Novel, flexible, and conformationally defined analogs of gepirone: synthesis and 5-HT1A, 5-HT2A, and D2 receptor activity

Bioorg Med Chem. 2005 Feb 15;13(4):1195-200. doi: 10.1016/j.bmc.2004.11.019.

Abstract

Novel, flexible arylpiperazine gepirone analogs (1a-3a) with a mixed 5-HT1A/5-HT2A receptor profile, low D2 receptor affinity, and agonistic (2a) or partial agonistic (1a, 3a) activity toward 5-HT1A receptor sites were synthesized. Their conformationally restricted counterparts (1b-3b) were selective 5-HT1A ligands (over 5-HT2A and D2 receptors), which turned out to be agonists (2b, 3b), or partial agonist (1b) of 5-HT1A receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine Agonists / chemical synthesis
  • Dopamine Agonists / chemistry
  • Dopamine Agonists / pharmacology
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A / drug effects*
  • Receptor, Serotonin, 5-HT2A / drug effects*
  • Receptors, Dopamine D2 / drug effects*
  • Serotonin Receptor Agonists / chemical synthesis
  • Serotonin Receptor Agonists / chemistry
  • Serotonin Receptor Agonists / pharmacology

Substances

  • Dopamine Agonists
  • Pyrimidines
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Dopamine D2
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • gepirone