ABSTRACT
A novel series of ketolides with 11,12-sulfur contained aryl alkyl side chains were synthesized and evaluated for their antibacterial activity. These ketolides exhibited potent activity against key macrolide sensitive and resistant respiratory pathogens. The newly synthesized 9a, 9e, 9k and 9n showed a similar antimicrobial spectrum and comparable activity to telithromycin, the commercial ketolide antibacterial.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Ketolides/chemistry , Ketolides/pharmacology , Sulfur/chemistry , Anti-Bacterial Agents/chemical synthesis , Ketolides/chemical synthesis , Microbial Sensitivity TestsABSTRACT
A series of novel derivatives of macrolide with 4''-O-mono- or disaccharides were synthesized. The corresponding glycosyl trichloroacetimidates were used as the donors in the glycosylations. The in vitro antibacterial activities of 7a-f and 13-16 against a panel of susceptible and resistant pathogens were tested. The modification of 4''-O-mono- or disaccharides may lead to the understanding of interaction of the macrolide and the bacterial ribosome.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Gram-Positive Bacteria/drug effects , Macrolides/chemistry , Macrolides/pharmacology , Anti-Bacterial Agents/chemical synthesis , Drug Resistance, Bacterial , Glycosylation , Gram-Positive Bacterial Infections/drug therapy , Humans , Macrolides/chemical synthesis , Staphylococcus/drug effects , Streptococcus/drug effectsABSTRACT
In an effort to find new antibiotics, a novel series of 14-membered macrolides with imidazo[4,5-b]pyridinyl sulfur contained alkyl side chains has been synthesized based on commercially available clarithromycin. Chemical transformation of hydroxy group at position C-3 afforded range of ketolides and acylides. Compared to telithromycin, compound 15a demonstrated improved in vitro activity against erythromycin-susceptible and -resistant strains.
