Unsymmetrical non-adamantyl N,N-diaryl urea and amide inhibitors of soluble expoxide hydrolase

被引：25

作者：

Anandan, Sampath-Kumar ^{[1
]}

Webb, Heather K. ^{[1
]}

Do, Zung N. ^{[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 / 15期

关键词：

sEH inhibitors; Non-adamantyl; Unsymmetrical urea; EPOXIDE HYDROLASE; 12-(3-ADAMANTAN-1-YL-UREIDO)DODECANOIC ACID; 1,3-DISUBSTITUTED UREAS; THERAPEUTIC TARGET; POTENT INHIBITORS; METABOLISM; PHARMACOKINETICS; HYPERTENSION; RIMANTADINE; ANTAGONIST;

D O I：

10.1016/j.bmcl.2009.05.102

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Incorporation of an adamantyl group in prototypical soluble expoxide hydrolase (sEH) inhibitors afforded improved enzyme potency. We explored replacement of the adamantyl group in unsymmetrical ureas and amides with substituted aryl rings to identify equipotent and metabolically stable sEH inhibitors. We found that aryl rings, especially those substituted in the para position with a strongly electron withdrawing substituent, afforded enzyme IC50 values comparable to the adamantyl compounds in an ether substituted, unsymmetrical N,N'-diaryl urea or amide scaffold. (C) 2009 Elsevier Ltd. All rights reserved.

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收藏

页码：4259 / 4263

页数：5

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