Design, synthesis and biological evaluation of N-substituted α-hydroxyimides and 1,2,3-oxathiazolidine-4-one-2,2-dioxides with anticonvulsant activity

In this investigation, we studied a family of compounds with an oxathiazolidine-4-one-2,2-dioxide skeleton and their amide synthetic precursors as new anticonvulsant drugs. The cyclic structures were synthesized using a three-step protocol that include solvent-free reactions and microwave-assisted h...

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Autores principales: Sabatier, Laureano Leonel, Palestro, Pablo Hernán, Enrique, Andrea Verónica, Pastore, Valentina, Sbaraglini, María Laura, Martín, Pedro, Gavernet, Luciana
Formato: Articulo
Lenguaje:Inglés
Publicado: 2019
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/107975
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6713207&blobtype=pdf
https://www.tandfonline.com/doi/full/10.1080/14756366.2019.1651722
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Sumario:In this investigation, we studied a family of compounds with an oxathiazolidine-4-one-2,2-dioxide skeleton and their amide synthetic precursors as new anticonvulsant drugs. The cyclic structures were synthesized using a three-step protocol that include solvent-free reactions and microwave-assisted heating. The compounds were tested <i>in vivo</i> through maximal electroshock seizure test in mice. All the structures showed activity at the lower doses tested (30 mg/Kg) and no signs of neurotoxicity were detected. Compound encoded as 1g displayed strong anticonvulsant effects in comparison with known anticonvulsants (ED<sup>50</sup> = 29 mg/Kg). First approximations about the mechanisms of action of the cyclic structures were proposed by docking simulations and <i>in vitro</i> assays against sodium channels (patch clamp methods).