Design and Synthesis of Novel Symmetric Fluorene-2,7-Diamine Derivatives as Potent Hepatitis C Virus Inhibitors.

ABSTRACT: Hepatitis C virus (HCV) is an international challenge. Since the discovery of NS5A direct-acting antivirals, researchers turned their attention to pursue novel NS5A inhibitors with optimized design and structure. Herein we explore highly potent hepatitis C virus (HCV) NS5A inhibitors; the novel analogs share a common symmetrical prolinamide 2,7-diaminofluorene scaffold. Modification of the 2,7-diaminofluorene backbone included the use of (S)-prolinamide or its isostere (S,R)-piperidine-3-caboxamide, both bearing different amino acid residues with terminal carbamate groups. Compound 26 exhibited potent inhibitory activity against HCV genotype (GT) 1b (effective concentration (EC₅₀) = 36 pM and a selectivity index of >2.78 × 10⁶). Compound 26 showed

SUBMITTER: Mousa MHA 

PROVIDER: S-EPMC8064491 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature