Modification of the structure of 4, 6-disubstituted 2-(4-alkyl-1-piperazinyl)pyridines: synthesis and their 5-HT2A receptor activity

Arch Pharm (Weinheim). 2003 Apr;336(2):104-10. doi: 10.1002/ardp.200390006.

Abstract

Structure-activity relationship studies of a series of novel 4, 6-disubstituted 2-(1-piperazinyl)pyridines were conducted to revise our model of serotonin 5-HT(2A) receptor antagonist. Target compounds were synthesized using the benzotriazole-assisted Katritzky method. The majority of those compounds were found to be selective 5-HT(2A)/5-HT(1A) receptor ligands, though less potent than their previously described pyrimidine counterparts. In particular, the three compounds 6-8 showed the highest 5-HT(2A) receptor affinity (K(i) = 34-78 nM) and were classified as 5-HT(2A) antagonists in in vivo experiments. The influence of the structural modifications on the in vitro results was discussed; however, the elucidation of the role of the central core system requires further studies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ligands
  • Male
  • Mice
  • Models, Biological
  • Piperazines / chemical synthesis
  • Piperazines / chemistry*
  • Piperazines / pharmacology
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists / chemical synthesis
  • Serotonin Antagonists / chemistry
  • Serotonin Antagonists / pharmacology
  • Structure-Activity Relationship

Substances

  • Ligands
  • Piperazines
  • Pyridines
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists