Aroyl substituted tricyclic compound, preparation method therefor and use thereof

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

in the formula,

R 1 and R 2 are each independently selected from: H, C 1-6 alkoxy and C 1-6 thioalkyl; or R 1 and R 2 combining with the carbon atoms to which they are attached form: C═O or C═S; the C 1-6 alkoxy and the C 1-6 thioalkyl are each independently unsubstituted or substituted by 1, 2, 3 or 4 substituents independently selected from group S1;

R 3 and R 4 are each independently selected from: C 1-6 alkyl and C 3-6 monocyclic cycloalkyl; or R 3 and R 4 combining with the carbon atoms to which they are attached form: C 3-6 monocyclic cycloalkyl or 3- to 6-membered monocyclic heterocyclyl, the 3- to 6-membered monocyclic heterocyclyl has 1 or 2 heteroatoms selected from N and O as ring atoms; wherein C 1-6 alkyl, C 3-6 monocyclic cycloalkyl and 3- to 6-membered monocyclic heterocyclyl are each independently unsubstituted or substituted by 1, 2, 3 or 4 substituents independently selected from group S1;

n is 0;

E is NR 5 , O or N;

R 5 is H, C 1-6 alkyl, deuterated C 1-6 alkyl, —C 1-4 alkylene-hydroxy, —C 1-4 alkylene-C 1-6 alkoxy or —C 1-4 alkylene-NR a R b ;

when E is NR 5 or O, “ ” connected with E represents a single bond;

when E is N, “ ” connected with E represents a double bond and R 2 is absent;

A is CR 6 or N; wherein, R 6 is H;

B is CR 7 ; wherein, R 7 is H;

G 1 is C 6-14 aryl or 5- to 6-membered monocyclic heteroaryl; the 5- to 6-membered monocyclic heteroaryl has 1 or 2 heteroatoms selected from N, O and S as ring atoms, and the C 6-14 aryl and the 5- to 6-membered monocyclic heteroaryl are unsubstituted or substituted by 1, 2, 3 or 4 substituents independently selected from group S2;

G 2 is C 6-14 aryl or 5- to 6-membered monocyclic heteroaryl; the 5- to 6-membered monocyclic heteroaryl has 1 or 2 heteroatoms selected from N, O and S as ring atoms, and the C 6-14 aryl and the 5- to 6-membered monocyclic heteroaryl are unsubstituted or substituted by 1, 2, 3 or 4 substituents independently selected from group S2;

L is CR 8 R 9 or O; wherein, R 8 and R 9 are each independently H;

i is 0 or 1;

substituents in the group S1 are selected from: deuterium, halogen, cyano, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, deuterated C 1-6 alkoxy, —C 1-4 alkylene-hydroxy, —C(O)C 1-6 alkyl, —C(O)C 3-6 monocyclic cycloalkyl, 3- to 6-membered monocyclic heterocyclyl, —O—C 3-6 monocyclic cycloalkyl, —NR a R b and —OR c , wherein the 3- to 6-membered monocyclic heterocyclyl has 1 or 2 heteroatoms selected from N and O as ring atoms;

substituents in the group S2 are selected from: halogen, cyano, C 1-6 alkyl, halo C 1-6 alkyl, deuterated C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkoxy, deuterated C 1-6 alkoxy, C 3-6 monocyclic cycloalkyl, halo C 3-6 monocyclic cycloalkyl, —O—C 3-6 monocyclic cycloalkyl, —NR a R b and —OR c ;

R a and R b are each independently C 1-6 alkyl;

R c is —C 1-4 alkylene-C 1-6 alkoxy or C 3-6 monocyclic cycloalkyl substituted by 1 or 2 halogens;

a carbon atom marked at “*” is a chiral carbon atom or an achiral carbon atom.

