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
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
收藏
页码:295 / 300
页数:6
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