Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 22, Issue 5, Pages 1548-1557Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2014.01.040
Keywords
Soluble epoxide hydrolase; Inhibitors; Epoxyeicosatrienoic acids; Cyclopropyl urea; DOCA-salt rat; Renal protection
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Epoxyeicosatrienoic acids (EETs) are known to have beneficial pharmacological effects on various cardiovascular events. However, EETs are biologically metabolized by soluble epoxide hydrolase (sEH) to less active metabolites. In our search for potent sEH inhibitors, we optimized a series of cyclopropyl urea derivatives and identified compound 38 as a potent sEH inhibitor with minimal CYP inhibition and good oral absorption in rats. Administration of 38 to DOCA-salt rats suppressed urinary albumin and MCP-1 excretion without affecting systolic blood pressure. (C) 2014 Elsevier Ltd. All rights reserved.
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