US 12,486,265 B2
2-aminopyrimidine compounds and pharmaceutical compositions and uses thereof
Bo Liang, Shanghai (CN); Qiu Jin, Shanghai (CN); Huanming Chen, Shanghai (CN); Zhijun Zhang, Shanghai (CN); Tian Xia, Shanghai (CN); Bo Hua, Shanghai (CN); and Gang Liu, Shanghai (CN)
Assigned to Shanghai Zhimeng Biopharma, Inc., (CN)
Appl. No. 17/636,164
Filed by Shanghai Zhimeng Biopharma, Inc., Shanghai (CN)
PCT Filed Aug. 12, 2020, PCT No. PCT/CN2020/108722
§ 371(c)(1), (2) Date Feb. 17, 2022,
PCT Pub. No. WO2021/031960, PCT Pub. Date Feb. 25, 2021.
Claims priority of application No. 201910764971.6 (CN), filed on Aug. 19, 2019.
Prior Publication US 2022/0340563 A1, Oct. 27, 2022
Int. Cl. C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) 15 Claims
 
1. A compound represented by formula I, a stereoisomer or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein,
X is N;
Y is selected from the group consisting of NH and O;
Z is selected from the group consisting of —N(H)C(O)R4 and —OH;
R1 and R3 are independently selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, hydroxyl and amino; the alkyl is optionally substituted by 1-3 substituents selected from the group consisting of halogen, hydroxyl, C1-C6 alkylamino, C1-C6 alkoxy, cyano, C1-C6 alkyl-C(O)NH—, C1-C6 alkyl-NH—C(O)—, C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 heterocycloalkyl, halogen-substituted C1-C6 alkyl, C3-C10 heteroaryl and C6-C12 aryl;
R2 is selected from the group consisting of C3-C10 cycloalkyl, C3-C10 heterocycloalkyl, —NR8R9, —OR8, —SR8, —S(O)2R8, —N(R10)COR11, —N(R10)S(O)2R11, —CONR10R11, —COR10 and —S(O)2NR10R11; the cycloalkyl and the heterocycloalkyl are optionally substituted by 1-3 substituents selected from the group consisting of halogen, hydroxyl, C1-C6 alkylamino, C1-C6 alkoxy, cyano, C1-C6 alkyl-C(O)NH—, ═O, C1-C6 alkyl-NH—C(O)—, C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 heterocycloalkyl, halogen-substituted C1-C6 alkyl, C3-C10 heteroaryl and C6-C12 aryl;
R4, R5 and R6 are independently selected from the group consisting of halogen, C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 heterocycloalkyl, C3-C10 heteroaryl and C6-C12 aryl;
the alkyl, cycloalkyl, heterocycloalkyl, heteroaryl and aryl are optionally substituted by 1-3 substituents selected from the group consisting of halogen, hydroxyl, amino, C1-C6 alkylamino, C1-C6 alkoxy, cyano, C1-C6 alkyl-C(O)NH—, C1-C6 alkyl-NH—C(O)—, C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 heterocycloalkyl, halogen-substituted C1-C6 alkyl, C3-C10 heteroaryl and C6-C12 aryl;
R8 is selected from the group consisting of C3-C10 cycloalkyl, C3-C10 heterocycloalkyl, C3-C10 heteroaryl and C6-C10 aryl; the cycloalkyl, heterocycloalkyl, heteroaryl and aryl are optionally substituted by 1-3 substituents selected from the group consisting of halogen, hydroxyl, amino, C1-C6 alkylamino, C1-C6 alkoxy, cyano, C1-C6 alkyl-C(O)NH—, C1-C6 alkyl-NH—C(O)—, C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 heterocycloalkyl, halogen-substituted C1-C6 alkyl, C3-C10 heteroaryl and C6-C12 aryl;
R9, R10 and R11 are independently selected from the group consisting of hydrogen, hydroxyl, C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 heterocycloalkyl, C3-C10 heteroaryl and C6-C10 aryl, and the alkyl, cycloalkyl, heterocycloalkyl, heteroaryl and aryl are optionally substituted by 1-3 substituents selected from the group consisting of halogen, hydroxyl, amino, (C1-C6 alkyl)2N—, C1-C6 alkoxy, cyano, C1-C6 alkyl-C(O)NH—, C1-C6 alkyl-NH—C(O)—, C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 heterocycloalkyl, halogen substituted C1-C6 alkyl, C3-C10 heteroaryl and C6-C12 aryl;
or R10 and R11 and the N, C or S to which they are respectively connected form C3-C10 heterocycloalkyl, 6-12 membered fused heterocyclyl or C3-C10 heteroaryl, and the heterocycloalkyl is optionally substituted by 1-3 substituents selected from the group consisting of halogen, hydroxyl, amino, (C1-C6 alkyl)2N—, C1-C6 alkoxy, cyano, C1-C6 alkyl-C(O)NH—, C1-C6 alkyl-NH—C(O)—, C1-C6 alkyl, C3-C10 cycloalkyl, C3-C10 heterocycloalkyl, halogen substituted C1-C6 alkyl, C1-C6 alkoxy, C3-C10 heteroaryl and C6-C12 aryl;
and, the heterocycloalkyl comprises 1, 2 or 3 heteroatoms selected from N, O or S;
the heteroaryl comprises 1, 2 or 3 heteroatoms selected from N, O or S;
the 6-12 membered fused heterocyclyl comprises 1, 2, 3 or 4 heteroatoms selected from N, O or S.