Novel C-2 Substituted Carbapenem Derivatives. Part II. Synthesis and Structure-activity Relationships of Isoxazolin-2-yl, Isoxazolidin-2-yl and 2-Pyrazolin-2-yl Carbapenems Generated Using 1,3-Dipolar Cycloaddition Chemistry.
作者:GEORGE BURTON、GRAHAM J. CLARKE、JAMES D. DOUGLAS、A. JOHN EGLINGTON、COLIN H. FRYDRYCH、JEREMY D. MINKS、NICHOLAS W. HIRD、ERIC HUNT、STEPHEN F. MOSS、ANTOINETTE NAYLOR、NEVILLE H. NICHOLSON、MICHAEL J. PEARSON
DOI:10.7164/antibiotics.49.1266
日期:——
A series of carbapenems containing novel C-2 semisaturated heterocyclic substituents were synthesised by 1,3 dipolar cycloaddition reactions of nitrile oxides, nitrile imines and a nitrone to 2-vinylcarbapenem. The isoxazoline and isoxazolidine compounds showed potent antibacterial activity but moderate stability to human dehydropeptidase 1 (DHP-1). Stability to DHP-1 was improved by methyl substitution
一系列含有新型C-2半饱和杂环取代基的碳青霉烯类化合物是通过腈类氧化物,腈亚胺和硝酮的1,3偶极环加成反应合成2乙烯基卡巴南而合成的。异恶唑啉和异恶唑烷化合物显示有效的抗菌活性,但对人脱氢肽酶1(DHP-1)的稳定性中等。通过异恶唑啉环中的甲基取代提高了对DHP-1的稳定性,但以抗菌活性为代价。吡唑啉对DHP-1表现出优异的稳定性,但对革兰氏阴性生物的效力降低。