Quinazolindione derivatives as potent 5-HT3A receptor antagonists

Bioorg Med Chem. 2009 Jul 1;17(13):4793-6. doi: 10.1016/j.bmc.2009.04.029. Epub 2009 Apr 19.

Abstract

5-HT(3A) receptor antagonists have been used mainly for the treatment of nausea and vomiting. These days, the antagonists are of special interest due to their therapeutic potential to treat other diseases such as depression, psychotic disorder, drug abuse, and irritable bowel syndrome. To discover novel 5-HT(3A) receptor antagonists, we screened our in-house small molecule library, resulting in identifying the quinazolindione derivatives as potent 5-HT(3A) receptor antagonists. For the purpose of structure-activity relationship study, 24 quinazolindione analogues were biologically evaluated against 5-HT(3A) receptor. Among those, KKHT10612 shows the best antagonistic effect against 5-HT(3A) receptor with an IC(50) value of 0.8 microM which is comparable with that of the reference compound, MDL72222, and selectivity over T-type calcium channel as well.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Mice
  • Molecular Structure
  • Oocytes / physiology
  • Piperidines / chemical synthesis
  • Piperidines / chemistry*
  • Piperidines / pharmacology*
  • Quinazolines / chemical synthesis
  • Quinazolines / chemistry*
  • Quinazolines / pharmacology*
  • Receptors, Serotonin, 5-HT3 / metabolism*
  • Serotonin 5-HT3 Receptor Antagonists*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Structure-Activity Relationship
  • Xenopus

Substances

  • 3-(4-methoxybenzyl)-N-(3-(2-piperidin-1-yl)ethyl)-2,4-dioxoquinazoline-7-carboxamide
  • Piperidines
  • Quinazolines
  • Receptors, Serotonin, 5-HT3
  • Serotonin 5-HT3 Receptor Antagonists
  • Small Molecule Libraries