Discovery of 3,3-disubstituted piperidine-derived trisubstituted ureas as highly potent soluble epoxide hydrolase inhibitors
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、James R. Tata、Joel P. Berger、Steven L. Colletti
DOI:10.1016/j.bmcl.2009.07.138
日期:2009.9
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. (C) 2009 Elsevier Ltd. All rights reserved.