Synthesis and Biological Evaluation of Indole and Thienopyrimidine Derivatives as 5-HT6 Receptor Ligands

Abstract

The theme of the research work is design and synthesis of novel molecules which have potent affinity towards 5-HT 6 receptors. Based on this concept, design and synthesis of novel 5-(N-substituted piperazinyl)- newlineN1-aryl (sulfonyl, carbonyl and methylene) indole derivatives and fused thieno pyrimidine derivatives were undertaken and evaluated the in-vitro activity of these derivatives. 5-(N-substituted piperazinyl)-N1-arylsulfonyl indoles were found to have potent affinity towards 5-HT 6 receptors. So newlinethese derivatives were further taken up for their evaluation in in-vivo studies. They have good selectivity over other receptors and no CYP liabilities. These derivatives were further profiled in animal models of newlinecognition like Novel Object Recognition Test (NORT) and Morris water maze. Oral administration of these compounds has shown improvement in performance of rats in NORT and significantly reversed scopolamine newlineinduced special memory deficit in Morris water maze test indicating improvement in cognitive potential of the compounds. newline