Exploratory solid-phase synthesis of factor Xa inhibitors:: Discovery and application of P3-heterocyclic amides as novel types of non-basic arginine surrogates

被引：7

作者：

Ho, JZ ^{[1
]}

Levy, OE ^{[1
]}

Gibson, TS ^{[1
]}

Nguyen, K ^{[1
]}

Semple, JE ^{[1
]}

机构：

[1] Corvas Int Inc, Dept Med Chem, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 24期

关键词：

D O I：

10.1016/S0960-894X(99)00628-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel FXa inhibitors 2a-m and 3a-f was discovered that feature heterocyclic carboxamides tethered to a d-diaminobutyric acid sidechain. These neutral amide derivatives serve as novel P-3 d-arginine mimics. Pyrazine carboxamide scaffolds afforded the most potent FXa inhibitors (e.g., 2b IC50 = 4.6 nM). The synthesis and biological activity of two focused libraries are reported. (C) 1999 Elsevier Science Ltd. All rights reserved.

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页码：3459 / 3464

页数：6

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