Burmistrov Vladimir, Morisseau Christophe, D'yachenko Vladimir, Rybakov Victor B, Butov Gennady M, Hammock Bruce D
Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, CA, 95616, USA.
Department of Chemistry, Technology and Equipment of Chemical Industry, Volzhsky Polytechnic Institute (branch) Volgograd State Technical University, Volzhsky, 404121, Russia.
J Fluor Chem. 2019 Apr;220:48-53. doi: 10.1016/j.jfluchem.2019.02.005. Epub 2019 Feb 13.
A series of soluble epoxide hydrolase (sEH) inhibitors containing 2-fluorophenyl fragment was developed. Inhibition potency of the described compounds ranges from 0.7 to 630.9 nM. 1-(Adamantan-1-ylmethyl)-3-(2-fluorophenyl) urea (, IC = 0.7 nM) and 1-(adamantan-2-yl)-3-(2-fluorophenyl) urea (, IC =1.0 nM) were found to be the most potent sEH inhibitors within the described series. Crystal results suggest that potency is probably enhanced by extra hydrogen bond between the fluorine atom and catalytic tyrosine residues.
开发了一系列含有2-氟苯基片段的可溶性环氧化物水解酶（sEH）抑制剂。所述化合物的抑制活性范围为0.7至630.9 nM。发现1-（金刚烷-1-基甲基）-3-（2-氟苯基）脲（，IC = 0.7 nM）和1-（金刚烷-2-基）-3-（2-氟苯基）脲（，IC = 1.0 nM）是所述系列中最有效的sEH抑制剂。晶体结果表明，氟原子与催化酪氨酸残基之间的额外氢键可能会增强活性。
