Novel bicyclic lactam inhibitors of thrombin:: Potency and selectivity optimization through P1 residues

被引：15

作者：

Lévesque, S

St-Denis, Y

Bachand, B

Préveille, P

Leblond, L

Winocour, PD

Edmunds, JJ

Rubin, JR

Siddiqui, MA

机构：

[1] Shire Biochem Inc, Laval, PQ H7V 4A7, Canada

[2] Pfizer Global Res & Dev, Ann Arbor, MI 48105 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 24期

关键词：

D O I：

10.1016/S0960-894X(01)00661-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Peptidomimetic inhibitors of thrombin lacking the important Ser195-carbonyl interaction have been prepared. The binding energy lost after the removal of the activated carbonyl was recaptured through a series of modifications of the PI residues of the bicyclic lactam inhibitors. Selected substituted compounds displayed useful pharmacological profiles both in vitro and in vivo. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：3161 / 3164

页数：4

共 8 条

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