Synthesis and antibacterial activity of 1-oxacephem derivatives.
A number of new optically active 1-oxacephem compounds were synthesized and tested for antibacterial activity. Various 7 alpha-unsubstituted 1-oxacephem nuclei 2a approximately 3 and a 7 alpha-methoxy-1-oxacephem nucleus 3, reported previously, were converted into the corresponding phenylacetylamino-, 2-thienylacetylamino-, D-mandelylamino-, D-phenylglycylamino-, and arylmalonylamino-1-oxacephem carboxylic acids. All the compounds except for the phenylglycylamine derivatives exhibited four-to sixteen-fold enhanced antibacterial activity compared with that of the corresponding cephalosporins. A combination of the 7 alpha-methoxy-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-1-oxacephem nucleus and a 7 beta-arylmalonylamino side chain, as represented by compound 1 (disodium salt of 33), produced the highest efficacy among them: high antibacterial activity with a widely expanded spectrum against Gram-negative bacteria including resistant strains and Pseudomonas aeruginosa was observed.
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D002511:Cephalosporins / Q000138:chemical synthesis*; D002513:Cephamycins / Q000138:chemical synthesis* / Q000494:pharmacology; D009070:Moxalactam; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D002513:Cephamycins; D009070:Moxalactam