Novel sulfamides and sulfamates derived from amino esters: Synthetic studies and anticonvulsant activity

VILLALBA MARIA LUISA; ENRIQUE ANDREA; HIGGS JOSEFINA; CASTAÑO ROCIO; GOICOECHEA SOFIA; TABORDA FACUNDO; GAVERNET LUCIANA; LICK DANIELA; MARDER MARIEL; BRUNO BLANCH LUIS E.

EUROPEAN JOURNAL OF PHARMACOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 774 p. 55 - 63

0014-2999

We report herein the design and optimization of a novel series of sulfamides and sulfamates derivedfrom amino esters with anticonvulsant properties. The structures were designed based on the pharmacophoricpattern previously proposed, with the aim of improving the anticonvulsant action. The compounds were obtained by a new synthetic procedure with microwave assisted heating and the use of adsorbents in the isolation process. All the derivatives showed protection against the maximal electroshock seizure test (MES test) in mice at the lowest dose tested (30 mg/kg) but they did not show significant protection against the chemical induced convulsion by pentylenetetrazole. These results verify the ability of the computational model for designing new anticonvulsants structures with anti-MES activity. Additionally, we evaluated the capacity of the synthesized structures to bind to the benzodiazepinebinding site (BDZ-bs) of the γ-aminobutiric acid receptor (GABAA receptor). Some of them showedmedium to low affinity for the BDZ-bs