期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 19, 期 13, 页码 3398-3404出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.05.036
关键词
Soluble epoxide hydrolase; sEH; Spirocyclic secondary amines; Spontaneously hypertensive rats; Tertiary ureas
Spirocyclic secondary amine-derived trisubstituted ureas were identified as highly potent, bioavailable and selective soluble epoxide hydrolase (sEH) inhibitors. Despite good oral exposure and excellent ex vivo target engagement in blood, one such compound, rac-1a, failed to lower blood pressure acutely in spontaneously hypertensive rats (SHRs). This study posed the question as to whether sEH inhibition provides a robust mechanism leading to a significant antihypertensive effect. (C) 2009 Elsevier Ltd. All rights reserved.
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