Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ 07065-0900, USA.
J Med Chem. 2009 Aug 27;52(16):5009-12. doi: 10.1021/jm900725r.
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.
报告称，4-取代哌啶衍生的三取代脲是高效且选择性的 sEH 抑制剂。SAR 概述了提高 sEH 活性和降低离子通道及 CYP 毒性的方法。作为基准化合物 2d，具有最小的脱靶活性和良好的 PK 特征，表现出显著的体外和离体靶标结合。优势对映异构体 entA-2d 也可引起大鼠肠系膜动脉舒张作用。
