Details of the Drug

General Information of Drug (ID: DMMC0I7)

Drug Name
METHIOTHEPIN
Synonyms
methiothepin; Metitepine; Methiothepine; Metitepinum; Metitepina; Metitepine [INN]; Metitepinum [INN-Latin]; Metitepina [INN-Spanish]; BRN 0626221; 20229-30-5; (+-)-10-(4-Methylpiperazinyl)-8-(methylthio)-10,11-dihydrodibenzo(b,f)thiepin; (+-)-8-Methylthio-10-(4-methylpiperazino)-10,11-dihydrodibenzo(b,f)thiepin; (+-)-1-(10,11-Dihydro-8-(methylthio)dibenzo(b,f)thiepin-10-yl)-4-methylpiperazine; CHEBI:64203; 1-(10,11-Dihydro-8-(methylthio)dibenzo(b,f)thiepin-10-yl)-4-methylpiperazine; NCGC00024665-03; DSSTox_CID_24000
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 356.6
Topological Polar Surface Area (xlogp) 4.2
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 4
Chemical Identifiers
Formula
C20H24N2S2
IUPAC Name
1-methyl-4-(3-methylsulfanyl-5,6-dihydrobenzo[b][1]benzothiepin-5-yl)piperazine
Canonical SMILES
CN1CCN(CC1)C2CC3=CC=CC=C3SC4=C2C=C(C=C4)SC
InChI
InChI=1S/C20H24N2S2/c1-21-9-11-22(12-10-21)18-13-15-5-3-4-6-19(15)24-20-8-7-16(23-2)14-17(18)20/h3-8,14,18H,9-13H2,1-2H3
InChIKey
RLJFTICUTYVZDG-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
4106
ChEBI ID
CHEBI:64203
CAS Number
20229-30-5
TTD ID
D0X6MT

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
5-HT 5A receptor (HTR5A) TTRUFDT 5HT5A_HUMAN Inhibitor [2]
5-HT 6 receptor (HTR6) TTJS8PY 5HT6R_HUMAN Inhibitor [3]
5-HT 7 receptor (HTR7) TTO9X1H 5HT7R_HUMAN Inhibitor [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
5-HT 6 receptor (HTR6) DTT HTR6 1.23E-05 -0.12 -0.71
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 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. (Ligand id: 89).
2 Higher-end serotonin receptors: 5-HT(5), 5-HT(6), and 5-HT(7). J Med Chem. 2003 Jul 3;46(14):2795-812.
3 5-Cyclic amine-3-arylsulfonylindazoles as novel 5-HT6 receptor antagonists. J Med Chem. 2010 Mar 25;53(6):2521-7.
4 Novel quinazolinone derivatives as 5-HT7 receptor ligands. Bioorg Med Chem. 2008 Mar 1;16(5):2570-8.
5 Cloning and characterisation of the human 5-HT5A serotonin receptor. FEBS Lett. 1994 Dec 5;355(3):242-6.
6 Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31.
7 Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69.
8 Expression of functional mouse 5-HT5A serotonin receptor in the methylotrophic yeast Pichia pastoris: pharmacological characterization and localization. FEBS Lett. 1995 Dec 27;377(3):451-6.
9 Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization. Mol Pharmacol. 1993 Mar;43(3):313-9.
10 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.
11 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J Med Chem. 2000 Mar 9;43(5):1011-8.
12 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.
13 5-HT6 receptors and Alzheimer's disease. Alzheimers Res Ther. 2013; 5(2): 15.
14 Latrepirdine, a potential novel treatment for Alzheimer's disease and Huntington's chorea. Curr Opin Investig Drugs. 2010 January; 11(1): 80-91.
15 Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs. Nat Rev Drug Discov. 2018 Nov;17(11):804-822.
16 The Serotonin-6 Receptor as a Novel Therapeutic Target. Exp Neurobiol. 2011 December; 20(4): 159-168.
17 PF-05212377 Alzheimer's Disease (Phase 2). Pfizer.
18 Activation of 5-HT6 receptors modulates sleep-wake activity and hippocampal theta oscillation. ACS Chem Neurosci. 2013 Jan 16;4(1):191-9.
19 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.
20 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
21 Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity. Front Behav Neurosci. 2015 Jan 15;8:453.
22 AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders. J Alzheimers Dis. 2016 May 25;53(2):583-620.
23 Pharmacological characteristics of ATI-9242, a Novel Atypical Antipsychotic. FASEB J, April, 2010, 24(Meeting Abstract Supplement),773.12.
24 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
25 Acyltransferase inhibitors: a patent review (2010-present).Expert Opin Ther Pat. 2015 Feb;25(2):145-58.
26 [(3)H]-SB-269970--A selective antagonist radioligand for 5-HT(7) receptors. Br J Pharmacol. 2000 May;130(2):409-17.
27 Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.