title: Discovery of 2-iminobenzimidazoles as potent hepatitis C virus inhibitors with a novel mechanism of action.
abstract: In this report we describe 2-iminobenzimidazole (IBI) analogs, identified during the course of a phenotypic high-throughput screening campaign, as novel hepatitis C virus (HCV) inhibitors. A series of IBI derivatives was synthesized and evaluated for their inhibitory activity against infectious HCV. Among the IBIs derivatives studied in this work, we identified promising compounds with high antiviral efficacy, high selectivity index and good microsomal stability. Noteworthy, the IBI series exhibited inhibitory activity on early and late steps of the viral cycle, but not in the HCV replicon system demonstrating a mechanism of action distinct from clinical-stage and approved anti-HCV drugs. Overall, our results suggest that IBIs are predestinated for further exploration as lead compounds for novel HCV interventions.
authors.affiliation: Applied Molecular Virology, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea. Electronic address: mpwindisch@ip-korea.org.
authors.forename: Marc Peter
authors.initials: MP
authors.lastname: Windisch
authors.affiliation: Medicinal Chemistry Group, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Suyeon
authors.initials: S
authors.lastname: Jo
authors.affiliation: Applied Molecular Virology, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Applied Molecular Virology, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Applied Molecular Virology, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Keumhyun
authors.initials: K
authors.lastname: Kim
authors.affiliation: Medicinal Chemistry Group, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Sunju
authors.initials: S
authors.lastname: Kong
authors.affiliation: DMPK Group, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Hyangsuk
authors.initials: H
authors.lastname: Jeong
authors.affiliation: DMPK Group, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Late Discovery Program, Institut Pasteur Korea (IP-K), Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Zaesung
authors.initials: Z
authors.lastname: No
authors.affiliation: Medicinal Chemistry Group, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea. Electronic address: jyhwang@krict.re.kr.
authors.forename: Jong Yeon
authors.initials: JY
authors.lastname: Hwang
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D016174:Hepacivirus / Q000187:drug effects*; D007097:Imines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D007097:Imines
keywords: Entry; Hepatitis C virus; Iminobenzimidazole; Phenotypic screening; Release