RT Journal Article
T1 Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors.
A1 Codony, Sandra
A1 Entrena, José M
A1 Calvó-Tusell, Carla
A1 Jora, Beatrice
A1 González-Cano, Rafael
A1 Osuna, Sílvia
A1 Corpas, Rubén
A1 Morisseau, Christophe
A1 Pérez, Belén
A1 Barniol-Xicota, Marta
A1 Griñán-Ferré, Christian
A1 Pérez, Concepción
A1 Rodríguez-Franco, María Isabel
A1 Martínez, Antón L
A1 Loza, M Isabel
A1 Pallàs, Mercè
A1 Verhelst, Steven H L
A1 Sanfeliu, Coral
A1 Feixas, Ferran
A1 Hammock, Bruce D
A1 Brea, José
A1 Cobos, Enrique J
A1 Vázquez, Santiago
AB 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.
YR 2022
FD 2022-10-12
LK http://hdl.handle.net/10668/22591
UL http://hdl.handle.net/10668/22591
LA en
DS RISalud
RD Apr 19, 2025