2 . The compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 1 , wherein,

in R 1 and R 2 , the C 1-6 alkoxy is each independently C 1-3 alkoxy;

or, in R 1 and R 2 , the C 1-6 thioalkyl is each independently C 1-3 thioalkyl;

or, in R 1 and R 2 , the C 1-6 alkoxy and the C 1-6 thioalkyl are each independently unsubstituted;

or, in R 3 and R 4 , the C 1-6 alkyl is each independently C 1-3 alkyl;

or, in R 3 and R 4 , the C 1-6 alkyl, the C 3-6 monocyclic cycloalkyl and the 3- to 6-membered heterocyclyl are each independently unsubstituted or substituted by 1 or 2 substituents selected from group S1;

or, in R 5 , the C 1-6 alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl;

or, in R 5 , the deuterated C 1-6 alkyl is deuterated C 1-3 alkyl;

or, in R 5 , the —C 1-4 alkylene-hydroxy is —C 1-2 alkylene-hydroxy;

or, in R 5 , the —C 1-4 alkylene-C 1-6 alkoxy is —C 1-2 alkylene-C 1-3 alkoxy;

or, in R 5 , the —C 1-4 alkylene-NR a R b is —C 1-2 alkylene-NR a R b ;

or, A is CH;

or, B is CH;

or, in G 1 , the C 6-14 aryl is phenyl;

or, in G 1 , the 5- to 6-membered monocyclic heteroaryl is pyridinyl, pyrimidinyl, furyl, pyrrolyl, thiazolyl, pyrazolyl or thienyl;

or, in G 1 , the C 6-14 aryl and the 5- to 6-membered monocyclic heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents independently selected from group S2;

or, in G 2 , the C 6-14 aryl is phenyl;

or, in G 2 , the 5- to 6-membered monocyclic heteroaryl is pyridinyl, pyrimidinyl, furyl, pyrrolyl, thiazolyl or pyrazolyl;

or, in G 2 , the C 6-14 aryl and the 5- to 6-membered monocyclic heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents independently selected from group S2;

or, in G 2 , substituents in the group S2 are selected from: halogen, cyano, —C 1-6 alkyl, halo C1-6 alkyl, C 1-6 alkoxy, deuterated C 1-6 alkoxy and C 3-6 monocyclic cycloalkyl;

or, in L, the CR 8 R 9 is CH 2 ;

or, in the substituents in group S1, the halogen is each independently fluorine or chlorine;

or, in the substituents in group S1, the C 1-6 alkyl is each independently C 1-3 alkyl;

or, in the substituents in group S1, the C 1-6 alkoxy is each independently C 1-3 alkoxy;

or, in the substituents in group S1, the halo C 1-6 alkoxy is each independently halo C 1-3 alkoxy;

or, in the substituents in group S1, the deuterated C 1-6 alkoxy is each independently deuterated C 1-3 alkoxy;

or, in the substituents in group S1, the C 1-4 alkylene-hydroxy is each independently C 1-2 alkylene-hydroxy;

or, in the substituents in group S1, the —C(O)C 1-6 alkyl is each independently —C(O)C 1-3 alkyl;

or, in the substituents in group S1, the —NR a R b is each independently —N(CH 3 ) 2 ;

or, in the substituents in group S1, the —OR c is each independently —OCH 2 CH 2 OCH 3 or —CH 2 CH 2 OCH 2 CH 3 ;

or, in the substituents in group S2, the halogen is each independently fluorine, chlorine, bromine or iodine;

or, in the substituents in group S2, the C 1-6 alkyl is each independently C 1-3 alkyl;

or, in the substituents in group S2, the halo C 1-6 alkyl is each independently halo C 1-3 alkyl;

or, in the substituents in group S2, the deuterated C 1-6 alkyl is each independently deuterated C 1-3 alkyl;

or, in the substituents in group S2, the C 1-6 alkoxy is each independently C 1-3 alkoxy;

or, in the substituents in group S2, the halo C 1-6 alkoxy is each independently halo C 1-3 alkoxy;

or, in the substituents in group S2, the deuterated C 1-6 alkoxy is each independently deuterated C 1-3 alkoxy;

