Although all-oral direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) treatment is now a reality, today's HCV drugs are expensive, and more affordable drugs are still urgently needed. In this work, we report the identification of the 2-phenyl-4,5,6,7-Tetrahydro-1H-indole chemical scaffold that inhibits cellular replication of HCV genotype 1b and 2a subgenomic replicons. The anti-HCV genotype 1b and 2a profiling and effects on cell viability of a selected representative set of derivatives as well as their chemical synthesis are described herein. The most potent compound 39 displayed EC₅₀ values of 7.9 and 2.6 μM in genotype 1b and 2a, respectively. Biochemical assays showed that derivative 39 had no effect on HCV NS5B polymerase, NS3 helicase, IRES mediated translation and selected host factors. Thus, future work will involve both the chemical optimization and target identification of 2-phenyl-4,5,6,7-Tetrahydro-1H-indoles as new anti-HCV agents.

尽管现在已经实现了用于丙型肝炎病毒（HCV）治疗的全口服直接作用抗病毒（DAA）治疗，但是当今的HCV药物价格昂贵，并且仍然急需价格更实惠的药物。在这项工作中，我们报告了抑制HCV基因型1b和2a亚基因组复制子细胞复制的2-苯基-4,5,6,7-四氢-1 H-吲哚化学支架的鉴定。本文描述了抗HCV基因型1b和2a的概况分析以及对一组选定代表性代表衍生物的细胞活力的影响以及它们的化学合成。最有效的化合物39在基因型1b和2a中显示的EC ₅₀值分别为7.9和2.6μM。生化分析表明，衍生物39对HCV NS5B聚合酶，NS3解旋酶，IRES介导的翻译和选定的宿主因子无影响。因此，未来的工作将涉及化学优化和2-苯基-4,5,6,7-四氢-1 H-吲哚作为新型抗HCV药物的目标识别。