Synthesis and antibacterial activity of O-methylazithromycin derivatives.
A series of O-methylazithromycin derivatives have been synthesized and their antibacterial activities were compared with those of azithromycin (1). O-Methylation of 1 proceeded stepwise by the two main pathways beginning at the C-6 and C-11 hydroxyl groups, individually. Among O-methyl derivatives, 6-O-methylazithromycin A (11) was slightly less active than 1. The methylation of the secondary hydroxyl group at the C-11 position resulted surprisingly in an increase of their in vitro activity. The antibacterial activities of novel azalides decreased with increasing the number of the methyl groups introduced.
Kobrehel
G
G
PLIVA, Research and Development, Zagreb, Yugoslavia.
Lazarevski
G
G
Dokić
S
S
Kolacny-Babić
L
L
Kucisec-Iepes
N
N
Cvrlje
M
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017963:Azithromycin; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D004917:Erythromycin; D017963:Azithromycin