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Pàgina inicial > Articles > Articles publicats > Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain : |
Data: | 2022 |
Resum: | 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. |
Ajuts: | Agencia Estatal de Investigación SAF2017-82771-R Agencia Estatal de Investigación RTI2018-093955-B-C21 Agencia Estatal de Investigación RTI2018-101032-J-I00 Agencia Estatal de Investigación PID2019-106285RB-C21 Agencia Estatal de Investigación PID2020-118127RB-I00 Agencia Estatal de Investigación PGC2018-102192-B-I00 Agencia Estatal de Investigación PID2020-118127RB-I00 |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Publicat a: | Journal of Medicinal Chemistry, Vol. 65 (october 2022) , p. 13660-13680, ISSN 1520-4804 |
21 p, 5.7 MB |