Zhang C Y, Hu S C, Zhou H S, Duan T H
Division of Semisynthetic Antibiotics, China Pharmaceutical University, Nanjing.
Yao Xue Xue Bao. 1991;26(3):175-82.
In order to develop oral cephalosporin exhibiting broad-spectrum activity, a series of cephalosporin derivatives (VIII1-12) bearing 1, 2, 3-triazolymethyl substituents on the C3 position were synthesized. 7-Phenylacetamido-3-methyl-3-cephem-4-carboxylic acid (I) was employed as starting material and converted to VIII by procedures of esterification and oxidation, bromination, azido-substitution, dipolarcycloaddition, deprotection, cleavage, and condensation. Minimum inhibitory concentration (MIC) values in vitro showed that VIII2-4.9-11 had a wide antibacterial spectrum against Gram positive and Gram negative bacteria and possessed high activities. Further biological evaluation and the study of oral absorption for the six compounds will be performed.
为了开发具有广谱活性的口服头孢菌素，合成了一系列在C3位带有1,2,3-三唑甲基取代基的头孢菌素衍生物（VIII1-12）。以7-苯乙酰氨基-3-甲基-3-头孢烯-4-羧酸（I）为起始原料，通过酯化、氧化、溴化、叠氮取代、偶极环加成、脱保护、裂解和缩合等步骤转化为VIII。体外最低抑菌浓度（MIC）值表明，VIII2-4.9-11对革兰氏阳性菌和革兰氏阴性菌具有广谱抗菌活性且活性较高。将对这六种化合物进行进一步的生物学评价和口服吸收研究。
