RESUMO
A series of 1beta-methyl-2-(naphthosultamyl)methyl-carbapenems bearing dicationic groups on the naphthosultamyl moiety was prepared and evaluated for activity against resistant gram-positive bacteria. Based on a combination of excellent in vitro antibacterial activity, acceptable mouse acute toxicity, and a desirable fragmentation pattern on beta-lactam ring opening, the analog 2g (L-786,392) was selected for extended evaluation.
Assuntos
Carbapenêmicos/síntese química , Bactérias Gram-Positivas/efeitos dos fármacos , Lactamas/farmacologia , Tiazóis/farmacologia , Animais , Carbapenêmicos/química , Carbapenêmicos/farmacologia , Carbapenêmicos/toxicidade , Resistência Microbiana a Medicamentos , Humanos , Lactamas/química , Lactamas/farmacocinética , Camundongos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Tiazóis/química , Tiazóis/farmacocinéticaRESUMO
A series of O-Me derivatives of 9-deoxo-8a-aza-8a-homoerythromycin has been prepared and evaluated for antibacterial activity. The relative rates of methylation of the four available hydroxyls (4", 6, 11 and 12) in 2',3'-bis-Cbz protected 9-deoxo-8a-aza-8a-homoerythromycin were compared to those given in a published report for the similarly protected 9a-azalide. An incongruity in the results prompted reinvestigation of the O-methylation of the 9a-azalide, and an error in structure assignment in the published report was discovered: the compound reported as the 6-OMe-9a-azalide has been determined to be the 12-OMe derivative.
Assuntos
Antibacterianos/síntese química , Eritromicina/análogos & derivados , Antibacterianos/química , Antibacterianos/farmacologia , Eritromicina/síntese química , Eritromicina/química , Eritromicina/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Cinética , Espectroscopia de Ressonância Magnética , Metilação , Testes de Sensibilidade Microbiana , Estrutura MolecularRESUMO
Direct O-methylation of various derivatives of 9-deoxo-8a- and 9a-aza-8a-homo-erythromycin (2',3'-bis-Cbz protected) gives 6-OMe derivatives only in a small number of special cases. The 6-OMe-azalides can, however, be synthesized beginning from clarithromycin.