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Discovery of 3,3-disubstituted piperidine-derived trisubstituted ureas as highly potent soluble epoxide hydrolase inhibitors

  作者 Shen, HC; Ding, FX; Deng, QL; Xu, SY; Chen, HS; Tong, XC; Tong, V; Zhang, XP; Chen, YL; Zhou, GC; Pai, LY; Alonso-Galicia, M; Zhang, B; Roy, S; Tata, JR; Berger, JP; Colletti, SL  
  选自 期刊  Bioorganic & Medicinal Chemistry Letters;  卷期  2009年19-18;  页码  5314-5320  
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[摘要]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.

 
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