Studies on beta-lactam antibiotics. III. Syntheses and antibacterial activities of new 3-(1,3-dithiolan-2-yl)cephalosporins, YM-22508, YM-16457 and their prodrug-type esters.
The syntheses and biological activities of new 7-beta-[(Z)-2-(2-amino-4-thiazolyl)-2-hydroxy-iminoacetamido]-3-(1 ,3- dithiolan-2-yl)-3-cephem-4-carboxylic acid (YM-22508, 1a), 7-beta-[(Z)-2-(2-amino-4-thiazolyl)-2- methoxyiminoacetamido]-3-(1,3-dithiolan-2-yl)-3-cephem-4-carboxyli c acid (YM-16457, 1d) and their prodrug-type esters are described. Among them, YM-22561 (1c), the 1-acetoxyethyl ester of 1a, showed good in vivo efficacy in mice against infections of Staphylococcus aureus Smith, Streptococcus pyogenes S 23 and Escherichia coli NY-17 and a long plasma T1/2 in mice.
Nagano
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N
Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Satoh
M
M
Hara
R
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002511:Cephalosporins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D004927:Escherichia coli Infections / Q000188:drug therapy; D007700:Kinetics; D051379:Mice; D015394:Molecular Structure; D013203:Staphylococcal Infections / Q000188:drug therapy; D013290:Streptococcal Infections / Q000188:drug therapy; D013297:Streptococcus pyogenes
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C068896:YM 16457; C068895:YM 22508