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EP-4741376-A1 - NITROGEN-CONTAINING HETEROCYCLIC DERIVATIVE INHIBITOR, AND PREPARATION METHOD THEREFOR AND USE THEREOF

EP4741376A1EP 4741376 A1EP4741376 A1EP 4741376A1EP-4741376-A1

Abstract

The present invention relates to a nitrogen-containing heterocyclic derivative inhibitor, and a preparation method therefor and the use thereof. In particular, the present invention relates to a compound as represented by general formula (I), a preparation method therefor, a pharmaceutical composition containing the compound, and the use thereof as an inhibitor in the treatment of diseases such as cardiovascular diseases and cerebrovascular diseases, wherein the definition of each substituent in general formula (I) is the same as that defined in the description.

Inventors

  • DENG, Xinxian
  • DONG, JIAQIANG
  • YU, WENSHENG
  • JIN, Fangfang
  • WANG, Tingjun

Assignees

  • Shanghai Hansoh Biomedical Co., Ltd.
  • Jiangsu Hansoh Pharmaceutical Group Co., Ltd.

Dates

Publication Date
20260513
Application Date
20240704

Claims (17)

  1. A compound as represented by general formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof: characterised in that ring A is selected from ring B is selected from C 3-12 cycloalkyl, 3- to 12-membered heterocyclyl, C 6-14 aryl, or 5- to 14-membered heteroaryl; L 1 is selected from a bond, -(CH 2 ) n -, -(CH 2 ) n C(O)(CR aa R bb ) n1 -, - (CH 2 ) n C(O)NR aa (CH 2 ) n1 -, -(CH 2 ) n (CR aa R bb ) n2 -, -(CR aa R bb ) n O(CH 2 ) n1 -, - (CH 2 ) n O(CR aa R bb ) n1 -, -(CR aa R bb ) n3 S(CH 2 ) n4 -, -(CH 2 ) n S(CR aa R bb ) n3 -, - (CR aa R bb ) n3 (CH 2 ) n NR cc -, -(CH 2 ) n NR aa (CR bb R cc ) n -, -(CH 2 ) n NR aa C(O)-, - (CH 2 ) n P(O) p R aa -, -(CH 2 ) n S(O) m -, -(CH 2 ) n C(O)NR aa R bb -, -(CH 2 ) n NR cc C(O)R dd -, - (CH 2 ) n S(O) m NR aa R bb -, and -(CH 2 ) n NR cc S(O) m R dd -; R aa , R bb , R cc and R dd are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, deuteroalkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, deuteroalkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; alternatively, any two adjacent or non-adjacent substituents are connected to form cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl, or heteroaryl can be optionally further substituted; preferably, L 1 is selected from a bond, -C(O)-, or -C(O)NH-; R a is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, oxo, thio, alkylthio, deuteroalkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -(CH 2 ) n R A1 , -(CH 2 ) n OR A1 , -(CH 2 ) n C(O) R A1 , -(CH 2 ) n C(O)OR A1 , - (CH 2 ) n S(O) m R A1 , -(CH 2 ) n NR A2 R A3 , -(CH 2 ) n NR A2 C(O)OR A3 , - (CH 2 ) n NR A2 C(O)(CH 2 ) n1 R A3 , -(CH 2 ) n NR A2 C(O)NR A2 R A3 , - (CH2) n C(O)NR A2 (CH2) n1 R A3 , -OC(R A1 R A2 ) n (CH2) n1 R A3 , or -(CH2) n NR A2 S(O) m R A3 , wherein the amino, alkyl, alkenyl, alkynyl, alkylthio, deuteroalkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; R A1 -R A3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, alkyl, deuteroalkyl, haloalkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the amino, alkyl, deuteroalkyl, haloalkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; alternatively, any two adjacent or non-adjacent R a are connected to form cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; R b is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, oxo, thio, deuteroalkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, - (CH 2 ) n R B1 , -(CH 2 ) n OR B1 , -(CH 2 ) n C(O) R B1 , -(CH 2 ) n C(O)O R B1 , -(CH 2 ) n S(O) m R B1 , -(CH 2 ) n NR B2 R B3 , -(CH 2 ) n NR B2 C(O)OR B3 , -(CH 2 ) n NR B2 C(O)(CH 2 ) n1 R B3 , - (CH 2 ) n NR B2 C(O)NR B2 R B3 , -(CH 2 ) n C(O)NR B2 (CH 2 ) n1 R B3 , -OC(R B1 R B2 ) n (CH 2 ) n1 R B3 , or -(CH 2 ) n NR B2 S(O) m R B3 , wherein the amino, alkyl, alkenyl, alkynyl, deuteroalkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; R B1 -R B3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, alkyl, deuteroalkyl, haloalkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the amino, alkyl, deuteroalkyl, haloalkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; alternatively, any two adjacent or non-adjacent R b are connected to form cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; R c is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, oxo, thio, deuteroalkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, - (CH 2 ) n R C1 , -(CH 2 ) n OR C1 , -(CH 2 ) n C(O) R C1 , -(CH 2 ) n C(O)O R C1 , -(CH 2 ) n S(O) m R C1 , -(CH 2 ) n NR C2 R C3 , -(CH 2 ) n NR C2 C(O)OR C3 , -(CH 2 ) n NR C2 C(O)(CH 2 ) n1 R C3 , - (CH 2 ) n NR C2 C(O)NR C2 R C3 , -(CH 2 ) n C(O)NR C2 (CH 2 ) n1 R C3 , -OC(R C1 R C2 ) n (CH 2 ) n1 R C3 , or -(CH 2 ) n NR C2 S(O) m R C3 , wherein the amino, alkyl, alkenyl, alkynyl, deuteroalkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; R C1 -R C3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, alkyl, deuteroalkyl, haloalkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the amino, alkyl, deuteroalkyl, haloalkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; alternatively, any two adjacent or non-adjacent R c are connected to form cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; R d is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, alkyl, alkenyl, alkynyl, oxo, thio, deuteroalkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, - (CH 2 ) n R D1 , -(CH 2 ) n OR D1 , -(CH 2 ) n C(O) R D1 , -(CH 2 ) n C(O)O R D1 , -(CH 2 ) n S(O) m R D1 , -(CH 2 ) n NR D2 R D3 , -(CH 2 ) n NR D2 C(O)OR D3 , -(CH 2 ) n NR D2 C(O)(CH 2 ) n1 R D3 , - (CH 2 ) n NR D2 C(O)NR D2 R D3 , -(CH 2 ) n C(O)NR D2 (CH 2 ) n1 R D3 , - OC(R D1 R D2 ) n (CH 2 ) n1 R D3 , or -(CH 2 ) n NR D2 S(O) m R D3 , wherein the amino, alkyl, alkenyl, alkynyl, deuteroalkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; R D1 -R D3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, alkyl, deuteroalkyl, haloalkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the amino, alkyl, deuteroalkyl, haloalkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; alternatively, any two adjacent or non-adjacent R d are connected to form cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; alternatively, any two R c and R d are connected to form cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl, and heteroaryl can be optionally further substituted; x is 0, 1, 2, or 3; y is 0, 1, 2, or 3; z is 0, 1, 2, or 3; e is 0, 1, 2, or 3; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; n1 is 0, 1, 2, 3, or 4; n2 is 0, 1, 2, 3, or 4; n3 is 0, 1, 2, 3, or 4; and n4 is 0, 1, 2, 3, or 4.
  2. The compound or the stereoisomer or pharmaceutically acceptable salt thereof according to claim 1, characterised in that the compound is further as represented by general formula (I-A): wherein ring B is selected from C 3-6 cycloalkyl, phenyl, 5-membered nitrogen-containing heterocyclyl, 6-membered nitrogen-containing heterocyclyl, 5-membered nitrogen-containing heteroaryl, 6-membered nitrogen-containing heteroaryl, 5-membered fused 5-membered bicyclic nitrogen-containing heteroaryl, 5-membered fused 6-membered bicyclic nitrogen-containing heteroaryl, 6-membered fused 5-membered bicyclic nitrogen-containing heteroaryl, 6-membered fused 6-membered bicyclic nitrogen-containing heteroaryl, 5-membered fused 5-membered bicyclic nitrogen-containing heterocyclyl, 5-membered fused 6-membered bicyclic nitrogen-containing heterocyclyl, 6-membered fused 5-membered bicyclic nitrogen-containing heterocyclyl or 6-membered fused 6-membered bicyclic nitrogen-containing cycloaryl; R c-1 is selected from halogen, amino, hydroxyl, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, oxo, thio, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, 5- to 12-membered heteroaryl, -(CH 2 ) n R C1 , -(CH 2 ) n OR