Plasmin inhibitors with hydrophobic amino acid-based linker between hydantoin moiety and benzimidazole scaffold enhance inhibitory activity.

In this letter we report the design and synthesis of a series of plasmin inhibitors, which share the amino acid-based linker with limited free rotation between the hydantoin moiety and the benzimidazole scaffold. Our studies led to potent plasmin inhibitors and yielded important new insights into their structure-activity relationship for binding to the active site of plasmin.