2-Hydroxy-1-oxo-1, 2-dihydroisoquinoline-3-carboxylic Acid with Inbuilt β-NHydroxy-γ-keto-acid Pharmacophore as HCV NS5B Polymerase Inhibitors

…, PT Chang, MH Chuang, TR Chern…

Index: Deore; Chen; Chang; Chuang; Chern; Wang Current Medicinal Chemistry, 2012 , vol. 19, # 4 p. 613 - 624

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Citation Number: 5

Abstract

The inbuilt 2-N-hydroxy-1-oxo-3-carboxylic acid of isoquinolone was designed as pyrophosphate mimic for hepatitis C NS5B polymerase. Various 2-hydroxy-1-oxo-1, 2- dihydroisoquinoline-3-carboxylic acid derivatives 11a-p were synthesized and evaluated as HCV NS5B polymerase inhibitors. Compound 11c exhibited moderate inhibitory potency based on the inorganic pyrophosphate generation (IC50= 9.5 μM) and based on NTP ...