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Record Information
Version2.0
Creation Date2009-07-21 20:27:35 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2883
Identification
Common NameEthotoin
ClassSmall Molecule
DescriptionEthotoin is a hydantoin derivative and anticonvulsant. Ethotoin exerts an antiepileptic effect without causing general central nervous system depression. The mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges. Ethotoin is no longer commonly used.
Compound Type
  • Amide
  • Amine
  • Anticonvulsant
  • Drug
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+-)-3-Ethyl-5-phenylhydantoin
1-Ethyl-2,5-dioxo-4-phenylimidazolidine
3-Ethyl-5-phenyl-2,4-imidazolidinedione
3-Ethyl-5-phenyl-imidazolidine-2,4-dione
3-Ethyl-5-phenylhydantoin
3-Ethyl-5-phenylimidazolidin-2,4-dione
Accenon
Ethotoïne
Ethotoinum
Etotoina
Peganone
Pegoanone
Chemical FormulaC11H12N2O2
Average Molecular Mass204.225 g/mol
Monoisotopic Mass204.090 g/mol
CAS Registry Number86-35-1
IUPAC Name3-ethyl-5-phenylimidazolidine-2,4-dione
Traditional Nameethotoin
SMILESCCN1C(O)=NC(C1=O)C1=CC=CC=C1
InChI IdentifierInChI=1/C11H12N2O2/c1-2-13-10(14)9(12-11(13)15)8-6-4-3-5-7-8/h3-7,9H,2H2,1H3,(H,12,15)
InChI KeyInChIKey=SZQIFWWUIBRPBZ-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylhydantoins. These are heterocyclic aromatic compounds containing an imiazolidinedione moiety substituted by a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzolidines
Sub ClassImidazolidines
Direct ParentPhenylhydantoins
Alternative Parents
Substituents
  • 5-phenylhydantoin
  • Phenylimidazolidine
  • Alpha-amino acid or derivatives
  • N-acyl urea
  • Ureide
  • Monocyclic benzene moiety
  • Benzenoid
  • Dicarboximide
  • Urea
  • Carbonic acid derivative
  • Carboxylic acid derivative
  • Azacycle
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point94°C
Boiling PointNot Available
Solubility5280 mg/L
LogP1.05
Predicted Properties
PropertyValueSource
Water Solubility2.38 g/LALOGPS
logP1.11ALOGPS
logP1.07ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)11.29ChemAxon
pKa (Strongest Basic)-8.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area49.41 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity55.05 m³·mol⁻¹ChemAxon
Polarizability20.68 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-6980000000-86b5edde33787fa5b3d5JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0zfr-4920000000-137fae4223f8b51dd5cdJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0a4i-1190000000-3ade8f65bbabe08f852aJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0udi-1190000000-56ad3615dcbc3fbecdbcJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0udi-6980000000-86b5edde33787fa5b3d5JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0zfr-4920000000-137fae4223f8b51dd5cdJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0a4i-1190000000-3ade8f65bbabe08f852aJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0udi-1190000000-56ad3615dcbc3fbecdbcJSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-053f-4900000000-890da1feecbdd89e1320JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4i-1900000000-f71513d432cabc6ae596JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-1900000000-f71513d432cabc6ae596JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0690000000-2b14fabe2a8a38bfd87aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0zfr-2920000000-b4abc6e3540650b9fc2cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0pb9-6900000000-ce4d6190e87bedc270a9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0890000000-bc1ed1767185b47b35dbJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0ugi-6930000000-d8856c4e6ba455c06408JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0udi-8900000000-81cbbd6924131f65bccfJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0udi-6920000000-01714c9dcd6c4cf02362JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureFairly rapidly absorbed, however, the extent of oral absorption is not known.
Mechanism of ToxicityThe mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges. Ethotoin inhibits nerve impulses in the motor cortex by lowering sodium ion influx, limiting tetanic stimulation.
MetabolismHepatic. The drug exhibits saturable metabolism with respect to the formation of N-deethyl and p-hydroxyl-ethotoin, the major metabolites. Half Life: 3 to 9 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the control of tonic-clonic (grand mal) and complex partial (psychomotor) seizures.
Minimum Risk LevelNot Available
Health EffectsMay cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
SymptomsSymptoms of overdose include drowsiness, loss of or impaired muscle coordination, nausea, visual disturbance, and, at very high doses, coma.
TreatmentTreatment should be begun by inducing emesis; gastric lavage may be considered as an alternative. General supportive measures will be necessary. A careful evaluation of blood-forming organs should be made following recovery. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00754
HMDB IDHMDB14892
PubChem Compound ID3292
ChEMBL IDCHEMBL1095
ChemSpider ID3176
KEGG IDC07839
UniProt IDNot Available
OMIM ID
ChEBI ID4888
BioCyc IDNot Available
CTD IDNot Available
Stitch IDEthotoin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkEthotoin
References
Synthesis Reference

Close, W.J.; U.S. Patent 2,793,157; May 21, 1957; assigned to Abbott Laboratories.

MSDST3D2883.pdf
General References
  1. SCHWADE ED, RICHARDS RK, EVERETT GM: Peganone, a new antiepileptic drug. Dis Nerv Syst. 1956 May;17(5):155-8. [13317788 ]
  2. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
References
  1. Kobayashi K, Yamagami S, Higuchi T, Hosokawa M, Chiba K: Key structural features of ligands for activation of human pregnane X receptor. Drug Metab Dispos. 2004 Apr;32(4):468-72. [15039302 ]