%0 Journal Article
%A Codony, Sandra
%A Entrena, José M
%A Calvó-Tusell, Carla
%A Jora, Beatrice
%A González-Cano, Rafael
%A Osuna, Sílvia
%A Corpas, Rubén
%A Morisseau, Christophe
%A Pérez, Belén
%A Barniol-Xicota, Marta
%A Griñán-Ferré, Christian
%A Pérez, Concepción
%A Rodríguez-Franco, María Isabel
%A Martínez, Antón L
%A Loza, M Isabel
%A Pallàs, Mercè
%A Verhelst, Steven H L
%A Sanfeliu, Coral
%A Feixas, Ferran
%A Hammock, Bruce D
%A Brea, José
%A Cobos, Enrique J
%A Vázquez, Santiago
%T Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors.
%D 2022
%U http://hdl.handle.net/10668/22591
%X The 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.
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