RESUMO
Several new C-16 oximino and vinyl derivatives of amphotericin B are described. They are prepared by the reaction of a suitably protected amphotericin B C-16 aldehyde with hydroxylamine derivatives and Wittig reagents, respectively, followed by sequential removal of the protecting groups. The compounds possess potent antifungal activity in vitro, similar to or in some cases superior to that of amphotericin B itself. With the exception of the C-16 (Z)-methoxime, the new derivatives do not show significantly reduced haemolytic activity against mammalian erythrocytes compared with amphotericin B.
Assuntos
Anfotericina B/análogos & derivados , Oximas/síntese química , Compostos de Vinila/síntese química , Anfotericina B/química , Anfotericina B/uso terapêutico , Animais , Eritrócitos/efeitos dos fármacos , Cavalos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Oximas/química , Oximas/uso terapêutico , Relação Estrutura-Atividade , Compostos de Vinila/química , Compostos de Vinila/uso terapêuticoRESUMO
A number of C-2 aminoalkenylthio-carbapenem derivatives possessing both the (5R,6R, 8S)- and the (5R,6S,8R)-stereochemistries have been prepared from the olivanic acids MM 22382 and MM 22383, respectively. Certain members of this new class of compounds displayed potent, broad spectrum antibacterial activity as well as improved stability to human kidney homogenate.
Assuntos
Bactérias/efeitos dos fármacos , Carbapenêmicos/síntese química , Carbapenêmicos/química , Carbapenêmicos/farmacologia , Estabilidade de Medicamentos , Humanos , Rim/metabolismo , Estrutura Molecular , EstereoisomerismoRESUMO
A number of C-2 carboxyethenylthio-carbapenem derivatives possessing either the (5R,6R,8S)- or the (5R,6S,8R)-stereochemistries have been prepared from the olivanic acids MM 22382 (1) and MM 22383 (4), respectively. Their in vitro antibacterial activities and stabilities to human kidney homogenate are superior to those of the parent compounds, particularly in the latter series.
