Premium
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
Author(s) -
Moniz George A.,
Hammond Gerald B.
Publication year - 1997
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570340250
Subject(s) - aminoglutethimide , chemistry , aromatase , side chain , stereochemistry , aldehyde , biochemistry , organic chemistry , medicine , cancer , breast cancer , catalysis , polymer
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.