Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
J Med Chem. 2014 Apr 10;57(7):3154-60. doi: 10.1021/jm401977j. Epub 2014 Mar 31.
A series of oseltamivir analogues bearing an N-substituted guanidine unit were prepared and evaluated as inhibitors of neuraminidases from four strains of influenza. The two most potent analogues identified contain relatively small N-guanidine substituents (N-methyl and N-hydroxyl) and display enhanced inhibition with IC50 values in the low nanomolar range against neuraminidases from wild-type and oseltamivir-resistant strains. Potential advantages of including the N-hydroxyguanidine moiety in neuraminidase inhibitors are also discussed.
制备了一系列含有 N-取代胍基单元的奥司他韦类似物，并将其作为来自四种流感株的神经氨酸酶抑制剂进行了评估。鉴定出的两种最有效的类似物含有相对较小的 N-胍基取代基（N-甲基和 N-羟基），并且对野生型和奥司他韦耐药株的神经氨酸酶显示出增强的抑制作用，IC50 值在纳摩尔范围内。还讨论了在神经氨酸酶抑制剂中包含 N-羟基胍基部分的潜在优势。
