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

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• 作者：Hong C. Shen ; Fa-Xiang Ding ; Siyi Wang ; Qiaolin Deng ; Xiaoping Zhang ; Yuli Chen ; Gaochao Zhou ; Suoyu Xu ; Hsuan-shen Chen ; Xinchun Tong ; Vincent Tong ; Kaushik Mitra ; Sanjeev Kumar ; Christine Tsai ; Andr
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：August 27, 2009
• 年：2009
• 卷：52
• 期：16
• 页码：5009-5012
• 全文大小：837K
• 年卷期：v.52,no.16(August 27, 2009)
• ISSN：1520-4804

文摘

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 in vitro and ex vivo target engagement. The eutomer entA-2d also elicited vasodilation effect in rat mesenteric artery.