2-(Piperidin-4-yl)acetamides as potent inhibitors of soluble epoxide hydrolase with anti-inflammatory activity

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URI: https://hdl.handle.net/10347/45078
E-ISSN: 1424-8247
DOI: 10.3390/ph14121323

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2021-12-17

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Abstract

The pharmacological inhibition of soluble epoxide hydrolase (sEH) has been suggested as a potential therapy for the treatment of pain and inflammatory diseases through the stabilization of endogenous epoxyeicosatrienoic acids. Numerous potent sEH inhibitors (sEHI) have been developed, however many contain highly lipophilic substituents limiting their availability. Recently, a new series of benzohomoadamantane-based ureas endowed with potent inhibitory activity for the human and murine sEH was reported. However, their very low microsomal stability prevented further development. Herein, a new series of benzohomoadamantane-based amides were synthetized, fully characterized, and evaluated as sEHI. Most of these amides were endowed with excellent inhibitory potencies. A selected compound displayed anti-inflammatory effects with higher effectiveness than the reference sEHI, TPPU

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Amide| Benzohomoadamantane| DMPK properties| Piperidine| Soluble epoxide hydrolase

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Martín-López, J., Codony, S., Bartra, C., Morisseau, C., Loza, M. I., Sanfeliu, C., Hammock, B. D., Brea, J., & Vázquez, S. (2021). 2-(Piperidin-4-yl)acetamides as Potent Inhibitors of Soluble Epoxide Hydrolase with Anti-Inflammatory Activity. Pharmaceuticals, 14(12), 1323. https://doi.org/10.3390/ph14121323

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This research was funded by the Spanish Ministerio de Economía, Industria y Competitividad (Grants SAF2017-82771-R to S.V., PID2019-106285RB-C22 to C.S.), Grant PID2020-118127RB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe” to S.V., the Xunta de Galicia (ED431G 2019/02 and ED431C 2018/21), the Generalitat de Catalunya (2017 SGR 106, 2017 SGR 124 and 2017 SGR 1707). S.C. acknowledges a PhD fellowship from the Universitat de Barcelona (APIF grant). Partial support was provided by NIH-NIEHS River Award R35 ES03443, NIH-NIEHS Superfund Program P42 ES004699, NINDS R01 DK107767, and NIDDK R01 DK103616 to B.D.H. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health

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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
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Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica
Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS)