Novel thrombin inhibitors that are based on a macrocyclic tripeptide motif

被引：17

作者：

Greco, MN ^{[1
]}

Powell, ET ^{[1
]}

Hecker, LR ^{[1
]}

AndradeGordon, P ^{[1
]}

Kauffman, JA ^{[1
]}

Lewis, JM ^{[1
]}

Ganesh, V ^{[1
]}

Tulinsky, A ^{[1
]}

Maryanoff, BE ^{[1
]}

机构：

[1] MICHIGAN STATE UNIV,DEPT CHEM,E LANSING,MI 48824

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1996年 / 6卷 / 24期

关键词：

D O I：

10.1016/S0960-894X(96)00554-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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, relating ring size and modifications at the P3 and P1' positions to enzyme inhibition, are described. An X-ray crystallographic study was performed on a ternary complex formed from 3i, thrombin, and hirugen. Copyright (C) 1996 Elsevier Science Ltd

引用

页码：2947 / 2952

页数：6

共 17 条

[1]

BALASUBRAMANIAN B, 1995, BIOORG MED CHEM, V3

[2]

Berliner L.J., 1992, THROMBIN STRUCTURE F

[3] THE REFINED 1.9 A CRYSTAL-STRUCTURE OF HUMAN ALPHA-THROMBIN - INTERACTION WITH D-PHE-PRO-ARG CHLOROMETHYLKETONE AND SIGNIFICANCE OF THE TYR-PRO-PRO-TRP INSERTION SEGMENT [J].