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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/194101
Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors
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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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CODONY GISBERT, Sandra, ENTRENA, José m., CALVÓ-TUSELL, Carla, JORA, Beatrice elena, GONZÁLEZ CANO, Rafael c., OSUNA, Sílvia, CORPAS EXPÓSITO, Rubén, MORISSEAU, Christophe, PÉREZ, Belén, BARNIOL-XICOTA, Marta, GRIÑÁN FERRÉ, Christian, PÉREZ, Concepción, RODRÍGUEZ-FRANCO, María isabel, MARTÍNEZ, Antón l., LOZA, María isabel, PALLÀS I LLIBERÍA, Mercè, VERHELST, Steven h. l., SANFELIU I PUJOL, Coral, FEIXAS, Ferran, HAMMOCK, Bruce d., BREA, José, COBOS, Enrique j., VÁZQUEZ CRUZ, Santiago. Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors. _Journal of Medicinal Chemistry_. 2022. Vol. 65, núm. 20, pàgs. 13660-13680. [consulta: 6 de maig de 2026]. ISSN: 0022-2623. [Disponible a: https://hdl.handle.net/2445/194101]