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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
dc.contributor.author | Codony, Sandra | |
dc.contributor.author | Entrena Fernández, José Manuel | |
dc.contributor.author | González Cano, Rafael | |
dc.contributor.author | Cobos del Moral, Enrique José | |
dc.date.accessioned | 2022-11-09T09:00:47Z | |
dc.date.available | 2022-11-09T09:00:47Z | |
dc.date.issued | 2022-10-12 | |
dc.identifier.citation | J. Med. Chem. 2022, 65, 13660−13680. [https://doi.org/10.1021/acs.jmedchem.2c00515] | es_ES |
dc.identifier.uri | https://hdl.handle.net/10481/77839 | |
dc.description.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. | es_ES |
dc.description.sponsorship | Spanish Government SAF2017-82771-R RTI2018-093955-B-C21 PGC2018-102192-B-I00 RTI2018-101032-J-I00 Spanish MCIN/AEI | es_ES |
dc.description.sponsorship | ERDF A way of making Europe - MCIN/AEI PID2020-118127RB-I00 | es_ES |
dc.description.sponsorship | PID2019-106285RB | es_ES |
dc.description.sponsorship | ERDF A way of making Europe | es_ES |
dc.description.sponsorship | Xunta de Galicia | es_ES |
dc.description.sponsorship | European Commission ED431G 2019/02 | es_ES |
dc.description.sponsorship | ED431C 2018/21 | es_ES |
dc.description.sponsorship | Fundacio Bosch i Gimpera | es_ES |
dc.description.sponsorship | Universitat de Barcelona (F2I grant) Generalitat de Catalunya 2017 SGR 106 2017 SGR 1707 | es_ES |
dc.description.sponsorship | European Research Council (ERC) European Commission ERC-2015-StG-679001-NetMoDEzyme European Commission MSCA-IF-2014-EF661160-MetAccembly | es_ES |
dc.description.sponsorship | Universitat de Barcelona (APIF grant) | es_ES |
dc.description.sponsorship | Spanish Society of Medicinal Chemistry (SEQT) and Lilly FWO 12Y0720N | es_ES |
dc.description.sponsorship | Ministry of Science and Innovation, Spain (MICINN) Spanish Government RYC2020-029552-I | es_ES |
dc.description.sponsorship | United States Department of Health & Human Services | es_ES |
dc.description.sponsorship | National Institutes of Health (NIH) - USA R35 ES03443 P42 ES004699 | es_ES |
dc.description.sponsorship | United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Neurological Disorders & Stroke (NINDS) R01 DK107767 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01 DK103616 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Chemical Society | es_ES |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.identifier.doi | 10.1021/acs.jmedchem.2c00515 | |
dc.type.hasVersion | info:eu-repo/semantics/publishedVersion | es_ES |