Sykes R B, Koster W H, Bonner D P
Squibb Institute for Medical Research, Princeton, NJ 08540.
J Clin Pharmacol. 1988 Feb;28(2):113-9. doi: 10.1002/j.1552-4604.1988.tb05734.x.
The discovery of the monobactams led to the successful development of aztreonam as the first of this novel class of beta-lactam antibiotics to enter the clinical field. Continued structural modification on the monobactam nucleus has resulted in two additional compounds from this class that show interesting biologic properties. The first, SQ 83,360, is like aztreonam in exhibiting high activity against members of the Enterobacteriaceae but has the added characteristic of being exceptionally active against strains of Pseudomonas aeruginosa. Also, significant gains are made with SQ 83,360 in activity against Pseudomonas spp. and Acinetobacter. The second compound, tigemonam, is also like aztreonam, having good activity against Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae and showing good beta-lactam stability. Tigemonam differs from aztreonam in being well absorbed orally by experimental laboratory animals.
单环β-内酰胺类药物的发现促使氨曲南得以成功研发,成为这类新型β-内酰胺抗生素中首个进入临床领域的药物。对单环β-内酰胺核心结构的持续修饰已产生该类别的另外两种化合物,它们展现出有趣的生物学特性。第一种是SQ 83,360,与氨曲南一样,对肠杆菌科细菌具有高活性,但还具有对铜绿假单胞菌菌株异常活跃的额外特性。此外,SQ 83,360对假单胞菌属和不动杆菌属的活性也有显著提高。第二种化合物替莫南也与氨曲南相似,对肠杆菌科细菌、流感嗜血杆菌和淋病奈瑟菌具有良好活性,且表现出良好的β-内酰胺稳定性。替莫南与氨曲南的不同之处在于,实验动物口服时它能被很好地吸收。