RESUMO
A series of 1-(2-acyl-4-acylaminophenoxy)-3-isopropylaminopropan-2-ols has been synthesized and examined for beta-receptor blocking and antiarrhythmic activity. Several of these compounds are more than 20 times as active in blocking cardiac beta-receptors than vascular beta-receptors when given intravenously to anesthetized cats. The activities have been correlated quantitatively with partition and steric substitution constants. The observed relationships are consistent with a tentative proposal that the vascular receptor is situated in a more lipophilic environment than the cardiac receptor so that there is a differential transport effect between the two types of receptor.
Assuntos
Antagonistas Adrenérgicos beta/síntese química , Propanolaminas/síntese química , Antagonistas Adrenérgicos beta/farmacologia , Anilidas/síntese química , Anilidas/farmacologia , Animais , Arritmias Cardíacas/induzido quimicamente , Gatos , Cães , Frequência Cardíaca/efeitos dos fármacos , Isoproterenol/antagonistas & inibidores , Conformação Molecular , Especificidade de Órgãos , Ouabaína/antagonistas & inibidores , Propanolaminas/farmacologia , Receptores Adrenérgicos/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
The synthesis and antiallergic activity in the rat passive cutaneous anaphylactic reaction of a series of 2-phenyl-8-azapurin-6-ones are described. Early in the investigation, a linear free-energy equation was established in which the activity was related to the size and hydrogen bonding capacity of the ortho substituent in the phenyl ring. This relationship was used to provide guidance and limits for subsequent work leading to 2-o-propoxyphenyl-8-azapurin-6-one which is 40 times more potent than disodium cromoglycate. It is suggested that good antiallergic activity in this series is associated with coplanarity of the phenyl group with the azapurin-6-one which would be favored by a high degree of hydrogen bonding.
