Synthesis characterization and pharmacological evaluation of sulfones and sulfonamide derivatives of indole as 5HT6 receptor ligands

Abstract

According to a recent survey, almost half of the human diseases and disorders are the ones involving one or more of the G-protein coupled receptors (GPCRs). The GPCRs are the receptors of several endogenous neurotransmitters. Most of the neurotransmitters have been subject to a great deal of research in the past, including acetylcholine, adrenaline, nor-adrenaline, histamine etc; however, due to the lack of enough biochemical information and their physiological roles, some of the serotonin receptors received least attention in the past. However, due to phenomenal growth in the biochemical and genomic sciences, the newer information regarding this receptor family has stimulated a great deal of research in this field. Although the overall distribution and all the existing sub-types of serotonin receptors and their physiological functions are not yet known completely, the drug industry is in a quest to identify more and more new agonist or antagonist ligands for this receptor and its sub-types.Historically, the discovery of drugs acting though GPCRs has been extremely successful. As on today more than 30 % of launched drugs are targeted through GPCRs with annual worldwide sales of more than $ 40 billion. Among the 100 top-selling drugs, 25 % of them targeted members of this protein family. Since it has excellent potential for drug discovery,the GPCR family represents up to 30 % of the portfolio of many pharmaceutical companies.