Synthesis and structure-activity relationships of 7β-[(Z)-2-(2-aminothiazol-4-yl)-3-(substituted)-2- propenoyl-amino]-3-cephems with C-3 substitutions

Article abstract of DOI:10.7164/antibiotics.47.466

Synthesis and biological activity of a series of 7β-[(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 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-pentenoylamino]-3- carbamoyloxymethyl-3-cephem-4-carboxyiate hydrochloride hydrate (S-1108) was finally selected as the candidate for clinical evaluation.