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Record Information
Version3.6
Creation Date2012-09-06 15:16:51 UTC
Update Date2016-02-11 01:30:56 UTC
HMDB IDHMDB15000
Secondary Accession NumbersNone
Metabolite Identification
Common NameVardenafil
DescriptionVardenafil (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 stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting 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, resulting in erection. The tissue concentration of cGMP is regulated 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
Thumb
Synonyms
ValueSource
2-{2-ethoxy-5-[(4-ethylpiperazin-1-yl)sulfonyl]phenyl}-5-methyl-7-propylimidazo[5,1-F][1,2,4]triazin-4(1H)-oneChEBI
LevitraChEBI
VDNHMDB
Chemical FormulaC23H32N6O4S
Average Molecular Weight488.603
Monoisotopic Molecular Weight488.220574232
IUPAC Name2-{2-ethoxy-5-[(4-ethylpiperazin-1-yl)sulfonyl]phenyl}-5-methyl-7-propyl-1H,4H-imidazo[4,3-f][1,2,4]triazin-4-one
Traditional Namelevitra
CAS Registry Number224785-90-4
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 KeyInChIKey=SECKRCOLJRRGGV-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzenesulfonamides
Direct ParentBenzenesulfonamides
Alternative Parents
Substituents
  • Benzenesulfonamide
  • Phenol ether
  • N-alkylpiperazine
  • Alkyl aryl ether
  • 1,2,4-triazine
  • Triazine
  • Piperazine
  • N-substituted imidazole
  • 1,4-diazinane
  • Heteroaromatic compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Imidazole
  • Azole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Anti-Impotence Agents
  • Phosphodiesterase Inhibitors
  • Vasoconstrictor Agents
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point192 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility3.25e-01 g/LNot Available
LogP1.4Not Available
Predicted Properties
PropertyValueSource
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
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00862
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00862
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00862
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID99300
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkVardenafil
NuGOwiki LinkHMDB15000
Metagene LinkHMDB15000
METLIN IDNot Available
PubChem Compound110634
PDB IDVDN
ChEBI ID46295
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot 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. Epub 2008 Sep 8. [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. Epub 2008 Sep 8. [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. [16926278 ]
  2. Carrier S: Pharmacology of phosphodiesterase 5 inhibitors. Can J Urol. 2003 Feb;10 Suppl 1:12-6. [12625845 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [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. [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. [11890515 ]
  6. Scheen AJ: [Medication of the month. Vardenafil (Levitra)] Rev Med Liege. 2003 Sep;58(9):576-9. [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. [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. [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. [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. Epub 2009 Nov 24. [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. Epub 2009 Nov 24. [19934256 ]