New cephalosporins with 7-acyl groups derived from beta-ketoacids. II. Further modifications of 7-(3-oxobutyrylamino)-cephalosporins.
New cephalosporins modified in the acyl part of 7-(3'-oxobutyrylamino)cephalosporins (1), which have been described in the preceding paper, were synthesized by thiolation at the 2'- or the 4'-position, or by transforming the 3'-oxo group into a 3'-imino group. The most active compound in vitro was 3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-7-(4-methylthio-3-oxobutyrylamino)ceph-3-em-4-carboxylic acid (7c), which showed superior in vitro activity against Gram-positive and Gram-negative bacteria compared to the parent cephalosporin (1b) with the same 3-substituent. The ED50 value for 7c, however, was essentially equal to that of 1b in mice infected with Escherichia coli O-111.
D000818:Animals; D001419:Bacteria / Q000187:drug effects; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D004927:Escherichia coli Infections / Q000188:drug therapy; D007651:Keto Acids; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013329:Structure-Activity Relationship
D002511:Cephalosporins; D007651:Keto Acids