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Record Information
Version2.0
Creation Date2009-07-21 20:27:01 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2808
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.
Compound 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
Synonyms
Synonym
(e)-alpha-Cyano-N,N-diethyl-3,4-dihydroxy-5-nitrocinnamamide
2-Cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamide
Anxopone
Comtade
Comtan
Comtess
Entacapona
Entacaponum
N,N-Diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl) acrylamide
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
SMILES[H]\C(=C(\C#N)C(=O)N(CC)CC)C1=CC(=C(O)C(O)=C1)N(=O)=O
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 KeyInChIKey=JRURYQJSLYLRLN-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
LogP2.8
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-003r-4190000000-da6b28638ec4920bd58aJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0059-6004900000-14645ab585cbbed0ca38JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4i-0329000000-8d20a5650e9c1b1c8275JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-0329000000-8d20a5650e9c1b1c8275JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0009000000-6e08b463d5af43617517JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udr-1069000000-5075a6f93c2b72c3483aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fkc-9240000000-27e088a40b83e29661e0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0009000000-29c32f9a04e379fce5feJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-2009000000-6d53b89d8a9ecd3b180eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00dl-9100000000-5f330d3ad8cb0af17a9aJSpectraViewer
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)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00494
HMDB IDHMDB12226
PubChem Compound ID5281081
ChEMBL IDCHEMBL953
ChemSpider ID4444537
KEGG IDC07943
UniProt IDNot Available
OMIM ID
ChEBI ID4798
BioCyc IDCPD-7662
CTD IDNot Available
Stitch IDEntacapone
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkEntacapone
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.

MSDST3D2808.pdf
General References
  1. Bonifati V, Meco G: New, selective catechol-O-methyltransferase inhibitors as therapeutic agents in Parkinson's disease. Pharmacol Ther. 1999 Jan;81(1):1-36. [10051176 ]
  2. Najib J: Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson's disease. Clin Ther. 2001 Jun;23(6):802-32; discussion 771. [11440283 ]
  3. Chong BS, Mersfelder TL: Entacapone. Ann Pharmacother. 2000 Sep;34(9):1056-65. [10981253 ]
  4. Poewe WH, Deuschl G, Gordin A, Kultalahti ER, Leinonen M: Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study). Acta Neurol Scand. 2002 Apr;105(4):245-55. [11939936 ]
  5. Brooks DJ, Sagar H: Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson's disease: a randomised, placebo controlled, double blind, six month study. J Neurol Neurosurg Psychiatry. 2003 Aug;74(8):1071-9. [12876237 ]
  6. Forsberg M, Lehtonen M, Heikkinen M, Savolainen J, Jarvinen T, Mannisto PT: Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat. J Pharmacol Exp Ther. 2003 Feb;304(2):498-506. [12538800 ]
  7. Kaakkola S: Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. Drugs. 2000 Jun;59(6):1233-50. [10882160 ]
  8. Drugs.com [Link]
  9. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
O-methyltransferase activity
Specific Function:
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
Gene Name:
COMT
Uniprot ID:
P21964
Molecular Weight:
30036.77 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]