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.

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.

• Authors: Faisal Hayat, Sungjin Cho, Hyewhon Rhim, Ambily Nath Indu Viswanath, Ae Nim Pae, Jae Yeol Lee, Dong Joon Choo, Hea-Young Park Choo
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 21 Issue 17 Pg. 5573-82 (Sep 01 2013) ISSN: 1464-3391 [Electronic] England
• PMID: 23810425 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

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