title: Synthesis and evaluation of hexahydropyrimidines and diamines as novel hepatitis C virus inhibitors.
abstract: 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.
authors.affiliation: Medicinal Chemistry Group, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea. Electronic address: jongyeonhwang@gmail.com.
authors.forename: Jong Yeon
authors.initials: JY
authors.lastname: Hwang
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Suyeon
authors.initials: S
authors.lastname: Jo
authors.forename: Eunjung
authors.initials: E
authors.lastname: Park
authors.forename: Jihyun
authors.initials: J
authors.lastname: Choi
authors.forename: Sunju
authors.initials: S
authors.lastname: Kong
authors.forename: Dong-Sik
authors.initials: DS
authors.lastname: Park
authors.forename: Ja Myung
authors.initials: JM
authors.lastname: Heo
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Yoonae
authors.initials: Y
authors.lastname: Ko
authors.forename: Inhee
authors.initials: I
authors.lastname: Choi
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cechetto
authors.forename: Jaeseung
authors.initials: J
authors.lastname: Kim
authors.forename: Jinhwa
authors.initials: J
authors.lastname: Lee
authors.forename: Zaesung
authors.initials: Z
authors.lastname: No
authors.forename: Marc Peter
authors.initials: MP
authors.lastname: Windisch
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects*; D057166:High-Throughput Screening Assays; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D003959:Diamines; D011743:Pyrimidines
keywords: Diamines; Entry; Hepatitis C virus; Hexahydropyrimidine; Phenotypic screening; Release