West Nile Virus (WNV), a member of the Flavivirus genus of the Flaviviridae family, has emerged as an important mosquito-borne viral pathogen. No effective vaccines or antiviral agents are currently available for the prevention or treatment of WNV. WNV NS2B/NS3 protease is essential for viral replication, consequently, NS2B/NS3 pro emerged as an important validated target for the design and development of novel therapeutics against WNV.The isoindolin-1-one scaffold was utilized in the design and solution phase synthesis of focused libraries of compounds for screening against West Nile Virus (WNV) protease.Exploratory studies have lead to the identification of WNV protease inhibitors (structure I below) which could potentially serve as a launching pad for a hit-to-lead optimization campaign. The synthesis and screening results of derivatives (I) will be presented.

Inhibitors of West Nile Virus protease based on the isoindolin-1-one scaffold

243rd National Meeting (2012)

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