Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
   

 

TTD Target ID: TTDC00185

Target Information
Name5-hydroxytryptamine 6 receptor    
Type of targetClinical trial target    
Synonyms5-HT-6    
5-HT6 receptor    
Serotonin receptor    
Serotonin receptor 6    
DiseaseIrritable bowel syndrome
[ICD9: 564.1   ICD10: K58]
[1]
Nausea and vomiting
[ICD9: 787, 787.0   ICD10: R11]
[2][3]
Pruritus in chronic liver disease
[ICD9: 570-574, 698   ICD10: K70-K77, L29]
[4]
Schizophrenia
[ICD9: 295   ICD10: F20]
[5]
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.    
SequenceMVPEPGPTANSTPAWGAGPPSAPGGSGWVAAALCVVIALTAAANSLLIALICTQPALRNT SNFFLVSLFTSDLMVGLVVMPPAMLNALYGRWVLARGLCLLWTAFDVMCCSASILNLCLI SLDRYLLILSPLRYKLRMTPLRALALVLGAWSLAALASFLPLLLGWHELGHARPPVPGQC RLLASLPFVLVASGLTFFLPSGAICFTYCRILLAARKQAVQVASLTTGMASQASETLQVP RTPRPGVESADSRRLATKHSRKALKASLTLGILLGMFFVTWLPFFVANIVQAVCDCISPG LFDVLTWLGYCNSTMNPIIYPLFMRDFKRALGRFLPCPRCPRERQASLASPSLRTSHSGP RPGLSLQQVLPLPLPPDSDSDSDAGSGGSSGLRLTAQLLLPGEATQDPPLPTRAAAAVNF FNIDPAEPELRPHPLGIPTN
Related US Patent6,380,199
6,627,661
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]
1-Benzenesulfonyl-3-piperidin-3-yl-1H-indole[12]
1-Benzenesulfonyl-3-piperidin-4-yl-1H-indole[13]
1-Naphthalen-1-yl-piperazine[8]
1-phenylthio-N,N-dimethyltryptamine[14]
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]
2-Benzyl-4-piperazin-1-yl-1H-benzimidazole[19]
2-Ethyl-5-methoxy-3-piperidin-4-yl-1H-indole[20]
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-Indan-1-ylmethyl-phenylamine[23]
4-Inden- (1E)-ylidenemethyl-phenylamine[23]
5,6-dichloro-3,4-dihydroquinazolin-2-amine[26]
5- (4-Methylpiperazin-1-yl)-3-tosyl-1H-indazole[25]
5-MEO-DMT[27]
5-METHOXYTRYPTAMINE[28]
6- (piperazin-1-yl)-3-tosyl-1H-indazole[25]
6-tosyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole[29]
CHLOROPHENYLPIPERAZINE[30]
DIMEBOLIN[31]
Dimethyltryptamine[32]
E-6837[16]
EDMT[16]
HTR5A3- (2-Amino-ethyl)-2-methyl-1H-indol-5-ol[30]
L-745870[33]
METHIOTHEPIN[34]
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]
OCTOCLOTHEPIN[28]
QUIPAZINE[30]
RU-24969[20]
Ro-04-6790[16]
Ro-63-0563[35]
SB-243213[36]
SB-258585[19]
SB-271046[9]
SB-357134[35]
SEROTONIN[34]
SPIPERONE[30]
WAY-181187[37]
WAY-208466[17]
WAY-466[38]
[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]
SB-742457[6]
[125I]SB-258585[5]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Reduction of rectal sensitivity and post-prandial motility by granisetron, a 5 HT3-receptor antagonist, in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 1993 Apr;7(2):175-80. To Reference
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



 

Welcome to sign our Guestbook.

If you find any error in data or bug in web service, please kindly report it to Dr. Zhu.


Dr. Chen Yuzong
Deputy Director of Center for Computational Science and Engineering
Professor in Department of Pharmacy
National University of Singapore, Singapore


All rights reserved.

   
 
 
Computer-aided Drug Design
about BIDD |  databases |  software |  teaching |  research |  links

 

Department of Computational Science | National University of Singapore | Blk S17, 3 Science Drive 2, Singapore 117543