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. Epub 2020 May 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aniline Compounds / chemical synthesis
  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology*
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Dengue Virus / drug effects*
  • Dose-Response Relationship, Drug
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Quinazolines / chemical synthesis
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Aniline Compounds
  • Antiviral Agents
  • Quinazolines