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-...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1988-10, Vol.31 (10), p.1993-1997
Main Authors: Pfeil-Doyle, J, Draheim, S E, Kukolja, S, Ott, J L, Counter, F T
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Bacterial Infections - drug therapy
Bacterial Infections - microbiology
Biological Availability
Cephalosporins - blood
Cephalosporins - pharmacokinetics
Cephalosporins - therapeutic use
Gram-Negative Bacteria - drug effects
Gram-Positive Bacteria - drug effects
Mice
Microbial Sensitivity Tests
Structure-Activity Relationship
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Summary: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.
ISSN:0022-2623
DOI:10.1021/jm00118a023