Disulfiram

Base Information

• Chemical Name: Disulfiram
• CAS No.: 97-77-8
• Deprecated CAS: 11078-22-1,155-01-1
• Molecular Formula: C10H20N2S4
• Molecular Weight: 296.546
• Hs Code.: 29303000
• European Community (EC) Number: 202-607-8
• ICSC Number: 1438
• NSC Number: 756748,25953
• UNII: TR3MLJ1UAI
• DSSTox Substance ID: DTXSID1021322
• Nikkaji Number: J3.980B
• Wikipedia: Disulfiram
• Wikidata: Q409665
• NCI Thesaurus Code: C447
• RXCUI: 3554
• Pharos Ligand ID: MHVHBJPNP3G7
• Metabolomics Workbench ID: 43112
• ChEMBL ID: CHEMBL964
• Mol file: 97-77-8.mol

Synonyms:Alcophobin;Antabus;Antabuse;Anticol;Bis(diethylthiocarbamoyl) Disulfide;Dicupral;Disulfide, Tetraethylthiuram;Disulfiram;Esperal;Tetraethylthioperoxydicarbonic Diamide, ((H2N)C(S))2S2;Tetraethylthiuram Disulfide;Teturam

Chemical Property of Disulfiram

Chemical Property:

• Appearance/Colour: yellow-white crystals or grey powder
• Vapor Pressure: 0Pa at 25℃
• Melting Point: 69-71 °C(lit.)
• Refractive Index: 1.51
• Boiling Point: 369.023 °C at 760 mmHg
• PKA: 0.86±0.50(Predicted)
• Flash Point: 176.979 °C
• PSA: 121.26000
• Density: 1.205 g/cm³
• LogP: 3.62120
• Storage Temp.: Store at +4°C
• Solubility.: 0.004g/l
• Water Solubility.: 0.02 g/100 mL
• XLogP3: 3.9
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 7
• Exact Mass: 296.05093334
• Heavy Atom Count: 16
• Complexity: 201

Purity/Quality:

Disulfiram ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,N
• Hazard Codes: Xn,N
• Statements: 22-43-48/22-50/53
• Safety Statements: 24-37-60-61

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Chemical Classes: Pesticides -> Dithiocarbamates (Pesticide)
• Drug Classes: Substance Abuse Treatment Agents
• Canonical SMILES: CCN(CC)C(=S)SSC(=S)N(CC)CC
• Recent ClinicalTrials: DISulfiram for COvid-19 (DISCO) Trial
• Recent EU Clinical Trials: Phase II study of Vinorelbine, cisplatin, disulfiram and copper in CTC_EMT positive refractory metastatic breast cancer.
• Recent NIPH Clinical Trials: Phase 1 study of Disulfiram and Nivolumab for gastric cancer
• Inhalation Risk: Evaporation at 20 °C is negligible; a harmful concentration of airborne particles can, however, be reached quickly when dispersed, especially if powdered.
• Effects of Long Term Exposure: Repeated or prolonged contact may cause skin sensitization. The substance may have effects on the endocrine system, liver, nervous system and thyroid. This may result in impaired functions. Animal tests show that this substance possibly causes toxicity to human reproduction or development.
• Uses: Disulfiram , is a sulfur- and nitrogen-containing compound with several industrial uses, including applications as a rubber accelerator and vulcanizer, fungicide, and seed disinfectant. It is most commonly known as antabuse, a therapeutic agent for the treatment of alcohol abuse that causes nausea, vomiting, and other adverse effects when ethanol is ingested. Disulfiram is an inhibitor of aldehyde dehydrogenase so that it allows for buildup of the acetaldehyde metabolite of ethanol, causing unpleasant effects that are a deterrent to the ingestion of alcohol. Because of the buildup of acetaldehyde, disulfiram should be given with extreme caution, especially to individuals suffering from liver cirrhosis. It is used as rubber accelerator; vulcanizer; seed disinfectant; fungicide; alcohol deterrent. Alcohol deterrent;Dopamine beta-hydroxylase inhibitor;For the treatment and management of chronic alcoholism. Disulfiram is a copper and zinc chelator and an irreversible inhibitor of aldehyde dehydrogenase (IC50 = 0.1 mM) that has been indicated for the treatment of alcohol dependence. It also inhibits the copper-dependent enzyme dopamine β-hydroxylase, which prevents the breakdown of dopamine and has been considered as a treatment for cocaine dependence. When in complex with copper, disulfiram has been shown to inhibit purified 20S proteasome (IC50 = 7.5 μM) and 26S proteasome (IC50 = 20 μM) from MDA-MB-0231 breast cancer cells. Because disulfiram targets the ubiquitin-proteasome pathway, it has been investigated as an anti-cancer agent. Furthermore, at 250 nM it has been shown to induce reactive oxygen species, to activate JNK and p38 pathways, and to inhibit NF-κB activity, which suppresses self-renewal in cancer stem cells.
• Indications: Disulfiram is used as a second line treatment of alcohol dependence, behind acamprosate and naltrexone[8]. It is an aid for the management of selected chronic alcohol patients who want to remain in a state of enforced sobriety so that supportive and psychotherapeutic treatment may be applied to best advantage. However, it should be noted that disulfiram is not a cure for alcoholism. When used alone, without proper motivation and supportive therapy, it is unlikely that it will have any substantive effect on the drinking pattern of the chronic alcoholic dependence[5]. Disulfiram should not be taken if alcohol has been consumed in the last 12 hours[9]. Recently, more and more studies have shown that disulfiram has the potential for the treatment of cancer[12, 13] and HIV infections[10, 11]. Disulfiram (DSF) can reactivate latent HIV-1 expression in a primary cell model of virus latency and has the potential to deplete the latent HIV-1 reservoir in patients on combination antiretroviral therapy. DSF can reactivate latent HIV-1 expression via the Akt signaling pathway through depletion of PTEN[10]. Recent studies have disclosed a surprising, but mechanistically consistent, anticancer activity of disulfiram. Disulfiram has been successfully used to suppress hepatic metastases originating from ocular melanoma[12]. The anticancer mechanism of disulfiram is through inhibiting the 26S proteasome (The orderly degradation of cellular proteins is critical for normal cell cycling and function, and inhibition of the proteasome pathway results in cell-cycle arrest and apoptosis)[12-14]. Moreover, disulfiram was also found to have specific activity against zinc fingers and RING-finger ubiquitin E3 ligases that play an important role in cancer development[12, 13].
• Description: Disulfiram was first synthesized in the 1800s to improve the manufacturing process of rubber. A physician working in a rubber factory plant first observed in 1937 that factory workers who were exposed to disulfiram were intolerant to ethanol. In the 1940s, two scientists rediscovered the disulfiram– ethanol effects while researching antiparasitic therapies. This finding eventually led to the approval of the medication to be used as an ethanol deterrent by the Food and Drug Administration in 1951.
• Therapeutic Function: Alcohol deterrent
• Clinical Use: Adjunct in the treatment of chronic alcohol dependence
• Drug interactions: Potentially hazardous interactions with other drugsAlcohol: risk of severe disulfiram reaction.Anticoagulants: enhanced anticoagulant effect with coumarins.Antiepileptics: inhibition of metabolism of fosphenytoin and phenytoin (increased risk of toxicity).Paraldehyde: increased risk of toxicity with paraldehyde.

