Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors

被引：49

作者：

Burmistrov, Vladimir ^{[2
,3
]}

Morisseau, Christophe ^{[1
]}

Lee, Kin Sing Stephen ^{[1
]}

Shihadih, Diyala S. ^{[1
]}

Harris, Todd R. ^{[1
]}

Butov, Gennady M. ^{[2
,3
]}

Hammock, Bruce D. ^{[1
]}

机构：

[1] Univ Calif Davis, Ctr Comprehens Canc, Dept Entomol & Nematol, Davis, CA 95616 USA

[2] Volgograd State Tech Univ, Volzhsky Polytech Inst Branch, Dept Chem & Gen Chem Technol, Volzhsky, Russia

[3] Volgograd State Tech Univ, Volgograd, Russia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 09期

基金：

俄罗斯基础研究基金会;

关键词：

Soluble epoxide hydrolase; Inhibitor; Adamantane; Isocyanate; Diurea; EPOXYEICOSATRIENOIC ACIDS; WATER SOLUBILITY; BLOOD-PRESSURE; UREA; HYPERTENSION; HYDROLYSIS; MECHANISM; DISCOVERY;

D O I：

10.1016/j.bmcl.2014.03.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of inhibitors of the soluble epoxide hydrolase (sEH) containing two urea groups has been developed. Inhibition potency of the described compounds ranges from 2.0 mu M to 0.4 nM. 1,6-(Hexamethylene)bis[(adamant-1-yl) urea] (3b) was found to be a potent slow tight binding inhibitor (IC50 = 0.5 nM) with a strong binding to sEH (K-i = 3.1 nM) and a moderately long residence time on the enzyme (k(off) = 1.05 x 10(-3) s(-1); t(1/2) = 11 min). (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：2193 / 2197

页数：5

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