Metitepine

Metitepine
Clinical data
Other names	Methiothepin; Methiothepine; Ro 8-6837 (maleate); VUFB-6276 (mesylate)
Identifiers
	IUPAC name 1-methyl-4-(8-methylsulfanyl-5,6-dihydrobenzo[b][1]benzothiepin-6-yl)piperazine;
CAS Number	20229-30-5 ; 19728-88-2 (maleate);
PubChem CID	4106;
IUPHAR/BPS	89;
ChemSpider	3963;
UNII	55D94103HL;
ChEBI	CHEBI:64203;
CompTox Dashboard (EPA)	DTXSID2044000 ;
ECHA InfoCard	100.261.496
Chemical and physical data
Formula	C20H24N2S2
Molar mass	356.55 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN1CCN(CC1)C2Cc3ccccc3Sc4c2cc(cc4)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; Key:RLJFTICUTYVZDG-UHFFFAOYSA-N;

Metitepine (INNTooltip International Nonproprietary Name; developmental code names Ro 8-6837 (maleate), VUFB-6276 (mesylate)), also known as methiothepin, is a drug described as a "psychotropic agent" of the tricyclic group which was never marketed.^[1] It acts as a non-selective antagonist of serotonin, dopamine, and adrenergic receptors^[2]^[3]^[4] and has antipsychotic properties.^[5]

Synthesis

The reduction of 2-(4-methylsulfanylphenyl)sulfanylbenzoic acid, CID:2733664 (1) gives [2-(4-methylsulfanylphenyl)sulfanylphenyl]methanol, CID:12853582 (2). Halogenating with thionyl chloride gives 1-(chloromethyl)-2-(4-methylsulfanylphenyl)sulfanylbenzene, CID:12853583 (3). FGI with cyanide gives 2-[2-(4-methylsulfanylphenyl)sulfanylphenyl]acetonitrile, CID:12853584 (4). Alkali hydrolysis of the nitrile to 2-[2-(4-methylsulfanylphenyl)sulfanylphenyl]acetic acid, CID:12383832 (5). PPA cyclization to 3-methylsulfanyl-6H-benzo[b][1]benzothiepin-5-one, CID:827052 (6). The reduction with sodium borohydride gives 3-methylsulfanyl-5,6-dihydrobenzo[b][1]benzothiepin-5-ol, CID:13597048 (7). Halogenating with a second round of thionyl chloride gives 5-chloro-3-methylsulfanyl-5,6-dihydrobenzo[b][1]benzothiepine, CID:12404411. Alkylation with 1-methylpiperazine [109-01-3] completed the synthesis of Metitepine (9).

References

^ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 815–. ISBN 978-1-4757-2085-3.
^ Monachon MA, Burkard WP, Jalfre M, Haefely W (1972). "Blockade of central 5-hydroxytryptamine receptors by methiothepin". Naunyn Schmiedebergs Arch. Pharmacol. 274 (2): 192–7. doi:10.1007/BF00501854. PMID 4340797. S2CID 19577535.
^ Dall'Olio R, Vaccheri A, Montanaro N (1985). "Reduced head-twitch response to quipazine of rats previously treated with methiothepin: possible involvement of dopaminergic system". Pharmacol. Biochem. Behav. 23 (1): 43–8. doi:10.1016/0091-3057(85)90128-5. PMID 2994121. S2CID 29894323.
^ Roth BL, Driscol J. "PDSP K_i Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
^ Lemke TL, Williams DA (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 388–. ISBN 978-1-60913-345-0.
^ Jílek JO, Metyšová J, Svátek E, Jančik F, Pomykáček J, Protiva M (1973). "Neurotropic and psychotropic agents. LVI. Sulfoxides, N-oxides and sulfones derived from neuroleptic 10-piperazino-10, 11-dihydrodibenzo [b, f] thiepins". Collection of Czechoslovak Chemical Communications. 38 (2): 599–610. doi:10.1135/cccc19730599.
^ Jílek J, Pomykáček J, Dlabač A, Bartošová M, Protiva M (1980). "Neuroleptics of the 8-methylthio-10-piperazino-10, 11-dihydrodibenzo [b, f] thiepin series: New compounds and new procedures". Collection of Czechoslovak Chemical Communications. 45 (2): 504–516. doi:10.1135/cccc19800504.
^ Pelz K, Jirkovsky L, Adlerova E, Metysova J, Protiva M (1968). "Über die in 8-Stellung durch die Methyl-, tert. Butyl-, Methoxy-, Methylthio-und Methansulfonylgruppe substituierten 10-(4-Methylpiperazino)-10,11-dihydrodibenzo [b, f] thiepin-Derivate". Collection of Czechoslovak Chemical Communications. 33: 1895–1910. doi:10.1135/cccc19681895.

External links

Methiothepin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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[Elks2014-1] J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 815–. ISBN 978-1-4757-2085-3.

[pmid4340797-2] Monachon MA, Burkard WP, Jalfre M, Haefely W (1972). "Blockade of central 5-hydroxytryptamine receptors by methiothepin". Naunyn Schmiedebergs Arch. Pharmacol. 274 (2): 192–7. doi:10.1007/BF00501854. PMID 4340797. S2CID 19577535.

[pmid2994121-3] Dall'Olio R, Vaccheri A, Montanaro N (1985). "Reduced head-twitch response to quipazine of rats previously treated with methiothepin: possible involvement of dopaminergic system". Pharmacol. Biochem. Behav. 23 (1): 43–8. doi:10.1016/0091-3057(85)90128-5. PMID 2994121. S2CID 29894323.

