Aminopyrimidine compound as CDK2/4/6 triple inhibitor

1 . A compound represented by formula (I) or a pharmaceutically acceptable salt thereof,

wherein,

T is N or CH;

R 1 is

R 2 and R 3 are each independently H, F, Cl, Br, I, —CN, —OH, C 1-3 alkoxy or C 1-3 alkyl, wherein the C 1-3 alkoxy and the C 1-3 alkyl are optionally substituted with 1, 2 or 3 substituents independently selected from F, Cl, Br, —CN, —OH and —NH 2 ;

or R 2 and R 3 are joined together with the carbon atom to which they are attached form C 3-5 cycloalkyl, wherein the C 3-5 cycloalkyl is optionally substituted with 1, 2 or 3 R b ;

each R b is independently H, F, Cl, Br, I, —CN, —OH, C 1-3 alkoxy, C 1-3 alkyl or C 1-3 haloalkyl;

R 4 and R 5 are each independently H, F, Cl, Br, I, —CN, —OH, C 1-3 alkoxy or C 1-3 alkyl, wherein the C 1-3 alkoxy and the C 1-3 alkyl are optionally substituted with 1, 2 or 3 substituents independently selected from F, Cl, Br, —CN, —OH and —NH 2 ;

or R 3 and R 4 are joined together with the carbon atom to which they are attached form C 3-5 cycloalkyl, wherein the C 3-5 cycloalkyl is optionally substituted with 1, 2 or 3 R c ;

each R c is independently H, F, Cl, Br, I, —CN, —OH, C 1-3 alkoxy, C 1-3 alkyl or C 1-3 haloalkyl;

R 6 is H, F, Cl, Br, I, —CN, —OH, C 1-3 alkoxy, C 1-3 alkyl or C 1-3 haloalkyl;

R 7 is —NH 2 , C 1-3 alkylamino, C 1-6 alkyl, C 3-5 cycloalkyl, 4- to 6-membered heterocycloalkyl, 5- to 6-membered heteroaryl or phenyl, wherein the C 1-6 alkyl, the C 3-5 cycloalkyl, the 4- to 6-membered heterocycloalkyl, the 5- to 6-membered heteroaryl and the phenyl are optionally substituted with 1, 2 or 3 R d ;

each R d is independently H, F, Cl, Br, I, —CN, —OH, C 1-3 alkoxy or C 1-3 alkyl, wherein the C 1-3 alkoxy and the C 1-3 alkyl are optionally substituted with 1, 2 or 3 substituents independently selected from F, Cl, Br, —CN, —OH and —NH 2 ;

n is 0, 1 or 2;

the 4- to 6-membered heterocycloalkyl and the 5- to 6-membered heteroaryl respectively comprise 1, 2, 3 or 4 heteroatoms independently selected from N, —O— and —S—.

2 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 ,

each R b is independently H, F, Cl, Br, I, —CN, —OH, —OCH 3 , —CH 3 , —CF 3 or —CH 2 CH 3 ;

or, each Re is independently H, F, Cl, Br, I, —CN, —OH, —OCH 3 , —CH 3 , —CF 3 or —CH 2 CH 3 ;

or, each R d is independently H, F, Cl, Br, I, —CN, —OH, —OCH 3 , —CH 3 , —CF 3 , —CH 2 CH 3 or —CH(CH 3 ) 2 ;

or, R 2 and R 3 are joined together with the carbon atom to which they are attached form cyclopropyl, wherein the cyclopropyl is optionally substituted with 1, 2 or 3 R b ;

or, R 3 and R 4 are joined together with the carbon atom to which they are attached form cyclopropyl, wherein the cyclopropyl is optionally substituted with 1, 2 or 3 R c .

3 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 and R 3 are each independently H, F, Cl, Br, I, —CN, —OH, —OCH 3 , —CH 3 , —CF 3 or —CH 2 CH 3 ;

or, R 4 and R 5 are each independently H, F, Cl, Br, I, —CN, —OH, —OCH 3 , —CH 3 , —CF 3 or —CH 2 CH 3 ;

or, R 6 is H, F, Cl, Br, I, —CN, —OH, —OCH 3 , —CH 3 , or —CH 2 CH 3 .

4 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 7 is —NH 2 , —NH(CH 3 ), —NH(CH 2 CH 3 ), —N(CH 3 ) 2 , —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , cyclopropyl, cyclopentyl, azacyclobutyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, pyrazolyl, pyridyl or phenyl, wherein the —CH 3 , the —CH 2 CH 3 , the —CH 2 CH 2 CH 3 , the —CH(CH 3 ) 2 , the cyclopropyl, the cyclopentyl, the azacyclobutyl, the pyrrolidinyl, the tetrahydrofuranyl, the piperidinyl, the pyrazolyl, the pyridyl or the phenyl are optionally substituted with 1, 2 or 3 R d .

5 . The compound or the pharmaceutically acceptable salt thereof according to claim 4 , wherein R 7 is —NH 2 , —NH(CH 3 ), —NH(CH 2 CH 3 ), —N(CH 3 ) 2 , —C(R d ) 3 , —CH 2 CH 2 R d ,

6 . The compound or the pharmaceutically acceptable salt thereof according to claim 5 , wherein R 7 is —NH 2 , —NH(CH 3 ), —N(CH 3 ) 2 , —CH 3 , —CF 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH 2 OCH 3 ,

7 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is

8 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is:

9 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the pharmaceutically acceptable salt is a hydrochloride salt.

10 . A pharmaceutical composition, which comprises a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable carrier.

11 . A method for inhibiting CDK2/4/6 activity in a subject in need thereof, comprising administrating to the subject a medicament comprising the compound or the pharmaceutically acceptable salt thereof according to claim 1 .

12 . A method for treating solid tumor in a subject in need thereof, comprising administrating the compound or the pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

13 . The method according to claim 12 , wherein the solid tumor is colorectal cancer or breast cancer.

14 . A CDK4 inhibitor, wherein the CDK4 inhibitor is the compound or the pharmaceutically acceptable salt thereof according to claim 1 .

15 . A CDK6 inhibitor, wherein the CDK6 inhibitor is the compound or the pharmaceutically acceptable salt thereof according to claim 1 .

16 . A CDK2/4/6 triple inhibitor, wherein the CDK2/4/6 triple inhibitor is the compound or the pharmaceutically acceptable salt thereof according to claim 1 .