IP Library › Granted Patent US 12703701

Granted Patent B2

US 12703701 · App. 17/784,256 · Granted Aug 11, 2026

Pyrazole-containing polycyclic derivative inhibitor, preparation method therefor and application thereof

Inventors: Hualing Xiao (Shanghai, CN); Qiang Liu (Shanghai, CN); Xingyun Lu (Shanghai, CN); Jiaqiang Cai (Shanghai, CN); Rudi Bao (Shanghai, CN)

Assignees: Shanghai Hansoh Biomedical Co., Ltd.; Jiangsu Hansoh Pharmaceutical Group Co., Ltd.

C07D471/14 C07D498/14 C07D513/14

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Quick Facts

Patent No.: US 12703701
App. No.: 17/784,256
Granted: Aug 11, 2026
Kind: B2

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Abstract

Provided are a pyrazole-containing polycyclic derivative inhibitor, a preparation method therefor and an application thereof. In particular, provided are a compound as represented by formula (I), a preparation method therefor, a pharmaceutical composition containing the compound, and an application thereof as a P2X3 inhibitor in treatment of P2X3 receptor function disorders, particularly in treatment of neurogenic diseases, wherein the substituents in the formula (I) are the same as those in the description in definition.

Claims (126)

1 . A compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

wherein:

L 1 is selected from the group consisting of a bond, —(CH 2 ) n1 —, —(CH 2 ) n1 C(O)(CR aa R bb ) n2 —, —(CH 2 ) n1 C(O)NR aa (CH 2 ) n2 —, —(CH 2 ) n1 (CR aa R bb ) n2 —, —(CR aa R bb ) n1 O(CH 2 ) n2 —, —(CH 2 ) n1 O(CR aa R bb ) n2 —, —(CR aa R bb ) n1 S(CH 2 ) n2 —, —(CH 2 ) n1 S(CR aa R bb ) n2 —, —(CR aa R bb ) n1 (CH 2 ) n2 NR cc —, —(CH 2 ) n1 NR aa (CR bb R cc ) n2 —, —(CH 2 ) n1 NR aa C(O)—, —(CH 2 ) n1 P(O)R aa —, —(CH 2 ) n1 S(O) n2 —, —(CH 2 ) n1 S(O) n2 NR aa — and —(CH 2 ) n1 NR aa S(O) n2 —;

R aa , R bb , R cc are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy can be each optionally further substituted;

or, any two of R aa , R bb , R cc are bonded to form a cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl can be optionally further substituted;

L 2 is selected from the group consisting of —(CH 2 ) n3 C(O)(CR dd R ee ) n4 —, —(CH 2 ) n3 C(O)NR dd (CH 2 ) n4 —, —(CR dd R ee ) n3 O(CH 2 ) n4 —, —(CH 2 ) n3 O(CR dd R ee ) n4 —, —(CR dd R ee ) n3 S(CH 2 ) n4 —, —(CH 2 ) n3 S(CR dd R ee ) n4 —, —(CR dd R ee ) n3 (CH 2 ) n4 NR ff —, —(CH 2 ) n3 NR dd (CR ee R ff ) n4 —, —(CH 2 ) n3 NR dd C(O)—, —(CH 2 ) n3 P(O)R dd —, —(CH 2 ) n3 S(O) n4 —, —(CH 2 ) n3 S(O) n4 NR dd — and —(CH 2 ) n3 NR dd S(O) n4 —;

R dd , R ee , R ff are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy can be each optionally further substituted;

or, any two of R dd , R ee , R ff are bonded to form a cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl can be optionally further substituted;

ring A is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl;

R 1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy can be each optionally further substituted;

ring B is selected from the group consisting of cycloalkyl, heterocyclyl and heteroaryl;

R 2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy can be each optionally further substituted;

R 3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl can be each optionally further substituted;

