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Conivaptan

July 24, 2017
Common Name

Conivaptan Description

Conivaptan is only found in individuals that have used or taken this drug. It is a non-peptide inhibitor of antidiuretic hormone (vasopressin). It was approved in 2004 for hyponatremia (low blood sodium levels) caused by syndrome of inappropriate antidiuretic hormone (SIADH). Conivaptan inhibits both isotypes of the vasopressin receptor (V1a and V2).Conivaptan is a dual AVP antagonist with nanomolar affinity for human arginine vasopressin V1A and V2 receptors in vitro. This antagonism occurs in the renal collecting ducts, resliting in aquaresis, or excretion of free water. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 4'-((4,5-dihydro-2-methylimidazo(4,5-D)(1)Benzazepin-6(1H)-yl)carbonyl)-2-biphenylcarboxanilideChEBI YM 087HMDB YM-087HMDB Conivaptan hydrochlorideMeSH VaprisolMeSH

Chemical Formlia

C32H26N4O2 Average Molecliar Weight

498.5744 Monoisotopic Molecliar Weight

498.205576096 IUPAC Name

N-(4-{4-methyl-3,5,9-triazatricyclo[8.4.0.0²,⁶]tetradeca-1(14),2(6),3,10,12-pentaene-9-carbonyl}phenyl)-2-phenylbenzamide Traditional Name

vaprisol CAS Registry Number

210101-16-9 SMILES

CC1=NC2=C(CCN(C(=O)C3=CC=C(NC(=O)C4=CC=CC=C4C4=CC=CC=C4)C=C3)C3=CC=CC=C23)N1

InChI Identifier

InChI=1S/C32H26N4O2/c1-21-33-28-19-20-36(29-14-8-7-13-27(29)30(28)34-21)32(38)23-15-17-24(18-16-23)35-31(37)26-12-6-5-11-25(26)22-9-3-2-4-10-22/h2-18H,19-20H2,1H3,(H,33,34)(H,35,37)

InChI Key

IKENVDNFQMCRTR-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R, where R,R= benzene. Kingdom

Chemical entities Super Class

Organic compounds Class

Benzenoids Sub Class

Benzene and substituted derivatives Direct Parent

Benzanilides Alternative Parents

  • Biphenyls and derivatives
  • Benzazepines
  • Benzamides
  • Benzoyl derivatives
  • Azepines
  • Tertiary carboxylic acid amides
  • Imidazoles
  • Heteroaromatic compounds
  • Secondary carboxylic acid amides
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organooxygen compounds
  • Organonitrogen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • Benzanilide
  • Biphenyl
  • Benzazepine
  • Benzamide
  • Benzoic acid or derivatives
  • Benzoyl
  • Azepine
  • Azole
  • Heteroaromatic compound
  • Imidazole
  • Tertiary carboxylic acid amide
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Carboxylic acid derivative
  • Organoheterocyclic compound
  • Azacycle
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • benzazepine (CHEBI:681850 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Aquaresis promoters

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility1.75e-03 g/LNot Available LogP6.3Not Available

    Predicted Properties

    Property Value Source Water Solubility0.0018 mg/mLALOGPS logP5.23ALOGPS logP5.44ChemAxon logS-5.5ALOGPS pKa (Strongest Acidic)11.14ChemAxon pKa (Strongest Basic)6.23ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count3ChemAxon Hydrogen Donor Count2ChemAxon Polar Surface Area78.09 Å2ChemAxon Rotatable Bond Count4ChemAxon Refractivity150.83 m3·mol-1ChemAxon Polarizability55.51 Å3ChemAxon Number of Rings6ChemAxon Bioavailability1ChemAxon 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 DB00872

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00872

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB00872 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

    133239 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Conivaptan NuGOwiki Link

    HMDB15010 Metagene Link

    HMDB15010 METLIN ID

    Not Available PubChem Compound

    151171 PDB ID

    Not Available ChEBI ID

    681850

    Product: WH-4-024

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Ali F, Raufi MA, Washington B, Ghali JK: Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected]. Cardiovasc Drug Rev. 2007 Fall;25(3):261-79. [PubMed:17919259 ]
    2. Mao ZL, Stalker D, Keirns J: Pharmacokinetics of conivaptan hydrochloride, a vasopressin V(1A)/V(2)-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia and with or without congestive heart failure from a prospective, 4-day open-label study. Clin Ther. 2009 Jul;31(7):1542-50. doi: 10.1016/j.clinthera.2009.07.011. [PubMed:19695403 ]
    3. Ghali JK, Farah JO, Daifallah S, Zabalawi HA, Zmily HD: Conivaptan and its role in the treatment of hyponatremia. Drug Des Devel Ther. 2009 Dec 29;3:253-68. [PubMed:20054444 ]

