Entacapone (CHEM002210)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (1)XML
Record Information
Version1.0
Creation Date2009-07-21 20:27:01 UTC
Update Date2026-03-27 01:07:55 UTC
Accession NumberCHEM002210
Identification
Common NameEntacapone
ClassSmall Molecule
DescriptionEntacapone is a selective, reversible catechol-O-methyl transferase (COMT) inhibitor for the treatment of Parkinson's disease. It is a member of the class of nitrocatechols. When administered concomittantly with levodopa and a decarboxylase inhibitor (e.g., carbidopa), increased and more sustained plasma levodopa concentrations are reached as compared to the administration of levodopa and a decarboxylase inhibitor.
Contaminant Sources
  • FooDB Chemicals
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Amide
  • Amine
  • Antidyskinetic
  • Antiparkinson Agent
  • Central Nervous System Agent
  • Drug
  • Enzyme Inhibitor
  • Ester
  • Food Toxin
  • Metabolite
  • Nitrile
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
ValueSource
(e)-alpha-Cyano-N,N-diethyl-3,4-dihydroxy-5-nitrocinnamamideChEBI
ComtanChEBI
ComtessChEBI
EntacaponaChEBI
EntacaponumChEBI
N,N-Diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl) acrylamideChEBI
(e)-a-Cyano-N,N-diethyl-3,4-dihydroxy-5-nitrocinnamamideGenerator
(e)-Α-cyano-N,N-diethyl-3,4-dihydroxy-5-nitrocinnamamideGenerator
2-Cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamideHMDB
Orion brand OF entacaponeHMDB
Novartis brand OF entacaponeHMDB
Chemical FormulaC14H15N3O5
Average Molecular Mass305.286 g/mol
Monoisotopic Mass305.101 g/mol
CAS Registry Number130929-57-6
IUPAC Name(2E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide
Traditional Nameentacapone
SMILESCCN(CC)C(=O)C(=C\C1=CC(=C(O)C(O)=C1)[N+]([O-])=O)\C#N
InChI IdentifierInChI=1S/C14H15N3O5/c1-3-16(4-2)14(20)10(8-15)5-9-6-11(17(21)22)13(19)12(18)7-9/h5-7,18-19H,3-4H2,1-2H3/b10-5+
InChI KeyJRURYQJSLYLRLN-BJMVGYQFSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as hydroxycinnamic acids and derivatives. Hydroxycinnamic acids and derivatives are compounds containing an cinnamic acid (or a derivative thereof) where the benzene ring is hydroxylated.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassCinnamic acids and derivatives
Sub ClassHydroxycinnamic acids and derivatives
Direct ParentHydroxycinnamic acids and derivatives
Alternative Parents
Substituents
  • Hydroxycinnamic acid or derivatives
  • Nitrophenol
  • Nitrobenzene
  • Nitroaromatic compound
  • Catechol
  • 1-hydroxy-4-unsubstituted benzenoid
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Monocyclic benzene moiety
  • Benzenoid
  • Tertiary carboxylic acid amide
  • Carboxamide group
  • C-nitro compound
  • Organic nitro compound
  • Allyl-type 1,3-dipolar organic compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboxylic acid derivative
  • Carbonitrile
  • Nitrile
  • Organic oxoazanium
  • Organic 1,3-dipolar compound
  • Organic nitrogen compound
  • Organic zwitterion
  • Organic oxide
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Carbonyl group
  • Organopnictogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.08 g/LALOGPS
logP2.5ALOGPS
logP1.63ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)5.68ChemAxon
pKa (Strongest Basic)-0.036ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area130.38 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity80.51 m³·mol⁻¹ChemAxon
Polarizability29.48 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-003r-4190000000-da6b28638ec4920bd58aSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0059-6004900000-14645ab585cbbed0ca38Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4i-0329000000-8d20a5650e9c1b1c8275Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-0329000000-8d20a5650e9c1b1c8275Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0009000000-6e08b463d5af43617517Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udr-1069000000-5075a6f93c2b72c3483aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fkc-9240000000-27e088a40b83e29661e0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0009000000-29c32f9a04e379fce5feSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-2009000000-6d53b89d8a9ecd3b180eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00dl-9100000000-5f330d3ad8cb0af17a9aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0009000000-62e9f24f62db1840e2e0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-1292000000-28b9a09056bdc465cd19Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-1590000000-58fe447bc05aa8420188Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0039000000-85f49c3b07fd9b1dd7bdSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0pb9-1693000000-bf7093c3dc0b31a75e5dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4j-5910000000-658aee735015de149a67Spectrum
Toxicity Profile
Route of ExposureOral. Entacapone is rapidly absorbed (approximately 1 hour). The absolute bioavailability following oral administration is 35%.
Mechanism of ToxicityThe mechanism of action of entacapone is believed to be through its ability to inhibit COMT in peripheral tissues, altering the plasma pharmacokinetics of levodopa. When entacapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are greater and more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that at a given frequency of levodopa administration, these more sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to a greater reduction in the manifestations of parkinsonian syndrome.
