Aminoglutethimide (CHEM003763)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (2)XML
Record Information
Version1.0
Creation Date2014-09-11 05:17:25 UTC
Update Date2016-11-09 01:09:13 UTC
Accession NumberCHEM003763
Identification
Common NameAminoglutethimide
ClassSmall Molecule
DescriptionAn aromatase inhibitor that produces a state of 'medical' adrenalectomy by blocking the production of adrenal steroids. It also blocks the conversion of androgens to estrogens. Aminoglutethimide has been used in the treatment of advanced breast and prostate cancer. It was formerly used for its weak anticonvulsant properties.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Amide
  • Amine
  • Antineoplastic Agent, Hormonal
  • Aromatase Inhibitor
  • Drug
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
2-(p-Aminophenyl)-2-ethylglutarimideChEBI
3-Ethyl-3-(p-aminophenyl)-2,6-dioxopiperidineChEBI
alpha-(p-Aminophenyl)-alpha-ethylglutarimideChEBI
AminoglutethimidumChEBI
AminoglutetimidaChEBI
DL-AminoglutethimideChEBI
p-AminoglutethimideChEBI
CytadrenKegg
a-(p-Aminophenyl)-a-ethylglutarimideGenerator
Α-(p-aminophenyl)-α-ethylglutarimideGenerator
Ciba vision brand OF aminoglutethimideHMDB
Novartis brand OF aminoglutethimideHMDB
OrimetenHMDB
Chemical FormulaC13H16N2O2
Average Molecular Mass232.278 g/mol
Monoisotopic Mass232.121 g/mol
CAS Registry Number125-84-8
IUPAC Name3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione
Traditional Nameaminoglutethimide
SMILESCCC1(CCC(=O)NC1=O)C1=CC=C(N)C=C1
InChI IdentifierInChI=1S/C13H16N2O2/c1-2-13(8-7-11(16)15-12(13)17)9-3-5-10(14)6-4-9/h3-6H,2,7-8,14H2,1H3,(H,15,16,17)
InChI KeyROBVIMPUHSLWNV-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as aniline and substituted anilines. These are organic compounds containing an aminobenzene moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassAniline and substituted anilines
Direct ParentAniline and substituted anilines
Alternative Parents
Substituents
  • Aniline or substituted anilines
  • Tetrahydropyridine
  • Hydropyridine
  • Amino acid or derivatives
  • N-acylimine
  • Lactim
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboxylic acid derivative
  • Azacycle
  • Organopnictogen compound
  • Amine
  • Organic oxygen compound
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • 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
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point223-225°C
Boiling PointNot Available
SolubilityPractically insoluble in water
Predicted Properties
PropertyValueSource
Water Solubility0.37 g/LALOGPS
logP1.49ALOGPS
logP1.3ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)11.69ChemAxon
pKa (Strongest Basic)4.28ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area72.19 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity65.35 m³·mol⁻¹ChemAxon
Polarizability24.69 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0ue9-5960000000-f9b33cb2d18e6b01ae76Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0ue9-5960000000-f9b33cb2d18e6b01ae76Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-01q9-0930000000-1559858da10d4930e919Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0540-2960000000-949d8dddc3981b8c3e63Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0uxr-0905000000-155a653652a8dc132b5cSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-001j-3910000000-d92bbd37c74ab8b7828dSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0540-1970000000-fc41c032a79d79173387Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0540-2960000000-949d8dddc3981b8c3e63Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-001j-3910000000-d92bbd37c74ab8b7828dSpectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-00di-0910000000-2af28058ce65d2c2b40eSpectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-00di-0920000000-a50aa2833e911342e507Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-00di-0900000000-d172683054220fdf2313Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-05fr-0900000000-3564a0e475748f410e23Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-014i-0290000000-99e0c515559b4638490aSpectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-0159-0090000000-22908f241db3fc37cdbcSpectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-0a59-0900000000-6a7e540e50c50942e829Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-001i-0900000000-3c4030cf08f3c992fdacSpectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-0006-0900000000-8be298c9d42d7769f129Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-0006-0900000000-a290024caadd7d64fe8fSpectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-00kf-0940000000-ce0f2ff21762621367e5Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-0006-0900000000-24977ebbbf8d80633142Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00lr-0190000000-bd92b28e06f9a2c94ab1Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00lr-0590000000-2ecccc66bf459b9dff9bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00l2-2900000000-486145b0245b40ea818cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0090000000-b5c20a34adc0796f60c2Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01q9-1190000000-e50243f982300e3ad740Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9410000000-a3860f54f1f49a280fb8Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0090000000-62df4688c2e6b97f190fSpectrum
MSMass Spectrum (Electron Ionization)splash10-0f89-3950000000-013571ce504af9a2d603Spectrum
Toxicity Profile
Route of ExposureRapidly and completely absorbed from gastrointestinal tract. The bioavailability of tablets is equivalent to equal doses given as a solution.
Mechanism of ToxicityAminoglutethimide reduces the production of D5-pregnenolone and blocks several other steps in steroid synthesis, including the C-11, C-18, and C-21 hydroxylations and the hydroxylations required for the aromatization of androgens to estrogens, mediated through the binding of aminoglutethimide to cytochrome P-450 complexes. Specifically, the drug binds to and inhibits aromatase which is essential for the generation of estrogens from androstenedione and testosterone. A decrease in adrenal secretion of cortisol is followed by an increased secretion of pituitary adrenocorticotropic hormone (ACTH), which will overcome the blockade of adrenocortical steroid synthesis by aminoglutethimide. The compensatory increase in ACTH secretion can be suppressed by the simultaneous administration of hydrocortisone. Since aminoglutethimide increases the rate of metabolism of dexamethasone but not that of hydrocortisone, the latter is preferred as the adrenal glucocorticoid replacement. Although aminoglutethimide inhibits the synthesis of thyroxine by the thyroid gland, the compensatory increase in thyroid-stimulating hormone (TSH) is frequently of sufficient magnitude to overcome the inhibition of thyroid synthesis due to aminoglutethimide. In spite of an increase in TSH, aminoglutethimide has not been associated with increased prolactin secretion.
MetabolismHepatic. 34-54% of the administered dose is excreted in the urine as unchanged drug during the first 48 hours, and an additional fraction as an N-acetyl derivative. Route of Elimination: After ingestion of a single oral dose, 34%-54% is excreted in the urine as unchanged drug during the first 48 hours, and an additional fraction as the N-acetyl derivative. Half Life: 12.5 ± 1.6 hours
Toxicity ValuesOral LD50s (mg/kg): rats, 1800; dogs, >100. Intravenous LD50s (mg/kg): rats, 156; dogs, >100.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the suppression of adrenal function in selected patients with Cushing's syndrome, malignant neoplasm of the female breast, and carcinoma in situ of the breast.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include respiratory depression, hypoventilation, hypotension, hypovolemic shock due to dehydration, somnolence, lethargy, coma, ataxia, dizziness, fatigue, nausea, and vomiting.
TreatmentNot Available
Concentrations
Not Available
DrugBank IDDB00357
HMDB IDHMDB0014501
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkAminoglutethimide
Chemspider ID2060
ChEBI ID2654
PubChem Compound ID2145
Kegg Compound IDC07617
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Hoffmann, K.and Urech, E.; U.S. Patent 2,848,455; August 19,1958; assigned to Ciba Pharmaceutical Products, Inc.

MSDSNot Available
General References
1. https://www.ncbi.nlm.nih.gov/pubmed/?term=11916226
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=17602675
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=24350727