CAS 36791-04-5|CAS 36791-04-5|ribavirin|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...

General Information

Structure

Molecular Formula

C₈H₁₂N₄O₅

Molecular Mass

244.20468

Exact Mass

244.0807695

Charge

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

Canonic Smiles

OC[C@H]1O[C@H]([C@@H]([C@@H]1O)O)n1cnc(n1)C(=O)N

Isomeric Smiles

O1[C@@H]([C@@H](O)[C@@H](O)[C@@H]1n1nc(nc1)C(=O)N)CO

Calculated Properties

JChem

LogD (pH = 7.4)

-2.77

LogD (pH = 5.5)

-2.77

Log P

-2.77

Rotatable Bonds

H Donor

H Acceptors

Lipinski's Rule of Five

true

Acid pKa

11.88

Polar Surface Area

143.72

Polarizability

22.09

Molar Refractivity

64.57

LOG S

0.29

Data Source

Names and Identifiers

IUPAC Traditional name

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

Synonyms

1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1H-1,2,4-triazole-3-carboxamideRibavirin1-β-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide CopegusRibasphereRebetolRibavirinRBVRibavirine [INN-French]Ribavirin Triphosphate1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamideRibavirinum [INN-Latin]Ribavirina [INN-Spanish]ViramidTribavirinVirustazCotronakViratekRibamidilVirazidVirazoleVilonaVirazideribavirinRBV1-beta-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide

IUPAC name

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

Brand Name

RTPRibamidilVirazoleVarazidRibamidylVirazole 5'-triphosphateTribavirinRebetronVirazidRibamideCopegusRTCAViramidRebretronRibavirin-TPVilonaRebetolRibasphereRIBAVRTCRibavirin Capsules

API Name

Ribavirin

International Nonproprietary Name (INN)

ribavirineribavirinumribavirinribavirina

Names and Identifiers

Registration numbers

Properties

Physical Property

Hydrophobicity(logP)

-2.6

-2.348

Solubility

142 mg/mL (max, at 25°C)

Melting Point

165 - 167°C

Product Information

Purity

95+%

95%

98%

Salt Data

Free Base

Application(s)

Antiviral agent

Usually administered as an aerosol.

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

Pharmacology Properties

Gene Information

human ... IMPDH1(3614), IMPDH2(3615)

Mechanism of Action

Inhibitor of viral RNA guanylyl transferase and (guanine-7N-)-methyl transferase enzymes

Properties

Related Proteins

Molecular Spectra

No Data Available

Click here to submit data

Molecule 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.

ChEBI

CHEBI:63580

A 1-ribosyltriazole that is the 1-ribofuranosyl derivative of 1,2,4-triazole-3-carboxamide. A synthetic guanosine analogue, it is an inhibitor of HCV polymerase and possesses a broad spectrum of activity against DNA and RNA viruses.

Molecule Details

References

PubChem Literature

From Data Sources

• 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

• http://en.wikipedia.org/wiki/Ribavirin

• Witkowski, J.T. et al., J. Med. Chem., 1973, 16, 935, (synth, pharmacol)

• Martindale, The Extra Pharmacopoeia, 32nd edn., Pharmaceutical Press, 1999, 626

• Prusiner, P. et al., Nature (London), New Biol., 1973, 244, 116, (cryst struct)

• Johnson, E.M., J. Am. Coll. Toxicol., 1990, 9, 551, (tox, rev)

• Patterson, J.L. et al., Rev. Infect. Dis., 1990, 6, 1139, (rev)

• Ito, Y. et al., Tet. Lett., 1979, 2521, (synth)

• Nishimura, N. et al., Carbohydr. Res., 1998, 307, 211-215, (synth)

• Snell, N.J.C., Antiviral Chem. Chemother., 1991, 2, 257, (rev)

• Canonica, P.G., Antiviral Res., 1985, 75, (rev)

• Harvie, P. et al., J. Pharmacol. Exp. Ther., 1996, 279, 1009, (pharmacol)

• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, RJA500

• Arnold, S.D. et al., Appl. Occup. Environ. Hyg., 1991, 6, 271, (tox)

