1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide

• ChemBase ID: 690
• Molecular Formular: C8H12N4O5
• Molecular Mass: 244.20468
• Monoisotopic Mass: 244.0807695
• SMILES: O1[C@@H]([C@@H](O)[C@@H](O)[C@@H]1n1nc(nc1)C(=O)N)CO
• Canonical SMILES: OC[C@H]1O[C@H]([C@@H]([C@@H]1O)O)n1cnc(n1)C(=O)N
• InChI: InChI=1S/C8H12N4O5/c9-6(16)7-10-2-12(11-7)8-5(15)4(14)3(1-13)17-8/h2-5,8,13-15H,1H2,(H2,9,16)/t3-,4-,5-,8-/m1/s1
• InChIKey: IWUCXVSUMQZMFG-AFCXAGJDSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide
• IUPAC Traditional name: ribavirin; 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide
• Brand Name: Copegus; RIBAV; RTC; RTCA; RTP; Rebetol; Rebetron; Rebretron; Ribamide; Ribamidil; Ribamidyl; Ribasphere; Ribavirin Capsules; Ribavirin-TP; Tribavirin; Varazid; Vilona; Viramid; Virazid; Virazole; Virazole 5'-triphosphate
• Synonyms: Copegus; Rebetol; Ribasphere; 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1H-1,2,4-triazole-3-carboxamide; 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide; RBV; Ribavirin Triphosphate; Ribavirina [INN-Spanish]; Ribavirine [INN-French]; Ribavirinum [INN-Latin]; Ribavirin; 1-β-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide; Ribavirin; Tribavirin; Ribamidil; Vilona; Viramid; Viratek; Virazid; Virazide; Virazole; VirustazCotronak

Database IDs

• CAS Number: 36791-04-5; 36791-04-5
• MDL Number: MFCD00058564
• PubChem SID: 24278685; 46505883; 160964153
• PubChem CID: 37542

CALCULATED PROPERTIES

JChem

• Acid pKa: 11.878701
• H Acceptors: 7
• H Donor: 4
• LogD (pH = 5.5): -2.7682977
• LogD (pH = 7.4): -2.7683082
• Log P: -2.7682974
• Molar Refractivity: 64.5744 cm^3
• Polarizability: 20.505037 Å^3
• Polar Surface Area: 143.72 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -1.92
• LOG S: -0.87
• Solubility (Water): 3.32e+01 g/l

PROPERTIES

Physical Property

• Solubility: 142 mg/mL (max, at 25°C)
• Melting Point: 165 - 167°C
• Hydrophobicity(logP): -2.348; -2.6

Safety Information

• Storage Condition: -20°C
• Storage Warning: IRRITANT
• RTECS: XZ4250000
• European Hazard Symbols: Toxic (T)
• German water hazard class: 3
• Risk Statements: 61
• Safety Statements: 53-22-45
• TSCA Listed: false
• GHS Pictograms: GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H360
• GHS Precautionary statements: P201-P308 + P313
• Personal Protective Equipment: Eyeshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• Storage Temperature: 2-8°C

Pharmacology Properties

• Gene Information: human ... IMPDH1(3614), IMPDH2(3615)
• Mechanism of Action: Inhibitor of viral RNA guanylyl transferase and (guanine-7N-)-methyl transferase enzymes

Product Information

• Purity: 95%; 95+%; 98%
• Salt Data: Free Base
• Application(s): Antiviral agent; In combination with BDQ70-A , used for the treatment of malignant melanoma, Kaposi's sarcoma, warts, hairy cell leukaemia, hepatits B and C and non-Hodgkin's lymphoma; Usually administered as an aerosol.

DETAILS

DrugBank - DB00811

• Drug Groups: approved
• Description: A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [PubChem]
• Indication: For the treatment of chronic hepatitis C and for respiratory syncytial virus (RSV).
• Pharmacology: Ribavirin is an anti-viral drug active against a number of DNA and RNA viruses. It is a member of the nucleoside antimetabolite drugs that interfere with duplication of the viral genetic material. The drug inhibits the activity of the enzyme RNA dependent RNA polymerase, due to it's resemblence to building blocks of the RNA molecules. The oral form is used in the treatment of hepatitis C, in combination with interferon drugs. The aerosol form is used to treat respiratory syncytial virus-related diseases in children. The primary serious adverse effect of ribavirin is hemolytic anemia, which may worsen preexisting cardiac disease.
• Toxicity: Side effects include "flu-like" symptoms, such as headache, fatigue, myalgia, and fever. The LD₅₀ in mice is 2 g/kg orally and is associated with hypoactivity and gastrointestinal symptoms (estimated human equivalent dose of 0.17 g/kg, based on body surface area conversion).
• Affected Organisms: Hepatitis C virus, RSV and other RNA/DNA viruses
• Biotransformation: Hepatic. Results of in vitro studies using both human and rat liver microsome preparations indicated little or no cytochrome P450 enzyme-mediated metabolism of ribavirin, with minimal potential for P450 enzyme-based drug interactions. Ribavirin has two pathways of metabolism: (1) a reversible phosphorylation pathway in nucleated cells; and (2) a degradative pathway involving deribosylation and amide hydrolysis to yield a triazole carboxylic acid metabolite.
• Absorption: Rapidly and extensively absorbed following oral administration. However, due to first-pass metabolism, the absolute bioavailability averages 64%.
• Half Life: 9.5 hours
• Clearance: * Apparent cl=26 L/h [A single oral dose]
• References: Sidwell RW, Bailey KW, Wong MH, Barnard DL, Smee DF: In vitro and in vivo influenza virus-inhibitory effects of viramidine. Antiviral Res. 2005 Oct;68(1):10-7. [Pubmed] ; Sidwell RW, Huffman JH, Khare GP, Allen LB, Witkowski JT, Robins RK: Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. Science. 1972 Aug 25;177(50):705-6. [Pubmed] ; Alvarez D, Dieterich DT, Brau N, Moorehead L, Ball L, Sulkowski MS: Zidovudine use but not weight-based ribavirin dosing impacts anaemia during HCV treatment in HIV-infected persons. J Viral Hepat. 2006 Oct;13(10):683-9. [Pubmed] ; Bani-Sadr F, Carrat F, Pol S, Hor R, Rosenthal E, Goujard C, Morand P, Lunel-Fabiani F, Salmon-Ceron D, Piroth L, Pialoux G, Bentata M, Cacoub P, Perronne C: Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy. J Acquir Immune Defic Syndr. 2005 Sep 1;40(1):47-52. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S2504

