Amb motiu del tancament d'estiu, la validació de documents es reprendrà a partir del 28 d'agost de 2026. Disculpeu les molèsties.
Con motivo del cierre de verano, la validación de documentos se reanudará a partir del 28 de agosto de 2026. Disculpad las molestias
Due to the summer closure, document validation will resume starting August 28, 2026. We apologize for any inconvenience.

Fitxers

726508.pdf (5.51 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2022-10-27

Llicència de publicació

(c) Sandra Codony Gisbert, et al., 2022
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

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1021/acs.jmedchem.2c00515

Resum

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.

Matèries

Urea, Inflamació, Química clínica

Matèries (anglès)

Urea, Inflammation, Clinical chemistry

Citació

Col·leccions

Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

Citació

CODONY GISBERT, Sandra, et al. 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, num. 20, pags. 13660-13680. ISSN 0022-2623. [consulted: 15 of August of 2026]. Available at: https://hdl.handle.net/2445/194101

Exportar metadades

JSON - METS

Compartir registre