Non-urea functionality as the primary pharmacophore in soluble epoxide hydrolase inhibitors.
Inhibition of soluble epoxide hydrolase has been proposed as a promising new pharmaceutical target for diseases involving hypertension and vascular inflammation. The most potent sEH inhibitors reported to date contain a urea or amide moiety as the central or 'primary' pharmacophore. We evaluated replacing the urea pharmacophore with other functional groups such as thiourea, sulfonamide, sulfonylurea, aminomethylene amide, hydroxyamide, and ketoamide to identify novel and potent inhibitors. The hydroxyamide moiety was identified as a novel pharmacophore affording potency comparable to urea.
Anandan
Sampath-Kumar
SK
Arête Therapeutics, Inc., 3912 Trust Way, Hayward, CA 94545, USA. skumar@aretetherapeutics.com
Do
Zung N
ZN
Webb
Heather K
HK
Patel
Dinesh V
DV
Gless
Richard D
RD
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000577:Amides; D004851:Epoxide Hydrolases; D013890:Thiourea