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

SABATIER L; PALESTRO P; ENRIQUE AV; PASTORE V; SBARAGLINI ML; MARTIN P; GAVERNET L

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

TAYLOR & FRANCIS LTD

Lugar: Londres; Año: 2019

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 as-sisted 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 neu-rotoxicity were detected. Compound encoded as 1R7 displayed strong anticonvulsant effects in com-parison with known anticonvulsants (ED50= 29 mg/Kg). First approximations about the mechanisms of action of the cyclic structures were proposed by docking simulations and in vitro assays against sodium channels (patch clamp methods).