64224-21-1

Oltipraz (64224-21-1) upregulates the transcription factor NRF2 and prevents insulin resistance and obesity induced by high fat diet in C57BL/6J mice.1 Attenuates the progression of fibrosis in a rat model of nonalcoholic steatohepatitis.2 Oltipaz attenuates chronic hypoxia-induced cardiopulmonary alterations in mice.3 Promotes liver regeneration after partial hepatectomy.4 Off target effects: Activates constitutive androstane receptor (CAR).5

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Oltipraz is a synthetic, substituted 1,2-dithiole-3-thione previously used in humans as an antischistosomal agent. Animal studies have demonstrated that oltipraz is a potent inducer of Phase II detoxi fication enzymes, most notably glutathione-S-transferase (GST). Oltipraz is now known to be used for tumor prevention purposes.

schistosomicide, antineoplastic

ChEBI: A 1,2-dithiole that is 3H-1,2-dithiole-3-thione substituted at positions 4 and 5 by methyl and pyrazin-2-yl groups respectively.

Oltipraz is an activator of Nrf2. Nrf2 (NF-E2-related factor 2) is a transcription factor that binds to antioxidant response elements (AREs) and activates these genes. Oltipraz activates Nrf2 and subsequently elevates expression of the detoxification genes encoding anti-oxidant and multidrug resistance-associated proteins to mediate its chemopreventive efficacy.

The general procedure for the synthesis of 4-methyl-5-(pyrazin-2-yl)-3H-1,2-dithio-3-thione from methyl 2-methyl-3-oxo-3-(pyrazin-2-yl)propionate was as follows: P4S10 (12 g, 27.0 mmol), toluene (90 mL), and xylene (90 mL) were added to a reactor and heated to 120 °C. Subsequently, methyl 2-methyl-3-oxo-3-(pyrazin-2-yl)propionate (8.1 g, 45.1 mmol) was added to the reactor. The reaction mixture was refluxed at 135 °C for 4 h, after which it was cooled to 20 °C and filtered through diatomaceous earth. The solvent was removed under reduced pressure and the resulting solid was extracted with CH2Cl2. The organic layer was sequentially washed with aqueous K2CO3, dried over Na2SO4 and filtered. The solvent was again removed under reduced pressure and the crude product was dried under vacuum. The dried solid was washed with cold EtOAc and finally recrystallized in acetonitrile to afford the target product 4-methyl-5-(pyrazin-2-yl)-3H-1,2-dithio-3-thione (0.9 g, 10% yield) as solid.

This schistosomicide (FW = 226.35 g/mol; CAS 64224-21-1), also known as 5- (2-pyrazinyl) -4-methyl-1,2-dithiole-3-thione, is used to treat disease caused by parasitic flatworms and is also a potent cancer chemopreventive agent. Oltipraz was found to protect against chemically induced carcinogens within the lung, stomach, colon, and urinary bladder. The anti-HIV activity of the pharmaceutical is believed to be due to its ability to irreversibly inhibit HIV reverse transcriptase. Target (s) : CYP1A2 (1-3); CYP3A4; HIV I reverse transcriptase; RNA-directed DNA polymerase. 1. Sofowora, Choo, Mayo, Shyr & Wilkinson Cancer Chemother. Pharmaco

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1) Yu?et al. (2011),?Oltipraz upregulates the nuclear factor (erythroid-derived 2)-like 2 (NRF2) antioxidant system and prevents insulin resistance and obesity induced by a high-fat diet in C57BL/6J mice; Diabetologia,?54?922 2) Shimozono?et al. (2013),?Nrf2 activators attenuate the progression of nonalcoholic steatohepatitis-related fibrosis in a dietary rat model; Mol. Pharmacol,?84?62 3) Eba?et al. (2013),?The nuclear factor erythroid 2-related factor 2 activator oltipraz attenuates chronic hypoxia-induced cardiopulmonary alterations in mice; Am. J. Respir. Cell. Mol. Biol.,?49?324 4) Cho?et al. (2009), Oltipraz promotion of liver regeneration after partial hepatectomy: the role of PI3-kinase dependent C/EBPbeta and cyclin E regulation; Arch. Pharm. Res.,?32?625 5) Merrell?et al. (2008),?The Nrf2 activator oltipraz also activates the constitutive androstane receptor; Drug Metab. Dispos.,?36?1716