Identification of 4-anilino-6-aminoquinazoline derivatives as potential MERS-CoV inhibitors

Bioorg Med Chem Lett. 2020 Oct 15;30(20):127472. doi: 10.1016/j.bmcl.2020.127472. Epub 2020 Aug 8.

Abstract

New therapies for treating coronaviruses are urgently needed. A series of 4-anilino-6-aminoquinazoline derivatives were synthesized and evaluated to show high anti-MERS-CoV activities. N4-(3-Chloro-4-fluorophenyl)-N6-(3-methoxybenzyl)quinazoline-4,6-diamine (1) has been identified in a random screen as a hit compound for inhibiting MERS-CoV infection. Throughout optimization process, compound 20 was found to exhibit high inhibitory effect (IC50 = 0.157 μM, SI = 25) with no cytotoxicity and moderate in vivo PK properties.

Keywords: 4-Anilino-6-aminoquinazoline; Coronavirus; Inhibitor; MERS-CoV; Optimization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemical synthesis
  • Aniline Compounds / pharmacokinetics
  • Aniline Compounds / pharmacology*
  • Aniline Compounds / toxicity
  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / toxicity
  • Cell Line
  • Chlorocebus aethiops
  • Cricetulus
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Middle East Respiratory Syndrome Coronavirus / drug effects*
  • Molecular Structure
  • Quinazolines / chemical synthesis
  • Quinazolines / pharmacokinetics
  • Quinazolines / pharmacology*
  • Quinazolines / toxicity
  • Rats
  • Structure-Activity Relationship

Substances

  • Aniline Compounds
  • Antiviral Agents
  • Quinazolines