NOVEL THROMBIN INHIBITORS THAT ARE BASED ON A MACROCYCLIC TRIPEPTIDE MOTIF

Authors
GRECO MN POWELL ET HECKER LR ANDRADEGORDON P KAUFFMAN JA LEWIS JM GANESH V TULINSKY A MARYANOFF BE
Citation
Mn. Greco et al., NOVEL THROMBIN INHIBITORS THAT ARE BASED ON A MACROCYCLIC TRIPEPTIDE MOTIF, Bioorganic & medicinal chemistry letters, 6(24), 1996, pp. 2947-2952
Citations number
17
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
6
Issue
24
Year of publication
1996
Pages
2947 - 2952
Database
ISI
SICI code
0960-894X(1996)6:24<2947:NTITAB>2.0.ZU;2-O
Abstract
A series of macrocyclic alpha-keto amides containing the D-Phe-Pro-Arg (fPR) motif were synthesized and evaluated in vitro as inhibitors of human alpha-thrombin and bovine trypsin. Structure-function studies, r elating ring size and modifications at the P3 and P1' positions to enz yme inhibition, are described. An X-ray crystallographic study was per formed on a ternary complex formed from 3i, thrombin, and hirugen. Cop yright (C) 1996 Elsevier Science Ltd