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Record Information
Version3.6
Creation Date2006-10-17 11:32:11 UTC
Update Date2016-02-11 01:07:02 UTC
HMDB IDHMDB05039
Secondary Accession NumbersNone
Metabolite Identification
Common NameSildenafil
DescriptionSildenafil is a drug used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH), developed by the pharmaceutical company Pfizer. It was initially studied for use in hypertension (high blood pressure) and angina pectoris (a form of ischaemic cardiovascular disease). Phase I clinical trials under the direction of Ian Osterloh suggested that the drug had little effect on angina, but that it could induce marked penile erections; Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. The molecular structure of sildenafil is similar to that of cGMP and acts as a competitive binding agent of PDE5 in the corpus cavernosum, resulting in more cGMP and better erections. Without sexual stimulation, and therefore lack of activation of the NO/cGMP system, sildenafil should not cause an erection. Other drugs that operate by the same mechanism include tadalafil (Cialis) and vardenafil (Levitra); Sildenafil citrate, sold under the names Viagra, Revatio and generically under various other names, is a drug used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH), developed by the pharmaceutical company Pfizer. Viagra pills are blue and diamond-shaped with the words 'Pfizer' on one side, and 'VGR xx' (where xx stands for '25', '50' or '100', the dose of that pill in milligrams) on the other. Its primary competitors on the market are tadalafil (Cialis), and vardenafil (Levitra).
Structure
Thumb
Synonyms
ValueSource
1-((3-(4,7-dihydro-1-Methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-D)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazineChEBI
1-((3-(4,7-dihydro-1-Methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-D)pyrimidin-5-yl)-4-ethoxyphenyl)sulphonyl)-4-methylpiperazineGenerator
CavertaHMDB
RevatioHMDB
Sildenafil citrateHMDB
ViagraHMDB
Chemical FormulaC22H30N6O4S
Average Molecular Weight474.576
Monoisotopic Molecular Weight474.204924168
IUPAC Name5-{2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1-methyl-3-propyl-1H,4H,7H-pyrazolo[4,3-d]pyrimidin-7-one
Traditional Namerevatio
CAS Registry Number139755-83-2
SMILES
CCCC1=NN(C)C2=C1NC(=NC2=O)C1=C(OCC)C=CC(=C1)S(=O)(=O)N1CCN(C)CC1
InChI Identifier
InChI=1S/C22H30N6O4S/c1-5-7-17-19-20(27(4)25-17)22(29)24-21(23-19)16-14-15(8-9-18(16)32-6-2)33(30,31)28-12-10-26(3)11-13-28/h8-9,14H,5-7,10-13H2,1-4H3,(H,23,24,29)
InChI KeyInChIKey=BNRNXUUZRGQAQC-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
  • Pyrazolopyrimidine
  • Phenol ether
  • N-alkylpiperazine
  • N-methylpiperazine
  • Pyrimidone
  • Alkyl aryl ether
  • Pyrimidine
  • Piperazine
  • 1,4-diazinane
  • Heteroaromatic compound
  • Vinylogous amide
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Pyrazole
  • 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
BiofunctionNot Available
ApplicationNot Available
Cellular locationsNot Available
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.43 mg/mLALOGPS
logP2.35ALOGPS
logP1.65ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)7.27ChemAxon
pKa (Strongest Basic)5.97ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area109.13 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity139.44 m3·mol-1ChemAxon
Polarizability51.18 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0002900000-b281f59f40caaba85ac9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-4436900000-0c5804e76b9d495c76d6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0459-6292000000-5a32bfcdda2067978be9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0001900000-51b4957d0b3d25c41773View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01vk-0302900000-86c63c2fd17f7c5b7d6fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03dj-8916100000-e941afc576d544ed32a7View in MoNA
Biological Properties
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue Location
  • Liver
  • Smooth Muscle
PathwaysNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023606
KNApSAcK IDNot Available
Chemspider ID5023
KEGG Compound IDC07259
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkSildenafil
NuGOwiki LinkHMDB05039
Metagene LinkHMDB05039
METLIN IDNot Available
PubChem Compound5212
PDB IDVIA
ChEBI IDNot Available
References
Synthesis ReferenceDunn, Peter James; Wood, Albert Shaw. Process for preparation of Sildenafil by cyclization. Eur. Pat. Appl. (1997), 18 pp.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Kekilli M, Beyazit Y, Purnak T, Dogan S, Atalar E: Acute myocardial infarction after sildenafil citrate ingestion. Ann Pharmacother. 2005 Jul-Aug;39(7-8):1362-4. Epub 2005 May 24. [15914518 ]
  2. Kim NN, Goldstein I, Moreland RB, Traish AM: Alpha-adrenergic receptor blockade by phentolamine increases the efficacy of vasodilators in penile corpus cavernosum. Int J Impot Res. 2000 Mar;12 Suppl 1:S26-36. [10845762 ]
  3. Warrington JS, Shader RI, von Moltke LL, Greenblatt DJ: In vitro biotransformation of sildenafil (Viagra): identification of human cytochromes and potential drug interactions. Drug Metab Dispos. 2000 Apr;28(4):392-7. [10725306 ]
  4. Chua R, Keogh A, Miyashita M: Novel use of sildenafil in the treatment of portopulmonary hypertension. J Heart Lung Transplant. 2005 Apr;24(4):498-500. [15797756 ]
  5. Fekete F, Fabian E: [Effectiveness and adverse effects of sildenafil in erectile dysfunction] Orv Hetil. 2000 Jan 16;141(3):115-8. [10693332 ]
  6. Blount MA, Beasley A, Zoraghi R, Sekhar KR, Bessay EP, Francis SH, Corbin JD: Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation. Mol Pharmacol. 2004 Jul;66(1):144-52. [15213306 ]

Enzymes

General function:
Involved in catalytic activity
Specific function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
Gene Name:
PDE2A
Uniprot ID:
O00408
Molecular weight:
105145.485
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
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
General function:
Involved in catalytic activity
Specific function:
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP. Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'-GMP, respectively.
Gene Name:
PDE11A
Uniprot ID:
Q9HCR9
Molecular weight:
55699.16