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Vardenafil

July 24, 2017
Common Name

Vardenafil Description

Vardenafil (Levitra) is an oral therapy for the treatment of erectile dysfunction. It is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. During sexual stimliation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resliting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resliting in erection. The tissue concentration of cGMP is regliated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMPspecific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 2-{2-ethoxy-5-[(4-ethylpiperazin-1-yl)slifonyl]phenyl}-5-methyl-7-propylimidazo[5,1-F][1,2,4]triazin-4(1H)-oneChEBI LevitraChEBI 2-{2-ethoxy-5-[(4-ethylpiperazin-1-yl)sliphonyl]phenyl}-5-methyl-7-propylimidazo[5,1-F][1,2,4]triazin-4(1H)-oneGenerator VDNHMDB Trihydrate, vardenafil hydrochlorideMeSH Dihydrochloride, vardenafilMeSH Vardenafil hydrochlorideMeSH Vardenafil hydrochloride anhydrousMeSH Vardenafil hydrochloride trihydrateMeSH Anhydrous, vardenafil hydrochlorideMeSH Hydrochloride anhydrous, vardenafilMeSH Hydrochloride trihydrate, vardenafilMeSH Hydrochloride, vardenafilMeSH 1-(((3-(3,4-dihydro-5-Methyl)-4-oxo-7-propylimidazo(5,1-F)-as-triazin-2-yl)-4-ethoxyphenyl)slifonyl)-4-ethylpiperazineMeSH Vardenafil dihydrochlorideMeSH

Chemical Formlia

C23H32N6O4S Average Molecliar Weight

488.603 Monoisotopic Molecliar Weight

488.220574232 IUPAC Name

2-{2-ethoxy-5-[(4-ethylpiperazin-1-yl)slifonyl]phenyl}-5-methyl-7-propyl-1H,4H-imidazo[4,3-f][1,2,4]triazin-4-one Traditional Name

levitra CAS Registry Number

224785-90-4 SMILES

CCCC1=NC(C)=C2N1NC(=NC2=O)C1=C(OCC)C=CC(=C1)S(=O)(=O)N1CCN(CC)CC1

InChI Identifier

InChI=1S/C23H32N6O4S/c1-5-8-20-24-16(4)21-23(30)25-22(26-29(20)21)18-15-17(9-10-19(18)33-7-3)34(31,32)28-13-11-27(6-2)12-14-28/h9-10,15H,5-8,11-14H2,1-4H3,(H,25,26,30)

InChI Key

SECKRCOLJRRGGV-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as benzeneslifonamides. These are organic compounds containing a slifonamide group that is S-linked to a benzene ring. Kingdom

Chemical entities Super Class

Organic compounds Class

Benzenoids Sub Class

Benzene and substituted derivatives Direct Parent

Benzeneslifonamides Alternative Parents

  • Benzeneslifonyl compounds
  • Phenoxy compounds
  • Phenol ethers
  • N-alkylpiperazines
  • Alkyl aryl ethers
  • Organoslifonamides
  • N-substituted imidazoles
  • 1,2,4-triazines
  • Slifonyls
  • Heteroaromatic compounds
  • Trialkylamines
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • Benzeneslifonamide
  • Benzeneslifonyl group
  • Phenoxy compound
  • Phenol ether
  • Alkyl aryl ether
  • N-alkylpiperazine
  • 1,4-diazinane
  • N-substituted imidazole
  • Piperazine
  • Organoslifonic acid amide
  • Triazine
  • 1,2,4-triazine
  • Heteroaromatic compound
  • Slifonyl
  • Azole
  • Organoslifonic acid or derivatives
  • Organic slifonic acid or derivatives
  • Imidazole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Organooxygen compound
  • Organoslifur compound
  • Organic oxide
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • N-alkylpiperazine (CHEBI:46295 )
  • imidazotriazine (CHEBI:46295 )
  • N-slifonylpiperazine (CHEBI:46295 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-Impotence Agents
  • Phosphodiesterase Inhibitors
  • Vasoconstrictor Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point192 °CNot Available Boiling PointNot AvailableNot Available Water Solubility3.25e-01 g/LNot Available LogP1.4Not Available

    Predicted Properties

    Property Value Source Water Solubility0.33 mg/mLALOGPS logP2.18ALOGPS logP1.33ChemAxon logS-3.2ALOGPS pKa (Strongest Acidic)8.01ChemAxon pKa (Strongest Basic)6.21ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count8ChemAxon Hydrogen Donor Count1ChemAxon Polar Surface Area109.13 Å2ChemAxon Rotatable Bond Count7ChemAxon Refractivity142.71 m3·mol-1ChemAxon Polarizability53.22 Å3ChemAxon Number of Rings4ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-000f-0011900000-88f62b9a8f7aec917a41View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-0002-0092000000-cf98ecae287c01370dbcView 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 DB00862