    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. Ali F, Raufi MA, Washington B, Ghali JK: Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected]. Cardiovasc Drug Rev. 2007 Fall;25(3):261-79. [PubMed:17919259 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate a phosphatidyl- inositol-calcium second messenger system. Has been involved in social behaviors, including affiliation and attachment
    Gene Name:
    AVPR1A
    Uniprot ID:
    P37288
    Molecular weight:
    46799.1
    References
    1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    2. Ali F, Raufi MA, Washington B, Ghali JK: Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected]. Cardiovasc Drug Rev. 2007 Fall;25(3):261-79. [PubMed:17919259 ]
    3. Wada K, Matsukawa U, Fujimori A, Arai Y, Sudoh K, Sasamata M, Miyata K: A novel vasopressin dual V1A/V2 receptor antagonist, conivaptan hydrochloride, improves hyponatremia in rats with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Biol Pharm Bull. 2007 Jan;30(1):91-5. [PubMed:17202666 ]
    4. Walter KA: Conivaptan: new treatment for hyponatremia. Am J Health Syst Pharm. 2007 Jul 1;64(13):1385-95. [PubMed:17592003 ]
    5. Mao ZL, Stalker D, Keirns J: Pharmacokinetics of conivaptan hydrochloride, a vasopressin V(1A)/V(2)-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia and with or without congestive heart failure from a prospective, 4-day open-label study. Clin Ther. 2009 Jul;31(7):1542-50. doi: 10.1016/j.clinthera.2009.07.011. [PubMed:19695403 ]
    6. Ghali JK, Koren MJ, Taylor JR, Brooks-Asplund E, Fan K, Long WA, Smith N: Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia. J Clin Endocrinol Metab. 2006 Jun;91(6):2145-52. Epub 2006 Mar 7. [PubMed:16522696 ]
    7. Annane D, Decaux G, Smith N: Efficacy and safety of oral conivaptan, a vasopressin-receptor antagonist, evaluated in a randomized, controlled trial in patients with euvolemic or hypervolemic hyponatremia. Am J Med Sci. 2009 Jan;337(1):28-36. doi: 10.1097/MAJ.0b013e31817b8148. [PubMed:19057376 ]
    8. Ghali JK, Farah JO, Daifallah S, Zabalawi HA, Zmily HD: Conivaptan and its role in the treatment of hyponatremia. Drug Des Devel Ther. 2009 Dec 29;3:253-68. [PubMed:20054444 ]
    9. Ali F, Guglin M, Vaitkevicius P, Ghali JK: Therapeutic potential of vasopressin receptor antagonists. Drugs. 2007;67(6):847-58. [PubMed:17428103 ]
    10. Hoque MZ, Arumugham P, Huda N, Verma N, Afiniwala M, Karia DH: Conivaptan: promise of treatment in heart failure. Expert Opin Pharmacother. 2009 Sep;10(13):2161-9. doi: 10.1517/14656560903173237. [PubMed:19663609 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase
    Gene Name:
    AVPR2
    Uniprot ID:
    P30518
    Molecular weight:
    40278.6
    References
    1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    2. Wada K, Fujimori A, Matsukawa U, Arai Y, Sudoh K, Yatsu T, Sasamata M, Miyata K: Intravenous administration of conivaptan hydrochloride improves cardiac hemodynamics in rats with myocardial infarction-induced congestive heart failure. Eur J Pharmacol. 2005 Jan 10;507(1-3):145-51. Epub 2005 Jan 1. [PubMed:15659304 ]
    3. Palm C, Pistrosch F, Herbrig K, Gross P: Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia. Am J Med. 2006 Jul;119(7 Suppl 1):S87-92. [PubMed:16843091 ]
    4. Ali F, Raufi MA, Washington B, Ghali JK: Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected]. Cardiovasc Drug Rev. 2007 Fall;25(3):261-79. [PubMed:17919259 ]
    5. Wada K, Matsukawa U, Fujimori A, Arai Y, Sudoh K, Sasamata M, Miyata K: A novel vasopressin dual V1A/V2 receptor antagonist, conivaptan hydrochloride, improves hyponatremia in rats with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Biol Pharm Bull. 2007 Jan;30(1):91-5. [PubMed:17202666 ]
    6. Walter KA: Conivaptan: new treatment for hyponatremia. Am J Health Syst Pharm. 2007 Jul 1;64(13):1385-95. [PubMed:17592003 ]
    7. Mao ZL, Stalker D, Keirns J: Pharmacokinetics of conivaptan hydrochloride, a vasopressin V(1A)/V(2)-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia and with or without congestive heart failure from a prospective, 4-day open-label study. Clin Ther. 2009 Jul;31(7):1542-50. doi: 10.1016/j.clinthera.2009.07.011. [PubMed:19695403 ]
    8. Ghali JK, Koren MJ, Taylor JR, Brooks-Asplund E, Fan K, Long WA, Smith N: Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia. J Clin Endocrinol Metab. 2006 Jun;91(6):2145-52. Epub 2006 Mar 7. [PubMed:16522696 ]
    9. Annane D, Decaux G, Smith N: Efficacy and safety of oral conivaptan, a vasopressin-receptor antagonist, evaluated in a randomized, controlled trial in patients with euvolemic or hypervolemic hyponatremia. Am J Med Sci. 2009 Jan;337(1):28-36. doi: 10.1097/MAJ.0b013e31817b8148. [PubMed:19057376 ]
    10. Ghali JK, Farah JO, Daifallah S, Zabalawi HA, Zmily HD: Conivaptan and its role in the treatment of hyponatremia. Drug Des Devel Ther. 2009 Dec 29;3:253-68. [PubMed:20054444 ]
    11. Ali F, Guglin M, Vaitkevicius P, Ghali JK: Therapeutic potential of vasopressin receptor antagonists. Drugs. 2007;67(6):847-58. [PubMed:17428103 ]
    12. Hoque MZ, Arumugham P, Huda N, Verma N, Afiniwala M, Karia DH: Conivaptan: promise of treatment in heart failure. Expert Opin Pharmacother. 2009 Sep;10(13):2161-9. doi: 10.1517/14656560903173237. [PubMed:19663609 ]

    PMID: 2720677

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