3-Sulfonyl-1-carba-1-dethiacephems

The stability of the 1-carba-1-dethiacephalosporin framework has allowed the synthesis of a range of 3-sulfonyl-1-carba-1-dethiacephems unavailable for a variety of reasons in the cephem arena. The known p-nitrobenzyl 7 beta-(phenoxyacetamido)-3-[[(trifluoromethyl)sulfonyl]oxy]-1-carba -1- dethia-3-...

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Bibliographic Details
Published in:	Journal of medicinal chemistry Vol. 32; no. 11; pp. 2436 - 2442
Main Authors:	Crowell, Thomas A., Halliday, Basil D., McDonald, John H., Indelicato, Joseph M., Pasini, Carol E., Wu, Ernie C. Y.
Format:	Journal Article
Language:	English
Published:	Washington, DC American Chemical Society 01-11-1989
Subjects:	Cephalosporins - chemical synthesis Chemical Phenomena Chemistry Enterobacter cloacae Escherichia coli Exact sciences and technology Gram-Negative Bacteria - drug effects Gram-Positive Bacteria - drug effects Haemophilus influenzae Heterocyclic compounds Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives Organic chemistry Preparations and properties Proteus rettgeri Streptococcus pyogenes Staphylococcus aureus Nitro compound Sulfur nitrogen heterocycle Five membered ring Sulfone Angular nitrogen heterocycle Lactam Imine In vitro Sulfonate Structure activity relation Bicyclic compound Carboxamide Benzenic compound Fluorine Organic compounds Antibacterial agent Primary amine
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Summary:	The stability of the 1-carba-1-dethiacephalosporin framework has allowed the synthesis of a range of 3-sulfonyl-1-carba-1-dethiacephems unavailable for a variety of reasons in the cephem arena. The known p-nitrobenzyl 7 beta-(phenoxyacetamido)-3-[[(trifluoromethyl)sulfonyl]oxy]-1-carba -1- dethia-3-cephem-4-carboxylate served as a precursor to this series of compounds. Displacement of the enol triflate with various sulfinates in acetonitrile or DMF and deprotection of the intermediates led to 7 beta-[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]- 3-[alkyl(aryl)sulfonyl]-1-carba-1-dethia-3-cephem-4-carboxyl ic acids. The 3-sulfonyl-1-carba-1-dethiacephems display potent activity against both Gram-positive and Gram-negative bacteria. The following MIC's (microgram/mL) for the 3-cyclopropyl sulfone are representative: Staphylococcus aureus = 4, Streptococcus pyogenes = 1, Haemophilus influenzae = 0.25, Escherichia coli = 0.03, Enterobacter cloacae = 0.25, Proteus rettgeri = 0.25. The excellent in vitro antibacterial activity of this series indicates the potential of the carbacephalosporin framework for exploring substituents which are unknown or which produce unstable cephems.
Bibliography:	ark:/67375/TPS-NC04K5KZ-Z istex:A66FA08A252B713DC8633607944EC7580853AC18 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm00131a005