Non-urea functionality as the primary pharmacophore in soluble epoxide hydrolase inhibitors

被引：28

作者：

Anandan, Sampath-Kumar ^{[1
]}

Do, Zung N. ^{[1
]}

Webb, Heather K. ^{[1
]}

Patel, Dinesh V. ^{[1
]}

Gless, Richard D. ^{[1
]}

机构：

[1] Arete Therapeut Inc, Hayward, CA 94545 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 04期

关键词：

sEH inhibitors; Non-urea; Primary pharmacophore; 1,3-DISUBSTITUTED UREAS; THERAPEUTIC TARGET; POTENT INHIBITORS; WATER SOLUBILITY; HYPERTENSION; STROKE;

D O I：

10.1016/j.bmcl.2009.01.013

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Inhibition of soluble epoxide hydrolase has been proposed as a promising new pharmaceutical target for diseases involving hypertension and vascular inflammation. The most potent sEH inhibitors reported to date contain a urea or amide moiety as the central or 'primary' pharmacophore. We evaluated replacing the urea pharmacophore with other functional groups such as thiourea, sulfonamide, sulfonylurea, aminomethylene amide, hydroxyamide, and ketoamide to identify novel and potent inhibitors. The hydroxyamide moiety was identified as a novel pharmacophore affording potency comparable to urea. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1066 / 1070

页数：5

共 22 条

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