Synthesis and Properties of 1,3-Disubstituted Ureas and Their Isosteric Analogs Containing Polycyclic Fragments: IV.¹ 1-(Bicyclo[2.2.1]hept-5-en-2-yl)-3-(fluoro, chlorophenyl)ureas

Abstract: The reaction of bicyclo[2.2.1]hept-5-en-2-yl isocyanate with fluoro- andchloro-substituted anilines was used to synthesize in a yield of 25–68% a seriesof 1,3-disubstituted ureas containing a lipophilic group in their structure. Thesynthesized ureas are promising as inhibitors of RNA virus replication and humansoluble epoxide hydrolase

Synthesis and Properties of 1,3-Disubstituted Ureas and Their Isosteric Analogs Containing Polycyclic Fragments: V. 1-(Bicyclo[2.2.1]heptan-2-yl)-3-R- and 1-(1,7,7-Tricyclo[2.2.1]heptan-2-yl)-3-R-ureas

Abstract: A series of 1,3-disubstituted ureas containing a bicyclic lipophilic group ofnatural origin were synthesized by the reactions of bicyclo[2.2.1]heptane-2-ylisocyanate with amines in yields of up to 82% and by the reactions ofbicyclo[2.2.1]heptan-2-amine and 1,7,7-trimethylbicyclo[2.2.1]heptan-2-aminewith 1,1'-carbonyldiimidazole in yields of up to 94%. The synthesized ureas arepotent inhibitors of RNA virus replication and soluble epoxide hydrolase

Anti-Inflammatory Activity of Soluble Epoxide Hydrolase Inhibitors Based on Selenoureas Bearing an Adamantane Moiety

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