Codony, SandraEntrena, José M.Calvó-Tusell, CarlaJora, BeatriceGonzález-Cano, RafaelOsuna, SílviaCorpas, RubénMorisseau, ChristophePérez, BelénBarniol-Xicota, MartaGriñán-Ferré, ChristianPérez, ConcepciónRodríguez-Franco, María IsabelMartínez, Antón L.Loza García, María IsabelPallàs, MercèVerhelst, Steven H. L.Sanfeliu, CoralFeixas, FerranHammock, Bruce D.Brea Floriani, José ManuelCobos, Enrique J.Vázquez, Santiago2026-01-232026-01-232022-10-120022-2623https://hdl.handle.net/10347/45397The 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.eng© 2022 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/InhibitionInhibitorsPeptides and proteinsRodent modelsUrea23 Químicajournal article10.1021/acs.jmedchem.2c005151520-4804open access