Synthesis and antibacterial activity of novel 11-[3-[(arylcarbamoyl)oxy]propylamino]-11-deoxy-6-O-methyl-3-oxoerythromycin A 11-N,12-O-cyclic carbamate derivatives.
A series of novel 11-[3-[(arylcarbamoyl)oxy]propylamino]-11-deoxy-6-O-methyl-3-oxoerythromycin A 11-N,12-O-cyclic carbamate derivatives (6a-h) were designed, synthesized and evaluated for their antibacterial activities in vitro. Most of these compounds had significant antibacterial activity against two groups of pathogens of Methicillin-sensitive Staphylococcus aureus (MIC50=0.031-2 μg ml-1) except 6g and Methicillin-sensitive S. epidermidis (MIC50=0.031-0.5 μg ml-1). MIC90of 6d against Methicillin-resistant S. epidermidis was at least 16-fold better than that of erythromycin (EMA), azithromycin (AZM) and ABT-773. 6d and 6e had more potent antibacterial activity against S. pneumoniae than EMA, AZM and ABT-773. In particular, compounds 6d and 6e also showed relatively potent activity against Haemophilus influenzae and Streptococcus hemolyticus.
Shandong Xinhua Pharmaceutical Co., Ltd, Zibo City, Shandong Province, China.
Zhonghui
Z
Zheng
Shandong Xinhua Pharmaceutical Co., Ltd, Zibo City, Shandong Province, China.
Deping
D
Du
Shandong Xinhua Pharmaceutical Co., Ltd, Zibo City, Shandong Province, China.
Lili
L
Cao
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Jun
J
Liu
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Xiaofang
X
Chen
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D002219:Carbamates / Q000737:chemistry* / Q000494:pharmacology*; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006193:Haemophilus influenzae / Q000187:drug effects; D048628:Ketolides / Q000494:pharmacology; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects
C000617991:11-deoxy-3-des(hexopyranosyloxy)-6-O-methyl-11-(3-((3-methylphenylcarbamoyl)oxy)propylamino)-3-oxoerythromycin A 11-N,12-O-cyclic carbamate; C000617990:11-deoxy-3-des(hexopyranosyloxy)-6-O-methyl-11-(3-((4-nitrophenylcarbamoyl)oxy)propylamino)-3-oxoerythromycin A 11-N,12-O-cyclic carbamate; D000900:Anti-Bacterial Agents; D002219:Carbamates; D048628:Ketolides; D004917:Erythromycin; D017963:Azithromycin; C405499:cethromycin