C1 , -(CH 2 ) n C(O)R C1 , -(CH 2 ) n C(O)OR C1 , -(CH 2 ) n S(O) m R C1 , - (CH 2 ) n NR C2 R C3 , -(CH 2 ) n NR C2 C(O)OR C3 , -(CH 2 ) n NR C2 C(O)(CH 2 ) n1 R C3 , - (CH 2 ) n NR C2 C(O)NR C2 R C3 , -(CH 2 ) n C(O)NR C2 (CH 2 ) n1 R C3 , -OC(R C1 R C2 ) n (CH 2 ) n1 R C3 , or -(CH 2 ) n NR C2 S(O) m R C3 , wherein the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted and can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; R C1 -R C3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, or 5- to 12-membered heteroaryl, wherein the amino, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 1-3 hydroxyalkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; preferably, R c-1 is selected from -F, -Cl, -O-CH 3 , -CN, -CF 3 , -CH 3 , -O-CF 3 , -O-CH 3 , -O-CH(CH 3 ) 2 , R c-2 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, oxo, thio, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, 5- to 12-membered heteroaryl, -(CH 2 ) n R C1 , -(CH 2 ) n OR C1 , -(CH 2 ) n C(O)R C1 , - (CH 2 ) n C(O)OR C1 , -(CH 2 ) n S(O) m R C1 , -(CH 2 ) n NR C2 R C3 , -(CH 2 ) n NR C2 C(O)OR C3 , - (CH 2 ) n NR C2 C(O)(CH 2 ) n1 R C3 , -(CH 2 ) n NR C2 C(O)NR C2 R C3 , - (CH 2 ) n C(O)NR C2 (CH 2 ) n1 R C3 , -OC(R C1 R C2 ) n (CH 2 ) n1 R C3 , or -(CH 2 ) n NR C2 S(O) m R C3 , wherein the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted and can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; R C1 -R C3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, or 5- to 12-membered heteroaryl, wherein the amino, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 1-3 hydroxyalkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; preferably, R c-2 is selected from -H, -F, -Cl, -O-CH 3 , -CN, -CF 3 , -CH 3 , -O-CF 3 , -O-CH 3 , -O-CH(CH 3 ) 2 , R c-3 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, oxo, thio, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, 5- to 12-membered heteroaryl, -(CH 2 ) n R C1 , -(CH 2 ) n OR C1 , -(CH 2 ) n C(O)R C1 , - (CH 2 ) n C(O)OR C1 , -(CH 2 ) n S(O) m R C1 , -(CH 2 ) n NR C2 R C3 , -(CH 2 ) n NR C2 C(O)OR C3 , - (CH 2 ) n NR C2 C(O)(CH 2 ) n1 R C3 , -(CH 2 ) n NR C2 C(O)NR C2 R C3 , - (CH 2 ) n C(O)NR C2 (CH 2 ) n1 R C3 , -OC(R C1 R C2 ) n (CH 2 ) n1 R C3 , or -(CH 2 ) n NR C2 S(O) m R C3 , wherein the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted and can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; R C1 -R C3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, or 5- to 12-membered heteroaryl, wherein the amino, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 1-3 hydroxyalkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; preferably, R c-3 is selected from -H, -F, -Cl, -O-CH 3 , -CN, -CF 3 , -CD 3 , -CH 3 , - O-CF 3 , -O-CH 3 , -O-CH(CH 3 ) 2 , more preferably, R c-3 is selected from -H, -F, -Cl, -O-CH 3 , -CN, -CF 3 , -CH 3 , - O-CF 3 , -O-CH 3 , -O-CH(CH 3 ) 2 , m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; n1 is 0, 1, 2, 3, or 4.
  3. The compound or the stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-2, characterised in that the compound is further as represented by general formula (I-A-1):
  4. The compound or the stereoisomer or pharmaceutically acceptable salt thereof according to claim 1, characterised in that the compound is further as represented by general formula (I-2'): wherein L 1 is selected from a bond, -C(O)-, -C(O)NH-, -C(O)NCH 3 -, or -C(O)N(CH 3 ) 2 ; M 5 is selected from N or CR 5 ; R 5 is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, oxo, thio, C 1-6 alkylthio, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-12 aryl, and 5- to 14-membered heteroaryl, wherein the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkylthio, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-12 aryl, and 5- to 14-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl.
