Posted inUncategorized

Tipranavir

July 24, 2017
Common Name

Tipranavir Description

Tipranavir is only found in individuals that have used or taken this drug. It is a slifonamide-containing dyhydropyrone and a nonpeptidic protease inhibitor that targets the HIV protease. It is administered with ritonavir in combination therapy to treat HIV infections.Tipranavir inhibits the processing of the viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, thus preventing formation of mature virions. Two mechanisms are suggested in regards to the potency of tipranavir: 1. Tipravanir may bind to the active site of the protease enzyme with fewer hydrogen bonds than peptidic protease inhibitors, which reslits in increased flexibility, allowing it to fit into the active site of the enzyme in viruses that have become resistance to other protease inhibitors. This also enables tipranavir to adjust to amino acid substitutions at the active site. 2. Tipranavirs strong hydrogen bonding interaction with the amide backbone of the protease active site Asp30 may lead to its activity against resistant viruses. Structure

MOLSDFPDBSMILESInChI

Synonyms

Value Source TPVHMDB

Chemical Formlia

C31H33F3N2O5S Average Molecliar Weight

602.664 Monoisotopic Molecliar Weight

602.206227481 IUPAC Name

N-{3-[(1R)-1-[(2R)-6-hydroxy-4-oxo-2-(2-phenylethyl)-2-propyl-3,4-dihydro-2H-pyran-5-yl]propyl]phenyl}-5-(trifluoromethyl)pyridine-2-slifonamide Traditional Name

aptivus CAS Registry Number

174484-41-4 SMILES

CCC[C@@]1(CCC2=CC=CC=C2)CC(=O)C([C@H](CC)C2=CC(NS(=O)(=O)C3=NC=C(C=C3)C(F)(F)F)=CC=C2)=C(O)O1

InChI Identifier

InChI=1S/C31H33F3N2O5S/c1-3-16-30(17-15-21-9-6-5-7-10-21)19-26(37)28(29(38)41-30)25(4-2)22-11-8-12-24(18-22)36-42(39,40)27-14-13-23(20-35-27)31(32,33)34/h5-14,18,20,25,36,38H,3-4,15-17,19H2,1-2H3/t25-,30-/m1/s1

InChI Key

NZPXPXAGXYTROM-FYBSXPHGSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as linear diarylheptanoids. These are diarylheptanoids with an open heptane chain. The two aromatic rings are linked only by the heptane chain. Kingdom

Chemical entities Super Class

Organic compounds Class

Phenylpropanoids and polyketides Sub Class

Diarylheptanoids Direct Parent

Linear diarylheptanoids Alternative Parents

  • Slifanilides
  • Pyridineslifonamides
  • Phenylpropanes
  • Dihydropyranones
  • Organoslifonamides
  • Vinylogous esters
  • Vinylogous acids
  • Aminoslifonyl compounds
  • Heteroaromatic compounds
  • Cyclic ketones
  • Ketene acetals
  • Oxacyclic compounds
  • Azacyclic compounds
  • Organofluorides
  • Organonitrogen compounds
  • Organopnictogen compounds
  • Alkyl fluorides
  • Hydrocarbon derivatives
  • Organic oxides

    • Substituents

  • Linear 1,7-diphenylheptane skeleton
  • Slifanilide
  • Pyridine-2-slifonamide
  • Phenylpropane
  • Dihydropyranone
  • Monocyclic benzene moiety
  • Organoslifonic acid amide
  • Benzenoid
  • Pyridine
  • Organic slifonic acid or derivatives
  • Organoslifonic acid or derivatives
  • Slifonyl
  • Vinylogous ester
  • Vinylogous acid
  • Heteroaromatic compound
  • Aminoslifonyl compound
  • Ketene acetal or derivatives
  • Ketone
  • Cyclic ketone
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Organoslifur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Alkyl fluoride
  • Alkyl halide
  • Aromatic heteromonocyclic compound

    • Molecliar Framework

    Aromatic heteromonocyclic compounds External Descriptors

    Not Available Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-HIV Agents
  • HIV Protease Inhibitors

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility2.07e-04 g/LNot Available LogP6.9Not Available

    Predicted Properties

    Property Value Source Water Solubility0.000207 mg/mLALOGPS logP5.71ALOGPS logP7.81ChemAxon logS-6.5ALOGPS pKa (Strongest Acidic)5.96ChemAxon pKa (Strongest Basic)-3.3ChemAxon Physiological Charge-1ChemAxon Hydrogen Acceptor Count6ChemAxon Hydrogen Donor Count2ChemAxon Polar Surface Area105.59 Å2ChemAxon Rotatable Bond Count11ChemAxon Refractivity163.56 m3·mol-1ChemAxon Polarizability61.31 Å3ChemAxon Number of Rings4ChemAxon Bioavailability0ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Not Available Biological Properties Cellliar Locations

