Studies on 3'-quaternary ammonium cephalosporins - III. Synthesis and antibacterial activity of 3'-(3-aminopyrazolium)cephalosporins

Article abstract of DOI:10.1016/S0968-0896(96)00270-2

The synthesis and in vitro antibacterial activity of 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido] cephalosporins bearing N-mono or dialkyl and carbamoyl aminopyrazolium, and five- or six-membered rings fused to the 3-aminopyrazolium methyl groups at the 3-position, are described. Aminopyrazolium methyl cephalosporins (23e, f, i), with fused saturated and unsaturated rings were especially effective against Staphylococcus strains compared to 3-amino-2-methylpyrazolium methyl cephalosporin (1). Among the cephalosporins prepared in this work, 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino acetamidol-3-(4,5,6,7-tetrahydro-1-pyrazolo[1,5-a] pyrimidinio)methyl-3-cephem-4-carboxylate (23f) showed a good balance of antibacterial activity against both Gram-positive bacteria including Staphylococcus aureus and Gram-negative bacteria including P. aeruginosa. An imidazopyrazolium group at the 3-position in, for example, cephalosporin (23i) was particularly effective for improving antibacterial activity against MRSA.