DESIGN AND SYNTHESIS OF RING-CONSTRAINED BOROPEPTIDE THROMBIN INHIBITORS

Authors
FEVIG JM ABELMAN MM BRITTELLI DR KETTNER CA KNABB RM WEBER PC
Citation
Jm. Fevig et al., DESIGN AND SYNTHESIS OF RING-CONSTRAINED BOROPEPTIDE THROMBIN INHIBITORS, Bioorganic & medicinal chemistry letters, 6(3), 1996, pp. 295-300
Citations number
19
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
6
Issue
3
Year of publication
1996
Pages
295 - 300
Database
ISI
SICI code
0960-894X(1996)6:3<295:DASORB>2.0.ZU;2-I
Abstract
Ring-constrained boropeptide thrombin inhibitors were designed using i nformation from the X-ray crystal structure of 1 (3-Phenylpropionyl-Pr o-borolys-OH . HCl) bound to thrombin. The constraints utilized cycloh exane and pyrrolidine rings to preorganize an aromatic ring in an orie ntation allowing optimum edge-to-face interaction with the tryptophan 215 side chain located in the S3 specificity pocket of thrombin.