2-Amino-6-chloro-3,4-dihydroquinazoline: A novel 5-HT3 receptor antagonist with antidepressant character

Bioorg Med Chem Lett. 2013 Nov 1;23(21):5945-8. doi: 10.1016/j.bmcl.2013.08.072. Epub 2013 Aug 24.

Abstract

2-Amino-6-chloro-3,4-dihydroquinazoline HCl (A6CDQ, 4) binds at 5-HT3 serotonin receptors and displays antidepressant-like action in the mouse tail suspension test (TST). Empirically, 4 was demonstrated to be a 5-HT3 receptor antagonist (two-electrode voltage clamp recordings using frog oocytes; IC50=0.26μM), and one that should readily penetrate the blood-brain barrier (logP=1.86). 5-HT3 receptor antagonists represent a potential approach to the development of new antidepressants, and 4 is an example of a structurally novel 5-HT3 receptor antagonist that is active in a preclinical antidepressant model (i.e., the mouse TST).

Keywords: 5-HT(3) receptors; Antagonists; Antidepressants; TST (tail suspension test).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amination
  • Animals
  • Antidepressive Agents / chemistry*
  • Antidepressive Agents / pharmacology
  • Anura
  • Halogenation
  • Hindlimb Suspension
  • Mice
  • Quinazolines / chemistry*
  • Quinazolines / pharmacology
  • Receptors, Serotonin, 5-HT3 / metabolism*
  • Serotonin 5-HT3 Receptor Antagonists / chemistry*
  • Serotonin 5-HT3 Receptor Antagonists / pharmacology

Substances

  • Antidepressive Agents
  • Quinazolines
  • Receptors, Serotonin, 5-HT3
  • Serotonin 5-HT3 Receptor Antagonists