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

Abstract

ABSTRACT OF THE THESIS ENTITLED SYNTHESIS AND BIOLOGICAL EVALUATION OF ARYLSULFONAMIDES AND INDOLE DERIVATIVES AS SEROTONIN 5-HT 6 RECEPTOR LIGANDS newlineThe work presented in this thesis explores novel chemical series as GPCR ligands, especially as 5-HT 6 receptor ligands. The embodied work is an attempt to address the challenging medical requirements in the newlinefield of central nerous system (CNS) disorders, especially Alzheimers disease. These presented chemical serises were achieved through understanding of basic pharmacophoric requirements to get 5-HT 6 newlinereceptor activity in combination with structure based designing. The modifications were carried out on the basis of in-vitro and in-vivo results. The basic criteria for molecules designed in the presented serises was that, the molecules should have reasonable binding affinity towards 5- newlineHT 6 receptor with high selectivity (no nteraction with other closely related receptors), it should have acceptable cytochrome P450 liabilities, good metabolic stability and brain penetrative capabilities along with adequate systemic exposure. The other important criterion was that, the newlinecompound should also have activity in animal models of cognition like Morris Water Maze or Novel Object Recognition Task (NORT). The thesis is divided into six chapters and brief details are presented below. newline