OLTIPRAZ Chemical Properties

Melting point:

165-166

Boiling point:

408.1±55.0 °C(Predicted)

Density 

1.51±0.1 g/cm3(Predicted)

RTECS 

JP1293000

storage temp. 

2-8°C

solubility 

DMSO: >20mg/mL

pka

0.18±0.10(Predicted)

form 

Solid

color 

red

Sensitive 

Light Sensitive

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.

InChI

InChI=1S/C8H6N2S3/c1-5-7(12-13-8(5)11)6-4-9-2-3-10-6/h2-4H,1H3

InChIKey

CKNAQFVBEHDJQV-UHFFFAOYSA-N

SMILES

S1C(C2=NC=CN=C2)=C(C)C(=S)S1

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36/37/39-36/37

WGK Germany 

3

OLTIPRAZ Usage And Synthesis

Description

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

Chemical Properties

Dark Red Solid

Uses

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 detoxification enzymes, most notably glutathione-S-transferase (GST). Oltipraz is now known to be used for tumor prevention purposes.

Uses

schistosomicide, antineoplastic

Definition

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.

General Description

Oltipraz, a dithiol derivative, is a member of dithiolethiones class of organosulfur compounds. It has anti-tumor, antioxidative, anti- inflammatory and radioprotective properties. It provides protection from numerous carcinogens. Oltipraz functions as a schistosomicide.

Biochem/physiol Actions

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.

Synthesis

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.

storage

Store at +4°C

References

[1] Z YU. Oltipraz upregulates the nuclear factor (erythroid-derived 2)-like 2 [corrected](NRF2) antioxidant system and prevents insulin resistance and obesity induced by a high-fat diet in C57BL/6J mice.[J]. Diabetologia, 2011, 54 4: 922-934. DOI:10.1007/s00125-010-2001-8
[2] RIEKO SHIMOZONO. Nrf2 activators attenuate the progression of nonalcoholic steatohepatitis-related fibrosis in a dietary rat model.[J]. Molecular Pharmacology, 2013, 84 1: 62-70. DOI:10.1124/mol.112.084269
[3] SHUNSUKE EBA. The nuclear factor erythroid 2-related factor 2 activator oltipraz attenuates chronic hypoxia-induced cardiopulmonary alterations in mice.[J]. American Journal of Respiratory Cell and Molecular Biology, 2013, 49 2: 324-333. DOI:10.1165/rcmb.2011-0396oc
[4] IL JE CHO. Oltipraz promotion of liver regeneration after partial hepatectomy: The role of PI3-kinase-dependent C/EBPβ and cyclin E regulation[J]. Archives of Pharmacal Research, 2009, 32 4: 625-635. DOI:10.1007/s12272-009-1419-3
[5] MATTHEW D MERRELL. The Nrf2 activator oltipraz also activates the constitutive androstane receptor.[J]. Drug Metabolism and Disposition, 2008, 36 8: 1716-1721. DOI:10.1124/dmd.108.020867

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