Exploration of acetanilide derivatives of 1-(ω-phenoxyalkyl)uracils as novel inhibitors of Hepatitis C Virus replication

• DOI: 10.1038/srep29487
• Publication Date: 2016-07-13T06:55:16Z
• Authors: Andrea Magri; Alexander A. Ozerov; Vera L. Tunitskaya; Vladimir T. Value...; Ahmed Wahid; Mario Pirisi; Peter Simmonds; Alexander V. Ivanov; Mikhail S. Novikov; Arvind H. Patel
• Keywords: Acetanilide; Uracil; Structure–activity relationship

Abstract Hepatitis C Virus (HCV) is a major public health problem worldwide. While highly efficacious directly-acting antiviral agents have been developed in recent years, their high costs and relative inaccessibility make use limited. Here, we describe new 1-(ω-phenoxyalkyl)uracils bearing acetanilide fragment 3 position of pyrimidine ring as potential drugs against HCV. Using combination various biochemical assays vitro virus infection replication models, show that our compounds are able to significantly reduce viral genomic replication, independently genotype, with IC 50 values the nanomolar range. We also demonstrate can block de novo RNA synthesis effect dependent on chemical structure compounds. A detailed structure-activity relationship revealed most active were N -substituted uracil derivatives containing 6-(4-bromophenoxy)hexyl or 8-(4-bromophenoxy)octyl at 1 position.