  5. The compound or the stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-4, characterised in that the compound is further as represented by general formula (I-1-a): further preferably, the compound is as represented by wherein R a-1 -R a-4 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, oxo, thio, C 1-6 alkylthio, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-12 aryl, 5- to 14-membered heteroaryl, -(CH 2 ) n R A1 , -(CH 2 ) n OR A1 , - (CH 2 ) n C(O)R A1 , -(CH 2 ) n C(O)OR A1 , -(CH 2 ) n S(O) m R A1 , -(CH 2 ) n NR A2 R A3 , - (CH 2 ) n NR A2 C(O)OR A3 , -(CH 2 ) n NR A2 C(O)(CH 2 ) n1 R A3 , -(CH 2 ) n NR A2 C(O)NR A2 R A3 , -(CH 2 ) n C(O)NR A2 (CH 2 ) n1 R A3 , -OC(R A1 R A2 ) n (CH 2 ) n1 R A3 , or -(CH 2 ) n NR A2 S(O) m R A3 , wherein the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkylthio, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-12 aryl, and 5- to 14-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl, and the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 3-8 cycloalkyl, 3-to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; R A1 -R A3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 deuteroalkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3- to 12-membered heterocyclyl, C 6-14 aryl, or 5- to 14-membered heteroaryl, wherein the amino, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3- to 12-membered heterocyclyl, C 6-14 aryl, and 5- to 14-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-6 alkyl, C 1-6 deuteroalkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 deuteroalkoxy, C 1-6 haloalkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, 3- to 12-membered heterocyclyl, C 6-14 aryl, and 5- to 14-membered heteroaryl; m is 0, 1, or 2; n is 0, 1, 2, 3, or 4; and n1 is 0, 1, 2, 3, or 4.
  6. The compound or the stereoisomer or pharmaceutically acceptable salt thereof according to either claim 1 or 5, characterised in that ring B is selected from C 3-6 cycloalkyl, phenyl, 3- to 8-membered heterocyclyl, 7- to 10-membered bicyclic heterocyclyl, 5-membered heteroaryl, 6-membered heteroaryl, 5-membered fused 5-membered bicyclic heteroaryl, 5-membered fused 6-membered bicyclic heteroaryl, 6-membered fused 5-membered bicyclic heteroaryl, or 6-membered fused 6-membered bicyclic heteroaryl; more preferably, ring B is selected from C 3-6 cycloalkyl, phenyl, 5-membered nitrogen-containing heterocyclyl, 6-membered nitrogen-containing heterocyclyl, 7-to 10-membered bicyclic heterocyclyl, 5-membered nitrogen-containing heteroaryl, 6-membered nitrogen-containing heteroaryl, 5-membered fused 5-membered bicyclic nitrogen-containing heteroaryl, 5-membered fused 6-membered bicyclic nitrogen-containing heteroaryl, 6-membered fused 5-membered bicyclic nitrogen-containing heteroaryl, or 6-membered fused 6-membered bicyclic nitrogen-containing heteroaryl; further preferably, ring B is selected from pyridine, pyrimidine, pyridone, or pyrimidinone; further preferably, ring B is selected from pyridine, pyrimidine, benzene,
  7. The compound or the stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-4 or 6, characterised in that R a is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, oxo, thio, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, 5- to 12-membered heteroaryl, -(CH 2 ) n R A1 , -(CH 2 ) n OR A1 , -(CH 2 ) n C(O)R A1 , - (CH 2 ) n C(O)OR A1 , -(CH 2 ) n S(O) m R A1 , -(CH 2 ) n NR A2 R A3 , -(CH 2 ) n NR A2 C(O)OR A3 , - (CH 2 ) n NR A2 C(O)(CH 2 ) n1 R A3 , -(CH 2 ) n NR A2 C(O)NR A2 R A3 , - (CH 2 ) n C(O)NR A2 (CH 2 ) n1 R A3 , -OC(R A1 R A2 ) a (CH 2 ) n1 R A3 , or -(CH 2 ) n NR A2 S(O) m R A3 , wherein the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted and can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; R A1 -R A3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, or 5- to 12-membered heteroaryl, wherein the amino, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 1-3 hydroxyalkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; preferably, R