Synthesis and evaluation of hexahydropyrimidines and diamines as novel hepatitis C virus inhibitors
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- 作者：Jong Yeon Hwang ; Hee-Young Kim ; Suyeon Jo ; Eunjung Park ; Jihyun Choi ; Sunju Kong ; Dong-Sik Park ; Ja Myung Heo ; Jong Seok Lee ; Yoonae Ko ; Inhee Choi ; Jonathan Cechetto ; Jaeseung Kim ; Jinhwa Lee ; Zaesung No ; Marc Peter Windisch
- 关键词：Hepatitis C virus ; Phenotypic screening ; Hexahydropyrimidine ; Diamines ; Entry ; Release
- 刊名：European Journal of Medicinal Chemistry
- 出版年：December, 2013
- 年：2013
- 卷：70
- 期：Complete
- 页码：315-325
- 全文大小：893 K
文摘
In order to identify novel anti-hepatitis C virus (HCV) agents we devised cell-based strategies and screened phenotypically small molecule chemical libraries with infectious HCV particles, and identified a hit compound (1) containing a hexahydropyrimidine (HHP) core. During our cell-based SAR study, we observed a conversion of HHP 1 into a linear diamine (6), which is the active component in inhibiting HCV and exhibited comparable antiviral activity to the cyclic HHP 1. In addition, we engaged into the biological characterization of HHP and demonstrated that HHP does not interfere with HCV RNA replication, but with entry and release of viral particles. Here we report the results of the preliminary SAR and mechanism of action studies with HHP.