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

2016; Elsevier BV; Volume: 774; Linguagem: Inglês

10.1016/j.ejphar.2016.02.001

1879-0712

María L. Villalba, Andrea Enrique, Josefina Higgs, Rocío A. Castaño, Sofía Goicoechea, Facundo Taborda, Luciana Gavernet, Ileana D. Lick, Mariel Marder, Luis Enrique Bruno Blanch,

Phenothiazines and Benzothiazines Synthesis and Activities

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 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 benzodiazepine binding site (BDZ-bs) of the γ-aminobutiric acid receptor (GABAA receptor). Some of them showed medium to low affinity for the BDZ-bs.