Add time:08/28/2019         Source:sciencedirect.com

A series of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent BTK inhibitors were designed, synthesized and evaluated. These thieno[3,2-c]pyridin-4-amine derivatives displayed variant inhibitory activities against BTK in vitro. Among these, 7-pyrazol-4-yl substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amine subseries showed high BTK inhibition and several compounds displayed superior BTK inhibitory activity. Comprehensive SAR was disclosed and compound 13b showed excellent potency (IC50 = 11.8 nM), outstanding hydrophilicity (A log P = 3.53), and relatively good kinase selectivity, being a promising lead for further evaluation.

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