Shen Hong C, Ding Fa-Xiang, Deng Qiaolin, Xu Suoyu, Chen Hsuan-Shen, Tong Xinchun, Tong Vincent, Zhang Xiaoping, Chen Yuli, Zhou Gaochao, Pai Lee-Yuh, Alonso-Galicia Magdalena, Zhang Bei, Roy Sophie, Tata James R, Berger Joel P, Colletti Steven L
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA.
Bioorg Med Chem Lett. 2009 Sep 15;19(18):5314-20. doi: 10.1016/j.bmcl.2009.07.138. Epub 2009 Aug 6.
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.
3,3-二取代哌啶衍生的三取代脲entA-2b被发现是一种高效且选择性的可溶性环氧化物水解酶（sEH）抑制剂。尽管该化合物口服暴露良好，在全血中对sEH有出色的抑制作用，且具有显著的选择性，但化合物entA-2b在自发性高血压大鼠（SHR）中未能急性降低血压。这一观察结果进一步挑战了sEH抑制可作为治疗高血压患者可行方法的前提。
