Studies on cephalosporin antibiotics. VI. Synthesis, antibacterial activity and oral efficacy in mice of new 7.BETA.-((Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino)-acetamido)-3-(substituted alkylthio)cephalosporins.

Abstract

A series of new 7j?-[(Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino)acetamido]cephalosporins(1) having various substituted alkylthio groups at the C-3 position of the cephemnucleus were prepared and evaluated for antibacterial activity and oral absorption in rats. Of these, the cephalosporin with a cyanomethylthio group (la) showed the greatest activity against Staphylococcus aureus andGram-negative bacteria. Its pivaloyloxymethyl ester (6a), a representative prodrug, exhibited good in vivo efficacy in mice by oral administration. The structure-activity relationships of 1 are also presented.