1402547-53-8Relevant articles and documents
14,15-Epoxyeicosa-5,8,11-trienoic acid (14,15-EET) surrogates: Carboxylate modifications
Falck, John R.,Koduru, Sreenivasulu Reddy,Mohapatra, Seetaram,Manne, Rajkumar,Atcha, Raju,Manthati, Vijaya L.,Capdevila, Jorge H.,Christian, Sarah,Imig, John D.,Campbell, William B.
, p. 6965 - 6972 (2014/11/08)
The cytochrome P450 eicosanoid 14,15-epoxyeicosa-5,8,11-trienoic acid (14,15-EET) is a powerful endogenous autacoid that has been ascribed an impressive array of physiologic functions including regulation of blood pressure. Because 14,15-EET is chemically and metabolically labile, structurally related surrogates containing epoxide bioisosteres were introduced and have become useful in vitro pharmacologic tools but are not suitable for in vivo applications. A new generation of EET mimics incorporating modifications to the carboxylate were prepared and evaluated for vasorelaxation and inhibition of soluble epoxide hydrolase (sEH). Tetrazole 19 (ED50 0.18 μM) and oxadiazole-5-thione 25 (ED50 0.36 μM) were 12- and 6-fold more potent, respectively, than 14,15-EET as vasorelaxants; on the other hand, their ability to block sEH differed substantially, i.e., 11 vs >500 nM. These data will expedite the development of potent and specific in vivo drug candidates.
