Synthesis and biological evaluation of novel N1-phenylsulphonyl indole derivatives as potent and selective 5-HT6R ligands for the treatment of cognitive disorders.

Abstract

A series of 1-[3-(4-methyl piperazin-1-ylmethyl) phenylsulfonyl]-1H-indole and 1-[3-(4-ethyl piperazin-1-ylmethyl) phenylsulfonyl]-1H-indole derivatives were designed and synthesized as 5-HT6 receptor (5-HT6R) ligands. The lead compound 1-[4-methyl-3-(4-methyl piperazin-1-yl methyl) phenylsulfonyl]-1H-indole dihydrochloride (6b), in this series, has shown potent in vitro binding affinity, selectivity, good pharmacokinetics (PK) profile and activity in the animal models of cognition.

• Authors: Ramakrishna V S Nirogi, Thrinath Reddy Bandyala, Pamuletinarasimha Reddy Gangadasari, Mukkanti Khagga
• Journal: Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 31 Issue sup1 Pg. 1-15 ( 2016) ISSN: 1475-6374 [Electronic] England
• PMID: 27806648 (Publication Type: Journal Article)

Chemical References

• 1-(4-methyl-3-(4-methyl piperazin-1-yl methyl)phenylsulfonyl)-1H-indole dihydrochloride
• Antipsychotic Agents
• Indoles
• Ligands
• Piperazines
• Receptors, Serotonin
• serotonin 6 receptor

Topics

• Antipsychotic Agents (chemical synthesis, metabolism, pharmacokinetics, therapeutic use)
• Cognition Disorders (drug therapy, metabolism)
• Dose-Response Relationship, Drug
• Humans
• Indoles (chemical synthesis, chemistry, pharmacology)
• Ligands
• Molecular Structure
• Piperazines (chemical synthesis, chemistry, pharmacology)
• Receptors, Serotonin (metabolism)
• Structure-Activity Relationship