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-dihydrobenzobenzothiepin-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 methanol, CID:12853582 (2). Halogenating with thionyl chloride gives 1-(chloromethyl)-2-(4-methylsulfanylphenyl)sulfanylbenzene, CID:12853583 (3). FGI with cyanide gives 2-acetonitrile, CID:12853584 (4). Alkali hydrolysis of the nitrile to 2-acetic acid, CID:12383832 (5). PPA cyclization to 3-methylsulfanyl-6H-benzobenzothiepin-5-one, CID:827052 (6). The reduction with sodium borohydride gives 3-methylsulfanyl-5,6-dihydrobenzobenzothiepin-5-ol, CID:13597048 (7). Halogenating with a second round of thionyl chloride gives 5-chloro-3-methylsulfanyl-5,6-dihydrobenzobenzothiepine, CID:12404411. Alkylation with 1-methylpiperazine 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-Schmiedeberg's 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 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 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 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)

[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-Schmiedeberg's 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 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 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 thiepin-Derivate". Collection of Czechoslovak Chemical Communications. 33: 1895–1910. doi:10.1135/cccc19681895.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

Synthesis

See also

References

External links