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.
Kasai
M
M
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd., Japan.
Hatano
S
S
Kitagawa
M
M
Yoshimi
A
A
Shirahase
H
H
Nishimura
K
K
Kakeya
N
N
D000818:Animals; D001419:Bacteria / Q000187:drug effects; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002511:Cephalosporins / Q000494:pharmacology; D004285:Dogs; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
D002511:Cephalosporins; D011355:Prodrugs; C121334:ceftizoxime alapivoxil; D015296:Ceftizoxime