Design, synthesis and pharmacological evaluation of conformationally restricted N-arylsulfonyl-3-aminoalkoxy indoles as a potential 5-HT₆ receptor ligands

Abstract

A series of novel conformationally restricted N₁-arylsulfonyl-3-aminoalkoxy indoles were designed and synthesized as 5-HT₆ receptor (5-HT₆R) ligands. Many of the synthesized compounds have moderate in vitro-binding affinities at 5-HT₆R. The lead compound 8b (% inhibition = 97.2 at 1 μM) from this series has good pharmacokinetic profile in male Wister rats and is active in animal model of cognition like Morris water maze. The details of chemistry, SAR, pharmacokinetics and pharmacological data constitute the subject matter of this report.

Keywords::

• 5-HT₆ receptor ligands
• SAR
• conformationally restricted
• Morris water maze