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Telaprevir

July 24, 2017
Common Name

Telaprevir Description

Telaprevir (VX-950) is a highly selective and potent inhibitor of the HCV NS3-4A serine protease. It is a member of a class of antiviral drugs known as protease inhibitors and is the first hepatitis C drug that has demonstrated activity in patients who have failed prior therapy. On April 28, 2011, the FDA Antiviral Drugs Advisory Committee voted 18-0 to recommend approval telaprevir for people with genotype 1 chronic hepatitis C and was approved in the U.S. in May, 2011. Structure

MOLSDFPDBSMILESInChI

Synonyms

Value Source (1S,3AR,6as)-(2S)-2-cyclohexyl-N-(pyrazinylcarbonyl)glycyl-3-methyl-L-valyl-N-((1S)-1-((cyclopropylamino)oxoacetyl)butyl)octahydrocyclopenta(c)pyrrole-1-carboxamideChEBI IncivekChEBI VX 950ChEBI VX-950ChEBI AIDS-213006HMDB AIDS213006HMDB LY-570310HMDB MP-424HMDB VRT111950HMDB VX950 CPDMeSH

Chemical Formlia

C36H53N7O6 Average Molecliar Weight

679.8493 Monoisotopic Molecliar Weight

679.405732463 IUPAC Name

(3S)-3-{[(1S,3aR,6aS)-2-[(2S)-2-[(2S)-2-cyclohexyl-2-(pyrazin-2-ylformamido)acetamido]-3,3-dimethylbutanoyl]-octahydrocyclopenta[c]pyrrol-1-yl]formamido}-N-cyclopropyl-2-oxohexanamide Traditional Name

incivek CAS Registry Number

402957-28-2 SMILES

[H][C@@]12CCC[C@]1([H])[C@H](N(C2)C(=O)[C@@H](NC(=O)[C@@H](NC(=O)C1=NC=CN=C1)C1CCCCC1)C(C)(C)C)C(=O)N[C@@H](CCC)C(=O)C(=O)NC1CC1

InChI Identifier

InChI=1S/C36H53N7O6/c1-5-10-25(29(44)34(48)39-23-15-16-23)40-33(47)28-24-14-9-13-22(24)20-43(28)35(49)30(36(2,3)4)42-32(46)27(21-11-7-6-8-12-21)41-31(45)26-19-37-17-18-38-26/h17-19,21-25,27-28,30H,5-16,20H2,1-4H3,(H,39,48)(H,40,47)(H,41,45)(H,42,46)/t22-,24-,25-,27-,28-,30+/m0/s1

InChI Key

BBAWEDCPNXPBQM-GDEBMMAJSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as hybrid peptides. These are compounds containing at least two different types of amino acids (alpha, beta, gamma, delta) linked to each other through a peptide bond. Kingdom

Organic compounds Super Class

Organic acids and derivatives Class

Peptidomimetics Sub Class

Hybrid peptides Direct Parent

Hybrid peptides Alternative Parents

  • Valine and derivatives
  • N-acyl-alpha amino acids and derivatives
  • Alpha amino acid amides
  • Pyrazinecarboxamides
  • 2-heteroaryl carboxamides
  • N-acylpyrrolidines
  • Pyrrolidinecarboxamides
  • N-acyl amines
  • Tertiary carboxylic acid amides
  • Heteroaromatic compounds
  • Secondary carboxylic acid amides
  • Ketones
  • Azacyclic compounds
  • Organic oxides
  • Hydrocarbon derivatives
  • Organonitrogen compounds
  • Organopnictogen compounds

    • Substituents

  • Hybrid peptide
  • Valine or derivatives
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • N-substituted-alpha-amino acid
  • Alpha-amino acid or derivatives
  • Pyrazine carboxylic acid or derivatives
  • Pyrazinecarboxamide
  • 2-heteroaryl carboxamide
  • N-acylpyrrolidine
  • Pyrrolidine carboxylic acid or derivatives
  • Pyrrolidine-2-carboxamide
  • Fatty amide
  • N-acyl-amine
  • Fatty acyl
  • Pyrazine
  • Pyrrolidine
  • Tertiary carboxylic acid amide
  • Heteroaromatic compound
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Ketone
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Organopnictogen compound
  • Organic oxide
  • Organic nitrogen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Carbonyl group
  • Organonitrogen compound
  • Organooxygen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • oligopeptide (CHEBI:68595 )
  • pyrazines (CHEBI:68595 )
  • cyclopropanes (CHEBI:68595 )
  • cyclopentapyrrole (CHEBI:68595 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Protease Inhibitors

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility3.55e-02 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.035 mg/mLALOGPS logP2.56ALOGPS logP2.58ChemAxon logS-4.3ALOGPS pKa (Strongest Acidic)11.86ChemAxon pKa (Strongest Basic)-0.69ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count8ChemAxon Hydrogen Donor Count4ChemAxon Polar Surface Area179.56 Å2ChemAxon Rotatable Bond Count14ChemAxon Refractivity180.04 m3·mol-1ChemAxon Polarizability74.37 Å3ChemAxon Number of Rings5ChemAxon Bioavailability0ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB05521

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB05521

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB05521 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    2279948 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Telaprevir NuGOwiki Link

    HMDB15616 Metagene Link

    HMDB15616 METLIN ID

    Not Available PubChem Compound

    3010818 PDB ID

    Not Available ChEBI ID

    494996

    Product: Sulfamerazine (sodium salt)

    References Synthesis Reference Znabet A, Polak MM, Janssen E, de Kanter FJ, Turner NJ, Orru RV, Ruijter E. A highly efficient synthesis of telaprevir by strategic use of biocatalysis and multicomponent reactions. Chem Commun (Camb). 2010 Nov 14;46(42):7918-20. Epub 2010 Sep 20. Material Safety Data Sheet (MSDS) Not Available General References
    1. Kim JJ, Culley CM, Mohammad RA: Telaprevir: an oral protease inhibitor for hepatitis C virus infection. Am J Health Syst Pharm. 2012 Jan 1;69(1):19-33. doi: 10.2146/ajhp110123. [PubMed:22180548 ]
    2. Liu-Young G, Kozal MJ: Hepatitis C protease and polymerase inhibitors in development. AIDS Patient Care STDS. 2008 Jun;22(6):449-57. doi: 10.1089/apc.2007.0199. [PubMed:18479202 ]
    3. Forestier N, Zeuzem S: Telaprevir for the treatment of hepatitis C. Expert Opin Pharmacother. 2012 Mar;13(4):593-606. doi: 10.1517/14656566.2012.660524. Epub 2012 Feb 15. [PubMed:22332992 ]
    4. Garg V, Kauffman RS, Beaumont M, van Heeswijk RP: Telaprevir: pharmacokinetics and drug interactions. Antivir Ther. 2012;17(7):1211-21. doi: 10.3851/IMP2356. Epub 2012 Sep 7. [PubMed:22954756 ]
    5. Authors unspecified: Telaprevir. Drugs R D. 2010;10(3):179-202. doi: 10.2165/11586020-000000000-00000. [PubMed:20945948 ]

    Enzymes

    General function:
    Involved in monooxygenase activity
    Specific function:
    Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    References
    1. Kim JJ, Culley CM, Mohammad RA: Telaprevir: an oral protease inhibitor for hepatitis C virus infection. Am J Health Syst Pharm. 2012 Jan 1;69(1):19-33. doi: 10.2146/ajhp110123. [PubMed:22180548 ]

    PMID: 15837819

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