Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJS8PY)

• DTT Name: 5-HT 6 receptor (HTR6)
• Synonyms: Serotonin receptor 6; 5-hydroxytryptamine receptor 6; 5-HT6 receptor; 5-HT6; 5-HT-6
• Gene Name: HTR6
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Alzheimer disease [ICD-11: 8A20]
  Schizophrenia [ICD-11: 6A20]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: 5HT6R_HUMAN
• TTD ID: T16691
• Sequence:
  MVPEPGPTANSTPAWGAGPPSAPGGSGWVAAALCVVIALTAAANSLLIALICTQPALRNT
  SNFFLVSLFTSDLMVGLVVMPPAMLNALYGRWVLARGLCLLWTAFDVMCCSASILNLCLI
  SLDRYLLILSPLRYKLRMTPLRALALVLGAWSLAALASFLPLLLGWHELGHARPPVPGQC
  RLLASLPFVLVASGLTFFLPSGAICFTYCRILLAARKQAVQVASLTTGMASQASETLQVP
  RTPRPGVESADSRRLATKHSRKALKASLTLGILLGMFFVTWLPFFVANIVQAVCDCISPG
  LFDVLTWLGYCNSTMNPIIYPLFMRDFKRALGRFLPCPRCPRERQASLASPSLRTSHSGP
  RPGLSLQQVLPLPLPPDSDSDSDAGSGGSSGLRLTAQLLLPGEATQDPPLPTRAAAAVNF
  FNIDPAEPELRPHPLGIPTN
• Function: The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs. Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity. Is an activator of TOR signaling. This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Serotonergic synapse (hsa04726)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Serotonin receptors (R-HSA-390666)

Molecular Interaction Atlas (MIA) of This DTT

15 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LU AE58054	DMWGRQD	Schizophrenia	6A20	Phase 3	[2]
SB-742457	DM6L4ZT	Alzheimer disease	8A20	Phase 3	[3], [4]
AVN 211	DMVB4OS	Schizophrenia	6A20	Phase 2/3	[5]
AVN 101	DMJFLBC	Alzheimer disease	8A20	Phase 2	[5]
AVN 322	DMK2LGM	Cognitive impairment	6D71	Phase 2	[3]
PF-05212377	DMPVQYR	Alzheimer disease	8A20	Phase 2	[6]
SAM-531	DMHVJZ6	Alzheimer disease	8A20	Phase 2	[7]
SUVN-502	DMQD753	Alzheimer disease	8A20	Phase 2	[8]
SYN-120	DMPW0UL	Alzheimer disease	8A20	Phase 2	[9]
SYN120	DMDF7XB	Parkinson disease	8A00.0	Phase 2	[10]
11C-GSK-215083	DMQ0RXA	Neurodegenerative disorder	8A20-8A23	Phase 1	[11]
ABT-354	DMWN7D3	Alzheimer disease	8A20	Phase 1	[12]
AVN-322	DMNIVFJ	Alzheimer disease	8A20	Phase 1	[13]
BVT-74316	DMEP321	Obesity	5B81	Phase 1	[14]
PRX-07034	DM5TLAP	Obesity	5B81	Phase 1	[15]

2 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID30124346-Compound-13TABLE4	DMHTJVA	Attention deficit hyperactivity disorder	6A05.Z	Patented	[16]
PMID30124346-Compound-34TABLE4	DM2G3VE	Attention deficit hyperactivity disorder	6A05.Z	Patented	[16]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AVN 397	DMFCOZL	Alzheimer disease	8A20	Discontinued in Phase 2	[5]
SYN-114	DM4JPLM	Cognitive impairment	6D71	Discontinued in Phase 1	[17]
WAY-181187	DM8SVHI	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 1	[18]

105 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+/-)-nantenine	DM0L3GE	Discovery agent	N.A.	Investigative	[19]
1-(2-Methoxy-phenyl)-piperazine	DM3M4RA	Discovery agent	N.A.	Investigative	[20]
