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Bioorg Med Chem Lett. 2009 Sep 15;19(18):5314-20. doi: 10.1016/j.bmcl.2009.07.138. Epub 2009 Aug 6.

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

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1
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. hong_shen@merck.com

Abstract

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.

PMID:
19682899
DOI:
10.1016/j.bmcl.2009.07.138
[Indexed for MEDLINE]
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