title: Novel sulfamides and sulfamates derived from amino esters: Synthetic studies and anticonvulsant activity.
abstract: 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.
authors: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina.
authors: Maria L
authors: ML
authors: Villalba
authors: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina.
authors: Andrea V
authors: AV
authors: Enrique
authors: Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 (C1113AAD), Buenos Aires, Argentina.
authors: Josefina
authors: J
authors: Higgs
authors: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina.
authors: Rocío A
authors: RA
authors: Castaño
authors: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina.
authors: Sofía
authors: S
authors: Goicoechea
authors: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina.
authors: Facundo D
authors: FD
authors: Taborda
authors: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina. Electronic address: lgavernet@biol.unlp.edu.ar.
authors: Luciana
authors: L
authors: Gavernet
authors: Department of Chemistry, Faculty of Exact Sciences, National University of La Plata, CINDECA (CCT-La Plata-CONICET-UNLP), La Plata B1900BJW, Argentina.
authors: Ileana D
authors: ID
authors: Lick
authors: Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 (C1113AAD), Buenos Aires, Argentina.
authors: Mariel
authors: M
authors: Marder
authors: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 and 115, La Plata B1900BJW, Argentina.
authors: Luis E
authors: LE
authors: Bruno Blanch
mesh_terms: D000577:Amides / Q000737:chemistry*; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D004952:Esters; D008297:Male; D051379:Mice; D008958:Models, Molecular; D012640:Seizures / Q000188:drug therapy; D013451:Sulfonic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000577:Amides; D000927:Anticonvulsants; D002257:Carbonic Anhydrase Inhibitors; D004952:Esters; D013451:Sulfonic Acids; C005741:sulfamic acid; D002256:Carbonic Anhydrases
keywords: Epilepsy; MES test; Microwave assisted synthesis; Sulfamates; Sulfamides