Wang Peiyuan, Du Jinfa, Rachakonda Suguna, Chun Byoung-Kwon, Tharnish Phillip M, Stuyver Lieven J, Otto Michael J, Schinazi Raymond F, Watanabe Kyoichi A
Pharmasset Inc., Princeton, New Jersey 08540, USA.
J Med Chem. 2005 Oct 6;48(20):6454-60. doi: 10.1021/jm058223t.
Several 6- and 7-monosubstituted N3,5'-cyclo-4-(beta-d-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one derivatives as well as the 5-thiono analogue were synthesized, providing structure-anti-hepatitis C virus (HCV) activity relationships for the series. Among the compounds synthesized, the 6-bromo, 7-methylamino, and 5-thiono analogues exhibited more potent anti-HCV activity in an HCV subgenomic replicon cell based assay (EC90 = 1.9, 7.4, and 10.0 microM, respectively) than the lead compound N3,5'-cyclo-4-(beta-D-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one (EC90 = 79.8 microM).
合成了几种6-和7-单取代的N3,5'-环-4-(β-D-呋喃核糖基)-间三唑并[4,5-b]吡啶-5-酮衍生物以及5-硫代类似物，给出了该系列化合物的结构-抗丙型肝炎病毒(HCV)活性关系。在合成的化合物中，6-溴、7-甲氨基和5-硫代类似物在基于HCV亚基因组复制子细胞的试验中显示出比先导化合物N3,5'-环-4-(β-D-呋喃核糖基)-间三唑并[4,5-b]吡啶-5-酮(EC90 = 79.8 μM)更强的抗HCV活性(EC90分别为1.9、7.4和10.0 μM)。
