Discovery of thieno[3,2-c]pyridin-4-amines as novel Bruton's tyrosine kinase (BTK) inhibitors.

A novel series of BTK inhibitors bearing thieno[3,2-c]pyridin-4-amine framework as the core scaffold were designed, synthesized and well characterized. In this paper, twenty one compounds displayed variant inhibitory activities against BTK in vitro, and compound 14 g showed the most potent inhibitory activity against BTK enzyme, with the IC50 value of 12.8 nM. Moreover, compounds 14 g displayed relatively good kinase selectivity and was subsequently evaluated in vivo for profiling its PK properties. This work identified the thieno[3,2-c]pyridin-4-amine derivatives as novel BTK inhibitors and verified the value of thieno[3,2-c]pyridin-4-amine scaffold in drug design.