1-(3-(benzyloxy)-2-methylphenyl)piperazine	DMQ4MUF	Discovery agent	N.A.	Investigative	[21]
1-(3-(pentafluorosulfanyl)phenyl)propan-2-amine	DMX5N3V	Discovery agent	N.A.	Investigative	[22]
1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-indole	DM7W25U	Discovery agent	N.A.	Investigative	[23]
1-Benzenesulfonyl-3-piperidin-3-yl-1H-indole	DM1N4LK	Discovery agent	N.A.	Investigative	[24]
1-Benzenesulfonyl-3-piperidin-4-yl-1H-indole	DMRA9VG	Discovery agent	N.A.	Investigative	[25]
1-naphthylpiperazine	DM6BIWK	Discovery agent	N.A.	Investigative	[26], [20]
1-phenylthio-N,N-dimethyltryptamine	DM5REQ9	Discovery agent	N.A.	Investigative	[27]
2-(1-(phenylsulfonyl)-1H-indol-3-yl)ethanamine	DM3D8WI	Discovery agent	N.A.	Investigative	[28]
2-(1-benzyl-1H-inden-3-yl)-N,N-dimethylethanamine	DMB5LHA	Discovery agent	N.A.	Investigative	[29]
2-(1-benzyl-1H-indol-3-yl)-N,N-dimethylethanamine	DMML3XI	Discovery agent	N.A.	Investigative	[29]
2-(1-tosyl-1H-indol-3-yl)ethanamine	DMXCID6	Discovery agent	N.A.	Investigative	[28]
2-(1H-indol-3-yl)-N,N-dimethylethanamine	DMR9Q4Y	Discovery agent	N.A.	Investigative	[30]
2-(3-(phenylsulfonyl)-1H-indol-1-yl)ethanamine	DM94B7N	Discovery agent	N.A.	Investigative	[31]
2-(3-benzenesulfonyl)phenyl-1-aminoethane	DM3FBLT	Discovery agent	N.A.	Investigative	[32]
2-(3-phenylthio)phenyl)-1-aminoethane	DM4WOT6	Discovery agent	N.A.	Investigative	[32]
2-(4-(benzenesulfonyl)phenyl)-1-aminoethane	DMDAO5T	Discovery agent	N.A.	Investigative	[32]
2-Benzyl-4-piperazin-1-yl-1H-benzimidazole	DMYGKW5	Discovery agent	N.A.	Investigative	[33]
2-bromo-LSD	DMOYCWU	Discovery agent	N.A.	Investigative	[26]
2-Ethyl-5-methoxy-3-piperidin-4-yl-1H-indole	DMLC8OB	Discovery agent	N.A.	Investigative	[34]
2-methyl-5-HT	DM1S5CB	N. A.	N. A.	Investigative	[35]
3-(phenylsulfonyl)-1-(piperidin-3-yl)-1H-indole	DMSRHLC	Discovery agent	N.A.	Investigative	[36]
3-(phenylsulfonyl)-1-(piperidin-4-yl)-1H-indole	DM9QB0X	Discovery agent	N.A.	Investigative	[36]
3-(phenylsulfonyl)-1-(pyrrolidin-3-yl)-1H-indole	DMVKO5N	Discovery agent	N.A.	Investigative	[36]
4-((1H-indol-1-yl)methyl)benzenamine	DMRWZ6T	Discovery agent	N.A.	Investigative	[37]
4-(1H-Inden-1-ylmethyl)-phenylamine	DMMJI4R	Discovery agent	N.A.	Investigative	[38]
4-(1H-indol-1-ylsulfonyl)benzenamine	DMY5QBF	Discovery agent	N.A.	Investigative	[23]
4-(1H-Indol-3-ylmethyl)-phenylamine	DMK5CJO	Discovery agent	N.A.	Investigative	[38]
4-(2-benzenesulfonylphenyl)piperazine	DMAZ0LV	Discovery agent	N.A.	Investigative	[32]
4-(3-benzenesulfonamidophenyl)piperazine	DMLVZ6O	Discovery agent	N.A.	Investigative	[32]
4-(3-benzenesulfonylphenyl)piperazine	DMG4X13	Discovery agent	N.A.	Investigative	[32]
4-(3-Methyl-indole-1-sulfonyl)-phenylamine	DM67A4U	Discovery agent	N.A.	Investigative	[20]
4-(3H-Inden-1-ylmethyl)-phenylamine	DM3QJVT	Discovery agent	N.A.	Investigative	[38]
