
European Journal of Medicinal Chemistry (2021)
Update date:2022-07-30
Topics:
Kraj?ovi?ová, Soňa
Jorda, Radek
Vanda, David
Soural, Miroslav
Kry?tof, Vladimír
Herein, we report an efficient synthetic approach towards trisubstituted imidazo [4,5-c]pyridines designed as inhibitors of Bruton's tyrosine kinase (BTK). Two alternative synthetic routes for the simple preparation of desired compounds with variable substitutions at the N1, C4, C6 positions were introduced with readily available building blocks. Further, the developed synthetic approach was feasible for isomeric compounds bearing imidazo [4,5-b]pyridine scaffolds. In contrast to expectations based on previous studies, the imidazo [4,5-c]pyridine inhibitor exhibited a significantly higher activity against BTK compared to its imidazo [4,5-b]pyridine isomer. An inherent SAR study in the series of imidazo [4,5-c]pyridine compounds revealed a remarkably high tolerance of C6 substitutions for both hydrophobic and hydrophilic substituents. Preliminary cellular experiments indicated selective BTK targeting in Burkitt lymphoma and mantle cell lymphoma cell lines. The inhibitors could thus serve as starting points for further development, eventually leading to BTK inhibitors that could be used after ibrutinib failure.
Huaian Double Win Chemicals Co.,Ltd.
Contact:+86-13511538872
Address:Blk 43,Greenland Century Town,Huaian District, Huaian City,Jiangsu Province,China
Changzhou LanXu Chemical Co.,ltd.(expird)
Contact:86-0519-86330911,13656129734,15261186386
Address:Room 524, Depart.Chemical, Changzhou Science and Eductaion town, Jiangsu, China;Factory: Haian Fine Chemical Industry Park,Nantong,Jiangsu,China
Contact:86-10-62664360
Address:Building 10,No.18 AnNingZhuang East Road, GuangHua Pioneer Park,HaiDian District, BeiJing China
Hangzhou jls Flame Retardants Chemical Co.,Ltd
Contact:+86-571-87250387/87250386
Address:MOGANSHAN RODA 1418# SHANGCHENG INDUSTRIAL PARK
Jiangxi Hessence Chemicals Co., Ltd.
Contact:+86 796 3511924
Address:Chengxi Industrial Park, Jishui County, Jiangxi Province 331600 China.
Doi:10.1016/j.tetlet.2009.02.011
(2009)Doi:10.1021/acs.jafc.9b05507
(2019)Doi:10.1002/chem.201503123
(2015)Doi:10.1055/s-0030-1260199
(2011)Doi:10.1039/P19870002411
(1987)Doi:10.1039/b819959k
(2009)