a is selected from -H, -O-CHF 2 , -O-CF 3 , -O-CF 2 Cl, -O-CF 2 Br, -O-CH 2 -CHF 2 , -O-CH 2 -CF 3 -CHF 2 , -CF 3 , -CH 2 -OH, -CH 2 -CHF 2 , -CH(CH 3 )-OH, -(CH 2 ) 3 -OH, - C(CH 3 ) 2 -OH, -OH, -O-CH 3 , -CH 3 , -CF 3 , -F, -Cl, -CN, -NHCH 3 , -NH 2 , and/or, R c is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, oxo, thio, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, 5- to 12-membered heteroaryl, -(CH 2 ) n R C1 , -(CH 2 ) n OR C1 , -(CH 2 ) n C(O)R C1 , - (CH 2 ) n C(O)OR C1 , -(CH 2 ) n S(O) m R C1 , -(CH 2 ) n NR C2 R C3 , -(CH 2 ) n NR C2 C(O)OR C3 , - (CH 2 ) n NR C2 C(O)(CH 2 ) n1 R C3 , -(CH 2 ) n NR C2 C(O)NR C2 R C3 , - (CH 2 ) n C(O)NR C2 (CH 2 ) n1 R C3 , -OC(R C1 R C2 ) n (CH 2 ) n1 R C3 , or -(CH 2 ) n NR C2 S(O) m R C3 , wherein the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted and can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; R C1 -R C3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, or 5- to 12-membered heteroaryl, wherein the amino, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 1-3 hydroxyalkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; preferably, R c is selected from -H, -F, -Cl, -O-CH 3 , -CN, -CF 3 , -CH 3 , -O-CF 3 , -O-CH 3 , -O-CH(CH 3 ) 2 ,
  8. The compound or the stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-6, characterised in that R b is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, oxo, thio, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, 5- to 12-membered heteroaryl, -(CH 2 ) n R B1 , -(CH 2 ) n OR B1 , -(CH 2 ) n C(O)R B1 , - (CH 2 ) n C(O)OR B1 , -(CH 2 ) n S(O) m R B1 , -(CH 2 ) n NR B2 R B3 , -(CH 2 ) n NR B2 C(O)OR B3 , - (CH 2 ) n NR B2 C(O)(CH 2 ) n1 R B3 , -(CH 2 ) n NR B2 C(O)NR B2 R B3 , - (CH 2 ) n C(O)NR B2 (CH 2 ) n1 R B3 , -OC(R B1 R B2 ) n (CH 2 ) n1 R B3 , or -(CH 2 ) n NR B2 S(O) m R B3 , wherein the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted and can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; R B1 -R B3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, or 5- to 12-membered heteroaryl, wherein the amino, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 1-3 hydroxyalkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; preferably, R b is selected from -H or -F; and/or R d is selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, oxo, thio, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, 5- to 12-membered heteroaryl, -(CH 2 ) n R D1 , -(CH 2 ) n OR D1 , -(CH 2 ) n C(O)R D1 , - (CH 2 ) n C(O)OR D1 , -(CH 2 ) n S(O) m R D1 , -(CH 2 ) n NR D2 R D3 , -(CH 2 ) n NR D2 C(O)OR D3 , - (CH 2 ) n NR D2 C(O)(CH 2 ) n1 R D3 , -(CH 2 ) n NR D2 C(O)NR D2 R D3 , - (CH 2 ) n C(O)NR D2 (CH 2 ) n1 R D3 , -OC(R D1 R D2 ) n (CH 2 ) n1 R D3 , or -(CH 2 ) n NR D2 S(O) m R D3 , wherein the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted and can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; R D1 -R D3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, or 5- to 12-membered heteroaryl, wherein the amino, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 1-3 hydroxyalkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; preferably, R d is selected from -H, -D, -F, -Cl, -CN, -CH 3 , -CF 3 , -CH(CH 3 ) 2 , -C(CH 3 ) 3 , - C(CH 3 ) 2 -OH, -C(CH 3 ) 2 - CH 2 -OH, -O-CH 3 , -CH 2 -NH 2 , -CH 2 -OH, -NH 2 , -OH,
  9. The compound or the stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 5-6, characterised in that R a-1 -R a-4 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxyl, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, oxo, thio, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, 5- to 12-membered heteroaryl, -(CH 2 ) n R A1 , -(CH 2 ) n OR A1 , -(CH 2 ) n C(O)R A1 , - (CH 2 ) n C(O)OR A1 , -(CH 2 ) n S(O) m R A1 , -(CH 2 ) n NR A2 R A3 , -(CH 2 ) n NR A2 C(O)OR A3 , - (CH 2 ) n NR A2 C(O)(CH 2 ) n1 R A3 , -(CH 2 ) n NR A2 C(O)NR A2 R A3 , - (CH2) n C(O)NR A2 (CH2) n1 R A3 , -OC(R