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Atazanavir

July 24, 2017
Common Name

Atazanavir Description

Atazanavir (formerly known as BMS-232632) is an antiretroviral drug of the protease inhibitor (PI) class. Like other antiretrovirals, it is used to treat infection of human immunodeficiency virus (HIV). Atazanavir is distinguished from other PIs in that it can be given once-daily (rather than requiring mlitiple doses per day) and has lesser effects on the patients lipid profile (the amounts of cholesterol and other fatty substances in the blood). Like other protease inhibitors, it is used only in combination with other HIV medications. The U.S. Food and Drug Administration (FDA) approved atazanavir on June 20, 2003. [Wikipedia] Structure

MOLSDFPDBSMILESInChI

Synonyms

Value Source AtazanavirumChEBI ATZChEBI LatazanavirChEBI ZrivadaChEBI Atazanavir slifateHMDB Atazanavir sliphateHMDB ATVHMDB BMS-232632HMDB ReyatazMeSH Slifate, atazanavirMeSH 3,12-Bis(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phenylmethyl)-6-((4-(2-pyridinyl)phenyl)methyl)-2,5,6,10,13-pentaazatetradecanedioic acid dimethyl esterMeSH

Chemical Formlia

C38H52N6O7 Average Molecliar Weight

704.8555 Monoisotopic Molecliar Weight

704.389748048 IUPAC Name

methyl N-[(1S)-1-{[(2S,3S)-3-hydroxy-4-[(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethyl-N-{[4-(pyridin-2-yl)phenyl]methyl}butanehydrazido]-1-phenylbutan-2-yl]carbamoyl}-2,2-dimethylpropyl]carbamate Traditional Name

atazanavir CAS Registry Number

198904-31-3 SMILES

COC(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)[C@@H](O)CN(CC1=CC=C(C=C1)C1=CC=CC=N1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C(C)(C)C

InChI Identifier

InChI=1S/C38H52N6O7/c1-37(2,3)31(41-35(48)50-7)33(46)40-29(22-25-14-10-9-11-15-25)30(45)24-44(43-34(47)32(38(4,5)6)42-36(49)51-8)23-26-17-19-27(20-18-26)28-16-12-13-21-39-28/h9-21,29-32,45H,22-24H2,1-8H3,(H,40,46)(H,41,48)(H,42,49)(H,43,47)/t29-,30-,31+,32+/m0/s1

InChI Key

AXRYRYVKAWYZBR-GASGPIRDSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as valine and derivatives. These are compounds containing valine or a derivative thereof resliting from reaction of valine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom. Kingdom

Organic compounds Super Class

Organic acids and derivatives Class

Carboxylic acids and derivatives Sub Class

Amino acids, peptides, and analogues Direct Parent

Valine and derivatives Alternative Parents

  • Alpha amino acid amides
  • Phenylpyridines
  • Phenylbutylamines
  • Amphetamines and derivatives
  • N-acyl amines
  • Heteroaromatic compounds
  • Methylcarbamates
  • Secondary carboxylic acid amides
  • Secondary alcohols
  • Carboxylic acid hydrazides
  • Organic carbonic acids and derivatives
  • Azacyclic compounds
  • Organopnictogen compounds
  • Hydrocarbon derivatives
  • Organonitrogen compounds
  • Organic oxides
  • Carbonyl compounds

    • Substituents

  • Valine or derivatives
  • Alpha-amino acid amide
  • 2-phenylpyridine
  • Phenylbutylamine
  • Amphetamine or derivatives
  • Monocyclic benzene moiety
  • Fatty amide
  • N-acyl-amine
  • Fatty acyl
  • Benzenoid
  • Pyridine
  • Methylcarbamate
  • Heteroaromatic compound
  • Carbamic acid ester
  • Carboxamide group
  • Carboxylic acid hydrazide
  • Carbonic acid derivative
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Azacycle
  • Organoheterocyclic compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organic nitrogen compound
  • Alcohol
  • Carbonyl group
  • Organooxygen compound
  • Organopnictogen compound
  • Aromatic heteromonocyclic compound

    • Molecliar Framework

    Aromatic heteromonocyclic compounds External Descriptors

  • carbohydrazide (CHEBI:37924 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • 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 Solubility3.27e-03 g/LNot Available LogP4.5Not Available

    Predicted Properties

    Property Value Source Water Solubility0.0033 mg/mLALOGPS logP4.08ALOGPS logP4.54ChemAxon logS-5.3ALOGPS pKa (Strongest Acidic)11.92ChemAxon pKa (Strongest Basic)4.42ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count7ChemAxon Hydrogen Donor Count5ChemAxon Polar Surface Area171.22 Å2ChemAxon Rotatable Bond Count18ChemAxon Refractivity191.8 m3·mol-1ChemAxon Polarizability76.83 Å3ChemAxon Number of Rings3ChemAxon Bioavailability0ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , negativesplash10-0udi-0000000900-7e1de2ac8606722b93f7View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , negativesplash10-059i-0400009000-c82421a6236ad955ce10View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , negativesplash10-0a4i-0900103000-7e2d2a1d46db762c8c86View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , negativesplash10-0a4i-0900000000-54848dbe98136e86d7e2View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , negativesplash10-0a4i-0900000000-2745c98fc68f31b0aaa1View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-052r-0400109000-34888fbaf35d6a59436bView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-0a4i-0900000000-fb11fc296b4de898b8a4View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-0a4i-2900000000-0560d48dd9132e669b65View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-0a4i-4900000000-6dd9a933c1ce344af8c7View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-052b-9600000000-58436dc182a136e41b03View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-0002-9200000000-a88ad624324598b24604View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-0a4i-0000000900-f123f82b3d344e90c694View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-0a4i-0000000900-cf94e4d3f230d6e92145View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-052r-0309021800-183f6ac31fcaa7a51e41View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-014r-0905010000-a81a2d1bd38bef65bb85View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-014i-0901000000-4a2200f029d64a0c92bcView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-0a4i-0001000900-f20b29539c5c221e8f65View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-014i-0903000000-d1f4ac03716e2751bf4fView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-014i-0900000000-5bc5083ca9dae2cb839aView in MoNA 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