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00862

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB00862 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

    99300 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Vardenafil NuGOwiki Link

    HMDB15000 Metagene Link

    HMDB15000 METLIN ID

    Not Available PubChem Compound

    110634 PDB ID

    VDN ChEBI ID

    46295

    Product: NSC-41590

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not Available

    Enzymes

    General function:
    Involved in 3,5-cyclic-nucleotide phosphodiesterase activity
    Specific function:
    Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
    Gene Name:
    PDE6H
    Uniprot ID:
    Q13956
    Molecular weight:
    9074.36
    References
    1. Zhang XJ, Cahill KB, Elfenbein A, Arshavsky VY, Cote RH: Direct allosteric regulation between the GAF domain and catalytic domain of photoreceptor phosphodiesterase PDE6. J Biol Chem. 2008 Oct 31;283(44):29699-705. doi: 10.1074/jbc.M803948200. Epub 2008 Sep 8. [PubMed:18779324 ]
    General function:
    Involved in 3,5-cyclic-nucleotide phosphodiesterase activity
    Specific function:
    Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
    Gene Name:
    PDE6G
    Uniprot ID:
    P18545
    Molecular weight:
    9643.09
    References
    1. Zhang XJ, Cahill KB, Elfenbein A, Arshavsky VY, Cote RH: Direct allosteric regulation between the GAF domain and catalytic domain of photoreceptor phosphodiesterase PDE6. J Biol Chem. 2008 Oct 31;283(44):29699-705. doi: 10.1074/jbc.M803948200. Epub 2008 Sep 8. [PubMed:18779324 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5-GMP.
    Gene Name:
    PDE5A
    Uniprot ID:
    O76074
    Molecular weight:
    99984.14
    References
    1. Blount MA, Zoraghi R, Ke H, Bessay EP, Corbin JD, Francis SH: A 46-amino acid segment in phosphodiesterase-5 GAF-B domain provides for high vardenafil potency over sildenafil and tadalafil and is involved in phosphodiesterase-5 dimerization. Mol Pharmacol. 2006 Nov;70(5):1822-31. Epub 2006 Aug 22. [PubMed:16926278 ]
    2. Carrier S: Pharmacology of phosphodiesterase 5 inhibitors. Can J Urol. 2003 Feb;10 Suppl 1:12-6. [PubMed:12625845 ]
    3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    4. Kim NN, Huang YH, Goldstein I, Bischoff E, Traish AM: Inhibition of cyclic GMP hydrolysis in human corpus cavernosum smooth muscle cells by vardenafil, a novel, selective phosphodiesterase type 5 inhibitor. Life Sci. 2001 Sep 28;69(19):2249-56. [PubMed:11669467 ]
    5. Saenz de Tejada I, Angulo J, Cuevas P, Fernandez A, Moncada I, Allona A, Lledo E, Korschen HG, Niewohner U, Haning H, Pages E, Bischoff E: The phosphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new PDE5 inhibitor vardenafil. Int J Impot Res. 2001 Oct;13(5):282-90. [PubMed:11890515 ]
    6. Scheen AJ: [Medication of the month. Vardenafil (Levitra)]. Rev Med Liege. 2003 Sep;58(9):576-9. [PubMed:14626653 ]
    7. Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, Moon J, Yoon JM, Hyun YL, Kim E, Eum SJ, Park SY, Lee JO, Lee TG, Ro S, Cho JM: Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature. 2003 Sep 4;425(6953):98-102. [PubMed:12955149 ]
    8. Wang H, Ye M, Robinson H, Francis SH, Ke H: Conformational variations of both phosphodiesterase-5 and inhibitors provide the structural basis for the physiological effects of vardenafil and sildenafil. Mol Pharmacol. 2008 Jan;73(1):104-10. Epub 2007 Oct 24. [PubMed:17959709 ]
    9. Zoraghi R, Francis SH, Corbin JD: Critical amino acids in phosphodiesterase-5 catalytic site that provide for high-affinity interaction with cyclic guanosine monophosphate and inhibitors. Biochemistry. 2007 Nov 27;46(47):13554-63. Epub 2007 Nov 3. [PubMed:17979301 ]
    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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    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.
    Gene Name:
    CYP3A5
    Uniprot ID:
    P20815
    Molecular weight:
    57108.065
    References
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

    PMID: 16715118

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