Design, Synthesis, and In Vitro Evaluation of Potential West Nile Virus Protease Inhibitors Based on the 1-Oxo-1,2,3,4-tetrahydroisoquinoline and 1-Oxo-1,2-dihydroisoquinoline Scaffolds

The 1-oxo-1, 2, 3, 4-tetrahydroisoquinoline and 1-Oxo-1, 2-dihydroisoquinoline scaffolds were utilized in the design and solution phase synthesis of focused libraries of compounds for screening against West Nile Virus (WNV) protease. Exploratory studies have led to the identification of a WNV protease inhibitor (a 1-oxo-1, 2-dihydroisoquinoline-based derivative, 12j) which could potentially serve as a launching pad for a hit-to-lead optimization campaign. The identified hit was devoid of any inhibitory activity toward a panel of mammalian serine proteases.