Discovery of 3,3-disubstituted piperidine-derived trisubstituted ureas as highly potent soluble epoxide hydrolase inhibitors
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- 作者：Hong C. Shen ; Fa-Xiang Ding ; Qiaolin Deng ; Suoyu Xu ; Hsuan-shen Chen ; Xinchun Tong ; Vincent Tong ; Xiaoping Zhang ; Yuli Chen ; Gaochao Zhou ; Lee-Yuh Pai ; Magdalena Alonso-Galicia ; Bei Zhang ; Sophie Roy
- 关键词：Inhibitors ; Ureas ; sEH ; Soluble epoxide hydrolase
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2009
- 出版时间：15 September 2009
- 年：2009
- 卷：19
- 期：18
- 页码：5314-5320
- 全文大小：2273 K
文摘
3,3-Disubstituted piperidine-derived trisubstituted urea entA-2b was discovered as a highly potent and selective soluble epoxide hydrolase (sEH) inhibitor. Despite the good compound oral exposure, excellent sEH inhibition in whole blood, and remarkable selectivity, compound entA-2b failed to lower blood pressure acutely in spontaneously hypertensive rats (SHRs). This observation further challenges the premise that sEH inhibition can provide a viable approach to the treatment of hypertensive patients.