Misiek M, Pursiano T A, Crast L B, Leitner F, Price K E
Antimicrob Agents Chemother. 1972 Jan;1(1):54-66. doi: 10.1128/AAC.1.1.54.
Structure-activity relationships were examined for a number of 7-[alpha-(N,N'-substituted-amidinothio)-acetamido] cephalosporanic acids, including several wherein the amidino group was cyclized into six, seven, and eight-membered rings and a series wherein alkyl, cycloalkyl, alkenyl, and alkynyl radicals were substituted on the nitrogens of the noncyclized amidino group. Derivatives containing an unsubstituted cyclized amidino group had comparable antibacterial activity in vitro and in general had a spectrum of activity broader than that of cephalothin, especially against cephalothin-resistant strains of Escherichia, Klebsiella, and Proteus. When administered parenterally, the cephalosporin with the six-membered cyclized amidino group was as effective as cephalothin in experimental infections of mice produced by cephalothin-sensitive gram-negative organisms and more efficacious in infections caused by cephalothin-resistant strains. Among the cephalosporins with noncyclized amidino groups, those with an ethyl substituent on one of the nitrogens and a C(2)-C(4) alkyl radical, particularly propyl on the other, were the most active. They not only had a better profile of activity in vitro than cephalothin and the cephalosporin derivatives having a cyclized amidino group, but were also more efficacious in infections of mice.
对多种7-[α-(N,N'-取代脒硫基)-乙酰胺基]头孢烷酸进行了构效关系研究，其中包括几种脒基环化为六元、七元和八元环的化合物，以及一系列在未环化脒基的氮原子上被烷基、环烷基、烯基和炔基取代的化合物。含有未取代环化脒基的衍生物在体外具有相当的抗菌活性，并且一般来说，其活性谱比头孢噻吩更宽，尤其是对头孢噻吩耐药的大肠杆菌、克雷伯菌和变形杆菌菌株。经肠胃外给药时，具有六元环化脒基的头孢菌素在由头孢噻吩敏感革兰氏阴性菌引起的小鼠实验感染中与头孢噻吩效果相当，而在由头孢噻吩耐药菌株引起的感染中更有效。在具有未环化脒基的头孢菌素中，那些在其中一个氮原子上有乙基取代基且在另一个氮原子上有C(2)-C(4)烷基（特别是丙基）的化合物活性最高。它们不仅在体外比头孢噻吩和具有环化脒基的头孢菌素衍生物具有更好的活性谱，而且在小鼠感染中也更有效。
