Albrecht H A, Beskid G, Christenson J G, Georgopapadakou N H, Keith D D, Konzelmann F M, Pruess D L, Rossman P L, Wei C C
Roche Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
J Med Chem. 1991 Sep;34(9):2857-64. doi: 10.1021/jm00113a026.
A series of cephalosporins has been prepared in which the 3'-position was linked to the nitrogen of the antibacterial quinolone ciprofloxacin through a carbamate function. Like the ester-linked and quaternary-linked dual-action cephalosporins reported earlier, these carbamate-linked compounds exhibited a broad antibacterial spectrum derived from both cephalosporin-like and quinolone-like activities, suggesting a dual mode of action. Studies to elucidate details of the mechanism of action have been inconclusive. Ciprofloxacin liberated as a consequence of bacterial enzyme-mediated reactions may contribute to the second mode of action, although some evidence indicates that the intact carbamate-linked bifunctional molecules may possess intrinsically both beta-lactam and quinolone activities.
已制备了一系列头孢菌素，其中3'-位通过氨基甲酸酯官能团与抗菌喹诺酮环丙沙星的氮相连。与早期报道的酯连接和季铵连接的双作用头孢菌素一样，这些氨基甲酸酯连接的化合物表现出源自头孢菌素样和喹诺酮样活性的广谱抗菌谱，表明其具有双重作用模式。阐明作用机制细节的研究尚无定论。由细菌酶介导的反应释放出的环丙沙星可能有助于第二种作用模式，尽管一些证据表明完整的氨基甲酸酯连接的双功能分子可能本身就同时具有β-内酰胺和喹诺酮活性。
