Title : Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors - Codony_2022_J.Med.Chem_65_13660 |
Author(s) : Codony S , Entrena JM , Calvo-Tusell C , Jora B , Gonzalez-Cano R , Osuna S , Corpas R , Morisseau C , Perez B , Barniol-Xicota M , Grinan-Ferre C , Perez C , Rodriguez-Franco MI , Martinez AL , Loza MI , Pallas M , Verhelst SHL , Sanfeliu C , Feixas F , Hammock BD , Brea J , Cobos EJ , Vazquez S |
Ref : Journal of Medicinal Chemistry , 65 :13660 , 2022 |
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. |
PubMedSearch : Codony_2022_J.Med.Chem_65_13660 |
PubMedID: 36222708 |
Codony S, Entrena JM, Calvo-Tusell C, Jora B, Gonzalez-Cano R, Osuna S, Corpas R, Morisseau C, Perez B, Barniol-Xicota M, Grinan-Ferre C, Perez C, Rodriguez-Franco MI, Martinez AL, Loza MI, Pallas M, Verhelst SHL, Sanfeliu C, Feixas F, Hammock BD, Brea J, Cobos EJ, Vazquez S (2022)
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
65 :13660
Codony S, Entrena JM, Calvo-Tusell C, Jora B, Gonzalez-Cano R, Osuna S, Corpas R, Morisseau C, Perez B, Barniol-Xicota M, Grinan-Ferre C, Perez C, Rodriguez-Franco MI, Martinez AL, Loza MI, Pallas M, Verhelst SHL, Sanfeliu C, Feixas F, Hammock BD, Brea J, Cobos EJ, Vazquez S (2022)
Journal of Medicinal Chemistry
65 :13660