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Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors
[Image: see text] 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 t...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical Society
2022
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9620236/ https://www.ncbi.nlm.nih.gov/pubmed/36222708 http://dx.doi.org/10.1021/acs.jmedchem.2c00515 |
| _version_ | 1784821320976957440 |
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| author | Codony, Sandra Entrena, José M. Calvó-Tusell, Carla Jora, Beatrice González-Cano, Rafael Osuna, Sílvia Corpas, Rubén Morisseau, Christophe Pérez, Belén Barniol-Xicota, Marta Griñán-Ferré, Christian Pérez, Concepción Rodríguez-Franco, María Isabel Martínez, Antón L. Loza, M. Isabel Pallàs, Mercè Verhelst, Steven H. L. Sanfeliu, Coral Feixas, Ferran Hammock, Bruce D. Brea, José Cobos, Enrique J. Vázquez, Santiago |
| author_facet | Codony, Sandra Entrena, José M. Calvó-Tusell, Carla Jora, Beatrice González-Cano, Rafael Osuna, Sílvia Corpas, Rubén Morisseau, Christophe Pérez, Belén Barniol-Xicota, Marta Griñán-Ferré, Christian Pérez, Concepción Rodríguez-Franco, María Isabel Martínez, Antón L. Loza, M. Isabel Pallàs, Mercè Verhelst, Steven H. L. Sanfeliu, Coral Feixas, Ferran Hammock, Bruce D. Brea, José Cobos, Enrique J. Vázquez, Santiago |
| author_sort | Codony, Sandra |
| collection | PubMed |
| description | [Image: see text] 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. |
| format | Online Article Text |
| id | pubmed-9620236 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | American Chemical Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-96202362022-11-01 Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors Codony, Sandra Entrena, José M. Calvó-Tusell, Carla Jora, Beatrice González-Cano, Rafael Osuna, Sílvia Corpas, Rubén Morisseau, Christophe Pérez, Belén Barniol-Xicota, Marta Griñán-Ferré, Christian Pérez, Concepción Rodríguez-Franco, María Isabel Martínez, Antón L. Loza, M. Isabel Pallàs, Mercè Verhelst, Steven H. L. Sanfeliu, Coral Feixas, Ferran Hammock, Bruce D. Brea, José Cobos, Enrique J. Vázquez, Santiago J Med Chem [Image: see text] 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. American Chemical Society 2022-10-12 2022-10-27 /pmc/articles/PMC9620236/ /pubmed/36222708 http://dx.doi.org/10.1021/acs.jmedchem.2c00515 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
| spellingShingle | Codony, Sandra Entrena, José M. Calvó-Tusell, Carla Jora, Beatrice González-Cano, Rafael Osuna, Sílvia Corpas, Rubén Morisseau, Christophe Pérez, Belén Barniol-Xicota, Marta Griñán-Ferré, Christian Pérez, Concepción Rodríguez-Franco, María Isabel Martínez, Antón L. Loza, M. Isabel Pallàs, Mercè Verhelst, Steven H. L. Sanfeliu, Coral Feixas, Ferran Hammock, Bruce D. Brea, José Cobos, Enrique J. Vázquez, Santiago Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors |
| title | Synthesis, In Vitro
Profiling, and In Vivo Evaluation
of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication
for Soluble Epoxide Hydrolase Inhibitors |
| title_full | Synthesis, In Vitro
Profiling, and In Vivo Evaluation
of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication
for Soluble Epoxide Hydrolase Inhibitors |
| title_fullStr | Synthesis, In Vitro
Profiling, and In Vivo Evaluation
of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication
for Soluble Epoxide Hydrolase Inhibitors |
| title_full_unstemmed | Synthesis, In Vitro
Profiling, and In Vivo Evaluation
of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication
for Soluble Epoxide Hydrolase Inhibitors |
| title_short | Synthesis, In Vitro
Profiling, and In Vivo Evaluation
of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication
for Soluble Epoxide Hydrolase Inhibitors |
| title_sort | synthesis, in vitro
profiling, and in vivo evaluation
of benzohomoadamantane-based ureas for visceral pain: a new indication
for soluble epoxide hydrolase inhibitors |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9620236/ https://www.ncbi.nlm.nih.gov/pubmed/36222708 http://dx.doi.org/10.1021/acs.jmedchem.2c00515 |
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