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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2006-10-17 11:32:11 UTC
Update Date2022-03-07 02:49:25 UTC
HMDB IDHMDB0005039
Secondary Accession Numbers
  • HMDB05039
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
Data?1582752342
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
AphrodilKegg
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
Desmethyl sildenafilHMDB
HydroxyhomosildenafilHMDB
1-((3-(6,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-D)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine citrateHMDB
Lactate, sildenafilHMDB
NCX-911HMDB
Nitrate, sildenafilHMDB
AcetildenafilHMDB
Sildenafil nitrateHMDB
NCX 911HMDB
HomosildenafilHMDB
Citrate, sildenafilHMDB
Sildenafil, desmethylHMDB
DesmethylsildenafilHMDB
Sildenafil lactateHMDB
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 KeyBNRNXUUZRGQAQC-UHFFFAOYSA-N
Chemical Taxonomy
Description 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
  • Benzenesulfonyl group
  • Phenoxy compound
  • Phenol ether
  • Alkyl aryl ether
  • Pyrimidone
  • N-methylpiperazine
  • N-alkylpiperazine
  • Piperazine
  • Pyrimidine
  • Organosulfonic acid amide
  • 1,4-diazinane
  • Pyrazole
  • Sulfonyl
  • Organosulfonic acid or derivatives
  • Organic sulfonic acid or derivatives
  • Azole
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Lactam
  • Ether
  • Azacycle
  • Organoheterocyclic compound
  • Organooxygen compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organosulfur compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
Role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M+H]+CBM212.730932474
[M+H]+Not Available210.825http://allccs.zhulab.cn/database/detail?ID=AllCCS00000882
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.43 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity139.44 m³·mol⁻¹ChemAxon
Polarizability51.18 ųChemAxon
Number of Rings4ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+208.63531661259
DarkChem[M-H]-207.09731661259
DeepCCS[M+H]+211.15530932474
DeepCCS[M-H]-208.7630932474
DeepCCS[M-2H]-241.74930932474
DeepCCS[M+Na]+217.06830932474
AllCCS[M+H]+209.532859911
AllCCS[M+H-H2O]+207.532859911
AllCCS[M+NH4]+211.432859911
AllCCS[M+Na]+211.932859911
AllCCS[M-H]-205.032859911
AllCCS[M+Na-2H]-206.132859911
AllCCS[M+HCOO]-207.532859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
SildenafilCCCC1=NN(C)C2=C1NC(=NC2=O)C1=C(OCC)C=CC(=C1)S(=O)(=O)N1CCN(C)CC15075.6Standard polar33892256
SildenafilCCCC1=NN(C)C2=C1NC(=NC2=O)C1=C(OCC)C=CC(=C1)S(=O)(=O)N1CCN(C)CC13724.7Standard non polar33892256
SildenafilCCCC1=NN(C)C2=C1NC(=NC2=O)C1=C(OCC)C=CC(=C1)S(=O)(=O)N1CCN(C)CC14112.6Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Sildenafil,1TMS,isomer #1CCCC1=NN(C)C2=C1N([Si](C)(C)C)C(C1=CC(S(=O)(=O)N3CCN(C)CC3)=CC=C1OCC)=NC2=O3859.8Semi standard non polar33892256
Sildenafil,1TMS,isomer #1CCCC1=NN(C)C2=C1N([Si](C)(C)C)C(C1=CC(S(=O)(=O)N3CCN(C)CC3)=CC=C1OCC)=NC2=O3901.2Standard non polar33892256
Sildenafil,1TMS,isomer #1CCCC1=NN(C)C2=C1N([Si](C)(C)C)C(C1=CC(S(=O)(=O)N3CCN(C)CC3)=CC=C1OCC)=NC2=O5427.6Standard polar33892256
Sildenafil,1TBDMS,isomer #1CCCC1=NN(C)C2=C1N([Si](C)(C)C(C)(C)C)C(C1=CC(S(=O)(=O)N3CCN(C)CC3)=CC=C1OCC)=NC2=O3980.5Semi standard non polar33892256
Sildenafil,1TBDMS,isomer #1CCCC1=NN(C)C2=C1N([Si](C)(C)C(C)(C)C)C(C1=CC(S(=O)(=O)N3CCN(C)CC3)=CC=C1OCC)=NC2=O4171.5Standard non polar33892256
Sildenafil,1TBDMS,isomer #1CCCC1=NN(C)C2=C1N([Si](C)(C)C(C)(C)C)C(C1=CC(S(=O)(=O)N3CCN(C)CC3)=CC=C1OCC)=NC2=O5372.7Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Sildenafil GC-MS (Non-derivatized) - 70eV, Positivesplash10-006t-9004300000-55c87eff7b6ad40ea3d52017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Sildenafil GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Sildenafil LC-ESI-qTof , Positive-QTOFsplash10-0059-2494500000-e3f8387aee5a0463363c2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Sildenafil LC-ESI-qTof , Positive-QTOFsplash10-05s0-3892000000-aa19715309275e16a6c02017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Sildenafil , positive-QTOFsplash10-0059-2494500000-e3f8387aee5a0463363c2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Sildenafil , positive-QTOFsplash10-05s0-3892000000-aa19715309275e16a6c02017-09-14HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Sildenafil 10V, Positive-QTOFsplash10-004i-0002900000-b281f59f40caaba85ac92015-04-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Sildenafil 20V, Positive-QTOFsplash10-004i-4436900000-0c5804e76b9d495c76d62015-04-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Sildenafil 40V, Positive-QTOFsplash10-0459-6292000000-5a32bfcdda2067978be92015-04-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Sildenafil 10V, Negative-QTOFsplash10-00di-0001900000-51b4957d0b3d25c417732015-04-25Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Sildenafil 20V, Negative-QTOFsplash10-01vk-0302900000-86c63c2fd17f7c5b7d6f2015-04-25Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Sildenafil 40V, Negative-QTOFsplash10-03dj-8916100000-e941afc576d544ed32a72015-04-25Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Sildenafil 10V, Positive-QTOFsplash10-004i-0000900000-c92b21b6524ea50403132021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Sildenafil 20V, Positive-QTOFsplash10-004i-0000900000-06d94f4626e8bee6e3892021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Sildenafil 40V, Positive-QTOFsplash10-006t-9101300000-ef50cfadb7bd34e881872021-09-23Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Sildenafil 10V, Negative-QTOFsplash10-00di-0000900000-1617a2dfdf2b96a0cd2c2021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Sildenafil 20V, Negative-QTOFsplash10-0002-0010900000-744efa093f1de0f36d622021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Sildenafil 40V, Negative-QTOFsplash10-003r-0272900000-aa5d9fef9c0fb52ad9232021-09-24Wishart LabView Spectrum
Biological Properties
Cellular LocationsNot Available
Biospecimen LocationsNot Available
Tissue Locations
  • Liver
  • Smooth Muscle
Pathways
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00203
Phenol Explorer Compound IDNot Available
FooDB IDFDB023606
KNApSAcK IDNot Available
Chemspider ID5023
KEGG Compound IDC07259
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkSildenafil
METLIN IDNot Available
PubChem Compound5212
PDB IDNot Available
ChEBI ID9139
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents 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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:15797756 ]
  5. Fekete F, Fabian E: [Effectiveness and adverse effects of sildenafil in erectile dysfunction]. Orv Hetil. 2000 Jan 16;141(3):115-8. [PubMed: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. [PubMed: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