The future of 5-HT6R ligands as potential therapeutic drugs seems quite exciting. There is an increasing research interest in the role of 5-HT6 receptors in higher cognitive processes such as memory, obesity and eating disorder. Selective agents are required for the proposed therapeutic application. A series of novel compounds 6a-t based on substituted 2-Arylsulfonylmethyl tryptamines as potential 5-HT6 receptor ligands is reported. Design, Synthesis, invitro binding data and structure-activity relationship have been discussed. Compound 6i was found to be the most potent, which can be further optimized to get the potential 5-HT6 receptor ligands.