Therapeutic Targets Database
BIDD Pharmainformatics Databases


TTD Target ID: TTDC00185

Target Information
Name5-hydroxytryptamine 6 receptor    
Type of targetClinical trial target    
5-HT6 receptor    
Serotonin receptor    
Serotonin receptor 6    
DiseaseIrritable bowel syndrome
[ICD9: 564.1   ICD10: K58]
Nausea and vomiting
[ICD9: 787, 787.0   ICD10: R11]
Pruritus in chronic liver disease
[ICD9: 570-574, 698   ICD10: K70-K77, L29]
[ICD9: 295   ICD10: F20]
Drug(s)AVN 211Phase II completedSchizophrenia
SB-742457Phase II completedAlzheimer's Disease, Dementia[6]
742457Phase IIDementia
AVN 101Phase IIAnxiety
AVN 101Phase IICognitive enhancer in Alzheimer's
AVN 322Phase IAlzheimer's disease
BioChemical ClassG-protein coupled receptor (rhodopsin family)    
PathwayCalcium signaling pathway
Neuroactive ligand-receptor interaction
UniProt IDP50406
FunctionThis is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulates adenylate cyclation.    
Related US Patent6,380,199
Target ValidationClick to Find Target Validation Information.    
QSAR ModelClick to Find Target QSAR Model.    
Inhibitor (+/-)-nantenine[7]
1- (2-Methoxy-phenyl)-piperazine[8]
1- (3-[9]
1- (3-[10]
1- (phenylsulfonyl)-4-[11]
2- (1-[15]
2- (1-benzyl-1H-inden-3-yl)-N,N-dimethylethanamine[16]
2- (1-benzyl-1H-indol-3-yl)-N,N-dimethylethanamine[16]
2- (1-tosyl-1H-indol-3-yl)ethanamine[15]
2- (3-[17]
2- (3-benzenesulfonyl)phenyl-1-aminoethane[18]
2- (3-phenylthio)phenyl)-1-aminoethane[18]
2- (4-[18]
3- (phenylsulfonyl)-1-[21]
3- (phenylsulfonyl)-1-[21]
3- (phenylsulfonyl)-1-[21]
4- ([22]
4- (1H-Inden-1-ylmethyl)-phenylamine[23]
4- (1H-Indol-3-ylmethyl)-phenylamine[23]
4- (1H-indol-1-ylsulfonyl)benzenamine[11]
4- (2-benzenesulfonylphenyl)piperazine[18]
4- (3-Methyl-indole-1-sulfonyl)-phenylamine[8]
4- (3-benzenesulfonamidophenyl)piperazine[18]
4- (3-benzenesulfonylphenyl)piperazine[18]
4- (3H-Inden-1-ylmethyl)-phenylamine[23]
4- (4,6-dinitro-1H-indol-1-ylsulfonyl)benzenamine[11]
4- (4-benzenesulfonamidophenyl)piperazine[18]
4- (4-benzenesulfonylphenyl)piperazine[18]
4- (4-methoxy-1H-indol-1-ylsulfonyl)benzenamine[24]
4- (6-methoxy-1H-indol-1-ylsulfonyl)benzenamine[24]
4- (Indan-1-ylsulfanyl)-phenylamine[23]
4- (Indane-1-sulfonyl)-phenylamine[23]
4- (Naphthalene-1-sulfonyl)-phenylamine[8]
4- (piperazin-1-yl)-1H-indole[11]
4- (piperazin-1-yl)-3-tosyl-1H-indazole[25]
4-Inden- (1E)-ylidenemethyl-phenylamine[23]
5- (4-Methylpiperazin-1-yl)-3-tosyl-1H-indazole[25]
6- (piperazin-1-yl)-3-tosyl-1H-indazole[25]
HTR5A3- (2-Amino-ethyl)-2-methyl-1H-indol-5-ol[30]
N,N-diethyl-2- (1H-indol-3-yl)ethanamine[27]
N,N-dimethyl-2- (1-tosyl-1H-indol-3-yl)ethanamine[22]
N- (3-[18]
N- (3-[18]
N- (3-[18]
N- (3-aminophenyl)benzenesulfonamide[18]
N- (4-[18]
N-phenyl-3- (2-aminoethyl)benzenesulfonamide[18]
[2- (3-Benzyl-3H-inden-1-yl)-ethyl]-methyl-amine[23]
[2- (3-Benzyl-3H-indol-1-yl)-ethyl]-dimethyl-amine[39]
[2- (3-Benzyl-indol-1-yl)-ethyl]-dimethyl-amine[23]
[2- (3H-Indol-1-yl)-ethyl]-dimethyl-amine[39]
AntagonistSB 258585[5]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
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Ref 2Effects of ondansetron on postoperative emesis in Chinese children. Acta Anaesthesiol Sin. 1998 Jun;36(2):87-91. To Reference
