Codony Gisbert, SandraEntrena, José M.Calvó-Tusell, CarlaJora, Beatrice ElenaGonzález Cano, Rafael C.Osuna, SílviaCorpas Expósito, RubénMorisseau, ChristophePérez, BelénBarniol-Xicota, MartaGriñán Ferré, ChristianPérez, ConcepciónRodríguez-Franco, María IsabelMartínez, Antón L.Loza, María IsabelPallàs i Llibería, Mercè, 1964-Verhelst, Steven H. L.Sanfeliu i Pujol, CoralFeixas, FerranHammock, Bruce D.Brea, JoséCobos, Enrique J.Vázquez Cruz, Santiago2023-02-242023-02-242022-10-270022-2623https://hdl.handle.net/2445/194101The 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.21 p.application/pdfeng(c) Sandra Codony Gisbert, et al., 2022http://creativecommons.org/licenses/by-nc-nd/3.0/es/UreaInflamacióQuímica clínicaUreaInflammationClinical chemistryinfo:eu-repo/semantics/article7265082023-02-24info:eu-repo/semantics/openAccess