A1 R A2 ) n (CH2) n1 R A3 , or -(CH2) n NR A2 S(O) m R A3 , wherein the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkylthio, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted and can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; the amino, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 10-membered heteroaryl; R A1 -R A3 are each independently selected from hydrogen, deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, or 5- to 12-membered heteroaryl, wherein the amino, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 1-3 hydroxyalkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl can be optionally further substituted with one or more substituents of deuterium, halogen, nitro, hydroxyl, mercapto, cyano, amino, oxo, thio, carboxyl, C 1-3 alkyl, C 1-3 deuteroalkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 deuteroalkoxy, C 1-3 haloalkoxy, C 2-4 alkenyl, C 2-4 alkynyl, C 3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C 6-10 aryl, and 5- to 12-membered heteroaryl; preferably, R a-1 -R a-4 are each independently selected from -H, -O-CHF 2 , -O-CF 3 , -O-CF 2 Cl, -O-CF 2 Br, -O-CH 2 -CHF 2 , -O-CH 2 -CF 3 , -CHF 2 , -CF 3 , -CH 2 -OH, -CH 2 -CHF 2 , - CH(CH 3 )-OH, -(CH 2 ) 3 -OH, -C(CH 3 ) 2 -OH, -OH, -O-CH 3 , -CH 3 , -CF 3 , -F, -Cl, -CN, -NHCH 3 , -NH 2 , -CH 2 -CF 3 ,
  10. The compound as represented by general formula (I) or the stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-9, characterised in that the compound is selected from the following compounds: or
  11. A compound as represented by general formula (IV) or a stereoisomer or pharmaceutically acceptable salt thereof: characterised in that X 2 is amino, nitro, halogen, boronic acid, or boronate; the other groups are each as defined in claim 2.
  12. The compound as represented by general formula (IV) or the stereoisomer or pharmaceutically acceptable salt thereof according to claim 11, characterised in that the compound is selected from the following compounds:
  13. A method for preparing the compound as represented by general formula (I-A) according to claim 2, characterised in that the method comprises the following step: wherein X 3 is hydroxyl, amino, methylthio, halogen, boronic acid, or a boronate; a compound as represented by general formula (IV) reacts with a compound as represented by general formula (IV-1) to obtain the compound as represented by general formula (I-A); and the other groups are each as defined in claim 2.
  14. A pharmaceutical composition, characterised in that the pharmaceutical composition comprises a therapeutically effective dose of the compound as represented by general formula (I) or the stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-10, and one or more pharmaceutically acceptable carriers, diluents, or excipients.
  15. Use of the compound as represented by general formula (I) or the stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-10 or the pharmaceutical composition according to claim 14 in the preparation of a PCSK9 inhibitor drug.
  16. Use of the compound as represented by general formula (I) or the stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-10 or the pharmaceutical composition according to claim 14 in the preparation of an LDL-lowering drug.
  17. Use of the compound as represented by general formula (I) or the stereoisomer or pharmaceutically acceptable salt thereof according to any one of claims 1-10 or the pharmaceutical composition according to claim 14 in the preparation of a drug for treating a cardiovascular disease, a cerebrovascular disease, atherosclerosis and/or a related disease thereof or a symptom thereof; preferably in the preparation of a drug for stroke, hypercholesterolemia, hyperlipidaemia, hyperlipoproteinemia, hypertriglyceridemia, dyslipidaemia, abnormal lipoproteinemia, atherosclerosis, hepatic steatosis, metabolic syndrome and/or coronary artery disease.

