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.

Keywords:

• 5-Hydroxytryptamine-6 receptor
• animal models
• central nervous system
• cognition
• novel object recognition test
• structure–activity relationship

Acknowledgements

Mr. Venkateswarlu Jasti, CEO, Suven Life Sciences Ltd., Hyderabad, India is gratefully acknowledged.

Declaration of interest

The study is supported by discovery analytical, DMPK, In vitro, In vivo departments.