Tripeptidyl pyridinium methyl ketones as potent active site inhibitors of thrombin

Several substituted methyl ketone derivatives of tripeptides with a C-terminal arginyl residue were synthesized as active site inhibitors of human α-thrombin. The most active compound among this series was the pyridinium methyl ketone D-Cha-Pro-Arg-PMK, which was characterized as a slow-binding inhibitor with a Ki of 0.19 nM.