Abstract
A series of macrocyclic α-keto amides containing the D-Phe-Pro-Arg (fPR) motif were synthesized and evaluated in vitro as inhibitors of human α-thrombin and bovine trypsin. Structure-function studies, relating ring size and modifications at the P3 and P1' positions to enzyme inhibition, are described. An X-ray crystallo-graphic study was performed on a ternary complex formed from 3i, thrombin, and hirugen.
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