Synthesis and antiviral activity of 2‐substituted 4‐aminoquinoline and its analogous derivatives

Abstract

AbstractHerein we describe an efficient Lewis acid‐mediated one‐pot synthesis of 2‐substituted 4‐aminoquinolines from commercially available anthranilonitriles and substituted acetophenones via a Friedlander type annulation reaction. The protocol avoids any transition metal catalysts, has a wide substrate scope, and exclusively produces 4‐aminoquinolines in excellent yields. Screening of all the new compounds for in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells revealed nine analogues with good virus‐inhibiting activity and a favorable toxicity profile. Among them, two compounds, 3a (IC50: 1.7 μM, SI = 30) and 3l (IC50: 4.0 μM, SI = 25) with higher potency are the best anti‐influenza hit analogues for further structural optimization.