Finger-loop inhibitors of the HCV NS5b polymerase. Part 1: Discovery and optimization of novel 1,6- and 2,6-macrocyclic indole series
- 作者：David McGowan ; dmcgowan@its.jnj.com ; Sandrine Vendeville ; Tse-I Lin ; Abdellah Tahri ; Lili Hu ; Maxwell D. Cummings ; Katie Amssoms ; Jan Martin Berke ; Maxime Canard ; Erna Cleiren ; Pascale Dehertogh ; Stefaan Last ; Els Fransen ; Elisabeth Van Der Helm ; Iris Van den Steen ; Leen Vijgen ; Marie-Claude Rouan ; Gregory Fanning ; Origè ; ne Nyanguile ; Kristof Van Emelen ; Kenneth Simmen ; Pierre Raboisson
- 关键词：JKRPMFOXHVVOBW-UHFFFAOYSA-N ; MIPLGURQVCDRMI-UHFFFAOYSA-N
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：1 July, 2012
- 卷：22
- 期：13
- 页码：4431-4436
- 文件大小：1411 K
摘要
Novel conformationaly constrained 1,6- and 2,6-macrocyclic HCV NS5b polymerase inhibitors, in which either the nitrogen or the phenyl ring in the C2 position of the central indole core is tethered to an acylsulfamide acid bioisostere, have been designed and tested for their anti-HCV potency. This transformational route toward non-zwitterionic finger loop-directed inhibitors led to the discovery of derivatives with improved cell potency and pharmacokinetic profile.