RESUMO
3-Aminotolypomycinoes and 3,16-diamino-16,17-dihydrotolypomycinones are formed by the addition of primary and secondary amines to tolypomycinone, obtained by mild hydrolysis of the antibiotic tolypomycin Y.3-Amino-16,17-dihydrotolypomycinones are formed by the addition of primary and secondary amines to 16,17-dihydrotolypomycinone. In vitro microbiological tests showed high antibacterial activity in compounds obtained by the addition of primary amines, which must be unbranched in the alpha position to the nitrogen atom to position 3 of the naphthoquinone ring. The relationship between structure and activity is described, and evidence is presented that hydrogen bonding between the amino NH bonded to C3 and the amide CO of tolypomycinone is very important for biological activity.
Assuntos
Rifamicinas/farmacologia , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Rifamicinas/síntese química , Salmonella paratyphi A/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
A series of compounds with a potential activity on both alpha and beta-adrenoreceptors were synthesized and evaluated with in vitro and in vivo tests. Aryloxypropanolamino derivatives N-substituted with alpha 2-benzodioxanylmethyl group showed a favourable alpha/beta ratio and a high selectivity towards beta 1 receptors. Substitution with different aralkyl groups afforded compounds with a low alpha-activity, although with a high potency and selectivity towards beta 1 receptors. The results are discussed on the basis of the working hypothesis and compared with those obtained for reference compounds.