Design synthesis and pharmacological evaluation of sulfonamide derivatives of Indole and Benzopyran as 5HT6R antagonists

Abstract

The theme of the research work is design and synthesis of novel molecules which have a potent affinity towards 5-HT6 receptors. Based on this concept, design and synthesis of novel (3-halo)-4-(piperazin-1-yl methyl)-N1-arylsulfonyl-1H-indole derivatives, [3-[(1-methylpiperidin-4-yl) methyl] arylsulfonyl]-1H-indole derivatives and (spiro)benzopyran derivatives was undertaken and evaluated the in-vitro activity of these derivatives. 4-(Piperazin-1-yl methyl)-N1-arylsulfonyl-1H-indole derivatives were found to have moderate to potent affinity towards 5-HT6 receptors. So some select compounds from this series were taken up for further evaluation in in-vivo animal studies. They have good selectivity over other closely related receptors and no CYP liabilities. These derivatives were further profiled in animal models of cognition like Object Recognition Test (ORT). Oral administration of these compounds has shown improvement in performance of rats in ORT indicating cognitive improvement potential of them. newline