Novel thrombin inhibitors that are based on a macrocyclic tripeptide motif

Novel thrombin inhibitors that are based on a macrocyclic tripeptide motif Original Research Article Pages 2947-2952 Michael N. Greco, Eugene T. Powell, Leonard R. Hecker, Patricia Andrade-Gordon, Jack A. Kauffman, Joan M. Lewis, Venkatapathy Ganesh, Alexander Tulinsky, Bruce E. Maryanoff Close Close preview | Purchase PDF (280 K) | Related articles | Related reference work articles AbstractAbstract | ReferencesReferences 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 P1ʹ positions to enzyme inhibition, are described. An X-ray crystallo-graphic study was performed on a ternary complex formed from 3i, thrombin, and hirugen. Article Outline • References