The inhibitory potency of the series of inhibitors of the soluble epoxide hydrolase (sEH) based on the selenourea moiety and containing adamantane and aromatic lipophilic groups ranges from 34.3 nM to 1.2 μM. The most active compound 5d possesses aliphatic spacers between the selenourea group and lipophilic fragments. Synthesized compounds were tested against the LPS-induced activation of primary murine macrophages. The most prominent anti-inflammatory activity, defined as a suppression of nitric oxide synthesis by LPS-stimulated macrophages, was demonstrated for compounds 4a and 5b. The cytotoxicity of the obtained substances was studied using human neuroblastoma and fibroblast cell cultures. Using these cell assays, the cytotoxic concentration for 4a was 4.7–18.4 times higher than the effective anti-inflammatory concentration. The genotoxicity and the ability to induce oxidative stress was studied using bacterial lux-biosensors. Substance 4a does not exhibit genotoxic properties, but it can cause oxidative stress at concentrations above 50 µM. Put together, the data showed the efficacy and safety of compound 4a.

A series of N,N′-(alkane-α,ω-diyl)bis[N′-(adamantan-1-yl)selenoureas] have been synthesized in 27–84% yields by the reaction of adamantan-1-yl isoselenocyanate with alkane-α,ω-diamines. The synthesized compounds melted in the range 105–164°C, which is lower by ~80°C than the melting point range of their isosteric analogs containing urea fragments. N,N′-(Alkane-α,ω-diyl)bis[N′-(adamantan-1-yl)selenoureas] are promising as inhibitors of human soluble epoxide hydrolase.

A new procedure has been proposed for the synthesis of 3-chloroadamantan-1-ylmethyl isocyanate starting from 2-(3-chloroadamantan-1-yl)acetic acid. Reactions of 3-chloroadamantan-1-ylmethyl isocyanate with fluoro- and chloroanilines and alkane-α,ω-diamines afforded two series of N,N′-disubstituted ureas containing a 3-chloroadamantan-1-yl substituent in 53–94% yields. The synthesized ureas are promising as inhibitors of human soluble epoxide hydrolase.

A one-stage method for the preparation of 1-[isocyanato(phenyl)methyl]adamantane containing a phenylmethylene fragment located between the adamantane fragment and the isocyanate group, and 1-[isocyanato(phenyl)methyl]-3,5-dimethyladamantane with additional methyl groups at the nodal positions of adamantane, with a yield of 95% and 89%, respectively, is described. The method includes the direct inclusion of an adamantane moiety through the reaction of phenylacetic acid ethyl ester with 1,3-dehydroadamantane or 3,5-dimethyl-1,3-dehydroadamantane followed by the hydrolysis of the obtained esters. The reaction of 1-[isocyanato(phenyl)methyl]adamantane with fluorine(chlorine)-containing anilines gave a series of 1,3-disubstituted ureas with 25–85% yield. 1-[Isocyanato(phenyl)methyl]-3,5-dimethyladamantane was involved in the reactions with fluorine(chlorine)-containing anilines and trans-4-amino-(cyclohexyloxy)benzoic acid to obtain another series of ureas with a yield of 29–74%. The resulting 1,3-disubstituted ureas are promising inhibitors of the human soluble epoxide hydrolase (hsEH).

The reaction of (S)-(–)-1-isocyanato-4,7,7-trimethyl-2-oxabicyclo[2.2.1]heptan-3-one with fluoro- and chloro-substituted anilines afforded a series of N,N′-disubstituted ureas containing a natural lipophilic camphanic acid moiety in 42–75% yield. The synthesized compounds are promising as inhibitors of human soluble epoxide hydrolase.