Solid-phase combinatorial approach for the optimization of soluble epoxide hydrolase inhibitors.
A 192-member library of N,N'-disubstituted urea inhibitors was synthesized by a solid-phase method. The ureas were tested for their inhibitory activities against recombinant human soluble epoxide hydrolase. Simple carbocyclic or para/meta-substituted phenyl groups showed inhibition potencies that were equal to or greater than adamantane-based sEH inhibitors, while the presence of bulky or ionizable groups close to the urea group dramatically decreased their activities.
Hwang
Sung Hee
SH
Department of Entomology and UCD Cancer Center, University of California, One Shields Avenue, Davis, CA 95616-8584, USA.
Morisseau
Christophe
C
Do
Zung
Z
Hammock
Bruce D
BD
D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D012995:Solubility; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry*
D004791:Enzyme Inhibitors; D014508:Urea; D004851:Epoxide Hydrolases