STRUCTURE-ACTIVITY-RELATIONSHIPS OF CEPHALOSPORINS HAVING A (DIMETHYLISOXAZOLIDINIO)VINYL MOIETY AT THEIR 3-POSITION

A series of cephalosporins having a (dimethylisoxazolidinio)vinyl grou p at their 3-position were synthesized to investigate their structure- activity relationships. With regard to the olefin geometry, the (E)-vi nyl compound exhibited higher in vitro activity than the (Z)-compound. Regarding the C-7 substituents, the replacement of 2-aminothiazole wi th 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 7 hyl-5-i soxazolidinio)vinyl]-3-cephem-4-carboxylate (YM-40220), which showed w ell-balanced in vitro activity and an excellent in vivo efficacy again st Staphylococcus aureus Smith, as a candidate for further development .