RESUMO
A series of quinoylalkyl side chains was designed and synthesized, followed by introduction into ketolides by coupling with building block 6 or 32. The corresponding targets 7a-n, 33b, and 33e were tested for their in vitro activities against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed a similar antibacterial spectrum and comparable activity to telithromycin. Among them, two C2-F ketolides, compounds 33b and 33e, displayed excellent activities against macrolide-sensitive and macrolide-resistant pathogens.
Assuntos
Antibacterianos/farmacologia , Haemophilus influenzae/efeitos dos fármacos , Cetolídeos/farmacologia , Quinolinas/farmacologia , Staphylococcus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Azitromicina/farmacologia , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana , Cetolídeos/síntese química , Cetolídeos/química , Resistência a Meticilina , Testes de Sensibilidade Microbiana , Estrutura Molecular , Quinolinas/química , Relação Estrutura-AtividadeRESUMO
Some novel josamycin derivatives bearing an arylalkyl-type side chain were designed and synthesized. By HWE or Wittig reaction, 16-aldehyde group of josamycin analogs were converted into unsaturated carbonyl compounds. They were evaluated for their in vitro antibacterial activities against a panel of respiratory pathogens. 8b and 8e exhibited comparable activities against a panel of respiratory pathogens, especially to resistant ones in the series of desmycarosyl josamycin analogs. Among of all the target molecules, 21 showed the best antibacterial activities.
