Solid-phase parallel synthesis applied to lead optimization: Discovery of potent analogues of the GPIIb/IIIa antagonist RWJ-50042

被引：35

作者：

Hoekstra, WJ

Maryanoff, BE

AndradeGordon, P

Cohen, JH

Costanzo, MJ

Damiano, BP

Haertlein, BJ

Harris, BD

Kauffman, JA

Keane, PM

McComsey, DF

Villani, FJ

Yabut, SC

机构：

[1] R. W. Johnson Pharmaceutical Res. I., Spring House

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1996年 / 6卷 / 20期

关键词：

FIBRINOGEN; NONPEPTIDE;

D O I：

10.1016/0960-894X(96)00438-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A study of beta-turn peptide mimetics, related to the C-terminal gamma-chain of fibrinogen and containing a nipecotic acid scaffold, led to RWJ-50042 (1), an interesting fibrinogen receptor (GPIIb/IIIa) antagonist. To enhance potency, we employed solid-phase parallel synthesis for the preparation of over 200 analogues in a protocol of optimization cycles. This strategy produced several promising nipecotamide analogues, such as 25, which is 35 times more potent than 1 in vitro. Copyright (C) 1996 Elsevier Science Ltd.

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页码：2371 / 2376

页数：6

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