US 12,221,432 B2
Estrogen receptor antagonist
Shuwen Duan, Shanghai (CN); Jianyu Lu, Shanghai (CN); Lihong Hu, Shanghai (CN); Charles Z. Ding, Shanghai (CN); Guoping Hu, Shanghai (CN); Jian Li, Shanghai (CN); and Shuhui Chen, Shanghai (CN)
Assigned to CHIA TAI TIANQING PHARMACEUTICAL GROUP CO., LTD., Lianyungang (CN)
Appl. No. 17/309,712
Filed by CHIA TAI TIANQING PHARMACEUTICAL GROUP CO., LTD., Lianyungang (CN)
PCT Filed Dec. 17, 2019, PCT No. PCT/CN2019/126046
§ 371(c)(1), (2) Date Jun. 16, 2021,
PCT Pub. No. WO2020/125640, PCT Pub. Date Jun. 25, 2020.
Claims priority of application No. 201811545117.2 (CN), filed on Dec. 17, 2018; application No. 201910611070.3 (CN), filed on Jul. 8, 2019; and application No. 201910877339.2 (CN), filed on Sep. 17, 2019.
Prior Publication US 2022/0033376 A1, Feb. 3, 2022
Int. Cl. C07D 401/06 (2006.01); A61P 35/00 (2006.01); C07D 209/20 (2006.01); C07D 401/14 (2006.01); C07D 409/14 (2006.01)
CPC C07D 401/06 (2013.01) [A61P 35/00 (2018.01); C07D 209/20 (2013.01); C07D 401/14 (2013.01); C07D 409/14 (2013.01)] 20 Claims
 
1. A compound of formula (II), an stereoisomer thereof or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein,
X is NH;
Y is selected from the group consisting of N and CR7;
Y is CH, and Y2 is N;
or, Y1 is N, and Y2 is CH or CF;
or, Y1 is CH, and Y2 is CH;
L is

OG Complex Work Unit Chemistry
ring A is selected from the group consisting of C6-10 aryl and 5-10 membered heteroaryl;
R1 is selected from the group consisting of H, halogen, CN, COOH, NH2, C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, the C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl being optionally substituted with 1, 2 or 3 Ra;
R2 is selected from the group consisting of C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, the C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl being optionally substituted with 1, 2 or 3 Rb;
R3 is selected from the group consisting of H, halogen, CN, NO2, OH, COOH, NH2, C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, the C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl being optionally substituted with 1, 2 or 3 Rc;
R13 is H or

OG Complex Work Unit Chemistry
R4 is selected from the group consisting of COOH, NH2, C1-6 alkyl, —NH—C1-6 alkyl, —N(C1-6 alkyl)2, —C(═O)—O—C1-6 alkyl, —C(═O)—S—C1-6 alkyl, C3-6 cycloalkyl, 3-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl, the C1-6 alkyl, —NH—C1-6 alkyl, —N(C1-6 alkyl)2, —C(═O)—O—C1-6 alkyl, —C(═O)—S—C1-6 alkyl, C3-6 cycloalkyl, 3-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl being optionally substituted with 1, 2 or 3 Rd;
R5 is selected from the group consisting of H, C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, the C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl being optionally substituted with 1, 2 or 3 Re;
R6, R7, R8 and R9 are each independently selected from the group consisting of H, halogen, CN, NO2, OH, COOH, NH2, C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, the C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl being optionally substituted with 1, 2 or 3 Rf;
R10, R11 and R12 are each independently selected from the group consisting of H, halogen, CN, NO2, OH, COOH, NH2, C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, the C1-6 alkyl, C1-6 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl being optionally substituted with 1, 2 or 3 Rg,
Ra, Rb, Rc, Rd, Re, Rf and Rg are each independently selected from the group consisting of H, F, Cl, Br, I, OH, CN, NH2, COOH, C(—O)NH2, C1-8 alkyl, C1-8 heteroalkyl, C3-6 cycloalkyl, 3-6 membered heterocycloalkyl and C3-6 cycloalkyl-C1-3 alkyl-, the C1-8 alkyl, C1-8 heteroalkyl, C3-6 cycloalkyl, 3-6 membered heterocycloalkyl and C3-6 cycloalkyl-C1-3 alkyl-being optionally substituted with 1, 2 or 3 R;
R is independently selected from the group consisting of F, Cl, Br, I, OH, CN, NH2, COOH, Me, Et, CF3, CHF2, CH2F, NHCH3, and N(CH3)2;
the C1-6 heteroalkyl, 3-6 membered heterocycloalkyl and 5-6 membered heteroaryl each comprise 1, 2, 3 or 4 heteroatoms or heteroatom groups each independently selected from the group consisting of —NH—, —O—, —S—, —O—N═, —C(═O)—O—, —C(═O)—S—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O)2— and N.