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ID: ALA1156003

Journal: Bioorg Med Chem Lett

Title: A strategy of employing aminoheterocycles as amide mimics to identify novel, potent and bioavailable soluble epoxide hydrolase inhibitors.

Authors: Shen HC, Ding FX, Deng Q, Xu S, Tong X, Zhang X, Chen Y, Zhou G, Pai LY, Alonso-Galicia M, Roy S, Zhang B, Tata JR, Berger JP, Colletti SL.

Abstract: Distinct from previously reported urea and amide inhibitors of soluble epoxide hydrolase (sEH), a novel class of inhibitors were rationally designed based on the X-ray structure of this enzyme and known amide inhibitors. The structure-activity relationship (SAR) study was focused on improving the sEH inhibitory activity. Aminobenzisoxazoles emerged to be the optimal series, of which a potent human sEH inhibitor 7t was identified with a good pharmacokinetics (PK) profile. The strategy of employing aminoheterocycles as amide replacements may represent a general approach to develop mimics of known hydrolase or protease inhibitors containing an amide moiety.

CiteXplore: 19700315

DOI: 10.1016/j.bmcl.2009.08.006