R a is selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thioxo, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH 2 ) n5 R gg , —(CH 2 ) n5 OR gg , —(CH 2 ) n5 C(O)OR gg , —(CH 2 ) n5 SR gg , —(CH 2 ) n5 NR gg C(O)(CH 2 ) n6 R hh , —(CH 2 ) n5 NR gg C(O)OR hh , —(CH 2 ) n5 NR gg C(O)NR hh R ii , —(CH 2 ) n5 NR gg R hh , —NR gg (CH 2 ) n5 R hh , —(CH 2 ) n5 C(O)NR gg (CH 2 ) n6 R hh , —(CH 2 ) n5 S(O) n6 R gg , —(CH 2 ) n5 NR gg S(O) n6 R hh , —CH═CH(CH 2 ) n5 R gg , —CH═CH(CH 2 ) n5 NR gg R hh , —CH═CH(CH 2 ) n5 NR gg C(O)R hh and —CH═CH(CH 2 ) n5 NR gg C(O)NR hh R ii , wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl can be each optionally further substituted;

R gg , R hh , R ii are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy can be each optionally further substituted;

or, any two of R gg , R hh , R ii are bonded to form a cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl can be optionally further substituted;

x is an integer from 0 to 6;

e is an integer from 0 to 6;

n1, n3, and n5 are each independently an integer from 0 to 3; and

n2, n4, and n6 are each independently an integer from 0 to 2.

2 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , wherein

R aa , R bb , R cc are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 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 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl;

or, any two of R aa , R bb , R cc are bonded to form a C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl or 5 to 14 membered heteroaryl, wherein the C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl or 5 to 14 membered heteroaryl is optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl;

n1 is an integer from 0 to 3; and

n2 is an integer from 0 to 2.

3 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , wherein

R dd , R ee , R ff are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 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 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl;

or, any two of R dd , R ee , R ff are bonded to form a C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl or 5 to 14 membered heteroaryl, wherein the C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl or 5 to 14 membered heteroaryl is optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl;

n3 is an integer from 0 to 3; and

n4 is an integer from 0 to 2.

4 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , wherein ring A is selected from the group consisting of C 3-8 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl.

5 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , wherein

R 1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl, C 6-14 aryloxy, 5 to 14 membered heteroaryl and 5 to 14 membered heteroaryloxy, wherein the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl, C 6-14 aryloxy, 5 to 14 membered heteroaryl and 5 to 14 membered heteroaryloxy are each optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl, C 6-14 aryloxy, 5 to 14 membered heteroaryl, 5 to 14 membered heteroaryloxy, —(CH 2 ) m1 OR a , —(CH 2 ) m1 SR a , —(CH 2 ) m1 C(O)R a , —(CH 2 ) m1 NR a R b , —(CH 2 ) m1 C(O)NR a R b , —(CH 2 ) m1 NR a C(O)R b and —(CH 2 ) m1 S(O) m2 R a ;

R a and R b are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 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 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl;

or, R a and R b are bonded to form a C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl or 5 to 14 membered heteroaryl, wherein the C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl or 5 to 14 membered heteroaryl is optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl;

m1 is an integer from 0 to 3; and

m2 is an integer from 0 to 2.

6 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , wherein

R 2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl.

7 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , wherein,

R 3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl.

8 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , wherein,

R a is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, oxo, thioxo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl, 5 to 14 membered heteroaryl, —(CH 2 ) n5 R gg , —(CH 2 ) n5OR gg , —(CH 2 ) n5 C(O)OR gg , —(CH 2 ) n5 SR gg , —(CH 2 ) n5 NR gg C(O)(CH 2 ) n6 R hh , —(CH 2 ) n5 NR gg C(O)OR hh , —(CH 2 ) n5 NR gg C(O)NR hh R ii , (CH 2 ) n5 NR gg R hh , —NR gg (CH 2 ) n5 R hh , and —(CH 2 ) n5 C(O)NR gg (CH 2 ) n6 R hh ;

R gg , R hh , R ii are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 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 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl;

or, any two of R gg , R hh , R ii are bonded to form a C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl or 5 to 14 membered heteroaryl, wherein the C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl or 5 to 14 membered heteroaryl is optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl;

n5 is an integer from 0 to 3; and

n6 is an integer from 0 to 2.

9 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , wherein ring B is shown as following:

wherein:

M 1 , M 2 , M 3 and M 4 are each independently selected from the group consisting of —CR A1 —, —C(O)—, —N—, —CR A1 R A2 — and —NR A3 —; and at least one of M 1 , M 2 , M 3 and M 4 is N;

R A1 , R A2 , R A3 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy can be each optionally further substituted.

