Copper R D
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Am J Med. 1992 Jun 22;92(6A):2S-6S. doi: 10.1016/0002-9343(92)90600-g.
The carbacephems are a new class of beta-lactam antibiotics that are similar in structure to the cephalosporins. Carbacephems differ from cephalosporins, however, in the substitution of a sulfur atom in the dihydrothiazine ring with a methylene group to form a tetrahydropyridine ring. The result of this structural difference is the carbacephem class. Carbacephems have remarkable chemical stability that allows for structural manipulation in a manner that could not be done previously with the cephalosporin ring system. Potent broad-spectrum antibiotics result from the incorporation at the 3 position of substituents that include quaternary pyridinium or imidazole, sulfones, and heterocyclic thiazole structures. Because of the chemical stability of the carbacephems, these highly electronegative side chains can be added to the 3 or 3' position of the tetrahydropyridine ring system. Increasing the electronegativity of these side chains can increase the microbiologic activity of the compounds. In addition, utilizing the side chains that have traditionally conferred good oral absorption on the cephalosporins offers the possibility of a new series of broad-spectrum oral antibiotics. Loracarbef is the first carbacephem to undergo clinical development, and other experimental carbacephems are being produced with the aim of developing potent oral antibiotics that can be used against pathogens that cause infections commonly found in the outpatient setting.
碳头孢烯类是一类新型的β-内酰胺抗生素，其结构与头孢菌素相似。然而，碳头孢烯类与头孢菌素的不同之处在于，二氢噻嗪环中的硫原子被亚甲基取代，形成了四氢吡啶环。这种结构差异的结果就是碳头孢烯类。碳头孢烯类具有显著的化学稳定性，这使得对其结构进行操控成为可能，而这在以前使用头孢菌素环系统时是无法做到的。在3位引入包括季铵吡啶或咪唑、砜和杂环噻唑结构的取代基后，就产生了强效的广谱抗生素。由于碳头孢烯类具有化学稳定性，这些高电负性的侧链可以连接到四氢吡啶环系统的3位或3'位。增加这些侧链的电负性可以提高化合物的微生物活性。此外，利用传统上能使头孢菌素具有良好口服吸收性的侧链，有望开发出一系列新型的广谱口服抗生素。洛拉卡贝是首个进入临床开发阶段的碳头孢烯类药物，目前正在研发其他实验性碳头孢烯类药物，目的是开发出强效口服抗生素，用于对抗在门诊环境中常见的引起感染的病原体。
