RESUMO
A series of 4-substituted phenoxypropanolamines has been prepared and examined for beta-adrenoceptor activity. The 4-substituents, di- and triazole ring systems connected to the phenoxy ring by different length chains, were chosen as a means of introducing cardioselectivity. This has been achieved, especially in the 1-[4-[(4-chloropyrazol-1-yl)methoxy] phenoxy]-3-(isopropylamino)-2-propanol (11), the 4-[(2H-1,2,3-triazol-2-yl)methoxy] analogue (21), and the 4-[2-(2H-1,2,3-triazol-2-yl)ethoxy] analogue (22), which show potent beta 1-blockade with selectivity ratios in excess of 100:1. Structure-activity relationships are discussed, and the optimum position of the heteroatom in the 4-substituent is defined.
Assuntos
Antagonistas Adrenérgicos beta/síntese química , Propanolaminas/síntese química , Triazóis/síntese química , Animais , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Indicadores e Reagentes , Propanolaminas/farmacologia , Ratos , Receptores Adrenérgicos beta/efeitos dos fármacos , Receptores Adrenérgicos beta/fisiologia , Relação Estrutura-Atividade , Triazóis/farmacologiaRESUMO
A series of 4-substituted phenoxypropanolamines was prepared and examined for beta-adrenoceptor activity. Some of the compounds, especially the [4-[2-[[2-(4-fluorophenyl)ethyl] oxy]ethoxy]phenoxy]propanolamines (14, 15, and 24), showed potent beta 1-blockade with virtually no beta 2-blockade at doses over a 1000 times greater. The compounds also possessed partial agonist activity. Structure-activity relationships are discussed, and conclusions are drawn about the binding sites on beta-adrenoceptors.
Assuntos
Agonistas Adrenérgicos beta/farmacologia , Propanolaminas/síntese química , Agonistas Adrenérgicos beta/metabolismo , Animais , Bioensaio , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Indicadores e Reagentes , Isoproterenol/farmacologia , Espectroscopia de Ressonância Magnética , Éteres Fenílicos/síntese química , Éteres Fenílicos/farmacologia , Propanolaminas/farmacologia , Ratos , Relação Estrutura-AtividadeRESUMO
The fibrillar sheath surrounding spores of Streptomyces griseus was separated from spores and partially purified by differential centrifugation. The reaction of isolated sheath material to various solvents and enzymes was monitored by electron microscopy. Fibrilar elements (rodlets) were apparently resistant to most solvents and enzymes used; only acetone induced any change in their appearance. Analysis of sheath material showed that its composition differed considerably from that of spore walls, having a low content of nitrogen (1.7% w/w), amino sugars (0.067% w/w) and carbohydrate (0.036% w/w). It was suggested that the sheath may be at least partially inorganic in nature.
