Synthesis and SAR of conformationally restricted inhibitors of soluble epoxide hydrolase.
A series of conformationally restricted inhibitors of human soluble epoxide hydrolase (sEH) has been developed. Inhibition potency of the described compounds ranges from 4.2 microM to 1.1 nM against recombinant sEH. N-(1-Acetylpiperidin-4-yl)-N'-(adamant-1-yl) urea (5a) was found to be a potent inhibitor (IC(50) = 7.0 nM) that was also orally bioavailable in canines.
Jones
Paul D
PD
Department of Entomology and Cancer Research Center, One Shields Avenue, University of California, Davis, 95616, USA.
Tsai
Hsing-Ju
HJ
Do
Zung N
ZN
Morisseau
Christophe
C
Hammock
Bruce D
BD
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001682:Biological Availability; D004285:Dogs; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D014508:Urea; D004851:Epoxide Hydrolases