Aminoglutethimide

Patent 2,453,234 November 9,1948 assigned to American Enka Corporation 

Chemical Name 3-(4-Aminophenyl)-3-ethyl-2,6-piperidinedione Common Name a-(p-aminophenyl)-a-ethyl-glutarimide Structural Formula  

Trade Name Manufacturer Country Year Introduced 

The 0 -(p-nitrophenyl)-0 -ethyl-glutarimide starting material can be prepared as follows 217 g of a-phenyl-a-ethyl-glutarimide are dissolved in 800 g of concentrated sulfuric acid with subsequent cooling to about -10°C and nitration is carried out at -10°to +10°C by slow addition of a mixed acid consisting of 110 g of concentrated sulfuric acid and 110 g of 63% nitric acid. The nitration solution is stirred into ice, the separated nitro compound taken up in methylene or ethylene chloride, the solution washed with water and sodium carbonate solution until 

2 g of a-(p-nitrophenyl) -a-ethyl-glutarimide of MP 137°-139°C dissolved in ethyl acetate, are reduced In the presence of nickel with hydrogen in a shaking flask at 50°-70°C until the absorption of hydrogen falls off. The catalyst is then filtered off with suction and the solution concentrated and cooled, as a result of which colorless crystals of MP 146°-149°C are obtained. Recrystallization from methanol gives pure a-(p-aminophenyl)-a-ethyl-glutarimide of MP 149°-150°C (yield 97%). 

Instead of ethyl acetate another solvent can be used in the above reduction, such as methanol or ethanol. 

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Anastrazole is a nonsteroidal, type H, aromatase inhibitor that is 200 times more potent than aminoglutethimide. It is eliminated primarily via hqDatic metabolism, has a terminal half life of 50 h with steady state concentrations achieved approximately 10 days with once daily dosing regimens. It is administered orally at a dose of 1 mg/day that achieves near maximal aromatase inhibition and hence estrogen suppression in breast cancer patients. No effect on adrenal steroidogenesis has been observed at up to ten times the daily recommended dose. When used in the metastatic setting, anastrozole has been shown... 

C4H(j02 96-33-3) see Aminoglutethimide Eprosartan Glutethimide Hexobendine Levocabastine Nialamide Phenglutarimide Pioglitazone Remifentanil Vincamine acrylonitrile... 

Inhibitors of Adrenal Steroidogenesis Aminoglutethimide Inhibits conversion of 250 mg every High incidence of Used in ACTH-independent cases... 

Etomidate Inhibits 1 7, 20-lyase, 6 g/day Limited clinical hypokalemia, edema, hypertension. Injection-site pain, aminoglutethimide if used in combination. Intravenous route of administration... 

Aminoglutethimide blocks the conversion of androgens to estrogens and decreases the synthesis of glucocorticoids. 

Combination therapy with metyrapone and aminoglutethimide appears more effective than either agent alone for various etiologies of Cushing s disease with fewer side effects and is useful for inoperable patients. 

Androgen synthesis inhibitors provide symptomatic, but brief, relief in approximately 50% of patients. Aminoglutethimide causes adverse effects in 50% of patients, such as lethargy, ataxia, dizziness, and self-limiting rash. The adverse effects of ketoconazole are GI intolerance, transient increases in liver and renal function tests, and hypoadrenalism. 

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