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- ItemSynthesis, in Vitro Profiling, and in Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors(Washington, DC : ACS, 2022) Codony, Sandra; Entrena, José M.; Calvó-Tusell, Carla; Jora, Beatrice; González-Cano, Rafael; Osuna, Sílvia; Corpas, Rubén; Morisseau, Christophe; Pérez, Belén; Barniol-Xicota, Marta; Griñán-Ferré, Christian; Pérez, Concepción; Rodríguez-Franco, María Isabel; Martínez, Antón L.; Loza, M. Isabel; Pallàs, Mercè; Verhelst, Steven H. L.; Sanfeliu, Coral; Feixas, Ferran; Hammock, Bruce D.; Brea, José; Cobos, Enrique J.; Vázquez, SantiagoThe soluble epoxide hydrolase (sEH) has been suggested as a pharmacological target for the treatment of several diseases, including pain-related disorders. Herein, we report further medicinal chemistry around new benzohomoadamantane-based sEH inhibitors (sEHI) in order to improve the drug metabolism and pharmacokinetics properties of a previous hit. After an extensive in vitro screening cascade, molecular modeling, and in vivo pharmacokinetics studies, two candidates were evaluated in vivo in a murine model of capsaicin-induced allodynia. The two compounds showed an anti-allodynic effect in a dose-dependent manner. Moreover, the most potent compound presented robust analgesic efficacy in the cyclophosphamide-induced murine model of cystitis, a well-established model of visceral pain. Overall, these results suggest painful bladder syndrome as a new possible indication for sEHI, opening a new range of applications for them in the visceral pain field.