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[PMID]: | 23321016 |
[Au] Autor: | Pastore V; Sabatier L; Enrique A; Marder M; Bruno-Blanch LE |
[Ad] Endereço: | Química Medicinal, Departamento de Ciencias Biológicas, UNLP, calle 47 y 115, B1900BJW La Plata, Argentina. vpastore@qb.ffyb.uba.ar |
[Ti] Título: | Synthesis and anticonvulsant activity of bioisosteres of trimethadione, N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides from α-hydroxyamides. |
[So] Source: | Bioorg Med Chem;21(4):841-6, 2013 Feb 15. | [Is] ISSN: | 1464-3391 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | The synthesis and anticonvulsant activity of novel heterocycles N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides, bioisosteres of trimethadione (TMD, oxazolidine-2,4-dione) and phenytoin (PHE), are described. TMD is an anticonvulsant drug widely used against absences seizures in the early 80's and PHE is an antiepileptic drug with a wide spectrum activity. The intermediates of synthesis of N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides, α-hydroxyamides, were obtained using microwave assisted synthesis. Anticonvulsant screening was performed in mice after intraperitoneal administration in the maximal electroshock seizure test (MES) and subcutaneous pentylenetetrazole seizures test (scPTZ). These new compounds showed a wide spectrum activity and were no neurotoxic in the RotoRod test. α-Hydroxyamides and N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides were 3-4700 times more potent than valproic acid in the MES test. Quantification of anticonvulsant protection was calculated (ED(50)) for the most active candidates; α-hydroxyamides 3a-c and 3e, and N-derivative-oxathiazolidine-4-one-2,2-dioxides 5a-c with ED(50) values of 9.1, 53.9, 44.6, 25.2, 15.1, 91.1 and 0.06mg/kg, respectively, in the MES test. |
[Mh] Termos MeSH primário: |
Amidas/química Anticonvulsivantes/síntese química Tiazolidinas/química Trimetadiona/química
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[Mh] Termos MeSH secundário: |
Animais Anticonvulsivantes/química Anticonvulsivantes/toxicidade Comportamento Animal/efeitos dos fármacos Masculino Camundongos Micro-Ondas Fenitoína/química Convulsões/induzido quimicamente Convulsões/tratamento farmacológico Relação Estrutura-Atividade Trimetadiona/síntese química Trimetadiona/toxicidade
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Amides); 0 (Anticonvulsants); 0 (Thiazolidines); 6158TKW0C5 (Phenytoin); R7GV3H6FQ4 (Trimethadione) |
[Em] Mês de entrada: | 1308 |
[Cu] Atualização por classe: | 131121 |
[Lr] Data última revisão:
| 131121 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 130117 |
[St] Status: | MEDLINE |
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