785T3 (da) * 2017-10-18 2023-04-03 Jubilant Epipad LLC Imidazo-pyridine forbindelser som pad-inhibitorer
JP7447080B2 (ja) * 2018-08-08 2024-03-11 ブリストル－マイヤーズ スクイブ カンパニー Ｐａｄ４阻害剤としての置換チエノピロール

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WO2014015905A1 (fr) * 2012-07-26 2014-01-30 Glaxo Group Limited 2-(azaindol-2-yl)benzimidazoles utilisés comme inhibiteurs de pad4
WO2016185279A1 (fr) * 2015-05-21 2016-11-24 Glaxosmithkline Intellectual Property Development Limited Dérivés de benzoimidazole en tant qu'inhibiteurs de pad4
WO2017100594A1 (fr) * 2015-12-09 2017-06-15 Padlock Therapeutics, Inc. Inhibiteurs bicycliques de pad4
WO2019161803A1 (fr) * 2018-02-26 2019-08-29 南京药捷安康生物科技有限公司 Inhibiteur de peptidylarginine déiminase et son utilisation

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11976083B2 (en) 2020-04-30 2024-05-07 Gilead Sciences, Inc. Inhibitors of peptidylarginine deiminases
US11878965B2 (en) 2020-12-22 2024-01-23 Gilead Sciences, Inc. Inhibitors of peptidylarginine deiminases

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