10 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 9 , wherein,

M 1 is N, and M 2 , M 3 and M 4 are each independently CR A1 ;

R A1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3 to 8 membered heterocyclyl containing 1 to 3 atoms selected from the group consisting of N, O and S, C 6-10 aryl and 5 to 10 membered heteroaryl containing 1 to 3 atoms selected from the group consisting of N, O and S.

11 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , wherein ring B is shown as following:

wherein:

M 6 , M 7 and M 8 are each independently selected from the group consisting of —CR A4 —, —C(O)—, —N—, —O—, —S—, —CR A4 R A5 — and —NR A6 —;

R A4 , R A5 , R A6 are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy can be each optionally further substituted.

12 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , wherein,

ring A is selected from

M 5 is selected from the group consisting of —N— and —CR 4 —;

R 4 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6 -14 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 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-12 aryl and 5 to 12 membered heteroaryl.

13 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is further shown as formula (II):

wherein e is an integer from 0 to 3.

14 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 13 , wherein the compound is further shown as formula (III):

wherein:

R 5 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, oxo, thioxo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl;

R b is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-8 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl; and

y is an integer from 0 to 3.

15 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 14 , wherein the compound is further shown as formula (IV):

wherein:

ring C is selected from the group consisting of C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl, or ring C is absent;

R c is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl, C 6-14 aryloxy, 5 to 14 membered heteroaryl, 5 to 14 membered heteroaryloxy, —(CH 2 ) m3 OR c , —(CH 2 ) m3 SR c , —(CH 2 ) m3 C(O)R c , —(CH 2 ) m3 NR c R d , —(CH 2 ) m3 C(O)NR c R d , —(CH 2 ) m3 NR c C(O)R d and —(CH 2 ) m3 S(O) m4 R c , wherein the amino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl, C 6-14 aryloxy, 5 to 14 membered heteroaryl and 5 to 14 membered heteroaryloxy are each optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl, C 6-14 aryloxy, 5 to 14 membered heteroaryl and 5 to 14 membered heteroaryloxy;

R c and R d are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 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 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl;

or, R c and R d are bonded to form a C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl or 5 to 14 membered heteroaryl, wherein the C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl or 5 to 14 membered heteroaryl is optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl;

m3 is an integer from 0 to 3;

m4 is an integer from 0 to 2; and

z is an integer from 0 to 6.

16 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 13 , wherein the compound is further shown as formula (V):

wherein:

R 1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 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 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-12 aryl and 5 to 12 membered heteroaryl;

R 2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 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 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 aryl and 5 to 14 membered heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-12 aryl and 5 to 12 membered heteroaryl;

e is an integer from 0 to 3.

17 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 16 , wherein:

R 1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 3-12 cycloalkyl, 3 to 12 membered heterocyclyl, C 6-14 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 deuterated alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 3-8 cycloalkyl, 3 to 8 membered heterocyclyl, C 6-10 aryl and 5 to 10 membered heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, oxo, C 1-3 alkyl, C 2-3 alkenyl, C 2-3 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, 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 10 membered heteroaryl;

R 2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 alkyl, C 2-3 alkenyl, C 2-3 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 1-3 hydroxyalkyl, C 3-8 cycloalkyl, 3 to 8 membered heterocyclyl, C 6-10 aryl and 5 to 10 membered heteroaryl;

R 3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-3 alkenyl, C 2-3 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-8 cycloalkyl, 3 to 8 membered heterocyclyl, C 6-10 aryl and 5 to 10 membered heteroaryl; and

e is an integer from 0 to 3.

18 . A compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, wherein the specific structure of the compound is as follows:

19 . A method for preparing the compound of formula (III), a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 14 , comprising the following step of:

reacting a compound of formula (III-2) with a compound of formula (III-3) to obtain the target compound of formula (III);

wherein:

X 2 is halogen.

20 . A method for preparing the compound of formula (V), a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 16 , comprising the following step of:

reacting a compound of formula (V-2) with a compound of formula (V-3) to obtain the target compound of formula (V);

wherein:

X 5 is halogen.

21 . A pharmaceutical composition comprising a therapeutically effective dose of the compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , and one or more pharmaceutically acceptable carriers or excipients.

