Ohki H, Kawabata K, Inamoto Y, Okuda S, Kamimura T, Sakane K
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Bioorg Med Chem. 1997 Mar;5(3):557-67. doi: 10.1016/s0968-0896(96)00270-2.
The synthesis and in vitro antibacterial activity of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]cephalos porins 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, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(4,5, 6, 7-tetrahydro-1-pyrazolo[1,5-a]pyrimidinio)methyl-3-cephem-4-carbox ylate (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.
描述了带有N-单烷基或二烷基以及氨基甲酰基氨基吡唑鎓的7β-[(Z)-2-(2-氨基噻唑-4-基)-2-甲氧基亚氨基乙酰胺基]头孢菌素的合成及其体外抗菌活性，以及在3-位与3-氨基吡唑鎓甲基相连的五元或六元环。与3-氨基-2-甲基吡唑鎓甲基头孢菌素(1)相比，带有稠合饱和与不饱和环的氨基吡唑鎓甲基头孢菌素(23e、f、i)对葡萄球菌菌株特别有效。在本研究制备的头孢菌素中，7β-[(Z)-2-(2-氨基噻唑-4-基)-2-甲氧基亚氨基乙酰胺基]-3-(4,5,6,7-四氢-1-吡唑并[1,5-a]嘧啶鎓)甲基-3-头孢烯-4-羧酸酯(23f)对包括金黄色葡萄球菌在内的革兰氏阳性菌和包括铜绿假单胞菌在内的革兰氏阴性菌均表现出良好的抗菌活性平衡。例如，头孢菌素(23i) 3-位的咪唑并吡唑鎓基团对提高抗耐甲氧西林金黄色葡萄球菌的抗菌活性特别有效。
