US 11,739,090 B2
Substituted pyrazlo[3,4-c]pyridines as selective BTK kinase inhibitors
Chunli Shen, Shanghai (CN); XiaWei Wei, Sichuan (CN); Chengde Wu, Shanghai (CN); Guoping Hu, Shanghai (CN); Ning Jiang, Sichuan (CN); Wei Zheng, Sichuan (CN); Jian Li, Shanghai (CN); and Shuhui Chen, Shanghai (CN)
Assigned to JUMBO DRUG BANK CO., LTD., Sichuan (CN)
Appl. No. 17/763,732
Filed by JUMBO DRUG BANK CO., LTD., Sichuan (CN)
PCT Filed Sep. 25, 2020, PCT No. PCT/CN2020/117690
§ 371(c)(1), (2) Date Mar. 25, 2022,
PCT Pub. No. WO2021/057893, PCT Pub. Date Apr. 1, 2021.
Claims priority of application No. 201910919180.6 (CN), filed on Sep. 26, 2019; and application No. 202010330226.3 (CN), filed on Apr. 24, 2020.
Prior Publication US 2022/0324864 A1, Oct. 13, 2022
Int. Cl. A61K 31/437 (2006.01); C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) 16 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein:
L1 is —CH2—, —CH2CH2—, —C(O)NH—, or —O—;
ring A is phenyl or a 5- or 6-membered heteroaryl, wherein the 5- or 6-membered heteroaryl contains 1, 2, 3, or 4 heteroatoms or heteroatomic groups independently selected from the group consisting of N, NH, O, and S;
each R1 is independently F, Cl, Br, I, CN, NH2, or OH;
m is 0, 1, 2, or 3;
T1 is CH or N;
each R3 is independently F, Cl, Br, I, CN, NH2, or OH;
n is 0, 1, 2, or 3;
M is C3-6 cycloalkyl or a 3- to 6-membered heterocycloalkyl, wherein the 3- to 6-membered heterocycloalkyl contains 1, 2, 3, or 4 heteroatoms or heteroatomic groups independently selected from the group consisting of —C(O)—, N, —NH—, —O—, —S—, and —S(O)—, and further wherein the C3-6 cycloalkyl or 3- to 6-membered heterocycloalkyl is optionally substituted with 1, 2, or 3 independently selected Rb substituents;
each Rb is independently F, Cl, Br, I, or CH3;
L2 is —CH2—, —CH2CH2—, —C(O)—, —C(O)NH—, or —O—;
R2 is H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl is optionally substituted with 1, 2, or 3 independently selected Ra substituents;
each Ra is independently F, Cl, Br, I, CN, C1-3 alkyl, NH2, NHC1-3 alkyl, OH, or OC1-3 alkyl, wherein each C1-3 alkyl, NHC1-3 alkyl, or OC1-3 alkyl is optionally and independently substituted with 1, 2, or 3 independently selected R substituents; and
each R is independently F, Cl, Br, or I;
with the proviso that n and m are not simultaneously 0.
 
14. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound according to claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, as an active ingredient.