Synthesis and structure-activity relationships in the cefpirome series. I. 7-(2-(2-aminothiazol-4-yl)-2-(z)-oxyiminoacetamido)-3-((substituted-1-pyridinio)methyl)-ceph-3-em-4-carboxylates

7-[2-(2-Aminothiazol-4-yl)-2-(Z)-oxyiminoacetamido]-3-[(substituted-1-pyridinio)methyl]ceph-3-em-4-carboxylates II are a group of β-lactam antibiotics with extraordinary high antibacterial activity. The promising member of this group, cefpirome (HR 810, II-1) is a candidate for clinical use. Synthetic pathways to II starting from cefotaxime derivatives I or 7-aminocephalosporanic acid (7-ACA) are described. A preferred method for the conversion of I to II or 7-ACA to precursors III respectively employs iodotrimethylsilane and an excess of the pyridine base. Structure-activity studies reveal an optimum overall activity in the series of pyridines with fused saturated and unsaturated rings or cyclopropyl- and alkoxy substituents. Favorable oxyimino substituents are methyl, ethyl, difluoromethyl and carbamoylmethyl groups. Acidic substituents lead to decreased activity against Staphylococcus aureus SG 5.11. Introduction of halogen in the thiazole nucleus causes improvement of activity against the K1 β-lactamase producing Klebsiella aerogenes 1082 E strain.