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Title: | Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors |
Author: | 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, 1964- Verhelst, Steven H. L. Sanfeliu i Pujol, Coral Feixas, Ferran Hammock, Bruce D. Brea, José Cobos, Enrique J. Vázquez Cruz, Santiago |
Keywords: | Urea Inflamació Química clínica Urea Inflammation Clinical chemistry |
Issue Date: | 27-Oct-2022 |
Publisher: | American Chemical Society |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1021/acs.jmedchem.2c00515 |
It is part of: | Journal of Medicinal Chemistry, 2022, vol. 65, num. 20, p. 13660-13680 |
URI: | http://hdl.handle.net/2445/194101 |
Related resource: | https://doi.org/10.1021/acs.jmedchem.2c00515 |
ISSN: | 0022-2623 |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
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