• Sidwell, R.W. et al., Science (Washington, D.C.), 1972, 177, 705, (pharmacol)

• Omar, R.F. et al., Toxicol. Appl. Pharmacol., 1997, 143, 140, (tox)

• Kreishman, G.P. et al., J.A.C.S., 1972, 94, 5894, (pmr, cmr)

• Canonica, P.G., Antibiotics (N.Y.), 1983, 6, 161, (rev)

• Chang, T.W. et al., Drugs, 1981, 22, 111, (rev, pharmacol)

• Shults, R.A. et al., J. Occup. Environ. Med., 1996, 38, 257, (tox)

• Smith, R.A. et al., Int. Congr. Symp. Ser. R. Soc. Med., 1986, 108, 3

References

Bioactivity

PubChem BioAssay

Bioactivity

Names and Identifiers

IUPAC Traditional name

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

Synonyms

IUPAC name

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

Brand Name

RTPRibamidilVirazoleVarazidRibamidylVirazole 5'-triphosphateTribavirinRebetronVirazidRibamideCopegusRTCAViramidRebretronRibavirin-TPVilonaRebetolRibasphereRIBAVRTCRibavirin Capsules

API Name

Ribavirin

International Nonproprietary Name (INN)

ribavirineribavirinumribavirinribavirina

Properties

Physical Property

Hydrophobicity(logP)

-2.6

-2.348

Solubility

142 mg/mL (max, at 25°C)

Melting Point

165 - 167°C

Product Information

Purity

95+%

95%

98%

Salt Data

Free Base

Application(s)

Antiviral agent

Usually administered as an aerosol.

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

Pharmacology Properties

Gene Information

human ... IMPDH1(3614), IMPDH2(3615)

Mechanism of Action

Inhibitor of viral RNA guanylyl transferase and (guanine-7N-)-methyl transferase enzymes

Molecule 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

Toxicity

Affected Organisms

Hepatitis C virus, RSV and other RNA/DNA viruses

Biotransformation

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]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

S2504

R9644

References

PubChem Literature

From Data Sources

• 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

• http://en.wikipedia.org/wiki/Ribavirin

• Witkowski, J.T. et al., J. Med. Chem., 1973, 16, 935, (synth, pharmacol)

• Martindale, The Extra Pharmacopoeia, 32nd edn., Pharmaceutical Press, 1999, 626

• Prusiner, P. et al., Nature (London), New Biol., 1973, 244, 116, (cryst struct)

• Johnson, E.M., J. Am. Coll. Toxicol., 1990, 9, 551, (tox, rev)

• Patterson, J.L. et al., Rev. Infect. Dis., 1990, 6, 1139, (rev)

• Ito, Y. et al., Tet. Lett., 1979, 2521, (synth)

• Nishimura, N. et al., Carbohydr. Res., 1998, 307, 211-215, (synth)

• Snell, N.J.C., Antiviral Chem. Chemother., 1991, 2, 257, (rev)

• Canonica, P.G., Antiviral Res., 1985, 75, (rev)

• Harvie, P. et al., J. Pharmacol. Exp. Ther., 1996, 279, 1009, (pharmacol)

• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, RJA500

• Arnold, S.D. et al., Appl. Occup. Environ. Hyg., 1991, 6, 271, (tox)

• Sidwell, R.W. et al., Science (Washington, D.C.), 1972, 177, 705, (pharmacol)

• Omar, R.F. et al., Toxicol. Appl. Pharmacol., 1997, 143, 140, (tox)

• Kreishman, G.P. et al., J.A.C.S., 1972, 94, 5894, (pmr, cmr)

• Canonica, P.G., Antibiotics (N.Y.), 1983, 6, 161, (rev)

• Chang, T.W. et al., Drugs, 1981, 22, 111, (rev, pharmacol)

• Shults, R.A. et al., J. Occup. Environ. Med., 1996, 38, 257, (tox)

• Smith, R.A. et al., Int. Congr. Symp. Ser. R. Soc. Med., 1986, 108, 3

Bioactivity

PubChem BioAssay

Molecule

ID:690