Research Area: Infection
Biological Activity:
Ribavirin (Copegus) is an anti-viral agent indicated for severe RSV infection (individually), hepatitis C infection and other viral infections. In this form ribavirin interferes with RNA metabolism required for viral replication. Ribavirin 5’ mono- di- and tri-phosphates are all inhibitors of certain viral RNA-dependent RNA polymerases which are a feature of anti-sense RNA viruses. Ribavirin 5’-monophosphate inhibits cellular inosine monophosphate dehydrogenase, thereby depleting intracellular pools of GTP. Ribavirin enhances host T-cell-mediated immunity against viral infection through helping to switch the host T-cell phenotype from type 2 to type 1. [1][2]

Sigma Aldrich - R9644

Biochem/physiol Actions
Antiviral agent. Its metabolite, ribavirin 5′-phosphate, is an inhibitor of inosine monophosphate (IMP) dehydrogenase. Used to inhibit purine (GTP pools) biosynthesis at the level of inosine monophosphate (IMP) dehydrogenase and as a precursor to the di- and tri-phosphates which inhibit viral RNA-dependent RNA polymerases.
Antiviral agent used against a wide variety of human viral infections, in particular, chronic hepatitis C, HIV, and adenovirus. Its metabolite, ribavirin 5′-phosphate, is an inhibitor of inosine monophosphate (IMP) dehydrogenase, but many other mechanisms of action are also supported with experimental evidence.1
General description
Analog of the imidazole nucleotide intermediates in purine nucleotide biosynthesis.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. R9644.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

REFERENCES

• Bani-Sadr F, Carrat F, Pol S, Hor R, Rosenthal E, Goujard C, Morand P, Lunel-Fabiani F, Salmon-Ceron D, Piroth L, Pialoux G, Bentata M, Cacoub P, Perronne C: Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy. J Acquir Immune Defic Syndr. 2005 Sep 1;40(1):47-52. Pubmed
• Sidwell RW, Bailey KW, Wong MH, Barnard DL, Smee DF: In vitro and in vivo influenza virus-inhibitory effects of viramidine. Antiviral Res. 2005 Oct;68(1):10-7. Pubmed
• Sidwell RW, Huffman JH, Khare GP, Allen LB, Witkowski JT, Robins RK: Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. Science. 1972 Aug 25;177(50):705-6. Pubmed
• Alvarez D, Dieterich DT, Brau N, Moorehead L, Ball L, Sulkowski MS: Zidovudine use but not weight-based ribavirin dosing impacts anaemia during HCV treatment in HIV-infected persons. J Viral Hepat. 2006 Oct;13(10):683-9. Pubmed
• http://en.wikipedia.org/wiki/Ribavirin
• Kreishman, G.P. et al., J.A.C.S., 1972, 94, 5894, (pmr, cmr)
• Sidwell, R.W. et al., Science (Washington, D.C.), 1972, 177, 705, (pharmacol)
• Witkowski, J.T. et al., J. Med. Chem., 1973, 16, 935, (synth, pharmacol)
• Prusiner, P. et al., Nature (London), New Biol., 1973, 244, 116, (cryst struct)
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• Snell, N.J.C., Antiviral Chem. Chemother., 1991, 2, 257, (rev)
• Arnold, S.D. et al., Appl. Occup. Environ. Hyg., 1991, 6, 271, (tox)
• Shults, R.A. et al., J. Occup. Environ. Med., 1996, 38, 257, (tox)
• Harvie, P. et al., J. Pharmacol. Exp. Ther., 1996, 279, 1009, (pharmacol)
• Omar, R.F. et al., Toxicol. Appl. Pharmacol., 1997, 143, 140, (tox)
• Nishimura, N. et al., Carbohydr. Res., 1998, 307, 211-215, (synth)
• Martindale, The Extra Pharmacopoeia, 32nd edn., Pharmaceutical Press, 1999, 626
• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, RJA500