84201-40-1Relevant articles and documents
Thiolytic chemistry of alternative precursors to the major metabolite of the cancer chemopreventive oltipraz
Navamal, Mettachit,McGrath, Colleen,Stewart, Jennifer,Blans, Patrick,Villamena, Frederick,Zweier, Jay,Fishbein, James C.
, p. 9406 - 9413 (2002)
The compounds 7-methyl-6,8-bis(methyldisulfanyl)pyrrolo[1,2- a]pyrazine (5; "bis disulfide") and methanethiosulfonic acid S-((6-(methanesulfonylsulfanyl)-7-methyl)pyrrolo[1,2-a]pyrazin -8-yl) ester (6; "bis methanesulfonic acid thioester") have been synthesized to serve as alternative precursors to the major metabolite, 4, of the cancer chemopreventive oltipraz, 1, to test whether they possess similar biological activities. In the present work the mechanisms by which these compounds react with glutathione have been investigated in order to validate the assumption that they would be chemically competent in the presence of the biological thiols to give the oltipraz metabolite. A kinetic and product study was carried out in mainly aqueous media, ≤15% ethanol by volume, at 37 °C. The kinetic analysis and identification of intermediates by electrospray HPLC/MS indicate that compound 5 decomposes in two sequential reactions via thiol-disulfide interchange involving removal of the two thiomethyl groups. In contrast, 6 decomposes in three sequential steps, the first entailing formation of the diglutathionyl adduct, followed by two subsequent thiol disulfide interchange reactions involving loss of the glutathionyl moieties. Both 5 and 6, as well as oltipraz itself, give nearly quantitative yields of the metabolite 4 in reactions with glutathione. Analysis of the decay of 6 by EPR spin trapping methods indicates that less than 0.2% of the reaction flux proceeds through radicals more stable than the hydroxyl radical.
Electro-organic Synthesis and X-Ray Crystal Structure of the Novel Complex 2,7-Dimethyl-6,8-bis(methylthio)pyrrolopyrazinium Tri-iodomercurate(II)
Vaccher, Claude,Berthelot, Pascal,Debaert, Michel,Darchen, Andre,Burgot, Jean Louis,et al.
, p. 391 - 394 (2007/10/02)
Electroreduction of oltipraz (INN), 4-methyl-5-(pyrazin-2-yl)-1,2-dithiole-3-thione and methylation leads to the known metabolite, 6,8-bis(methylthio)-7-methylpyrrolopyrazine on a glassy carbon cathode or to the novel mercury(II) title complex on a mercury cathode.The crystal structure of this complex is presented.The comlex crystallizes in the triclinic space group P1- with a = 10.620(2), b = 11.944(2), c = 9.665(2) Angstroem, α = 121.16(1), β = 102.68(1), γ = 95.38(1) degree, Z = 2.The structure was solved and refined on the basis of 3162 significant data, to a final R value of 0.026.The electrochemical behaviour has been investigated by voltammetry.
STUDY OF THE REDUCTIVE METABOLISM PATHWAY OF 4-METHYL-5-(2-PYRAZINYL)-1,2-DITHIOLE-3-THIONE. AN ELECTROCHEMICAL APPROACH.
Largeron, M.,Fleury, D.,Fleury, M. B.
, p. 409 - 416 (2007/10/02)
In slightly basic aqueous-ethanol medium or in acetonitrile, electrochemical reduction of 4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (OLTIPRAZ 35972 R.P., antischistosomal drug) affords a convenient route to pyrrolopyrazine derivatives, which are found as metabolites of the drug in host urine.A transient species in the reduction process which is endowed with schistosomicidal activity is isolated.
