Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Pecic, Stevan¹  Pakhomova, Svetlana²  Newcomer, Marcia E.²  Morisseau, Christophe^3,4  Hammock, Bruce D.^3,4  Zhu, Zhengxiang¹  Rinderspacher, Alison¹  Deng, Shi-Xian¹ 

[1] Columbia Univ, Dept Med, New York, NY 10032 USA

[2] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA

[3] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA

[4] Univ Calif Davis, UCD Canc Ctr, Davis, CA 95616 USA

关键词: Soluble epoxide hydrolase;    Non-urea inhibitors;    Hypertension;    Human liver microsomes stability;   

DOI  :  10.1016/j.bmcl.2012.11.084

来源: Elsevier

【 摘 要 】

A series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed. The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs. Structure-activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development. Published by Elsevier Ltd.

【 授权许可】

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