Cephalosporins. VI. Synthesis and structure-activity relationships of new 7 beta-[(Z)-2-alkoxyimino-2-(2-aminothiazol-4-yl)acetamido]cephalosporins with a tetraxolopyridazine at the 3-position.

The synthesis and in vitro activity of 7 beta-[(Z)-2-alkoxyimino- 2-(2-aminothiazol-4-yl) acetamido]cephalosporins with a tetrazolo[1,5-b]pyridazine at the 3-position are described. These cephalosporins showed excellent activity against Gram-negative bacteria, including beta-lactamase producing strains. The most interesting compound of the series was 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino acetamido] -3-(8-carboxytetrazolo[1,5-b]pyridazin-6-yl)- thiomethyl-3-cephem-4-carboxylic acid (9, FCE 20485) because of its extraordinarily long half-life and marked in vivo activity.

Cephalosporins. III. Synthesis and structure-activity relationships of 7-vinylenethioacetamid:o cephalosporins with a tetrazolo-pyridazine at the 3-position.

The synthesis and in vitro activity of 7-vinylenethioacetamido cephalosporins with a tetrazolo-pyridazine at the 3-position are described. These cephalosporins showed good activity against Gram-positive and Gram-negative bacteria. 7-[(Z)-beta-carboxyvinylenethio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8- amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid (K 13176, 21) was significantly more active in vitro and in vivo than cefazolin against Gram-negative bacteria.

New broad-spectrum alkylthio cephalosporins.

A series of 7-substituted alkyl-thio-acylaminocephalosporins with the following general formula were prepared and tested for in vitro antibacterial activity: (formula: see text). We tried in our research to find any relationship between antibacterial activity and pharmacokinetic properties on the one hand, and chemical structure on the other. The most interesting products were also studied for their in vivo antibacterial activity in experimental acute systemic infections in the mouse.