4-(4,6-dinitro-1H-indol-1-ylsulfonyl)benzenamine	DMI1598	Discovery agent	N.A.	Investigative	[23]
4-(4-benzenesulfonamidophenyl)piperazine	DMP0G1W	Discovery agent	N.A.	Investigative	[32]
4-(4-benzenesulfonylphenyl)piperazine	DM0DZFX	Discovery agent	N.A.	Investigative	[32]
4-(4-methoxy-1H-indol-1-ylsulfonyl)benzenamine	DMA7LEO	Discovery agent	N.A.	Investigative	[39]
4-(6-methoxy-1H-indol-1-ylsulfonyl)benzenamine	DM3L5I6	Discovery agent	N.A.	Investigative	[39]
4-(Indan-1-ylsulfanyl)-phenylamine	DMHI50W	Discovery agent	N.A.	Investigative	[38]
4-(Indane-1-sulfonyl)-phenylamine	DM201UM	Discovery agent	N.A.	Investigative	[38]
4-(Naphthalene-1-sulfonyl)-phenylamine	DMI5XB1	Discovery agent	N.A.	Investigative	[20]
4-(piperazin-1-yl)-1H-indole	DMM1RCS	Discovery agent	N.A.	Investigative	[23]
4-(piperazin-1-yl)-3-tosyl-1H-indazole	DM1HM3F	Discovery agent	N.A.	Investigative	[40]
4-Indan-1-ylmethyl-phenylamine	DM6YON7	Discovery agent	N.A.	Investigative	[38]
4-Inden-(1E)-ylidenemethyl-phenylamine	DM23E0R	Discovery agent	N.A.	Investigative	[38]
5,6-dichloro-3,4-dihydroquinazolin-2-amine	DMN1S35	Discovery agent	N.A.	Investigative	[41]
5-(4-Methylpiperazin-1-yl)-3-tosyl-1H-indazole	DMNSIF2	Discovery agent	N.A.	Investigative	[40]
5-CT	DM260KD	Discovery agent	N.A.	Investigative	[42]
5-MEO-DMT	DMG0EL7	Discovery agent	N.A.	Investigative	[43]
5-METHOXYTRYPTAMINE	DMARCKD	Discovery agent	N.A.	Investigative	[44]
6-(piperazin-1-yl)-3-tosyl-1H-indazole	DMM9G0J	Discovery agent	N.A.	Investigative	[40]
6-tosyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole	DMVL218	Discovery agent	N.A.	Investigative	[45]
alpha-ergocryptine	DMMPOEK	Discovery agent	N.A.	Investigative	[46]
alpha-methyl-5-HT	DMCAYXF	Discovery agent	N.A.	Investigative	[46]
AMR-SIX-1	DM7WTKJ	Obesity	5B81	Investigative	[47]
BRL-15572	DMM61Y2	Discovery agent	N.A.	Investigative	[48]
bufotenine	DMD1SY9	Discovery agent	N.A.	Investigative	[35]
Chlorophenylpiperazine	DMOA8L2	Discovery agent	N.A.	Investigative	[49]
DIMEBOLIN	DMV8ZQG	Discovery agent	N.A.	Investigative	[50]
DM-1451	DMM0VDK	Discovery agent	N.A.	Investigative	[51]
E-6837	DMJ2P0N	Discovery agent	N.A.	Investigative	[29]
E6801	DM7LGAF	Discovery agent	N.A.	Investigative	[44]
EDMT	DMS3AXK	Discovery agent	N.A.	Investigative	[52], [29]
EMD-386088	DM3AGUQ	Discovery agent	N.A.	Investigative	[34]
fluperlapine	DM9KIPU	Discovery agent	N.A.	Investigative	[53]
lergotrile	DMDV67S	Discovery agent	N.A.	Investigative	[26]
LY 165,163	DM9IU21	Discovery agent	N.A.	Investigative	[26]
m-chlorophenylpiperazine	DMM1J2D	Discovery agent	N.A.	Investigative	[26]
METHIOTHEPIN	DMMC0I7	Discovery agent	N.A.	Investigative	[54]
MPDT	DMYX31S	Discovery agent	N.A.	Investigative	[52]
N,N-diethyl-2-(1H-indol-3-yl)ethanamine	DM0UBI9	Discovery agent	N.A.	Investigative	[43]
N,N-dimethyl-2-(1-tosyl-1H-indol-3-yl)ethanamine	DMYUQDK	Discovery agent	N.A.	Investigative	[37]
N-(3-(2-aminoethyl)phenyl)benzenesulfonamide	DMP8547	Discovery agent	N.A.	Investigative	[32]
N-(3-(3-aminopropyl)phenyl)benzenesulfonamide	DMW59AY	Discovery agent	N.A.	Investigative	[32]
N-(3-(aminomethyl)phenyl)benzenesulfonamide	DMSC862	Discovery agent	N.A.	Investigative	[32]
N-(3-aminophenyl)benzenesulfonamide	DMJ6FP7	Discovery agent	N.A.	Investigative	[32]
N-(4-(2-aminoethyl)phenyl)benzenesulfonamide	DM1V83P	Discovery agent	N.A.	Investigative	[32]
N-phenyl-3-(2-aminoethyl)benzenesulfonamide	DMWH86J	Discovery agent	N.A.	Investigative	[32]
OCTOCLOTHEPIN	DM0UADK	Discovery agent	N.A.	Investigative	[44]
OPC 4392	DMQOJY2	Discovery agent	N.A.	Investigative	[51]
Quipazine	DMPY6IG	Discovery agent	N.A.	Investigative	[49]
Ro-04-6790	DM6H8JM	Discovery agent	N.A.	Investigative	[29]
SB 258585	DM2QJKZ	Discovery agent	N.A.	Investigative	[55]
SB-214111	DMH1CFX	Discovery agent	N.A.	Investigative	[56]
SB-271046	DM5VJAF	Discovery agent	N.A.	Investigative	[21]
SB-357134	DMFTO8R	Discovery agent	N.A.	Investigative	[57]
SB399885	DMFMK89	Discovery agent	N.A.	Investigative	[58]
SEL-73	DMFKE6C	Psychiatric disorder	6E8Z	Investigative	[47]
Serotonin	DMOFCRY	Discovery agent	N.A.	Investigative	[54]
SUVN-501	DMT8PKC	Neurological disorder	6B60	Investigative	[47]
SUVN-504	DMZCKDH	Vomiting	MD90	Investigative	[47]
SUVN-507	DM2UMK8	Neurological disorder	6B60	Investigative	[47]
TFMPP	DMAC8TP	Discovery agent	N.A.	Investigative	[26]
WAY-208466	DM9K2LU	Discovery agent	N.A.	Investigative	[31]
WAY-466	DMMOH51	Discovery agent	N.A.	Investigative	[59]
[125I]SB-258585	DMXWZCB	Discovery agent	N.A.	Investigative	[55]
[2-(3-Benzyl-3H-inden-1-yl)-ethyl]-methyl-amine	DMAJCVL	Discovery agent	N.A.	Investigative	[38]
[2-(3-Benzyl-3H-indol-1-yl)-ethyl]-dimethyl-amine	DMU5P8O	Discovery agent	N.A.	Investigative	[60]
[2-(3-Benzyl-indol-1-yl)-ethyl]-dimethyl-amine	DMBTRN6	Discovery agent	N.A.	Investigative	[38]
[2-(3H-Indol-1-yl)-ethyl]-dimethyl-amine	DM1RW4U	Discovery agent	N.A.	Investigative	[60]
[3H]5-CT	DMEAHFZ	Discovery agent	N.A.	Investigative	[47]
[3H]LSD	DM0YJHS	Discovery agent	N.A.	Investigative	[51]
[3H]Ro 63-0563	DM5XSMN	Discovery agent	N.A.	Investigative	[1], [57]
[3H]spiperone	DMWHEV8	Discovery agent	N.A.	Investigative	[49]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Schizophrenia	6A20	Pre-frontal cortex	6.43E-01	0.04	0.12
Schizophrenia	6A20	Superior temporal cortex	3.59E-02	-0.05	-0.48
Alzheimer's disease	8A00.0	Entorhinal cortex	1.23E-05	-0.12	-0.71

References

• [1] The 5-hydroxytryptamine6 receptor-selective radioligand [3H]Ro 63-0563 labels 5-hydroxytryptamine receptor binding sites in rat and porcine striatum. Mol Pharmacol. 1998 Sep;54(3):577-83.
• [2] Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats. Int J Neuropsychopharmacol. 2010 Sep;13(8):1021-33.
• [3] 5-HT6 receptors and Alzheimer's disease. Alzheimers Res Ther. 2013; 5(2): 15.
• [4] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [5] Latrepirdine, a potential novel treatment for Alzheimer's disease and Huntington's chorea. Curr Opin Investig Drugs. 2010 January; 11(1): 80-91.
• [6] PF-05212377 Alzheimer's Disease (Phase 2). Pfizer.
• [7] Activation of 5-HT6 receptors modulates sleep-wake activity and hippocampal theta oscillation. ACS Chem Neurosci. 2013 Jan 16;4(1):191-9.
• [8] Novel and Potent 5-Piperazinyl Methyl-N1-aryl Sulfonyl Indole Derivatives as 5-HT6 Receptor Ligands. ACS Med Chem Lett. 2010 October 14; 1(7): 340-344.
• [9] The Serotonin-6 Receptor as a Novel Therapeutic Target. Exp Neurobiol. 2011 December; 20(4): 159-168.
• [10] Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs. Nat Rev Drug Discov. 2018 Nov;17(11):804-822.
• [11] Radiosynthesis and characterization of 11C-GSK215083 as a PET radioligand for the 5-HT6 receptor. J Nucl Med. 2012 Feb;53(2):295-303.
• [12] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035134)
• [13] AVN-322 is a Safe Orally Bio-Available Potent and Highly Selective Antagonist of 5-HT6R with Demonstrated Ability to Improve Impaired Memory in Animal Models. Curr Alzheimer Res. 2017;14(3):268-294.
• [14] Pharmacological targeting of the serotonergic system for the treatment of obesity. J Physiol. 2009 January 1; 587(Pt 1): 49-60.
• [15] Low-dose prazosin in combination with 5-HT6 antagonist PRX-07034 has antipsychotic effects. Can J Physiol Pharmacol. 2015 Jan;93(1):13-21.
• [16] 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
• [17] Lewy bodies. Proc Natl Acad Sci U S A. 2006 February 7; 103(6): 1661-1668.
• [18] Neuropharmacological profile of novel and selective 5-HT6 receptor agonists: WAY-181187 and WAY-208466.Neuropsychopharmacology.2008 May;33(6):1323-35.
• [19] Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31.
• [20] 1-(1-Naphthyl)piperazine as a novel template for 5-HT6 serotonin receptor ligands. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1707-11.
• [21] Synthesis and SAR of tolylamine 5-HT6 antagonists. Bioorg Med Chem Lett. 2009 May 1;19(9):2409-12.
• [22] The synthesis and biological activity of pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine. Bioorg Med Chem. 2007 Nov 1;15(21):6659-66.
• [23] Binding of amine-substituted N1-benzenesulfonylindoles at human 5-HT6 serotonin receptors. Bioorg Med Chem Lett. 2005 Dec 1;15(23):5298-302.
• [24] Conformationally constrained N1-arylsulfonyltryptamine derivatives as 5-HT6 receptor antagonists. Bioorg Med Chem Lett. 2005 Nov 1;15(21):4780-5.
• [25] N1-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives are potent and selective 5-HT6 receptor antagonists. Bioorg Med Chem Lett. 2005 Jan 17;15(2):379-83.
• [26] Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. Mol Pharmacol. 1993 Mar;43(3):320-7.
• [27] Binding of serotonin and N1-benzenesulfonyltryptamine-related analogs at human 5-HT6 serotonin receptors: receptor modeling studies. J Med Chem. 2008 Feb 14;51(3):603-11.
• [28] 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. J Med Chem. 2007 Nov 15;50(23):5535-8.
• [29] Indene-based scaffolds. 2. An indole-indene switch: discovery of novel indenylsulfonamides as 5-HT6 serotonin receptor agonists. J Med Chem. 2009 Feb 12;52(3):675-87.
• [30] Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects. Arch Gen Psychiatry. 1994 Feb;51(2):85-97.
• [31] Novel 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines are potent 5-HT(6) agonists. Bioorg Med Chem. 2009 Jul 15;17(14):5153-63.
• [32] Binding of sulfonyl-containing arylalkylamines at human 5-HT6 serotonin receptors. J Med Chem. 2006 Aug 24;49(17):5217-25.