Ref 3Simultaneous determination of granisetron and its 7-hydroxy metabolite in human plasma by reversed-phase high-performance liquid chromatography utilizing fluorescence and electrochemical detection. J Chromatogr A. 1995 Feb 10;692(1-2):195-202. To Reference
Ref 4Treatment of pruritus in chronic liver disease with the 5-hydroxytryptamine receptor type 3 antagonist ondansetron: a randomized, placebo-controlled, double-blind cross-over trial. Eur J Gastroenterol Hepatol. 1998 Oct;10(10):865-70. To Reference
Ref 55-HT6 receptor binding sites in schizophrenia and following antipsychotic drug administration: autoradiographic studies with [125I]SB-258585. Synapse. 2002 Sep 1;45(3):191-9. To Reference
Ref 6GSK. Product Development Pipeline. February 2009. To Reference
Ref 7Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. Epub 2009 Nov 20.Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. To Reference
Ref 8Bioorg Med Chem Lett. 2005 Mar 15;15(6):1707-11.1-(1-Naphthyl)piperazine as a novel template for 5-HT6 serotonin receptor ligands. To Reference
Ref 9Bioorg Med Chem Lett. 2009 May 1;19(9):2409-12. Epub 2009 Mar 25.Synthesis and SAR of tolylamine 5-HT6 antagonists. To Reference
Ref 10Bioorg Med Chem. 2007 Nov 1;15(21):6659-66. Epub 2007 Aug 15.The synthesis and biological activity of pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine. To Reference
Ref 11Bioorg Med Chem Lett. 2005 Dec 1;15(23):5298-302. Epub 2005 Sep 23.Binding of amine-substituted N1-benzenesulfonylindoles at human 5-HT6 serotonin receptors. To Reference
Ref 12Bioorg Med Chem Lett. 2005 Nov 1;15(21):4780-5.Conformationally constrained N1-arylsulfonyltryptamine derivatives as 5-HT6 receptor antagonists. To Reference
Ref 13Bioorg Med Chem Lett. 2005 Jan 17;15(2):379-83.N1-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives are potent and selective 5-HT6 receptor antagonists. To Reference
Ref 14J Med Chem. 2008 Feb 14;51(3):603-11. Epub 2008 Jan 18.Binding of serotonin and N1-benzenesulfonyltryptamine-related analogs at human 5-HT6 serotonin receptors: receptor modeling studies. To Reference
Ref 15J Med Chem. 2007 Nov 15;50(23):5535-8. Epub 2007 Oct 19.Discovery of N1-(6-chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl)tryptamine as a potent, selective, and orally active 5-HT(6) receptor agonist. To Reference
Ref 16J Med Chem. 2009 Feb 12;52(3):675-87.Indene-based scaffolds. 2. An indole-indene switch: discovery of novel indenylsulfonamides as 5-HT6 serotonin receptor agonists. To Reference
Ref 17Bioorg Med Chem. 2009 Jul 15;17(14):5153-63. Epub 2009 May 29.Novel 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines are potent 5-HT(6) agonists. To Reference
Ref 18J Med Chem. 2006 Aug 24;49(17):5217-25.Binding of sulfonyl-containing arylalkylamines at human 5-HT6 serotonin receptors. To Reference
Ref 19J Med Chem. 2010 Feb 11;53(3):1357-69.Benzimidazole derivatives as new serotonin 5-HT6 receptor antagonists. Molecular mechanisms of receptor inactivation. To Reference
Ref 20Bioorg Med Chem Lett. 2005 Oct 1;15(19):4230-4.2-Alkyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles as novel 5-HT6 receptor agonists. To Reference