Description

The present application claims the right of priority forCN202310818758.5 filed on July 04, 2023;CN 202311011109.0 filed on August 10, 2023;CN 202311227801.7 filed on September 21, 2023;CN 202311552677.1 filed on November 17, 2023;CN 202410052828.5 filed on January 12, 2024;CN 202410173281.4 filed on February 06, 2024;CN 202410407937.4 filed on April 03, 2024; andCN 202410426055.2 filed on April 09, 2024. Technical Field The present disclosure belongs to the field of drug synthesis and specifically relates to a nitrogen-containing heterocyclic derivative inhibitor, and a preparation method therefor and the use thereof. Background Art Cardiovascular disease (CVD) is the leading cause of death in the world, and a high level of low-density lipoprotein cholesterol (LDL-C) is the main risk factor. The accumulation of LDL-C on the inner wall of arteries leads to atherosclerosis and may cause an inflammatory response, leading to cardiovascular events such as heart attack and stroke. Statins can reduce serum LDL-C and are main lipid-lowering drugs in clinic at present. However, patients who are intolerant to statins or who fail to achieve the therapeutic goal when receiving a tolerant dose of treatment, e.g., patients with familial hypercholesterolemia, are still at risk. The discovery of PCSK9 inhibitors provides a more positive treatment method for homozygous and heterozygous patients with familial hypercholesterolemia. Non-statin Ezetimibe combined with a statin can reduce LDL-C by 15-20%, whereas a PCSK9 inhibitor combined with a statin can significantly reduce LDL-C by 54-74%. PCSK9 inhibitors can also overcome unbearable side effects of statins, e.g., symptoms such as muscle pain. PCSK9 (Proprotein convertase subtilisin kexin type 9) is a serine protease, which is highly expressed in liver. Loss-of- function mutation in PCSK9 gene is related to a low level of LDL-C and a reduced cardiovascular risk (Cohen, J.C., 2006) and has been clinically confirmed to be a therapeutic target for hyperlipidaemia. PCSK9 is synthesised as an enzyme precursor that, after synthesis, undergoes autocatalytic cleavage in a cell, and the mature PCSK9 binds to a propeptide and is secreted to the extracellular space. The binding to the propeptide blocks the catalytic activity of PCSK9. PCSK9 is a main regulator for the level of low-density lipoprotein receptor (LDLR) on the surface of hepatocytes and can inhibit the circulating pathway of LDLR. The function of LDLR is the key to maintain cholesterol homeostasis, and it is responsible for the uptake and degradation of low-density lipoprotein. Circulating LDL binds to an N-terminal ligand binding domain of LDLR via apolipoprotein B100, and the LDL/LDLR complex is internalised by means of receptor-mediated endocytosis. A low-pH environment in the cell causes the LDLR to release LDL, the LDLR circulates back to the cell membrane, and the intracellular free LDL is sent to lysosomes and degraded. Secreted PCSK9 interferes with the circulating ability of LDLR by binding to LDLR on the surface of hepatocytes. After the PCSK9/LDLR complex migrates to acidic endosomal compartments via clathrin-coated pits, the conformational change of LDLR leads to the formation of additional binding sites with PCSK9. Therefore, PCSK9 accompanies LDLR to lysosomes for degradation, preventing LDLR circulation, thus up-regulating the LDL-C level. Familial hypercholesterolemia (FH) is a genetic disease of low-density lipoprotein cholesterol metabolism, which affects one in every 250 people and is characterised by a significant increase in the LDL-C level. The risk of coronary heart disease (CAD) in heterozygous patients with FH is 3-4 times that in normal people, and CAD often occurs 10 years earlier than in normal people on average. Statins can reduce the low-density lipoprotein cholesterol in heterozygous patients with FH. In Besseling's research, it is believed that a high-intensity statin therapy can reduce the risk and mortality of coronary heart disease by 44%. However, in many cases, the reduction of LDL-C is considered insufficient. The compensatory mechanism of statins involves up-regulating sterol regulatory element-binding protein 2 (SREBP-2) to thus activate LDL receptor and PCSK9, increase the expression and secretion of PCSK9 which will bind to LDLR, leading to an elevated LDL-C level in blood. Therefore, although statins can reduce LDL by inhibiting HMGCoA, the effect thereof on SREPB counteracts and balances this reduction. Adding a PCSK9 inhibitor to a statin therapy can help overcome this mechanism. Considering that patients with familial hypercholesterolemia may not fully benefit from statin therapies, alternative treatment approaches such as PCSK9 inhibitors are needed. Macromolecular PCSK9 inhibitors, Alirocumab and Evolocumab based on monoclonal antibodies, which can selectively bind to extracellular PCSK9 and prevent the interaction thereof with LDLR, have been approved by FDA for reducing t