Document Report Card

ID: ALA1152451

Journal: J Med Chem

Title: Discovery of a highly potent, selective, and bioavailable soluble epoxide hydrolase inhibitor with excellent ex vivo target engagement.

Authors: Shen HC, Ding FX, Wang S, Deng Q, Zhang X, Chen Y, Zhou G, Xu S, Chen HS, Tong X, Tong V, Mitra K, Kumar S, Tsai C, Stevenson AS, Pai LY, Alonso-Galicia M, Chen X, Soisson SM, Roy S, Zhang B, Tata JR, Berger JP, Colletti SL.

Abstract: 4-Substituted piperidine-derived trisubstituted ureas are reported as highly potent and selective inhibitors for sEH. The SAR outlines approaches to improve activity against sEH and reduce ion channel and CYP liability. With minimal off-target activity and a good PK profile, the benchmark 2d exhibited remarkable in vitro and ex vivo target engagement. The eutomer entA-2d also elicited vasodilation effect in rat mesenteric artery.

CiteXplore: 19645482

DOI: 10.1021/jm900725r