AS-924, a novel bifunctional prodrug of ceftizoxime

To improve the oral absorption of ceftizoxime (CZX), 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]- 3-cephem-4- carboxylic acid, we synthesized and evaluated a novel series of bifunctional prodrugs, in which L-alanine was introduced into the aminothiazole-oxime moiety at the C-7 position of the various lipophilic esters of CZX. Among these prodrugs, pivaloyloxymethyl 7beta-[(Z)-2-(2-(S)-alanylaminothiazol-4-yl)-2-methoxyiminoa cetamido]-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-negative bacteria.