or, in the substituents in group S2, the —NR a R b is each independently —N(CH 3 ) 2 ;

or, in the substituents in group S2, the —OR c is each independently —OCH 2 CH 2 OCH 3 or —OCH 2 CH 2 OCH 2 CH 3 ;

or, R a and R b are each independently C 1-3 alkyl;

or, in R c , the —C 1-4 alkylene-C 1-6 alkoxy is each independently-C 1-2 alkylene-C 1-3 alkoxy;

or, in R c , halogen in the C 3-6 monocyclic cycloalkyl substituted by 1 or 2 halogens is fluorine, chlorine or bromine;

or, in R c , C 3-6 monocyclic cycloalkyl in the C 3-6 monocyclic cycloalkyl substituted by 1 or 2 halogens is cyclopropyl.

3 . The compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 2 , wherein,

R 1 and R 2 are each independently selected from: H, methoxy, methylthio and ethylthio; or R 1 and R 2 combining with the carbon atoms to which they are attached form: C═O or C═S;

or, R 3 and R 4 are each independently selected from: —CH 3 , —CH 2 CH 3 , cyclopropyl, trifluoromethyl (CF 3 ), deuterated methyl (CD 3 ), —CH 2 OH, —CH 2 OCH 3 , —CH 2 OCF 3 , —CH 2 OCHF 2 , —CH 2 OCD 3 , —CH 2 OCH 2 CH 3 , —CH 2 OCH 2 CH 2 OCH 3 , —CH 2 CH 2 OCH 2 CH 3 , —CH 2 O-cyclopropyl, —CH 2 N(CH 3 ) 2 , —CH(OH)CH 3 and —CH 2 CH 3 OCH 3 ;

or, R 5 is H, methyl, ethyl, deuterated methyl, —CH 2 CH 2 OH, —CH 2 CH 2 OCH 3 or —CH 2 CH 2 N(CH 3 ) 2 ;

or, G 1 is phenyl, 2-chlorophenyl, 2-fluorophenyl, 2-trifluoromethylphenyl, 2-chloro-6-fluorophenyl, 2-chloro-3,4-difluorophenyl, 2-chloro-3-fluoro-4-methoxyphenyl, 2-chloro-4-cyclopentyloxyphenyl, 2-chloro-4-dimethylaminophenyl, 2-chloro-4-cyclopropyloxyphenyl, 2-chloro-4-methoxyphenyl, 2-chloro-4-isopropylphenyl, 2-chloro-4-cyclopropylphenyl, 2-chloro-4-methylphenyl, 2-chlorofuryl, furyl, thienyl, 2-bromothienyl, 2-chlorothienyl, pyridinyl, 3-chloropyridinyl, 2-methylphenyl, 2-chloro-4-cyanophenyl, 2-chloro-4-fluorophenyl, 2-iodophenyl, 2-chloro-5-fluorophenyl, 2-chloro-3-fluorophenyl, 2-chloro-trifluoromethoxyphenyl, 2-chloro-4-bromophenyl or 2,4-dichlorophenyl;

or, G 2 is phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-trifluoromethylpyridinyl, 3-methylpyridinyl, 3-trifluoromethylpyridinyl, 4-methylpyridinyl, 4-cyclopropylpyridinyl, 4,6-dimethylpyridinyl, 4-chloro-6-methylpyridinyl, 2-methyl-6-chloropyridinyl, 3-cyanophenyl, 3-fluoro-4-methylpyridinyl, pyridinyl, 3-fluoropyridinyl, 2-methoxyphenyl, 2-chlorophenyl, 3-methoxyphenyl, 2-fluoro-6-methoxyphenyl, pyrazolyl, 3-methylpyrazolyl, 2-methoxy-3-fluorophenyl, 2-fluoro-3-deuterated methoxyphenyl, 2,4-dimethylpyridinyl, 2-chloropyridyl, 2-methoxy-3-fluorophenyl or 2-deuterated methoxy-3-fluorophenyl;

or, L is CH 2 or O;

