2. Academic Validation
  3. Potent antiviral activity of novel multi-substituted 4-anilinoquin(az)olines

Potent antiviral activity of novel multi-substituted 4-anilinoquin(az)olines

  • Bioorg Med Chem Lett. 2020 Aug 15;30(16):127284. doi: 10.1016/j.bmcl.2020.127284.
Sirle Saul 1,  Szu-Yuan Pu 1,  William J Zuercher 2,  Shirit Einav 3,  Christopher R M Asquith 4
Affiliations

Affiliations

  • 1 Department of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 2 Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 3 Department of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: seinav@stanford.edu.
  • 4 Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: chris.asquith@unc.edu.
PMID: 32631507 DOI: 10.1016/j.bmcl.2020.127284
Abstract

Screening a series of 4-anilinoquinolines and 4-anilinoquinazolines enabled identification of potent novel inhibitors of Dengue virus (DENV). Preparation of focused 4-anilinoquinoline/quinazoline scaffold arrays led to the identification of a series of high potency 6-substituted bromine and iodine derivatives. The most potent compound 6-iodo-4-((3,4,5-trimethoxyphenyl)amino)quinoline-3-carbonitrile (47) inhibited DENV Infection with an EC50 = 79 nM. Crucially, these compounds showed very limited toxicity with CC50 values >10 µM in almost all cases. This new promising series provides an anchor point for further development to optimize compound properties.

Keywords

4-Anilinoquinazoline; 4-Anilinoquinoline; Antiviral; Dengue Virus; Flavivirus.

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