Discovery of a Highly Potent, Selective, and Bioavailable Soluble Epoxide Hydrolase Inhibitor with Excellent Ex Vivo Target Engagement

被引：41

作者：

Shen, Hong C. ^{[1
]}

Ding, Fa-Xiang ^{[1
]}

Wang, Siyi ^{[1
]}

Deng, Qiaolin ^{[1
]}

Zhang, Xiaoping ^{[1
]}

Chen, Yuli ^{[1
]}

Zhou, Gaochao ^{[1
]}

Xu, Suoyu ^{[1
]}

Chen, Hsuan-Shen ^{[1
]}

Tong, Xinchun ^{[1
]}

Tong, Vincent ^{[1
]}

Mitra, Kaushik ^{[1
]}

Kumar, Sanjeev ^{[1
]}

Tsai, Christine ^{[1
]}

Stevenson, Andra S. ^{[1
]}

Pai, Lee-Yuh ^{[1
]}

Alonso-Galicia, Magdalena ^{[1
]}

Chen, Xiaoli ^{[1
]}

Soisson, Stephen M. ^{[1
]}

Roy, Sophie ^{[1
]}

Zhang, Bei ^{[1
]}

Tata, James R. ^{[1
]}

Berger, Joel P. ^{[1
]}

Colletti, Steven L. ^{[1
]}

机构：

[1] Merck & Co Inc, Merck Res Labs, Rahway, NJ 07065 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 16期

关键词：

EPOXYEICOSATRIENOIC ACIDS; HYPERPOLARIZING FACTOR; BKCA CHANNELS; METABOLISM; ARTERIES;

D O I：

10.1021/jm900725r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

4-Substituted piperidine-derived trisubstituted ureas are reported as highly potent and selective inhibitors for sEH. The SAR Outlines approaches to improve activity against sEH and reduce ion channel and CYP liability. With minimal off-target activity and a good PK profile, the benchmark 2d exhibited remarkable tit vitro ;and ex vivo target engagement. The customer entA-2d also elicited vasodilation effect in tat mesenteric artery.

引用

页码：5009 / 5012

页数：4

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