Expanding the chemical space of anti‐HCV NS5A inhibitors by stereochemical exchange and peptidomimetic approaches

• DOI: 10.1002/ardp.201800017
• Publication Date: 2018-05-25T14:27:08Z
• Authors: Triveena M. Ramsis; Shereen E. Abdel ...; Niki Vassilaki; Efseveia Frakolaki; Ahmed A. M. Kamal; Grigoris Zoidis; Nermin S. Ahmed; Ashraf H. Abadi
• Keywords: Peptidomimetic; Lead compound; NS5A; Structure–activity relationship

Here we report a series of potent anti-HCV agents bearing symmetrical benzidine l-prolinamide backbone with different capping groups including alkyl/aryl carbamates natural and unnatural valine leucine amino acids. All compounds were investigated for their inhibitory activity in an HCV replicon assay on genotype 1b. The novel share some chemical clinical attributes commercially available NS5A inhibitors. Compounds 5 6 residue ethyl isobutyl showed EC50 values the picomolar range low toxicity profile selectivity indices several orders magnitude. These findings enlarge space from which inhibitors may be discovered by adopting acids, acids other than methyl as groups.