Upon high-throughput screening of synthetic small molecule libraries with the infectious hepatitis C virus (HCV) cell culture system, we identified an iminodipyridinopyrimidine (IDPP) scaffold. IDPP did not inhibit HCV replication, but exhibited very potent inhibitory activity on early and late steps of HCV life cycle. Applying an intensive structure-activity relationship (SAR) study, a promising IDPP Lead compound (12c) with excellent potency (EC₅₀ = 10 nM), high safety margin (SI > 2000), and an acceptable stability in human and rat liver microsomes (t_1/2 >60 min) was identified. Overall, our results suggest that the IDPP scaffold could be used for the development of novel HCV interventions.

在通过感染性丙型肝炎病毒（HCV）细胞培养系统对合成的小分子文库进行高通量筛选后，我们确定了亚氨基二吡啶并嘧啶（IDPP）支架。IDPP不会抑制HCV复制，但在HCV生命周期的早期和晚期都表现出非常强的抑制活性。应用深入的构效关系（SAR）研究，一种有前途的IDPP铅化合物（12c）具有出色的效价（EC ₅₀  = 10 nM），高安全裕度（SI> 2000），并在人和大鼠肝微粒体中具有可接受的稳定性（t _1/2 > 60分钟）被确定。总体而言，我们的结果表明IDPP支架可用于开发新的HCV干预措施。