Technology Process of Disulfiram

There total 43 articles about Disulfiram which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.8%

Diethyldithiocarbamic acid (147-84-2) → disulfiram (97-77-8)

Guidance literature:

With oxygen; In ethanol; at 20 - 30 ℃; for 0.1h; under 3000.3 Torr; Time; Flow reactor;

Reference yield: 99.0%

diethylamine (109-89-7) → disulfiram (97-77-8)

Guidance literature:

With triphenyl antimony oxide; In acetonitrile; for 24h; Ambient temperature;

DOI:10.1246/cl.1985.579

Reference yield: 98.99%

carbon disulfide (75-15-0,12122-00-8) + diethylamine (109-89-7) → disulfiram (97-77-8)

Guidance literature:

With oxygen; In isopropyl alcohol; at 50 ℃; for 1.5h; under 1275.13 Torr; Autoclave;

DOI:10.1080/00397910903537331

upstream raw materials:

carbon disulfide

N,N,N',N'-tetraethylthioamine

sodium N,N-diethyldithiocarbamate

sodium diethyldithiocarbamate trihydrate

Downstream raw materials:

carbon disulfide

diethylamino-thioxo-methanesulfenyl chloride

diethylammonium diethyldithiocarbamate

N,N-diethylthiocarbamoyl chloride

Refernces

• 1、 Tikhomirova,Peledina,Maizlish,Vashurin,Shaposhnikov. "Synthesis and Properties of Tetra-4-{[(1,1'-biphenyl)-4-yl]oxy}phthalocyanines and Their Sulfonic Acid Derivatives". . p. 742 - 750. Retrieved 2018.
• 2、 Vashurin,Kuzmin,Litova,Petrov,Pukhovskaya,Golubchikov. "Catalytic properties of cobalt complexes with tetrapyrazino porphyrazine and phthalocyanine derivatives". . p. 2064 - 2067. Retrieved 2014.
• 3、 Vashurin. "Non-covalent associates of metal phthalocyanines: the role of axial ligand and catalytic activity". . p. 2220 - 2228. Retrieved 2016.
• 4、 Vashurin,Badaukaite,Futerman,Pukhovskaya,Shaposhnikov,Golubchikov. "Catalytic properties of polymer matrix-immobilized cobalt complexes with sulfonated phthalocyanines". . p. 197 - 200. Retrieved 2013.
• 5、 Ansari, Mohammad A.,Chandrasekaran, Jayanthi,Sarkar, Sabyasachi. "One Pot Synthesis of Dinuclear Tungsten(V) Compounds Containing 2+ (X = O, S; Y = O, S) Cores by Thermally Induced Internal Electron-Transfer Processes". . p. 2265 - 2267. Retrieved 1988.
• 6、 Zheng, Siyuan,Wang, Kai,Luo, Guangsheng. "Microfluidic electrosynthesis of thiuram disulfides". supporting information. p. 582 - 591. Retrieved 2021/01/28.
• 7、 Xu, Hao-Xing,Zhao, Ze-Run,Patehebieke, Yeersen,Chen, Qian-Qian,Fu, Shun-Guo,Chang, Shuai-Jun,Zhang, Xu-Xu,Zhang, Zhi-Liang,Wang, Xiao. "Continuous-flow step-economical synthesis of thiuram disulfidesviavisible-light photocatalytic aerobic oxidation". supporting information. p. 1280 - 1285. Retrieved 2021/02/26.