Tsubouchi H, Tsuji K, Yasumura K, Matsumoto M, Shitsuta T, Ishikawa H
Microbiological Research Institute, Otsuka Pharmaceutical Company, Ltd., Tokushima, Japan.
J Med Chem. 1995 Jun 9;38(12):2152-7. doi: 10.1021/jm00012a015.
The preparation and biological evaluation of a series of 7-[2-(2-aminothiazol-4-yl)-2-(Z)-[(cyclopentyloxy)imino]acetamido] optically active 2-oxaisocephems, substituted at the 3-position with [(N-alkylpyridinium-4'-yl)thio]methyl groups, are described. The resulting family of parenteral compounds displays a broad spectrum of in vitro antibacterial activity. These compounds exhibit increased activity against Gram-positive organisms including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis which are resistant to most cephalosporins with a similar level of Gram-negative activity to that of the third-generation antibiotics. In vivo efficacy of new antibacterial agents in this investigation is excellent against both Gram-positive and Gram-negative bacteria as compared with reference compounds. The in vitro and in vivo antimicrobial activity and the structure-activity relationships are presented.
