Synthesis and Properties of N-(R-Adamantan-1-ylalkyl)-N′-[3(4)-fluorophenyl]thioureas—Target-Oriented Human Soluble Epoxide Hydrolase (hsEH) Inhibitors

Abstract

Reactions of 3(4)-fluorophenyl isothiocyanates with amines of the adamantane series in DMF afforded 86–93% of the corresponding N,N′-disubstituted thioureas that are target-oriented inhibitors of human soluble epoxide hydrolase (hsEH). The effect of isosteric replacement of hydrogen in the aromatic fragment by fluorine and of oxygen in the urea fragment by sulfur on the IC₅₀ value was estimated. The inhibitory activity increases twofold for the 3-fluorophenyl derivatives and ninefold for 4-fluorophenyl analogs.