RESUMO
The synthesis of new 2-imidazol(in)yl-alkyl derivatives of 2,3,3a,4-tetrahydro-1H-imidazo[5,1-c][1,4]benzoxazin-1-one is reported. Some compounds of the series have shown high affinity for alpha 2 receptors, high alpha 2/alpha 1 selectivity and alpha 2 antagonism in vitro (vas deferens). Owing to their selective alpha 2-antagonism associated to a novel structure, compounds 8 and 20 have been selected for further biological investigation as potential antidepressants.
Assuntos
Antagonistas Adrenérgicos alfa/síntese química , Imidazóis/síntese química , Oxazinas/síntese química , Antagonistas Adrenérgicos alfa/química , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Imidazóis/química , Imidazóis/farmacologia , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculos/efeitos dos fármacos , Norepinefrina/farmacologia , Oxazinas/química , Oxazinas/farmacologia , Ratos , Ratos Endogâmicos , Ducto Deferente/efeitos dos fármacosRESUMO
A series of 7-oxaaporphine derivatives was prepared. The compounds were evaluated as dopaminergic agents. None of them showed either affinity for dopamine receptors or activity in vivo in the climbing behavior (mice) and turning behavior (6-hydroxydopamine-lesioned rats) tests. The lack of activity is tentatively related to the effect of the oxygen atom on the pKa of these molecules.
Assuntos
Aporfinas/síntese química , Receptores Dopaminérgicos/efeitos dos fármacos , Animais , Aporfinas/metabolismo , Aporfinas/farmacologia , Comportamento Animal/efeitos dos fármacos , Fenômenos Químicos , Química , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Receptores Dopaminérgicos/fisiologia , Receptores de Dopamina D2 , Espectrofotometria Infravermelho , Relação Estrutura-AtividadeRESUMO
This paper describes the synthesis of 6-carboxy derivatives of 6H-dibenzo[b,d]pyran. These compounds are among the most rigid structures related to clofibrate ever synthesized, which means they have very few possible conformations of relative stability compared with the many for clofibrate. Compound 6H-2-chloro-6-methyl-dibenzo[b,d]pyran-6-carboxylic acid 3g showed very high hypolipidemic activity being 12 times more potent than clofibrate in reducing plasma cholesterol concentration in the hypercholesterolemic rat and 11 times more potent in reducing plasma triglyceride concentration in the normolipemic rat.
