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

• ChemBase编号: 241
• 分子式: C13H16N2O2
• 平均质量: 232.27834
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione
• IUPAC传统名: 3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione; aminoglutethimide
• 商标名: Cytadren; Elipten; Orimeten
• 别名: 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

登记号

• CAS号: 125-84-8
• EC号: 204-756-4
• MDL号: MFCD00010122
• PubChem SID: 24278142; 46506066; 160963704
• PubChem CID: 2145
• CHEBI ID: 2654
• ATC码: L02BG01
• CHEMBL: 488
• Chemspider ID: 2060
• DrugBank ID: DB00357
• KEGG ID: D00574
• 美国药典/FDA物质标识码: 0O54ZQ14I9
• 维基百科标题: Aminoglutethimide
• Medline Plus: a604039

理论计算性质

JChem

• Acid pKa: 11.691995
• 质子受体: 3
• 质子供体: 2
• LogD (pH = 5.5): 1.2744231
• LogD (pH = 7.4): 1.2991968
• Log P: 1.2995443
• 摩尔折射率: 65.3543 cm^3
• 极化性: 24.911802 Å^3
• 极化表面积: 72.19 Å^2
• 可自由旋转的化学键: 2
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 1.49
• LOG S: -2.8
• 溶解度: 3.71e-01 g/l

分子性质

理化性质

• 溶解度: 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
• 外观: white; White to Off-White Solid
• 熔点: 149-150°C; 152 - 154°C; 152-154 °C(lit.)
• 疏水性(logP): 0.766; 1.3

安全信息

• 保存条件: -20°C Freezer; Room Temperature (15-30°C)
• RTECS编号: MA4026950
• 欧盟危险性物质标志: 刺激性(Irritant) (Xi)
• 德国WGK号: 3
• 危险公开号: 36/37/38
• 安全公开号: 26-36
• GHS危险品标识: GHS07
• GHS警示词: Warning
• GHS危险声明: H315-H319-H335
• GHS警示性声明: P261-P305 + P351 + P338
• 个人保护装置: dust mask type N95 (US), Eyeshields, Gloves

药理学性质

• 作用靶点: Aromatase
• 给药途径: Oral
• 生物利用度: >95%
• 排泄: Renal
• 半衰期: 12.5 ± 1.6 hours
• 代谢: Hepatic
• 妊娠期药物分类: D (Australia); D (US)
• 相关基因信息: human ... CYP17A1(1586), CYP19A1(1588)rat ... Cyp19a1(25147)
• 生物活性机理: 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

产品相关信息

• 纯度: 95%
• 成盐信息: Free Base
• 应用领域: 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.

详细说明

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.

参考文献

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