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 García, María Isabel
A1 Pallàs, Mercè
A1 Verhelst, Steven H. L.
A1 Sanfeliu, Coral
A1 Feixas, Ferran
A1 Hammock, Bruce D.
A1 Brea Floriani, José Manuel
A1 Cobos, Enrique J.
A1 Vázquez, Santiago
K1 Inhibition
K1 Inhibitors
K1 Peptides and proteins
K1 Rodent models
K1 Urea
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.
PB ACS Publications
SN 0022-2623
YR 2022
FD 2022-10-12
LK https://hdl.handle.net/10347/45397
UL https://hdl.handle.net/10347/45397
LA eng
DS Minerva
RD 24 abr 2026