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Papers of the Week

Papers: 8 Oct 2022 - 14 Oct 2022

Pharmacology/Drug Development

2022 Oct 12

J Med Chem

Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors.


Codony S, Entrena JM, Calvó-Tusell C, Jora B, González-Cano R, Osuna S, Corpas R, Morisseau C, Pérez B, Barniol-Xicota M, Griñán-Ferré C, Pérez C, Rodríguez-Franco M I, Martínez AL, Loza IM, Pallàs M, Verhelst SHL, Sanfeliu C, Feixas F, Hammock BD, et al.
J Med Chem. 2022 Oct 12.
PMID: 36222708.


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.