22 . A method for treating a neurogenic disease in a patient in need thereof, the method comprising administering to the patient a therapeutically effective dose of the compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the neurogenic disease is selected from neuropathic pain or pain and discomfort related to uterine fibroid.

23 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 14 , wherein:

R b is selected from the group consisting of hydrogen, deuterium, halogen, amino, hydroxy, cyano, C 1-3 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, C 1-3 deuterated alkyl, C 1-3 haloalkyl, C 1-3 hydroxyalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 3-6 cycloalkyl, 3 to 10 membered heterocyclyl, C 6-12 aryl and 5 to 12 membered heteroaryl.

24 . The compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to claim 14 , wherein:

R b is selected from the group consisting of hydrogen, deuterium, fluorine, chlorine, bromine, amino, hydroxy, cyano, methyl, ethyl, propyl, vinyl, propenyl, allyl, ethynyl, propynyl, propargyl, deuterated methyl, deuterated ethyl, deuterated propyl, fluoromethyl, fluoroethyl, fluoropropyl, chloromethyl, chloroethyl, chloropropyl, bromomethyl, bromoethyl, bromopropyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, methoxy, ethoxy, propoxy, fluoromethoxy, fluoroethoxy, fluoropropoxy, chloromethoxy, chloroethoxy, chloropropoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxiranyl, oxetanyl, tetrahydrofuryl, tetrahydropyranyl, oxepanyl, aziridinyl, azetidinyl, azacyclopentyl, azacyclohexyl, azacycloheptyl, thienyl, pyrrolyl, pyridyl, pyranyl, piperazinyl, phenyl and naphthyl.

25 . A compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

wherein:

or, any two of R aa , R bb , R cc are bonded to form a cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl can be optionally further substituted;

L 2 is selected from the group consisting of —(CH 2 ) n3 C(O)(CR dd R ee ) n4 —, (CH 2 ) n3 C(O)NR dd (CH 2 ) n4 —, —(CR dd R ee ) n3 O(CH 2 ) n4 —, —(CH 2 ) n3 O(CR dd R ee ) n4 —, —(CR dd R ee ) n3 S(CH 2 ) n4 —, —(CH 2 ) n3 S(CR dd R ee ) n4 —, —(CR dd R ee ) n3 (CH 2 ) n4 NR ff —, —(CH 2 ) n3 NR dd (CR ee R ff ) n4 —, —(CH 2 ) n3 NR dd C(O)—, —(CH 2 ) n3 P(O)R dd —, —(CH 2 ) n3 S(O) n4 —, —(CH 2 ) n3 S(O) n4 NR dd — and —(CH 2 ) n3 NR dd S(O) n4 —;

or, any two of R dd , R ee , R ff are bonded to form a cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl can be optionally further substituted;

ring A is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl;

ring B is selected from the group consisting of cycloalkyl, heterocyclyl and heteroaryl;

R a is selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thioxo, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH 2 ) n5 R gg , —(CH 2 ) n5 OR gg , —(CH 2 ) n5 C(O)OR gg , —(CH 2 ) n5 SR gg , —(CH 2 ) n5 NR gg C(O)(CH 2 ) n6 R hh , —(CH 2 ) n5 NR gg C(O)OR hh , —(CH 2 ) n5 NR gg C(O)NR hh R ii , —(CH 2 ) n5 NR gg R hh , —NR gg (CH 2 ) n5 R hh , —(CH 2 ) n5 C(O)NR gg (CH 2 ) n6 R hh , —(CH 2 ) n5 C(O)R gg , —(CH 2 ) n5 S(O) n6 R gg , —(CH 2 ) n5 NR gg S(O) n6 R hh , —CH═CH(CH 2 ) n5 R gg , —CH═CH(CH 2 ) n5 NR gg R hh , —CH═CH(CH 2 ) n5 NR gg C(O)R hh and CH═CH(CH 2 ) n5 NR gg C(O)NR hh R ii , wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl can be each optionally further substituted;

or, any two of R gg , R hh , R ii are bonded to form a cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl can be optionally further substituted;

x is an integer from 0 to 6;

e is an integer from 0 to 6;

n1, n3, and n5 are each independently an integer from 0 to 3; and

n2, n4, and n6 are each independently an integer from 0 to 2.