PMID: 3754286Apr 1, 1986Paper

Synthesis and biochemical evaluation of analogues of aminoglutethimide based on phenylpyrrolidine-2,5-dione

Journal of Medicinal Chemistry
M J DalyM A Bunnett

Abstract

A series of (aminophenyl)pyrrolidine-2,5-diones has been prepared that bear structural similarities to aminoglutethimide (1, 3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione). The inhibitory activity of these compounds was evaluated toward human placental aromatase and bovine adrenal cholesterol side chain cleavage (CSCC) enzyme assay systems. Selective, competitive inhibition of the aromatase enzyme system was demonstrated by 5 (3-(4-aminophenyl)-1-methyl-pyrrolidine-2,5-dione, Ki = 1.75 microM), 6 (3-(4-aminophenyl)-1,3-dimethylpyrrolidine-2,5-dione, Ki = 1.75 microM), 7 (3-(4-aminophenyl)-3-methylpyrrolidine-2,5-dione, Ki = 0.8 microM), and 8 (3-(4-aminophenyl)-3-ethylpyrrolidine-2,5-dione, Ki = 1.0 microM). Compound 15 (3-(4-aminophenyl)pyrrolidine-2,5-dione) proved unexpectedly difficult to prepare following standard methods and was only moderately inhibitory toward aromatase (IC50 = 20 microM). Compound 16 (3-(4-aminophenyl)-3-ethyl-1-methylpyrrolidine-2,5-dione) was weakly inhibitory toward testosterone aromatization and totally inactive toward androstenedione aromatization. These compounds were either weak or ineffective inhibitors of the CSCC enzyme systems, while 1 gave Ki values toward aromatase and CSCC enzymes of 0.68...Continue Reading

Citations

Mar 1, 1987·Journal of Steroid Biochemistry·M H PourgholamiJ Dyas
Jul 1, 1988·Journal of Steroid Biochemistry·M A ShawH J Smith
Dec 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·R W HartmannM Palzer
Dec 1, 2003·Environmental Toxicology and Pharmacology·Michael D ColemanPaul J Nicholls
Jan 1, 1990·Journal of Enzyme Inhibition·A S BhatnagarK Schieweck
May 26, 2017·Chemical Communications : Chem Comm·Kiran R BettadapurKandikere Ramaiah Prabhu
Sep 11, 2008·Bioorganic & Medicinal Chemistry·Sabrina CastellanoGianluca Sbardella
Jul 12, 2002·Archiv der Pharmazie·Rolf W HartmannYan Zhuang
Jan 1, 1990·Acta Oncologica·P E Lønning
Oct 1, 1987·The Journal of Pharmacy and Pharmacology·S Rao, P J Nicholls
Jan 1, 1988·Journal of Enzyme Inhibition·L BantingM G Rowlands
Dec 31, 2020·Bioorganic Chemistry·Zefeng ZhaoXiaohui Zheng

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