Patent Evaluation: Preparation of orally active thioalkylthiocephalosporins

Summary

Novelty: A series of novel thioalkylthiocephalosporins is claimed. The compounds are said to be active against Gram-positive and Gram-negative bacteria.

Biology: Limited biological data are presented, but are restricted to one or two organisms per compound. For example, one compound is active against E. coli 7437 at 0.01 μg/ml. Another has similar activity and is orally absorbed in mice, the blood level after fifteen minutes being 18.7μg/ml.

Chemistry: The compounds are prepared by the reaction of a heterocyclicthio(alkyl)-thio-acetate with a cephalosporin containing an appropriate C-3 leaving group, such as mesylate. Alternatively, alkylation of a C-3 thio derivative can be used. Typical examples are 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxy-irnmoacetyl]amino-3-(tetrazol-5-yl)thiomethylthio-3-cephem-4-carboxylic acid and 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetyl]amino-3-(2-pyridylthiomethylthio)-3-cephem-4-carboxylic acid. Thirty examples are disclosed.

Structure: