Benzylamine-based selective and orally bioavailable inhibitors of thrombin

A series of p-aminomethylphenylalanine derivatives were investigated as novel thrombin inhibitors. This study led to potent inhibitors of thrombin (Ki up to 3.3 nM) that are trypsin-selective, highly orally bioavailable in rats, and highly permeable across Caco-2 cells. The P1 benzylamine binding mode in the thrombin active site was identified by X-ray crystallographic analysis.