On the relocation of the amino functionality to the ethyl side chain in aminoglutethimide: Synthesis and aromatase-inhibitory activity of 3-(2′-N,N-diethyl-amino)ethyl-3-phenylpiperidine-2,6-dione

✍ Scribed by George A. Moniz; Gerald B. Hammond

• Book ID: 102346006
• Publisher: Journal of Heterocyclic Chemistry
• Year: 1997
• Tongue: English
• Weight: 311 KB
• Volume: 34
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570340250

✦ Synopsis

Abstract

Aminoglutethimide [3‐(4‐aminophenyl)‐3‐ethylpiperidine‐2,6‐dione] has been used clinically in the treatment of metastatic breast carcinoma. Inhibition of tumor growth is due to interference with estrogen biosynthesis. However, its action is not specific and its metabolism gives rise to toxic and non‐inhibitory metabolites. We sought to explore the impact of relocating the amino group in aminoglutethimide to the ethyl side chain. To that end, we now report the synthesis and aromatase‐inhibitory activity of 3‐(2′‐N,N‐diethylamino)ethyl‐3‐phenylpiperidine‐2,6‐dione 5. The introduction of the amino functionality on the ethyl group is accomplished via reductive animation of aldehyde 8, prepared in three steps from benzyl cyanide. The synthetic route presented can be used for the preparation of related derivatives of aminoglutethimide.