Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors.
Publication Type:Journal Article
Source:Bioorg Med Chem Lett, Volume 23, Issue 2, p.417-21 (2013)
Keywords:Anti-Inflammatory Agents, Catalytic Domain, Epoxide Hydrolases, Humans, Inhibitory Concentration 50, Microsomes, Liver, Models, Molecular, Molecular Structure, Piperidines, Protease Inhibitors, Solubility, Structure-Activity Relationship, Urea, Vasodilator Agents
<p>A series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed. The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs. Structure-activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development.</p>