Ref 21Bioorg Med Chem Lett. 2010 Mar 1;20(5):1657-60. Epub 2010 Jan 21.3-(Arylsulfonyl)-1-(azacyclyl)-1H-indoles are 5-HT(6) receptor modulators. To Reference
Ref 22Bioorg Med Chem Lett. 2007 Mar 15;17(6):1691-4. Epub 2007 Jan 4.Further studies on the binding of N1-substituted tryptamines at h5-HT6 receptors. To Reference
Ref 23Bioorg Med Chem Lett. 2005 Apr 15;15(8):1987-91.Binding of isotryptamines and indenes at h5-HT6 serotonin receptors. To Reference
Ref 24Bioorg Med Chem Lett. 2006 Jul 15;16(14):3793-6. Epub 2006 May 18.Binding of methoxy-substituted N1-benzenesulfonylindole analogs at human 5-HT6 serotonin receptors. To Reference
Ref 25J Med Chem. 2010 Nov 11;53(21):7639-46.5-Piperazinyl-3-sulfonylindazoles as potent and selective 5-hydroxytryptamine-6 antagonists. To Reference
Ref 26Bioorg Med Chem Lett. 2008 Jan 1;18(1):256-61. Epub 2007 Oct 30.Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: structure-activity relationship elucidation. To Reference
Ref 27Bioorg Med Chem Lett. 2006 Nov 15;16(22):5832-5. Epub 2006 Aug 30.Interaction of N1-unsubstituted and N1-benzenesulfonyltryptamines at h5-HT6 receptors. To Reference
Ref 28J Med Chem. 2005 Mar 24;48(6):1781-95.Medicinal chemistry driven approaches toward novel and selective serotonin 5-HT6 receptor ligands. To Reference
Ref 29Bioorg Med Chem Lett. 2008 Jul 15;18(14):3929-31. Epub 2008 Jun 13.A regiospecific synthesis of a series of 1-sulfonyl azepinoindoles as potent 5-HT6 ligands. To Reference
Ref 30J Med Chem. 2003 Jul 3;46(14):2795-812.Higher-end serotonin receptors: 5-HT(5), 5-HT(6), and 5-HT(7). To Reference
Ref 31Eur J Med Chem. 2010 Feb;45(2):782-9. Epub 2009 Oct 31.8-Sulfonyl-substituted tetrahydro-1H-pyrido[4,3-b]indoles as 5-HT6 receptor antagonists. To Reference
Ref 32Strassman RJ, Qualls CR: Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects. Arch Gen Psychiatry. 1994 Feb;51(2):85-97. To Reference
Ref 33Bioorg Med Chem Lett. 2001 Jun 4;11(11):1375-7.Synthesis of potent and selective dopamine D(4) antagonists as candidate radioligands. To Reference
Ref 34J Med Chem. 2010 Mar 25;53(6):2521-7.5-Cyclic amine-3-arylsulfonylindazoles as novel 5-HT6 receptor antagonists. To Reference
Ref 35Bioorg Med Chem Lett. 2008 Jan 15;18(2):738-43. Epub 2007 Nov 17.Discovery of 3-aryl-3-methyl-1H-quinoline-2,4-diones as a new class of selective 5-HT6 receptor antagonists. To Reference
Ref 36Bioorg Med Chem Lett. 2008 Jul 15;18(14):3844-7. Epub 2008 Jun 21.Synthesis and structure-activity relationship of 1H-indole-3-carboxylic acid pyridine-3-ylamides: a novel series of 5-HT2C receptor antagonists. To Reference
Ref 37J Med Chem. 2009 Oct 8;52(19):6153-7.Identification of novel indanylsulfonamide guanylhydrazones as potent 5-HT6 serotonin receptor antagonists. To Reference
Ref 38J Med Chem. 2005 Jan 27;48(2):353-6.Discovery of 5-arylsulfonamido-3-(pyrrolidin-2-ylmethyl)-1H-indole derivatives as potent, selective 5-HT6 receptor agonists and antagonists. To Reference
Ref 39Bioorg Med Chem Lett. 2004 Sep 6;14(17):4569-73.Possible differences in modes of agonist and antagonist binding at human 5-HT6 receptors. To Reference


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