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

MARIA L VILLALBA ; ANDREA V ENRIQUE; JOSEFINA HIGGS; ROCIO A CASTAÑO; SOFIA GOICOECHEA; FACUNDO D TABORDA; LUCIANA GAVERNET; DANIELA I LICK; MARIEL MARDER; LUIS E BRUNO BLANCH

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 derived from amino esters with anticonvulsant properties. The structures were designed based on the pharmacophoric pattern 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 pentilenetetrazole. 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 benzodiazepine binding site (BDZ-bs) of the gamma-aminobutiric acid receptor (GABAA receptor). Some of them showed medium to low affinity for the BDZ-bs.