RESUMO
The synthesis and biological investigation of the series of amide and ester derivatives 10-20 of 5-(4-chlorobenzoyl)amino-3-methyl-4-isothiazolecarboxylic acid 5 are presented. Because the amide series of 5-benzoylamino-3-methyl-4-isothiazolecarboxylic acid 2 has been studied extensively and from this series denotivir (vratizolin) 4 became the antiviral drug. The influence of exchanging the N-benzoyl for a N-(4-chlorobenzoyl) group at position 5 of the isothiazole ring on the pharmacological activity of 5-benzoylamino-3-methyl-4-isothiazolecarboxylic acid 2 derivatives is dealt with here. The effect of structure modifications in the carboxylic group of the 5-(4-chlorobenzoyl)amino-3-methyl-4-isothiazolecarboxylic acid 5 series of derivatives on their biological activity is discussed. Some of the tested 5-(4-chlorobenzoyl)amino-3-methyl-4-isothiazolecarboxylamides revealed significant anti-inflammatory activity in carrageenan induced edema and air-pouch inflammation tests. Physicochemical properties of 6-(4-chlorophenyl)-3-methylisothiazolo[5,4-d]-4H-1,3-oxazin-4-one 6 are described. Its use in the synthesis of isothiazole derivatives and its reactivity are also presented.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Tiazóis/síntese química , Tiazóis/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Carragenina , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Edema/induzido quimicamente , Edema/prevenção & controle , Membrana Eritrocítica/efeitos dos fármacos , Feminino , Membro Posterior/efeitos dos fármacos , Ibuprofeno/química , Ibuprofeno/farmacologia , Camundongos , Camundongos Endogâmicos CBA , Estrutura Molecular , Coelhos , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Tiazóis/químicaRESUMO
An improved synthesis of the antiulcer drug Ranitidine from an oxazolidine derivative is reported.