[PDSP-4] Roth BL, Driscol J. "PDSP K_i Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.

[LemkeWilliams2012-5] Lemke TL, Williams DA (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 388–. ISBN 978-1-60913-345-0.

[6] Jílek JO, Metyšová J, Svátek E, Jančik F, Pomykáček J, Protiva M (1973). "Neurotropic and psychotropic agents. LVI. Sulfoxides, N-oxides and sulfones derived from neuroleptic 10-piperazino-10, 11-dihydrodibenzo [b, f] thiepins". Collection of Czechoslovak Chemical Communications. 38 (2): 599–610. doi:10.1135/cccc19730599.

[7] Jílek J, Pomykáček J, Dlabač A, Bartošová M, Protiva M (1980). "Neuroleptics of the 8-methylthio-10-piperazino-10, 11-dihydrodibenzo [b, f] thiepin series: New compounds and new procedures". Collection of Czechoslovak Chemical Communications. 45 (2): 504–516. doi:10.1135/cccc19800504.

[8] Pelz K, Jirkovsky L, Adlerova E, Metysova J, Protiva M (1968). "Über die in 8-Stellung durch die Methyl-, tert. Butyl-, Methoxy-, Methylthio-und Methansulfonylgruppe substituierten 10-(4-Methylpiperazino)-10,11-dihydrodibenzo [b, f] thiepin-Derivate". Collection of Czechoslovak Chemical Communications. 33: 1895–1910. doi:10.1135/cccc19681895.

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v t e Tricyclics
Classes	Acridine Anthracene Dibenzazepine Dibenzocycloheptene Dibenzodiazepine Dibenzothiazepine Dibenzothiepin Dibenzoxazepine Dibenzoxepin Phenothiazine Pyridazinobenzoxazine Pyridinobenzodiazepine Thioxanthene
Antidepressants (Tricyclic antidepressants (TCAs))	Amoxapine Amezepine Amineptine Amitriptyline Amitriptylinoxide Amoxapine Aptazapine Azepindole Batelapine Beloxepin Butriptyline Cianopramine Ciclazindol Cidoxepin Clomipramine Cotriptyline Cyanodothiepin Demexiptiline Depramine (balipramine) Desipramine (desmethylimipramine) Desmethylclomipramine Desmethyltrimipramine Dibenzepin Dimetacrine Dosulepin (dothiepin) Doxepin Enprazepine Fantridone Fluotracen Hepzidine Homopipramol Imipramine Imipraminoxide Intriptyline Iprindole Ketipramine Litracen Lofepramine Losindole Loxapine Maprotiline Mariptiline Mazindol Melitracen Metapramine Mezepine Mirtazapine Monometacrine Nitroxazepine Norbutriptyline Nordoxepin Northiaden (nordosulepin) Nortriptyline (noramitriptyline) Noxiptiline Octriptyline Opipramol Pipofezine Pirandamine Propizepine Protriptyline Quinupramine Spiroxepin Tandamine Tampramine Tianeptine Tienopramine Trimipramine
Antihistamines	Azatadine Bisulepin Cidoxepin Clobenzepam Cyproheptadine Dacemazine Deptropine Desloratadine Epinastine Etymemazine Fenethazine Hydroxyethylpromethazine Isopromethazine Isothipendyl Ketotifen Latrepirdine Loratadine Mebhydrolin Mequitazine Methdilazine Olopatadine Oxomemazine Perlapine Phenindamine Pimethixene Pirolate Promethazine Propiomazine Rupatadine Thiazinamium
Antipsychotics	Acetophenazine Alimemazine Amoxapine Asenapine Butaclamol Butaperazine Carfenazine (carphenazine) Carpipramine Chlorpromazine Chlorprothixene Ciclindole Citatepine Clocapramine Clomacran Clorotepine Clotiapine Clozapine Cyanothepin Doclothepin Docloxythepin Erizepine Flucindole Flumezapine Fluotracen Flupentixol Fluphenazine Gevotroline Homopipramol Isofloxythepin Levomepromazine/Methotrimeprazine Loxapine Maroxepin Meperathiepin Mesoridazine Metiapine Metitepine Metoxepin Mosapramine Naranol Octomethothepin Olanzapine Oxyclothepin Oxyprothepin Pentiapine Peradithiepin Perathiepin Perazine Perphenazine Periciazine Pinoxepin Piperacetazine Pipotiazine Piquindone Prochlorperazine Promazine Prothipendyl Quetiapine Savoxepin/Cipazoxapine Sulforidazine Tenilapine Thiethylperazine Thiopropazate Thioridazine Thiothixene Tilozepine Traboxopine Trifluoperazine Triflupromazine Trifluthepin Zotepine Zuclopenthixol
Anticonvulsants	Carbamazepine Dizocilpine Eslicarbazepine Eslicarbazepine acetate Etazepine Licarbazepine Oxcarbazepine Oxitriptyline
Anticholinergics	Darenzepine Dipitramine Nuvenzepine Pirenzepine Profenamine Rispenzepine Siltenzepine Telenzepine Tripitramine Tropatepine Zolenzepine
Others	Adosopine Aminopromazine Atiprosin Benzoctamine Botiacrine Carvedilol Cyclobenzaprine Damotepine Elanzepine Fluradoline Methylene blue Monatepil Oxetorone Pipazethate P7C3 Pinadoline Pitrazepin Pizotifen Serazapine Tipindole

Synthesis

See also

References

External links