Metitepine (INNTooltip International Nonproprietary Name; developmental code namesRo 8-6837 (maleate),VUFB-6276 (mesylate)), also known asmethiothepin, is adrug described as a "psychotropic agent" of thetricyclic ortetracyclic group which was never marketed.[1]
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).
^abRoth BL, Driscol J."PDSP Ki Database".Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved14 August 2017.
^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.PMID4340797.S2CID19577535.
^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.PMID2994121.S2CID29894323.
^Chapman ME, Wideman RF (April 2006). "Evaluation of the serotonin receptor blockers ketanserin and methiothepin on the pulmonary hypertensive responses of broilers to intravenously infused serotonin".Poult Sci.85 (4):777–86.doi:10.1093/ps/85.4.777.PMID16615363.
^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.