or, substituents in the group S1 are selected from: deuterium, fluorine, cyano, hydroxyl, methyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, deuterated methoxy, —CH 2 OH, —C(O)CH 3 , —C(O)-cyclopropyl, morpholinyl, —O-cyclopropyl, —N(CH 3 ) 2 , —OCH 2 CH 2 OCH 3 and —CH 2 CH 2 OCH 2 CH 3 ;

or, substituents in the group S2 are selected from: fluorine, chlorine, bromine, iodine, cyano, methyl, deuterated methyl, isopropyl, trifluoromethyl, methoxy, trifluoromethoxy, deuterated methoxy, cyclopropyl, —O-cyclopropyl, —O-cyclopentyl, —N(CH 3 ) 2 and —OCH 2 CH 2 OCH 3 .

4 . The compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 1 , wherein, i, G 1 , L, G 2 have any of the following definitions:

(1) i is 0, G 1 is phenyl, pyridinyl, furyl or thienyl; the phenyl, the pyridinyl, the furyl and the thienyl are unsubstituted or substituted by 1, 2, 3 or 4 substituents independently selected from group S2;

(2) i is 1, L is CR 8 R 9 or O, G 1 is phenyl or pyridyl, G 2 is phenyl, pyridyl or pyrazolyl; the phenyl, the pyridinyl and the pyrazolyl are unsubstituted or substituted by 1, 2, 3 or 4 substituents independently selected from group S2;

(3) i is 1, L is CR 8 R 9 , G 1 is phenyl, G 2 is pyrazolyl; the phenyl and the pyrazolyl are unsubstituted or substituted by 1, 2, 3 or 4 substituents independently selected from group S2;

(4) i is 1, L is O, G 1 is phenyl or pyridyl, G 2 is phenyl or pyridyl; the phenyl and the pyridinyl are unsubstituted or substituted by 1, 2, 3 or 4 substituents independently selected from group S2.

5 . The compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 1 , wherein, the structural moiety

is selected from:

6 . The compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 1 , wherein, the compound has any one of the following structures:

7 . The compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 1 , wherein, the compound has any one of the following structures:

8 . The compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 6 , wherein, R 1 is C 1-6 alkoxy or C 1-6 thioalkyl.

9 . The compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 1 , wherein, the compound has any one of the following structures:

10 . The compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 2 , wherein,

in R 1 and R 2 , the C 1-3 alkoxy is each independently methoxy;

or, in R 1 and R 2 , the C 1-3 thioalkyl is each independently methylthio or ethylthio;

or, in R 3 and R 4 , the C 1-3 alkyl is each independently methyl or ethyl;

or, in R 3 and R 4 , the C 3-6 monocyclic cycloalkyl is each independently cyclopropyl;

or, in R 5 , the C 1-6 alkyl is methyl or ethyl;

or, in R 5 , the deuterated C 1-3 alkyl is deuterated methyl;

or, in R 5 , the —C 1-2 alkylene-hydroxy is —CH 2 CH 2 OH;

or, in R 5 , the —C 1-2 alkylene-C 1-3 alkoxy is —CH 2 CH 2 OCH 3 ;

or, in R 5 , the —C 1-2 alkylene-NR a R b is —CH 2 CH 2 N(CH 3 ) 2 ;

or, in G 1 , the 5- to 6-membered monocyclic heteroaryl is pyridinyl, furyl or thienyl;

or, in G 1 , substituents in the group S2 are selected from: fluorine, chlorine, bromine, iodine, cyano, methyl, isopropyl, trifluoromethyl, methoxy, trifluoromethoxy, cyclopropyl, —O-cyclopropyl, —O-cyclopentyl, —N(CH 3 ) 2 and —OCH 2 CH 2 OCH 3 ;

or, in G 2 , the 5- to 6-membered monocyclic heteroaryl is pyridinyl or pyrazolyl;

or, in G 2 , substituents in the group S2 are selected from: fluorine, chlorine, cyano, methyl, trifluoromethyl, methoxy, deuterated methoxy and cyclopropyl;

