Synthesis and properties of 1-[(3-fluoroadamantan-1-yl)methyl]-3-R-ureas and 1,1′-(alkan-1,n-diyl)bis{3-[(3-fluoroadamantan-1-yl)methyl]ureas} as promising soluble epoxide hydrolase inhibitors

A two-step procedure to synthesize (3-fluoroadamantan-1-yl)methyl isocyanate from (3-hydroxyadamantane)acetic acid that involves fluorination with Ishikawa’s reagent on the first step of the synthesis was developed. The reaction of (3-fluoroadamantan-1-yl)methyl isocyanate with aliphatic diamines gave 1,3-disubstituted bis-diureas in 60–97% yields. A strong decrease in the melting points of the obtained ureas (up to ∼70–144 °C) was observed upon introduction of the fluorine atoms at the bridgehead positions of the adamantane unit.