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

ANDREA ENRIQUE; PEDRO MARTÍN; PABLO H. PALESTRO; MARIA LAURA SBARAGLINI; LAUREANO SABATIER; VALENTINA PASTORE; LUCIANA GAVERNET

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

TAYLOR & FRANCIS LTD

Lugar: Londres; Año: 2019 vol. 34 p. 1465 - 1473

1475-6366

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 in vivo 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 1R7 displayed strong anticonvulsant effects in comparison with known anticonvulsants (ED50= 29 mg/Kg). First approximations about the mechanisms of action of the cyclic structures were proposed by docking simulations and invitro assays against sodium channels (patch clamp methods).