SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF 7-BETA-[(Z)-2-(2-AMINOTHIAZOL-4-YL)-3-(SUBSTITUTED)-2-PROPENOYLAMINO]-3-CEPHEMS WITH C-3 SUBSTITUTIONS

Synthesis and biological activity of a series of 7 beta- [(Z)-2-(2-aminothiazol-4-yl)-3 -(substituted)2-propenoylamino]-3-cephem-4-carboxylic acids with C-3 substitutions and their pivaloyloxymethyl esters are described. These acid compounds exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Pivaloyloxymethyl esters of selected compounds in this series were found to be well absorbed from small intestine in mice. Pivaloyloxymethyl 7 beta-C(Z)2-(2-aminothiazol-4-yl)-2-pentenoylamino hydrochloride hydrate (S-1108) was finally selected as the candidate for clinical evaluation.