Discovery of novel potent and selective ligands for 5-HT2A receptor with quinazoline scaffold

Bioorg Med Chem Lett. 2015 Sep 15;25(18):3970-4. doi: 10.1016/j.bmcl.2015.07.030. Epub 2015 Jul 18.


A series of compounds with quinazoline scaffold were designed, synthesized and evaluated as novel potent 5-HT2A receptor ligands. N-(4-Chlorophenyl)-2-(piperazin-1-yl)quinazolin-4-amine (5o) has a Ki value of 14.04 ± 0.21 nM, with a selectivity more than 10,000 fold over 5-HT1A receptors (D1 and D2-like receptors). The functional assay showed that this compound is an antagonist to 5-HT2A receptor with an IC50 value of 1.66 μM.

Keywords: 5-HT(2A) receptor antagonist; Molecular docking; Quinazoline derivatives; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Ligands
  • Molecular Structure
  • Quinazolines / chemistry*
  • Quinazolines / pharmacology
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Serotonin 5-HT2 Receptor Antagonists / chemical synthesis
  • Serotonin 5-HT2 Receptor Antagonists / chemistry*
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology*
  • Structure-Activity Relationship


  • Ligands
  • Quinazolines
  • Receptor, Serotonin, 5-HT2A
  • Serotonin 5-HT2 Receptor Antagonists