3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione

• ChemBase ID: 241
• Molecular Formular: C13H16N2O2
• Molecular Mass: 232.27834
• Monoisotopic Mass: 232.12117776
• SMILES: O=C1NC(=O)CCC1(CC)c1ccc(N)cc1
• Canonical SMILES: CCC1(CCC(=O)NC1=O)c1ccc(cc1)N
• InChI: InChI=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)
• InChIKey: ROBVIMPUHSLWNV-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione
• IUPAC Traditional name: 3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione; aminoglutethimide
• Brand Name: Cytadren; Elipten; Orimeten
• Synonyms: Cytadren; Elipten; Orimeten; Aminoglutethimide; DL-Aminoglutethimide; 3-(4-Aminophenyl)-3-ethyl-2,6-piperidinedione; 3-(p-Aminophenyl)-3-ethylpiperidine-2,6-dione; (±)-p-AMINOGLUTETHIMIDE; 3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione; Aminoglutethimide (Cytadren); Dl-Aminoglutethimide; P-Aminoglutethimide; Aminoglutethimide

Database IDs

• CAS Number: 125-84-8
• EC Number: 204-756-4
• MDL Number: MFCD00010122
• PubChem SID: 160963704; 24278142; 46506066
• PubChem CID: 2145
• CHEBI ID: 2654
• ATC CODE: L02BG01
• CHEMBL: 488
• Chemspider ID: 2060
• DrugBank ID: DB00357
• KEGG ID: D00574
• Unique Ingredient Identifier: 0O54ZQ14I9
• Wikipedia Title: Aminoglutethimide
• Medline Plus: a604039

CALCULATED PROPERTIES

JChem

• Acid pKa: 11.691995
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): 1.2744231
• LogD (pH = 7.4): 1.2991968
• Log P: 1.2995443
• Molar Refractivity: 65.3543 cm^3
• Polarizability: 24.911802 Å^3
• Polar Surface Area: 72.19 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.49
• LOG S: -2.8
• Solubility (Water): 3.71e-01 g/l

PROPERTIES

Physical Property

• Solubility: 0.1 M HCl: soluble; 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: soluble1.2 mg/mL; acetonitrile: soluble; Chloroform; Dichloromethane; DMSO; Ethyl Acetate; H2O: slightly soluble0.2 mg/mL; Hexane; methanol: soluble; Practically insoluble in water
• Apperance: white; White to Off-White Solid
• Melting Point: 149-150°C; 152 - 154°C; 152-154 °C(lit.)
• Hydrophobicity(logP): 0.766; 1.3

Safety Information

• Storage Condition: -20°C Freezer; Room Temperature (15-30°C)
• RTECS: MA4026950
• European Hazard Symbols: Irritant (Xi)
• German water hazard class: 3
• Risk Statements: 36/37/38
• Safety Statements: 26-36
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H315-H319-H335
• GHS Precautionary statements: P261-P305 + P351 + P338
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves

Pharmacology Properties

• Target: Aromatase
• Admin Routes: Oral
• Bioavailability: >95%
• Excretion: Renal
• Half Life: 12.5 ± 1.6 hours
• Metabolism: Hepatic
• Pregnancy Category: D (Australia); D (US)
• Gene Information: human ... CYP17A1(1586), CYP19A1(1588)rat ... Cyp19a1(25147)
• Mechanism of Action: Androgen synthesis inhibitor; Aromatase inhibitor; Cholesterol desmolase inhibitor; Corticosteroid antagonist; Corticosteroid synthesis inhibitor; Inhibits hydroxylations required for aromatization of androgens to estrogens; Mineralocorticoid synthesis inhibitor

Product Information

• Purity: 95%
• Salt Data: Free Base
• Application(s): Inhibits adrenal corticosteroid synthesis; Now used as aromatase inhibitor for treatment of breast cancer in postmenopausal women and for treatment of secondary hyperaldosteronism and oedema; Originally used as anticonvulsant, withdrawn due to adrenotoxicity.

DETAILS

MP Biomedicals - 02153645

Inhibitor of cytochrome P-450-dependent hydroxylation reactions.

DrugBank - DB00357

• Drug Groups: approved
• Description: An 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. (From Martindale, The Extra Pharmacopoeia, 30th ed, p454)
• Indication: For 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.
• Pharmacology: Aminoglutethimide inhibits the enzymatic conversion of cholesterol to D5-pregnenolone, resulting in a decrease in the production of adrenal glucocorticoids, mineralocorticoids, estrogens, and androgens.
• Toxicity: Oral LD50s (mg/kg): rats, 1800; dogs, >100. Intravenous LD50s (mg/kg): rats, 156; dogs, >100. Symptoms of overdose include respiratory depression, hypoventilation, hypotension, hypovolemic shock due to dehydration, somnolence, lethargy, coma, ataxia, dizziness, fatigue, nausea, and vomiting.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. 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.
• Absorption: Rapidly and completely absorbed from gastrointestinal tract. The bioavailability of tablets is equivalent to equal doses given as a solution.
• Half Life: 12.5 ± 1.6 hours
• Protein Binding: 21-25%
• 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.
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - A9657

Biochem/physiol Actions
DL-Aminoglutethimide is a derivative of the sedative glutethimide. Originally introduced as an anticonvulsant, it was found to cause adrenal insufficiency. Blocks adrenal steroidogenesis by inhibiting the enzymatic conversion of cholesterol to pregnenolone. It also blocks the peripheral conversion (aromatization) of androgenic precursors to estrogens. The D-isomer is 30 times more potent at inhibiting aromatase activity, whereas the L-isomer is more potent at inhibiting cholesterol side-chain cleavage (steroidogenesis).
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. A9657.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - A609810

An aromatase inhibitor. Also blocks adrenal steroidogenesis.

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