Structure-activity relationships of cephalosporins having a (dimethylisoxazolidlinio)vinyl moiety at their 3-position

Article abstract of DOI:10.7164/antibiotics.49.1162

A series of cephalosporins having a (dimethylisoxazolidinio)vinyl group at their 3-position were synthesized to investigate their structure-activity relationships. With regard to the olefin geometry, the (E)-vinyl compound exhibited higher in vitro activity than the (Z)-compound. Regarding the C-7 substituents, the replacement of 2-aminothiazole with 5-amino-1,2,4-thiadiazole increased the anti-pseudomonal activity. Determination of the absolute configuration of the C-3 substituent is also presented. Among the compounds synthesized, we selected 7β-(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(fluoromethoxyimino)acetamido]-3 -cephem-4-carboxylate (YM-40220), which showed well-balanced in vitro activity and an excellent in vivo efficacy against Staphylococcus aureus Smith, as a candidate for further development.