Synthesis and characterization of 2鈥?C-Me branched C-nucleosides as HCV polymerase inhibitors
- 作者：Aesop Cho ; acho@gilead.com ; Lijun Zhang ; Jie Xu ; Darius Babusis ; Thomas Butler ; Rick Lee ; Oliver L. Saunders ; Ting Wang ; Jay Parrish ; Jason Perry ; Joy Y. Feng ; Adrian S. Ray ; Choung U. Kim
- 关键词：C-Nucleoside ; Antiviral ; HCV ; Polymerase inhibitor
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：15 June, 2012
- 卷：22
- 期：12
- 页码：4127-4132
- 文件大小：748 K
摘要
A series of 2鈥?C-methyl branched purine and pyrimidine C-nucleosides were prepared. Their anti-HCV activity and pharmacological properties were profiled, and compared with known 2鈥?C-Me N-nucleoside counterparts. In particular, 2鈥?C-Me 4-aza-7,9-dideazaadenosine C-nucleoside (2) was found to have potent and selective anti-HCV activity in vitro as well as a favorable pharmacokinetic profile and in vivo potential for enhanced potency over the corresponding N-nucleoside.