Ribavirin

Base Information

• Chemical Name: Ribavirin
• CAS No.: 36791-04-5
• Deprecated CAS: 66510-90-5,437710-49-1
• Molecular Formula: C8H12N4O5
• Molecular Weight: 244.207
• Hs Code.: 29349990
• European Community (EC) Number: 636-825-3
• NSC Number: 758650
• UNII: 49717AWG6K
• DSSTox Substance ID: DTXSID8023557
• Nikkaji Number: J17.798I
• Wikipedia: Ribavirin
• Wikidata: Q421862
• NCI Thesaurus Code: C807
• RXCUI: 9344
• Pharos Ligand ID: AX352DDRMJ3A
• Metabolomics Workbench ID: 43102
• ChEMBL ID: CHEMBL1643
• Mol file: 36791-04-5.mol

Synonyms:ICN 1229;ICN-1229;ICN1229;Rebetol;Ribamide;Ribamidil;Ribamidyl;Ribasphere;Ribavirin;Ribovirin;Tribavirin;Vilona;Viramide;Virazide;Virazole

Chemical Property of Ribavirin

Chemical Property:

• Appearance/Colour: Colourless solid
• Vapor Pressure: 3.03E-17mmHg at 25°C
• Melting Point: 174-176 °C
• Refractive Index: -36 ° (C=1, H2O)
• Boiling Point: 639.782 °C at 760 mmHg
• PKA: 12.95±0.70(Predicted)
• Flash Point: 340.728 °C
• PSA: 143.72000
• Density: 2.086 g/cm³
• LogP: -2.31120
• Storage Temp.: 2-8°C
• Solubility.: Freely soluble in water, slightly soluble in ethanol (96 per cent), slightly soluble or very slightly soluble in methylene chloride. It shows polymorphism (5.9).
• Water Solubility.: >=10 g/100 mL at 19 ºC
• XLogP3: -1.8
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 3
• Exact Mass: 244.08076950
• Heavy Atom Count: 17
• Complexity: 304

Purity/Quality:

99% ^*data from raw suppliers

Ribavirin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T, Xi
• Hazard Codes: T,Xi
• Statements: 61-36/38
• Safety Statements: 53-22-45-37/39-26

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antiviral Agents
• Canonical SMILES: C1=NC(=NN1C2C(C(C(O2)CO)O)O)C(=O)N
• Isomeric SMILES: C1=NC(=NN1[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O)C(=O)N
• Recent ClinicalTrials: Sofosbuvir, Daclatasvir, Ribavirin for Hepatitis C Virus (HCV) Cirrhotics
• Recent EU Clinical Trials: A Pilot study platform to investigate the pharmacodynamics on QT‐prolongation and pharmacokinetics after multiple dose administration of potential combination treatments for COVID-19 in healthy volunteers
• Recent NIPH Clinical Trials: Efficacy and safety of Glecaprevir/Pibrentasvir plus Ribavirin in Patients who failed Direct-acting antivirals; DAAs with chronic hepatitis C
• Uses: It is a kind of broad-spectrum antiviral drugs for treating influenza (influenza A and B viruses), adenovirus pneumonia, hepatitis, herpes, measles with prevention and treatment effect; it is also effective on treating the epidemic hemorrhagic fever, particularly effective treatment of patients in their early stages. Oral administration can cause diarrhea without other significant toxicity but may cause neutropenia. Large dose can inhibit the maturation of hemoglobin and red blood cells, causing reversible anemia. There have been reports regarding to the teratogenicity and embryo toxicity in animal experiments. Pregnant women should be hanged. Ribavirin is a broad-spectrum antiviral nucleoside drug used for treating influenza, adenovirus pneumonia of children, viral hepatitis, respiratory syncytial virus infection, acute keratitis, conjunctivitis, epidemic hemorrhagic fever and herpes zoster. Purine nucleoside analog; inhibits inosine monophosphate dehydrogenase (IMPDH). Used as an antiviral agent. aldosterone antagonist; antifibrogenic anti-infective, anti-fungal A broad spectrum antiviral nucleoside and inhibitor of inosine monophosphate dehydrogenase. Ribavirin is a guanosine analog with antiviral properties against DNA and RNA viruses, including respiratory syncytial virus, hepatitis C, and influenza. It acts as a prodrug that can be activated by either mono- or tri-phosphorylation by cellular kinases. These phosphorylated derivatives of ribavirin have diverse effects on both cellular and viral enzymes, resulting in suppression of viral replication.
• Production method: Take nucleotide or nucleoside as the starting material First hydrolyze the guanosine and guanylate upon the action of glacial acetic acid and acetic anhydride to generate ribose-1-phosphate, which is then subject to the catalysis of double-para-nitro phenol to have reaction with triazide amide to generate condensate with aminolysis to obtain the product. Guanosine (or guanylate) [acetic anhydride, glacial acetic acid]→[hydrolysis] ribose-1-phosphate [bis-(p-nitrophenol)-phosphate]→[triazide carboxamide] condensates [aminolysis]→Ribavirin Enzymatic synthesis First hydrolyze the guanosine and guanosine acid under the action of pyrimidine nucleoside phosphorylase to form ribose-1-phosphate which then, under the action of purine nucleoside phosphorylase, has reaction with triazide amide to directly generate triazole nucleosides. Guanosine (or guanylate) [pyrimidine nucleoside phosphorylase] → ribose-1 nucleic acid [purine nucleotide cyclase] → Ribavirin.
• Description: Ribavirin is a clinically useful antiviral medication for Hepatitis C, viral hemorrhagic fevers and other RNA and DNA viruses. The exact mechanism of its antiviral activity is uncertain. Various proposals include inhibition of viral polymerase1, RNA mutagenesis2, and inosine monophosphate dehydrogenase (IMPDH) inhibition3. Sensitizes tumor cells to anticancer agents 5-fluorouracil5 and doxorubicin6 via inhibition of eIF4E. Displays efficacy against atypical teratoid/rhabdoid tumors7 and inhibits glioma cell growth8.
• Indications: Ribavirin is a synthetic guanosine analogue that possesses broad antiviral inhibitory activity against many viruses, including influenza A and B, parainfluenza,RSV, HCV, HIV-1, and various herpesviruses, arenaviruses, and paramyxoviruses. Its exact mechanism of action has not been fully elucidated; however, it appears to inhibit the synthesis of viral mRNA through an effect on nucleotide pools. Following absorption, host cell enzymes convert ribavirin to its monophosphate, diphosphate, and triphosphate forms. Ribavirin monophosphate inhibits the guanosine triphosphate (GTP) synthesis pathway and subsequently inhibits many GTP-dependent processes. Ribavirin triphosphate inhibits the 5 capping of viral mRNA with GTP and specifically inhibits influenza virus RNA polymerase. Ribavirin may also act by increasing the mutation rate of RNA viruses, leading to the production of nonviable progeny virions. Ribavirin resistance has not been documented in clinical isolates.
• Clinical Use: RSV infections in infants (by nebulizer) in emergency situations (i.e. transplant recipients) Lassa fever Hepatitis C (in combination with interferon-α) Use in RSV pneumonia in infants is no longer routine. It reduces mortality from Hantaan virus, the agent responsible for hemorrhagic fever with renal syndrome. Ribavirin aerosol (Virazole) is indicated in the treatment of high-risk infants and young children with severe bronchiolitis or pneumonia due to RSV infection. Treatment is most effective if begun within 3 days of the onset of symptoms. Although ribavirin monotherapy is ineffective against HCV, oral ribavirin in combination with interferon-α (Rebatron) is approved for this indication and is effective in patients resistant to interferon therapy alone. Intravenous ribavirin may be useful in the therapy of Hantaan virus infection, Crimean or Congo virus hemorrhagic fever, Lassa fever, and severe adenovirus infection.
• Drug interactions: Potentially hazardous interactions with other drugs Antivirals: effects possibly reduced by abacavir; increased risk of toxicity with stavudine; increased side effects with didanosine - avoid; increased risk of anaemia with zidovudine - avoid. Azathioprine: possibly enhances myelosuppressive effects of azathioprine.

Technology Process of Ribavirin

There total 54 articles about Ribavirin 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: 99.71%

1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester (57198-04-6,39925-10-5) → ribavirin (36791-04-5,66510-90-5)

Guidance literature:

With ammonia; at 20 ℃; for 20h; under 5250.53 Torr; Temperature; Pressure; Autoclave; Green chemistry;

Reference yield: 95.0%

methyl 1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxylate (38934-69-9) → ribavirin (36791-04-5,66510-90-5)

Guidance literature:

With sodium methylate; diethylamine; In methanol; at 80 ℃; for 6h; Solvent;

Reference yield: 91.3%

methyl 1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxylate (39925-12-7) → ribavirin (36791-04-5,66510-90-5)

Guidance literature:

With ammonia; In methanol; overnight;

upstream raw materials:

7-methylinosine

1,2,4-triazole-3-carboxamide

7-methylguanosine

(1-β-D-erythrofuranosyl)orotic acid

Downstream raw materials:

5'-O-(4-methoxytrityl)ribavirin

ribavirin benzoate

1-(2',3'-di-O-isopropylidene-β-D-ribofuranosyl)<1,2,4>triazole-3-carboxamide

2',3',5'-Tri-O-acetyl-1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide

Refernces

• 1、 Shirae,Yokozeki,Uchiyama,Kubota. "Enzymatic production of ribavirin from purine nucleosides by Brevibacterium acetylicum ATCC 954". . p. 1777 - 1783. Retrieved 1988.
• 2、 Shirae,Yokozeki,Kubota. "Enzymatic production of ribavirin from pyrimidine nucleosides by Enterobacter aerogenes AJ 11125". . p. 1233 - 1237. Retrieved 1988.
• 3、 Wu, Jim Zhen,Walker, Heli,Lau, Johnson Y. N.,Hong, Zhi. "Activation and deactivation of a broad-spectrum antiviral drug by a single enzyme: Adenosine deaminase catalyzes two consecutive deamination reactions". . p. 426 - 431. Retrieved 2003.
• 4、 -. "Method for preparing ribavirin by one-pot method". Paragraph 0044-0057. . Retrieved 2020/09/20.
• 5、 -. "A 1/10 water ribavirin compounds and pharmaceutical compositions thereof (by machine translation)". Paragraph 0052; 0059; 0060. . Retrieved 2019/01/23.