or, in the substituents in group S1, the C 1-3 alkyl is each independently methyl;

or, in the substituents in group S1, the C 1-3 alkoxy is each independently methoxy or ethoxy;

or, in the substituents in group S1, the halo C 1-3 alkoxy is each independently difluoromethoxy or trifluoromethoxy;

or, in the substituents in group S1, the deuterated C 1-3 alkoxy is each independently deuterated methoxy;

or, in the substituents in group S1, the C 1-2 alkylene-hydroxy is each independently —CH 2 OH;

or, in the substituents in group S1, the —C(O)C 1-3 alkyl is each independently —C(O)CH 3 ;

or, in the substituents in group S2, the C 1-3 alkyl is each independently methyl or isopropyl;

or, in the substituents in group S2, the halo C 1-3 alkyl is each independently trifluoromethyl;

or, in the substituents in group S2, the deuterated C 1-3 alkyl is each independently deuterated methyl;

or, in the substituents in group S2, the C 1-3 alkoxy is each independently methoxy;

or, in the substituents in group S2, the halo C 1-3 alkoxy is each independently difluoromethoxy or trifluoromethoxy;

or, in the substituents in group S2, the deuterated C 1-3 alkoxy is each independently deuterated methoxy;

or, R a and R b are each independently methyl;

or, in R c , the —C 1-2 alkylene-C 1-3 alkoxy is each independently —CH 2 CH 2 OCH 3 or —CH 2 CH 2 OCH 2 CH 3 .

11 . The compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 3 , wherein,

R 3 is selected from: —CH 3 , —CH 2 CH 3 , trifluoromethyl, deuterated methyl and cyclopropyl, R 4 is selected from: —CH 3 , —CH 2 OH, —CH 2 OCH 3 , —CH 2 OCF 3 , —CH 2 OCHF 2 , —CH 2 OCF 3 , —CH 2 OCHF 2 , —CH 2 OCD 3 , —CH 2 OCH 2 CH 3 , —CH 2 OCH 2 CH 2 OCH 3 , —CH 2 CH 2 OCH 2 CH 3 , —CH 2 O-cyclopropyl, —CH 2 N(CH 3 ) 2 , —CH(OH)CH 3 and —CH 2 CH 3 OCH 3 ; or R 3 and R 4 combining with the carbon atoms to which they are attached form:

12 . The compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 7 , wherein, R 1 is C 1-6 alkoxy or C 1-6 thioalkyl.

13 . A pharmaceutical composition, comprising the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 1 ; and a pharmaceutically acceptable carrier.

14 . A method for treating small lymphocytic lymphoma, acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, acute promyelocytic leukemia, chronic myeloid leukemia, diffuse large B-cell lymphoma, intravascular large B-cell lymphoma, primary exudative lymphoma, Waldenstrom's macroglobulinemia, follicular lymphoma, multiple myeloma, mantle cell lymphoma, marginal zone lymphoma or non-Hodgkin lymphoma, comprising: administering an effective amount of the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 1 to the subject in need thereof.

15 . A method for inhibiting BTK and/or abnormal B-cell activation in a subject in need thereof, comprising: administering an effective amount of the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 1 to the subject in need thereof.

16 . A method for inhibiting BTK and/or abnormal B-cell activation in a subject in need thereof, comprising: administering an effective amount of the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 9 to the subject in need thereof.

17 . A method for treating small lymphocytic lymphoma, acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, acute promyelocytic leukemia, chronic myeloid leukemia, diffuse large B-cell lymphoma, intravascular large B-cell lymphoma, primary exudative lymphoma, Waldenstrom's macroglobulinemia, follicular lymphoma, multiple myeloma, mantle cell lymphoma, marginal zone lymphoma or non-Hodgkin lymphoma, comprising: administering an effective amount of the compound, the pharmaceutically acceptable salt thereof, the stereoisomer thereof, or the solvate thereof as claimed in claim 9 to the subject in need thereof.