Novel azalides derived from 16-membered macrolides. III. Azalides modified at the C-15 and 4'' positions: Improved antibacterial activities.
The design and synthesis of 16-membered azalides modified at the C-15 and 4'' positions are described. The compounds we report here are characterized by an arylpropenyl group attached to the C-15 position of macrolactone and a carbamoyl group at the C-4'' position in a neutral sugar. Introduction of alkylcarbamoyl groups to the C-4'' position was regioselectively achieved by unique and convenient methods via acyl migration. As a result of optimization at the C-3 and 15 positions, several compounds were found to have potent activity against mef- and erm-resistant bacterial strains. These results suggest that 16-membered azalides could be promising compounds as clinical candidates.
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan. tomoaki_miura@meiji.co.jp
Tomoaki
T
Miura
Satomi
S
Natsume
Kenichi
K
Kanemoto
Eiki
E
Shitara
Hideki
H
Fushimi
Takuji
T
Yoshida
Keiichi
K
Ajito
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007202:Indicators and Reagents; D018942:Macrolides / Q000138:chemical synthesis* / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D013296:Streptococcus pneumoniae / Q000187:drug effects
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D001426:Bacterial Proteins; D007202:Indicators and Reagents; D018942:Macrolides; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins