US 12,304,910 B2
Janus kinase (JAK) family inhibitor, preparation of same, and applications thereof
Yong Wu, Jiangsu (CN); Yanchun Gong, Jiangsu (CN); Wenbin Zhou, Jiangsu (CN); Daan Qin, Jiangsu (CN); Ya Zhang, Jiangsu (CN); and Yongqiang Liu, Jiangsu (CN)
Assigned to JIANGSU VCARE PHARMATECH CO., LTD., Jiangsu (CN)
Appl. No. 17/425,844
Filed by JIANGSU VCARE PHARMATECH CO., LTD., Jiangsu (CN)
PCT Filed Jan. 19, 2020, PCT No. PCT/CN2020/072949
§ 371(c)(1), (2) Date Jul. 26, 2021,
PCT Pub. No. WO2020/156271, PCT Pub. Date Aug. 6, 2020.
Claims priority of application No. 201910106479.X (CN), filed on Feb. 2, 2019; and application No. 202010050671.4 (CN), filed on Jan. 13, 2020.
Prior Publication US 2022/0177467 A1, Jun. 9, 2022
Int. Cl. C07D 471/04 (2006.01); A61P 1/00 (2006.01); A61P 3/10 (2006.01); A61P 7/00 (2006.01); A61P 7/02 (2006.01); A61P 9/10 (2006.01); A61P 11/02 (2006.01); A61P 11/06 (2006.01); A61P 17/00 (2006.01); A61P 19/02 (2006.01); A61P 25/00 (2006.01); A61P 25/28 (2006.01); A61P 27/02 (2006.01); A61P 29/00 (2006.01); A61P 31/12 (2006.01); A61P 31/20 (2006.01); A61P 31/22 (2006.01); A61P 35/00 (2006.01); A61P 35/02 (2006.01); A61P 37/00 (2006.01); A61P 37/02 (2006.01); A61P 37/06 (2006.01); C07D 471/08 (2006.01); C07D 471/10 (2006.01); C07D 487/04 (2006.01); C07D 487/10 (2006.01); C07D 498/08 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 37/06 (2018.01); C07D 519/00 (2013.01)] 13 Claims
 
1. A compound of formula (I) and a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein the ring A is selected from optionally substituted 4-12-membered heterocyclyl or 5-10-membered heteroaryl;
R1 is selected from H, hydroxyl, optionally substituted C1-C8alkyl, C3-C8 cycloalkyl, C2-C8 alkenyl, C2-C8 alkynyl, 4-12-membered heterocyclyl, 6-10-membered aryl or 5-10-membered heteroaryl;
R2 is selected from cyano, —C═ONR6R7, —C═ONR6NR7R8, —C═ONHOR6, —S(O)mR8, —S(O)m—NHR8 or —C═OOR6;
L is selected from amino, —NR6C═O—, —NR6C═ONR10—, —C═ONR10, —C═ONR6O—, —C═ONR6NR10—, —NR6S(O)m—, —S(O)mNR6—, —NR6S(O)mNR7—, —S(O)m—, —C═O— or —C═OO—;
or L is absent;
R3 is selected from H, optionally substituted C1-C8alkyl, C3-C8 cycloalkyl or —C═OR6;
R4 and R5 are each independently selected from H, deuterium, halogen, cyano, nitro, optionally substituted C1-C8 alkyl, C3-C8 cycloalkyl, 6-10-membered aryl or 5-10-membered heteroaryl;
R6, R7 and R10 are each independently selected from H, optionally substituted C1-C8 alkyl or C3-C8 cycloalkyl;
or, R10 taken with N and R1 to which it is attached can form an optionally substituted 4-12-membered heterocyclyl;
wherein the substituent groups in the ring A and R1 are each independently selected from one or more of halogen, hydroxyl, cyano, amino, sulfydryl, nitro, C1-C8 alkyl, C1-C8 alkoxy, C3-C8 cycloalkyl, 4-12-membered heterocyclyl, 6-10-membered aryl, 5-10-membered heteroaryl, —(CH2)nC═OOR8, —OC═OR8, —C═OR8, —C═ONR8R9, —NHC═OR8, —NR8R9, —OC—ONR8R9, —NHC═ONR8R9, —S(O)mR2, —S(O)m—NHR8, —NHC═OOR8 or —NHS(O)mR3;
m is selected from 1 or 2;
n is selected from 1, 2, 3, 4 or 5;
R8 and R9 are each independently selected from H, optionally substituted C1-C8 alkyl or C3-C8 cycloalkyl; and
the substituent groups in the R3, R4, R5, R6, R7, R8, R9 and R10 are each independently selected from one or more of deuterium, halogen, hydroxyl, cyano, amino, sulfydryl, nitro, C1-C8alkyl, C1-C8 alkoxy or C3-C8 cycloalkyl.