  • 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 DB01072

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01072

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01072 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

    130642 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Atazanavir NuGOwiki Link

    HMDB15205 Metagene Link

    HMDB15205 METLIN ID

    Not Available PubChem Compound

    148192 PDB ID

    DR7 ChEBI ID

    37924

    Product: 6S rRNA modificator

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Le Tiec C, Barrail A, Goujard C, Taburet AM: Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035-50. [PubMed:16176117 ]
    2. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. [PubMed:15585441 ]
    3. Swainston Harrison T, Scott LJ: Atazanavir: a review of its use in the management of HIV infection. Drugs. 2005;65(16):2309-36. [PubMed:16266202 ]
    4. von Hentig N: Atazanavir/ritonavir: a review of its use in HIV therapy. Drugs Today (Barc). 2008 Feb;44(2):103-32. doi: 10.1358/dot.2008.44.2.1137107. [PubMed:18389089 ]
    5. Croom KF, Dhillon S, Keam SJ: Atazanavir: a review of its use in the management of HIV-1 infection. Drugs. 2009 May 29;69(8):1107-40. doi: 10.2165/00003495-200969080-00009. [PubMed:19496633 ]
    6. Lopez-Cortes LF: [Pharmacology, pharmacokinetic features and interactions of atazanavir]. Enferm Infecc Microbiol Clin. 2008 Dec;26 Suppl 17:2-8. doi: 10.1016/S0213-005X(08)76613-8. [PubMed:20116610 ]

    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. Le Tiec C, Barrail A, Goujard C, Taburet AM: Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035-50. [PubMed:16176117 ]
    2. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. [PubMed:15585441 ]
    3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
    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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
    Gene Name:
    CYP2C9
    Uniprot ID:
    P11712
    Molecular weight:
    55627.365
    References
    1. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. [PubMed:15585441 ]

    Transporters

    General function:
    Involved in ATP binding
    Specific function:
    Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o- glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency
    Gene Name:
    ABCC1
    Uniprot ID:
    P33527
    Molecular weight:
    171589.5
    References
    1. Janneh O, Anwar T, Jungbauer C, Kopp S, Khoo SH, Back DJ, Chiba P: P-glycoprotein, multidrug resistance-associated proteins and human organic anion transporting polypeptide influence the intracellular accumulation of atazanavir. Antivir Ther. 2009;14(7):965-74. doi: 10.3851/IMP1399. [PubMed:19918100 ]
    2. Lucia MB, Golotta C, Rutella S, Rastrelli E, Savarino A, Cauda R: Atazanavir inhibits P-glycoprotein and multidrug resistance-associated protein efflux activity. J Acquir Immune Defic Syndr. 2005 Aug 15;39(5):635-7. [PubMed:16044020 ]
    General function:
    Involved in ATP binding
    Specific function:
    Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
    Gene Name:
    ABCB1
    Uniprot ID:
    P08183
    Molecular weight:
    141477.3
    References
    1. Perloff ES, Duan SX, Skolnik PR, Greenblatt DJ, von Moltke LL: Atazanavir: effects on P-glycoprotein transport and CYP3A metabolism in vitro. Drug Metab Dispos. 2005 Jun;33(6):764-70. Epub 2005 Mar 11. [PubMed:15764714 ]
    2. Lucia MB, Golotta C, Rutella S, Rastrelli E, Savarino A, Cauda R: Atazanavir inhibits P-glycoprotein and multidrug resistance-associated protein efflux activity. J Acquir Immune Defic Syndr. 2005 Aug 15;39(5):635-7. [PubMed:16044020 ]
    3. Chinn LW, Gow JM, Tse MM, Becker SL, Kroetz DL: Interindividual variability in the effect of atazanavir and saquinavir on the expression of lymphocyte P-glycoprotein. J Antimicrob Chemother. 2007 Jul;60(1):61-7. Epub 2007 May 17. [PubMed:17510066 ]
    4. Wood R: Atazanavir: its role in HIV treatment. Expert Rev Anti Infect Ther. 2008 Dec;6(6):785-96. doi: 10.1586/14787210.6.6.785. [PubMed:19053892 ]
    5. Janneh O, Anwar T, Jungbauer C, Kopp S, Khoo SH, Back DJ, Chiba P: P-glycoprotein, multidrug resistance-associated proteins and human organic anion transporting polypeptide influence the intracellular accumulation of atazanavir. Antivir Ther. 2009;14(7):965-74. doi: 10.3851/IMP1399. [PubMed:19918100 ]
    6. Storch CH, Theile D, Lindenmaier H, Haefeli WE, Weiss J: Comparison of the inhibitory activity of anti-HIV drugs on P-glycoprotein. Biochem Pharmacol. 2007 May 15;73(10):1573-81. Epub 2007 Jan 24. [PubMed:17328866 ]

    PMID: 21685476

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