2,6-修饰嘌呤2'-C-甲基核糖核苷作为丙型肝炎病毒复制抑制剂的合成与评价
Synthesis and Evaluation of 2,6-Modified Purine 2'-C-Methyl Ribonucleosides as Inhibitors of HCV Replication.
作者信息
Zhou Longhu, Zhang Hongwang, Tao Sijia, Ehteshami Maryam, Cho Jong Hyun, McBrayer Tamara R, Tharnish Philip, Whitaker Tony, Amblard Franck, Coats Steven J, Schinazi Raymond F
机构信息
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center , Atlanta, Georgia 30322, United States.
CoCrystal Pharma, Inc. , Tucker, Georgia 30084, United States.
出版信息
ACS Med Chem Lett. 2015 Nov 23;7(1):17-22. doi: 10.1021/acsmedchemlett.5b00402. eCollection 2016 Jan 14.
Abstract
A variety of 2,6-modified purine 2'-C-methylribonucleosides and their phosphoramidate prodrugs were synthesized and evaluated for inhibition of HCV RNA replication in Huh-7 cells and for cytotoxicity in various cell lines. Cellular pharmacology and HCV polymerase incorporation studies on the most potent and selective compound are reported.
摘要
合成了多种2,6-修饰的嘌呤2'-C-甲基核糖核苷及其磷酰胺酯前药，并评估了它们在Huh-7细胞中对丙型肝炎病毒（HCV）RNA复制的抑制作用以及在各种细胞系中的细胞毒性。报道了对最有效和最具选择性的化合物的细胞药理学和HCV聚合酶掺入研究。
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