US 12,390,472 B2
Polysubstituted benzene compound and preparation method and use thereof
Wei Peng, Suzhou (CN); Jun Xian, Southborough, MA (US); Yonghan Hu, Suzhou (CN); Yuchuan Wu, Beijing (CN); Xi Chen, Beijing (CN); Shaoqiang Huang, Beijing (CN); Xiao Liu, Beijing (CN); Xin Li, Suzhou (CN); Bin Huang, Suzhou (CN); and Dongdong Wu, Suzhou (CN)
Assigned to EVOPOINT BIOSCIENCES CO., LTD., Suzhou (CN)
Appl. No. 17/263,038
Filed by SUZHOU SINOVENT PHARMACEUTICALS CO., LTD., Suzhou (CN)
PCT Filed Jul. 26, 2019, PCT No. PCT/CN2019/098019
§ 371(c)(1), (2) Date Jan. 25, 2021,
PCT Pub. No. WO2020/020374, PCT Pub. Date Jan. 30, 2020.
Claims priority of application No. PCT/CN2018/097635 (WO), filed on Jul. 27, 2018.
Prior Publication US 2021/0308141 A1, Oct. 7, 2021
Int. Cl. A61K 31/5377 (2006.01); A61K 31/4433 (2006.01); A61K 31/4545 (2006.01); A61K 31/4709 (2006.01); A61K 31/496 (2006.01); A61K 31/5386 (2006.01); A61P 35/00 (2006.01); C07D 213/64 (2006.01); C07D 401/12 (2006.01); C07D 405/12 (2006.01); C07D 405/14 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 493/08 (2006.01); C07D 498/08 (2006.01)
CPC A61K 31/5377 (2013.01) [A61K 31/4433 (2013.01); A61K 31/4545 (2013.01); A61K 31/4709 (2013.01); A61K 31/496 (2013.01); A61K 31/5386 (2013.01); A61P 35/00 (2018.01); C07D 213/64 (2013.01); C07D 401/12 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 493/08 (2013.01); C07D 498/08 (2013.01)] 8 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Chemistry
or a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof, wherein:
X is selected from —O— and NR9, wherein Ry is ethyl;
Y is —O—;
R1 is selected from C5-C6 cycloalkyl and 5-8 membered heterocyclyl, wherein the C5-C6 cycloalkyl or the 5-8 membered heterocyclyl is optionally substituted with one or more groups selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkyl-S—, C1-C6 alkyl-C(═O)—, C1-C6 alkyl-S(O)—, C1-C6 alkyl-S(O)2—, C1-C6 alkyl-OC(═O)—, C1-C6 alkyl-OS(O)2—, halogen, —CN, —OH, and NR1′R1″, wherein R1′ and R1″ are each independently selected from H, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl, wherein the C1-C6 alkyl, the C2-C6 alkenyl, and the C2-C6 alkynyl are optionally substituted with one or more groups selected from C1-C6 alkoxy, halogen, —OH, —CN, —SH, and NH2;
R2 is selected from H, C1-C6 alkyl, and halogen;
R3, and R10 are H;
R4 is

OG Complex Work Unit Chemistry
 wherein Q is selected from covalent bond and —CH2—, and T is selected from 5-8 membered nitrogen-containing heterocyclyl, wherein the 5-8 membered nitrogen-containing heterocyclyl is optionally substituted with one or more groups selected from —OH, —SH, —NH2, halogen, —CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 alkyl-S—, C1-C6 alkyl-NH—, (C1-C6 alkyl)2N—, C1-C6 alkyl-C(═O)—, C1-C6 alkyl-S(O)—, C1-C6 alkyl-S(O)2—, C1-C6 alkyl-OC(═O)—, and C1-C6 alkyl-OS(O)2—;
R5 is selected from H and C1-C6 alkyl;
R6 is C1-C6 alkyl;
R7 is H; and
R8 is selected from C1-C6 alkyl, C1-C6 alkoxy, and —OH, wherein the C1-C6 alkyl is optionally substituted with —OH.