Oral absorption of cephalosporin antibiotics. 2. Expanded structure-activity relationships of 7-(arylacetamido)-3-substituted cephalosporins.
The structure-activity relationship for 7-arylacetamido cephalosporins has been extended. Modifications of the 7-aryl group led to improvements in microbiological activity against Gram-positive organisms. However, Gram-negative activity was generally much poorer than that of the lead compound 7-[(2-aminothiazol-4-yl)acetamido]-3-chloro-cephalosporanic acid (A). Modifications of the 3-position did not significantly change the microbiological activity or spectrum. Of the compounds selected for mouse protection studies (ED50's), 7-[(benzothien-3-yl)acetamido]-3-chloro cephalosporin and A showed the best per oral to subcutaneous ED50 ratios.
Pfeil-Doyle
J
J
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Draheim
S E
SE
Kukolja
S
S
Ott
J L
JL
Counter
F T
FT
D000284:Administration, Oral; D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D001682:Biological Availability; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D002511:Cephalosporins