Design and synthesis of novel series of 5-HT6 receptor ligands having indole, a central aromatic core and 1-amino-4 methyl piperazine as a positive ionizable group

Bioorg Med Chem. 2013 Sep 1;21(17):5573-82. doi: 10.1016/j.bmc.2013.05.051. Epub 2013 Jun 5.

Abstract

The exclusive distribution of 5-HT6 receptor in the brain regions and high affinity for antipsychotic and antidepressant drugs makes 5-HT6 receptor a promising target in treatment of CNS diseases. Based on a pharmacophore model reported in the literature, we designed and synthesized a novel series of 5-HT6 receptor ligands having indole as a central aromatic core and 1-amino-4-methyl piperazine as positive ionizable group. Out of 32 compounds we have successfully identified 10 new compounds as 5-HT6 receptor antagonists. The structure-activity relationship (SAR) studies have been carried out by mapping the compounds with the 3D QSAR model.

Keywords: 1-Amino-4-methylpiperazine; 3D QSAR; 5-HT(6) receptor antagonist; Pharmacophore mapping; Sulfonyl indole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Drug Design*
  • HEK293 Cells
  • Humans
  • Indoles / chemistry*
  • Ions / chemistry
  • Ligands
  • Piperazine
  • Piperazines / chemistry*
  • Protein Binding
  • Quantitative Structure-Activity Relationship
  • Receptors, Serotonin / chemistry*
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / chemistry
  • Serotonin Antagonists / metabolism
  • Structure-Activity Relationship

Substances

  • Indoles
  • Ions
  • Ligands
  • Piperazines
  • Receptors, Serotonin
  • Recombinant Proteins
  • Serotonin Antagonists
  • serotonin 6 receptor
  • Piperazine
  • indole