Drug discovery targets: 5-HT6 receptor

5‐HT6 antagonists as potential treatment for cognitive dysfunction

“…There have been a number of reviews on 5-HT 6 receptors, their functions, and potential therapeutic applications [Branchek and Blackburn, 2000;Davies et al, 2005;Glennon, 2003;Grailhe et al, 1997;Holenz et al, 2006;Mitchell and Neumaier, 2005;Russell and Dias, 2002;Slassi et al, 2002;Sleight et al, 1997;Wood et al, 2002;Woolley et al, 2004]. Here we give a comprehensive review on the medicinal chemistry and structure activity relationship (SAR) of 5-HT 6 ligand antagonists and discuss their potential therapeutic utility for the treatment of cognitive dysfunction.…”

Synthesis and Inhibition Effects on 5-HT6Receptor of Benzothiazole Derivatives

“…The aryl sulfonylpiperazine derivatives (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were designed to possess a sulfonamide group (SO 2 NH-) and a piperazine moiety as well as a hydrophobic aromatic ring through the structural analysis of the 5-HT 6 receptor antagonists as shown in Figure 1. In all the structures of 5-HT 6 receptor antagonists, three moieties are common such as piperazine ring, hydrophobic aromatic ring and sulfonamide group.…”

“…11,12 This modulatory activity suggests potential utility for 5-HT 6 receptor antagonists in the treatment of cognitive impairments associated with Alzheimer's disease and Schizophrenia. Clearly, there is much evidence that the 5-HT 6 receptor is involved in the pathogenesis of CNS diseases [13][14][15][16][17][18] related to cognitive or eating disorders, so it appears to be an attractive therapeutic target that should be exploited for drug development. Because it is known to be expressed almost exclusively in the CNS, [19][20][21][22][23] it is possible that new therapeutic agents targeting this receptor might have relatively few peripheral side effects.…”

“…25 As our continuing efforts to identify the novel 5-HT 6 antagonists, we have synthesized a novel series of aryl sulfonylpiperazine derivatives (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) containing piperazine motif as a 5-HT 6 receptor ligand in this report.…”

Design, synthesis and pharmacological evaluation of indolylsulfonamide amines as potent and selective 5-HT6receptor antagonists

“…Since then a lot of reports have been published regarding variations in N,N-dimethyl amino alkyl side chain on and around the indole nucleus and their affinity 21,32,33 ( Figure 2). Numerous selective antagonists of 5-HT 6 receptors have been disclosed during the last decade [34][35][36][37][38][39][40][41][42] and a pharmacophore model for this type of receptor antagonists has been developed based on known structurally diverse 5-HT 6 receptor antagonists [43][44][45][46][47][48][49] . In general, the model entails the positive ionizable atom (usually a secondary or tertiary amino group), a hydrogen bond acceptor group (usually a sulfone or sulfonamide group), a hydrophobic site (HYD) and -electron donor aromatic or heterocyclic ring (AR).…”