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  • Title: Discovery of spirocyclic secondary amine-derived tertiary ureas as highly potent, selective and bioavailable soluble epoxide hydrolase inhibitors.
    Author: Shen HC, Ding FX, Wang S, Xu S, Chen HS, Tong X, Tong V, Mitra K, Kumar S, Zhang X, Chen Y, Zhou G, Pai LY, Alonso-Galicia M, Chen X, Zhang B, Tata JR, Berger JP, Colletti SL.
    Journal: Bioorg Med Chem Lett; 2009 Jul 01; 19(13):3398-404. PubMed ID: 19481932.
    Abstract:
    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.
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