MetabolismMetabolized via isomerization to the cis-isomer, followed by direct glucuronidation of the parent and cis-isomer. Route of Elimination: Entacapone is almost completely metabolized prior to excretion, with only a very small amount (0.2% of dose) found unchanged in urine. As only about 10% of the entacapone dose is excreted in urine as parent compound and conjugated glucuronide, biliary excretion appears to be the major route of excretion of this drug. Half Life: 0.4-0.7 hour
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed as an adjunct to levodopa / carbidopa in the symptomatic treatment of patients with idiopathic Parkinson's Disease who experience the signs and symptoms of end-of-dose "wearing-off".
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSide effect include increase the occurrence of orthostatic hypotension, severe rhabdomyolysis, dyskinesia, hallucinations, hyperkinesia, hypokinesia, dizziness, fatigu,e gastrointestinal effects including abdominal pain constipation diarrhea nausea.
TreatmentManagement of Entacapone overdose is symptomatic; there is no known antidote to Comtan. Hospitalization is advised, and general supportive care is indicated. There is no experience with hemodialysis or hemoperfusion, but these procedures are unlikely to be of benefit, because Entacapone is highly bound to plasma proteins. An immediate gastric lavage and repeated doses of charcoal over time may hasten the elimination of Entacapone by decreasing its absorption/reabsorption from the GI tract. The adequacy of the respiratory and circulatory systems should be carefully monitored and appropriate supportive measures employed. (9)
Concentrations
Not Available
DrugBank IDDB00494
HMDB IDHMDB0012226
FooDB IDFDB028870
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDCPD-7662
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkEntacapone
Chemspider ID4444537
ChEBI ID4798
PubChem Compound ID5281081
Kegg Compound IDC07943
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Pandurang Deshpande, Parven Luthra, Anand Pandey, Dharmesh Dhameliya, “Process for the preparation of (E)-2-cyano-3-(3, 4-dihydroxy-5-nitrophenyl)-N, N-diethyl-2-propenamide (entacapone).” U.S. Patent US20060258877, issued November 16, 2006.

MSDSNot Available
General References
1. https://www.ncbi.nlm.nih.gov/pubmed/?term=11244274
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=11586115
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=11732751
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=12952501
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=15698633
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=15875340
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=15878587
8. https://www.ncbi.nlm.nih.gov/pubmed/?term=15992091
9. https://www.ncbi.nlm.nih.gov/pubmed/?term=19578428
10. https://www.ncbi.nlm.nih.gov/pubmed/?term=19879254
11. Durif F, Devaux I, Pere JJ, Delumeau JC, Bourdeix I: Efficacy and tolerability of entacapone as adjunctive therapy to levodopa in patients with Parkinson's disease and end-of-dose deterioration in daily medical practice: an open, multicenter study. Eur Neurol. 2001;45(2):111-8.
12. Factor SA, Molho ES, Feustel PJ, Brown DL, Evans SM: Long-term comparative experience with tolcapone and entacapone in advanced Parkinson's disease. Clin Neuropharmacol. 2001 Sep-Oct;24(5):295-9.
13. Leppanen J, Savolainen J, Nevalainen T, Forsberg M, Huuskonen J, Taipale H, Gynther J, Mannisto PT, Jarvinen T: Synthesis and in-vitro/in-vivo evaluation of orally administered entacapone prodrugs. J Pharm Pharmacol. 2001 Nov;53(11):1489-98.
14. Authors unspecified: Entacapone/levodopa/carbidopa combination tablet: Stalevo. Drugs R D. 2003;4(5):310-1.
15. Authors unspecified: Levodopa + carbidopa + entacapone. Entacapone: a second look: new preparations. Parkinson's disease: a modest effect. Prescrire Int. 2005 Apr;14(76):51-4.
16. Valkovic P, Benetin J, Blazicek P, Valkovicova L, Gmitterova K, Kukumberg P: Reduced plasma homocysteine levels in levodopa/entacapone treated Parkinson patients. Parkinsonism Relat Disord. 2005 Jun;11(4):253-6. Epub 2005 Apr 20.
17. Gottwald MD: Entacapone, a catechol-O-methyltransferase inhibitor for treating Parkinson's disease: review and current status. Expert Opin Investig Drugs. 1999 Apr;8(4):453-62.
18. Kinnings SL, Liu N, Buchmeier N, Tonge PJ, Xie L, Bourne PE: Drug discovery using chemical systems biology: repositioning the safe medicine Comtan to treat multi-drug and extensively drug resistant tuberculosis. PLoS Comput Biol. 2009 Jul;5(7):e1000423. doi: 10.1371/journal.pcbi.1000423. Epub 2009 Jul 3.
19. Hamaue N, Ogata A, Terado M, Tsuchida S, Yabe I, Sasaki H, Hirafuji M, Togashi H, Aoki T: Entacapone, a catechol-O-methyltransferase inhibitor, improves the motor activity and dopamine content of basal ganglia in a rat model of Parkinson's disease induced by Japanese encephalitis virus. Brain Res. 2010 Jan 14;1309:110-5. doi: 10.1016/j.brainres.2009.10.055. Epub 2009 Oct 29.