Studies on beta-lactam antibiotics. IX. Synthesis and biological activity of a new orally active cephalosporin, cefixime (FK027).
The synthesis and some biological properties of 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino) acetamido]-3-vinyl-3-cephem-4-carboxylic acid (3, FK027) are described. Diphenylmethyl 7-amino-3-vinyl-3-cephem-4-carboxylate hydrochloride (8), the cephem precursor to FK027 was prepared from 7-aminocephalosporanic acid (7-ACA) by two parallel routes differing primarily in the protection of the 7-amino group. Compound 8 was alternatively prepared from deacetylcephalosporin C sodium salt (DCCNa) with improved yields. Two pathways for the conversion of 8 to FK027 are provided. The new orally active cephalosporin, FK027, possesses a widely expanded antimicrobial activity and high stability to beta-lactamases.
D000284:Administration, Oral; D000818:Animals; D001419:Bacteria / Q000187:drug effects; D001646:Bile / Q000378:metabolism; D020682:Cefixime; D002439:Cefotaxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D006207:Half-Life; D051381:Rats; D011919:Rats, Inbred Strains
D020682:Cefixime; D002439:Cefotaxime