Novel Glycopeptide Antibiotics: N-Alkylated Derivatives Active Against Vancomycin-Resistant Enterococci.
作者:MICHAEL J. RODRIGUEZ、NANCY J. SNYDER、MARK J. ZWEIFEL、STEPHEN C. WILKIE、DOUGLAS R. STACK、ROBIN D.G. COOPER、THALIA I. NICAS、DEBORAH L. MULLEN、THOMAS F. BUTLER、RICHARD C. THOMPSON
DOI:10.7164/antibiotics.51.560
日期:——
naturally-occurring glycopeptide antibiotic, differing from vancomycin in the stereochemistry of the amino-sugar of the disaccharide function, and the presence of a third sugar attached at the benzylic position of amino acid residue 6. Despite these seemingly subtle differences, LY264826 is approximately 10 times more active than vancomycin against the enterococci. In the pursuit of new antibiotics active against multiresistant
LY264826(A82846B)是一种天然存在的糖肽抗生素,在双糖功能的氨基糖的立体化学方面与万古霉素不同,并且在氨基酸残基6的苄基位置上存在第三糖。尽管这些看似微妙的差异在于,LY264826的抗肠球菌活性约为万古霉素的10倍。为了追求对多抗革兰氏阳性生物具有活性的新抗生素,开发了广泛的侧链SAR,其侧重于LY264826在二糖部分的氨基官能团上的还原性烷基化。发现在侧链中具有不同程度的结构多样性(例如,不同的长度和刚性程度)的一系列新衍生物对耐万古霉素的肠球菌(MIC <1)具有有效的活性。