AS-924, a novel bifunctional prodrug of ceftizoxime

To improve the oral absorption of ceftizoxime (CZX), 7 beta-[(Z)-2-(2-amino thiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid, we synth esized and evaluated a novel series of bifunctional prodrugs, in which L-al anine was introduced into the aminothiazole-oxime moiety at the C-7 positio n of the various lipophilic esters of CZX. Among these prodrugs, pivaloylox ymethyl 7 beta-[(Z)-2-(2-(S)-alanylaminothlazol-4-yl)-methoxyiminoacetamido ]-3-cephem-4-carboxylate hydrochloride (ceftizoxime alapivoxil, AS-924) was well absorbed after oral administration in experimental animals and showed potent therapeutic effects in mice infected with Gram-positive and Gram-ne gative bacteria.