US 12,291,516 B2
Substituted 1-amino-1H-imidazole-5-carboxamide as Bruton's tyrosine kinase inhibitors
Qingjie Ding, Xinxiang (CN); Chunhua Ma, Xinxiang (CN); Yuqin Jiang, Xinxiang (CN); Guiqing Xu, Xinxiang (CN); Wei Li, Xinxiang (CN); Minghao Zhao, Xinxiang (CN); Qingyun Li, Xinxiang (CN); Dandan Zhang, Xinxiang (CN); Guojie Fan, Xinxiang (CN); Yang Li, Xinxiang (CN); Xin Shi, Xinxiang (CN); and Shouning Yang, Xinxiang (CN)
Assigned to Henan Zhiwei Biomedicine Co., Ltd., Xinxiang (CN)
Appl. No. 17/609,989
Filed by Henan Zhiwei Biomedicine Co., Ltd., Xinxiang (CN)
PCT Filed May 9, 2020, PCT No. PCT/CN2020/089407
§ 371(c)(1), (2) Date Nov. 9, 2021,
PCT Pub. No. WO2020/228637, PCT Pub. Date Nov. 19, 2020.
Claims priority of application No. 201910388246.3 (CN), filed on May 10, 2019.
Prior Publication US 2022/0259181 A1, Aug. 18, 2022
Int. Cl. C07D 401/14 (2006.01); A61P 35/00 (2006.01)
CPC C07D 401/14 (2013.01) [A61P 35/00 (2018.01)] 18 Claims
 
1. A compound represented by Formula I, or a pharmaceutically acceptable salt, active metabolite, tautomer, stereoisomer, or prodrug thereof,

OG Complex Work Unit Chemistry
wherein
R1 is selected from the group consisting of H, C1-6 alkyl, and R5C(O), where R5 is independently selected from the group consisting of C1-6 alkyl and C1-6 alkoxy;
Ar is selected from heteroaryl or heteroaryl substituted with a substituent selected from the group consisting of halogen, cyano, C1-6 alkyl, C1-6 alkoxy, C6 or C10 aryl, and C6 or C10 aryl substituted with a substituent selected from the group consisting of halogen, cyano, C1-6 alkyl optionally substituted with halogen, hydroxyl or C1-6 alkoxy;
n is an integer selected from 0 and 1;
X is a 4-8 membered nitrogen-containing heterocyclyl where the heterocyclyl is substituted on a nitrogen with Y; or a nitrogen-containing spiral heterocyclyl where the spiral heterocyclyl is substituted on a nitrogen with Y;
Y is selected from the group consisting of —CN, —C(═O)P, —S(═O)P and —S(═O2P; where
P is selected from

OG Complex Work Unit Chemistry
and
Rx is selected from the group consisting of H, halogen, cyano, C1-6 alkyl, C1-6 alkyl substituted with halogen, C1-6 alkoxy, C3-6 cycloalkyl, phenyl and —(CH2)mNR6R7;
R2 is selected from the group consisting of hydrogen, halogen, cyano, C1-6 alkyl, C1-6 alkyl substituted by substituents selected from the group consisting of F, hydroxyl and C1-6 alkoxy; C3-6 cycloalkyl and C3-6 cycloalkyl substituted with F;
R3 and R4 are independently selected from the group consisting of hydrogen; halogen; cyano; C6 or C10 aryl; heteroaryl; C1-6 alkyl; C1-6 alkyl substituted with C1-6 alkoxy, NR6R7, halogen, hydroxyl, C6 or C10 aryl, and heteroaryl; C3-6 cycloalkyl; C3-6 cycloalkyl substituted with halogen; C2-6 alkenyl; and C2-6 alkenyl substituted with a subtituent selected from the group consisting of C1-6 alkoxy, NR6R7, halogen, hydroxyl, C6 or C10 aryl and heteroaryl;
R6 and R7 are each independently selected from hydrogen, C1-6 alkyl or together with the nitrogen they substitute form a 4-6 membered heterocyclyl;
m is an integer selected from 1 to 3.