  • Cytoplasm
  • 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 DB00932

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00932

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB00932 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

    58539 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Tipranavir NuGOwiki Link

    HMDB15067 Metagene Link

    HMDB15067 METLIN ID

    Not Available PubChem Compound

    Not Available PDB ID

    Not Available ChEBI ID

    404696

    Product: 3,3,6-Triiodo-L-thyronine (sodium)

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Temesgen Z, Feinberg J: Tipranavir: a new option for the treatment of drug-resistant HIV infection. Clin Infect Dis. 2007 Sep 15;45(6):761-9. Epub 2007 Aug 7. [PubMed:17712762 ]
    2. Luna B, Townsend MU: Tipranavir: the first nonpeptidic protease inhibitor for the treatment of protease resistance. Clin Ther. 2007 Nov;29(11):2309-18. [PubMed:18158073 ]
    3. Doyon L, Tremblay S, Bourgon L, Wardrop E, Cordingley MG: Selection and characterization of HIV-1 showing reduced susceptibility to the non-peptidic protease inhibitor tipranavir. Antiviral Res. 2005 Oct;68(1):27-35. [PubMed:16122817 ]
    4. Authors unspecified: Tipranavir: PNU 140690, tipranivir. Drugs R D. 2006;7(1):55-62. [PubMed:16620137 ]

    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. Temesgen Z, Feinberg J: Tipranavir: a new option for the treatment of drug-resistant HIV infection. Clin Infect Dis. 2007 Sep 15;45(6):761-9. Epub 2007 Aug 7. [PubMed:17712762 ]
    2. Luna B, Townsend MU: Tipranavir: the first nonpeptidic protease inhibitor for the treatment of protease resistance. Clin Ther. 2007 Nov;29(11):2309-18. [PubMed:18158073 ]
    3. Li F, Wang L, Guo GL, Ma X: Metabolism-mediated drug interactions associated with ritonavir-boosted tipranavir in mice. Drug Metab Dispos. 2010 May;38(5):871-8. doi: 10.1124/dmd.109.030817. Epub 2010 Jan 26. [PubMed:20103582 ]
    4. Dumond JB, Vourvahis M, Rezk NL, Patterson KB, Tien HC, White N, Jennings SH, Choi SO, Li J, Wagner MJ, La-Beck NM, Drulak M, Sabo JP, Castles MA, Macgregor TR, Kashuba AD: A phenotype-genotype approach to predicting CYP450 and P-glycoprotein drug interactions with the mixed inhibitor/inducer tipranavir/ritonavir. Clin Pharmacol Ther. 2010 Jun;87(6):735-42. doi: 10.1038/clpt.2009.253. Epub 2010 Feb 10. [PubMed:20147896 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
    Gene Name:
    CYP2C19
    Uniprot ID:
    P33261
    Molecular weight:
    55944.565
    References
    1. Li F, Wang L, Guo GL, Ma X: Metabolism-mediated drug interactions associated with ritonavir-boosted tipranavir in mice. Drug Metab Dispos. 2010 May;38(5):871-8. doi: 10.1124/dmd.109.030817. Epub 2010 Jan 26. [PubMed:20103582 ]
    2. Dumond JB, Vourvahis M, Rezk NL, Patterson KB, Tien HC, White N, Jennings SH, Choi SO, Li J, Wagner MJ, La-Beck NM, Drulak M, Sabo JP, Castles MA, Macgregor TR, Kashuba AD: A phenotype-genotype approach to predicting CYP450 and P-glycoprotein drug interactions with the mixed inhibitor/inducer tipranavir/ritonavir. Clin Pharmacol Ther. 2010 Jun;87(6):735-42. doi: 10.1038/clpt.2009.253. Epub 2010 Feb 10. [PubMed:20147896 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
    Gene Name:
    CYP2D6
    Uniprot ID:
    P10635
    Molecular weight:
    55768.94
    References
    1. Li F, Wang L, Guo GL, Ma X: Metabolism-mediated drug interactions associated with ritonavir-boosted tipranavir in mice. Drug Metab Dispos. 2010 May;38(5):871-8. doi: 10.1124/dmd.109.030817. Epub 2010 Jan 26. [PubMed:20103582 ]
    2. Dumond JB, Vourvahis M, Rezk NL, Patterson KB, Tien HC, White N, Jennings SH, Choi SO, Li J, Wagner MJ, La-Beck NM, Drulak M, Sabo JP, Castles MA, Macgregor TR, Kashuba AD: A phenotype-genotype approach to predicting CYP450 and P-glycoprotein drug interactions with the mixed inhibitor/inducer tipranavir/ritonavir. Clin Pharmacol Ther. 2010 Jun;87(6):735-42. doi: 10.1038/clpt.2009.253. Epub 2010 Feb 10. [PubMed:20147896 ]

    PMID: 20075161

    Last updated on