RESUMO
Several N-benzylpiperazino derivatives of [1]benzopyrano[2,3-d]-1,2,3-triazol-9(1H)-one and its 5-methyl homologue have been prepared and evaluated for H1-antihistamine activity on guinea pig ileum. The most potent compounds were also evaluated for their ability to stabilize mast cells in the rat passive peritoneal anaphylaxis (PPA) system and were shown to inhibit histamine release at concentrations below those required to inhibit extravasation, suggesting that this might be relevant to their antianaphylactic activity in this system. The compound tested with the most potent H1-antihistamine activity was 6-[3-[4-(4-chlorobenzyl)-1-piperazinyl]propoxy][1]benzopyrano[2,3- d]-1,2,3-triazol-9(1H)-one, 28, which had a pA2 of 9.1 against histamine on guinea pig ileum, comparable to that of mepyramine, and inhibited histamine release in the rat PPA system with an IC50 value of 5.4 X 10(-6) M.
Assuntos
Antagonistas dos Receptores Histamínicos H1/síntese química , Mastócitos/efeitos dos fármacos , Triazóis/síntese química , Anafilaxia/prevenção & controle , Animais , Cobaias , Antagonistas dos Receptores Histamínicos H1/farmacologia , Liberação de Histamina/efeitos dos fármacos , Técnicas In Vitro , Ratos , Relação Estrutura-Atividade , Triazóis/farmacologiaRESUMO
Selected derivatives of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazole, a new heterocyclic ring system, and their S-oxides have been prepared and evaluated for antiallergic activity in the rat passive cutaneous anaphylaxis screen. Several of the compounds show intravenous potencies similar to or greater than that of disodium cromoglycate, the most potent being 6,7-dimethyl-9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazole and its 4,4-dioxide.
Assuntos
Óxidos S-Cíclicos/farmacologia , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Triazóis/farmacologia , Animais , Fenômenos Químicos , Química , Óxidos S-Cíclicos/síntese química , Masculino , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade , Triazóis/síntese químicaRESUMO
A series of the little compounds was prepared by cyclization of the appropriate 5-(aryloxy)-v-triazole-4-carboxylic acids and evaluated for antiallergic activity by the rat passive cutaneous anaphylaxis (PCA) screen. The most potent compounds were 6-(mesyloxy)-9-oxo-1H,9H-benzopyrano[2,3-d]-v-triazole and its 5-methyl homologue, which were some tenfold more potent than disodium cromoglycate. Dialkyl derivatives, especially those substituted at C-5 and C-6 or C-6 and C-7, and 6-methoxy compounds were also among the more potent compounds. One compound, 6,7-dimethyl-9-oxo-1H,9H-benzopyrano[2,3-d]-v-triazole, was further evaluated and shown to be a potent inhibitor of rat PCA when given orally.