• [33] Benzimidazole derivatives as new serotonin 5-HT6 receptor antagonists. Molecular mechanisms of receptor inactivation. J Med Chem. 2010 Feb 11;53(3):1357-69.
• [34] 2-Alkyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles as novel 5-HT6 receptor agonists. Bioorg Med Chem Lett. 2005 Oct 1;15(19):4230-4.
• [35] Functional and radioligand binding characterization of rat 5-HT6 receptors stably expressed in HEK293 cells. Neuropharmacology. 1997 Apr-May;36(4-5):713-20.
• [36] 3-(Arylsulfonyl)-1-(azacyclyl)-1H-indoles are 5-HT(6) receptor modulators. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1657-60.
• [37] Further studies on the binding of N1-substituted tryptamines at h5-HT6 receptors. Bioorg Med Chem Lett. 2007 Mar 15;17(6):1691-4.
• [38] Binding of isotryptamines and indenes at h5-HT6 serotonin receptors. Bioorg Med Chem Lett. 2005 Apr 15;15(8):1987-91.
• [39] Binding of methoxy-substituted N1-benzenesulfonylindole analogs at human 5-HT6 serotonin receptors. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3793-6.
• [40] 5-Piperazinyl-3-sulfonylindazoles as potent and selective 5-hydroxytryptamine-6 antagonists. J Med Chem. 2010 Nov 11;53(21):7639-46.
• [41] Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: structure-activity relationship elucidation. Bioorg Med Chem Lett. 2008 Jan 1;18(1):256-61.
• [42] Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor. J Neurochem. 1996 Jan;66(1):47-56.
• [43] Interaction of N1-unsubstituted and N1-benzenesulfonyltryptamines at h5-HT6 receptors. Bioorg Med Chem Lett. 2006 Nov 15;16(22):5832-5.
• [44] Medicinal chemistry driven approaches toward novel and selective serotonin 5-HT6 receptor ligands. J Med Chem. 2005 Mar 24;48(6):1781-95.
• [45] A regiospecific synthesis of a series of 1-sulfonyl azepinoindoles as potent 5-HT6 ligands. Bioorg Med Chem Lett. 2008 Jul 15;18(14):3929-31.
• [46] Identification of residues in transmembrane regions III and VI that contribute to the ligand binding site of the serotonin 5-HT6 receptor. J Neurochem. 1998 Nov;71(5):2169-77.
• [47] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 11).
• [48] SB-216641 and BRL-15572--compounds to pharmacologically discriminate h5-HT1B and h5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):312-20.
• [49] Higher-end serotonin receptors: 5-HT(5), 5-HT(6), and 5-HT(7). J Med Chem. 2003 Jul 3;46(14):2795-812.
• [50] 8-Sulfonyl-substituted tetrahydro-1H-pyrido[4,3-b]indoles as 5-HT6 receptor antagonists. Eur J Med Chem. 2010 Feb;45(2):782-9.
• [51] Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes. Neuropsychopharmacology. 1999 Jun;20(6):612-27.
• [52] 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J Med Chem. 2000 Mar 9;43(5):1011-8.
• [53] Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10.
• [54] 5-Cyclic amine-3-arylsulfonylindazoles as novel 5-HT6 receptor antagonists. J Med Chem. 2010 Mar 25;53(6):2521-7.
• [55] 5-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.
• [56] The distribution of 5-HT(6) receptors in rat brain: an autoradiographic binding study using the radiolabelled 5-HT(6) receptor antagonist [(125)I]S... Brain Res. 2002 Apr 26;934(1):49-57.
• [57] Discovery of 3-aryl-3-methyl-1H-quinoline-2,4-diones as a new class of selective 5-HT6 receptor antagonists. Bioorg Med Chem Lett. 2008 Jan 15;18(2):738-43.
• [58] SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition ... Eur J Pharmacol. 2006 Dec 28;553(1-3):109-19.
• [59] Discovery of 5-arylsulfonamido-3-(pyrrolidin-2-ylmethyl)-1H-indole derivatives as potent, selective 5-HT6 receptor agonists and antagonists. J Med Chem. 2005 Jan 27;48(2):353-6.
• [60] Possible differences in modes of agonist and antagonist binding at human 5-HT6 receptors. Bioorg Med Chem Lett. 2004 Sep 6;14(17):4569-73.