Design and synthesis of ring-constrained boropeptide thrombin inhibitors

被引：37

作者：

Fevig, JM

Abelman, MM

Brittelli, DR

Kettner, CA

Knabb, RM

Weber, PC

机构：

[1] DuPont Merck Pharmaceutical Company, Wilmington, DE 19880-0500

[2] Corvas International, Inc., San Diego, CA 92121

[3] Bayer Corporation, West Haven, CT 06516

[4] Schering-Plough Research Institute, Kenilworth, NJ 07033

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1996年 / 6卷 / 03期

关键词：

D O I：

10.1016/0960-894X(96)00015-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Ring-constrained boropeptide thrombin inhibitors were designed using information from the X-ray crystal structure of 1 (3-Phenylpropionyl-Pro-borolys-OH . HCl) bound to thrombin. The constraints utilized cyclohexane and pyrrolidine rings to preorganize an aromatic ring in an orientation allowing optimum edge-to-face interaction with the tryptophan 215 side chain located in the S3 specificity pocket of thrombin.

引用

页码：295 / 300

页数：6

共 19 条

[1] AROMATIC-AROMATIC INTERACTION - A MECHANISM OF PROTEIN-STRUCTURE STABILIZATION [J].