Synthesis and aromatase inhibitory activity of novel 1-(4-aminophenyl)-3-azabicyclo[3.1.0]hexane- and -[3.1.1]heptane-2,4- diones.
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Stanek J, Alder A, Bellus D, Bhatnagar AS, Hausler A, Schieweck K
Synthesis and aromatase inhibitory activity of novel 1-(4-aminophenyl)-3-azabicyclo[3.1.0]hexane- and -[3.1.1]heptane-2,4- diones.
J Med Chem. 1991 Apr;34(4):1329-34.
- PubMed ID
- 2016706 [ View in PubMed]
- Abstract
The synthesis of 3-(cyclohexymethyl)-1-(4-aminophenyl)-3-azabicyclo[3.1.0]hexane-2, 4-dione (1h), with its optical enantiomers, and a series of novel achiral 1-(4-aminophenyl)-3-azabicyclo[3.1.1]haptane-2,4-diones (2a-i,k) is described. These compounds were tested in vitro for inhibition of human placental aromatase, a cytochrome-P450-dependent enzyme responsible for the conversion of androgens to estrogens. All of them displayed enzyme-inhibiting activity, and 3-cyclohexyl derivative 2g and 3-cyclohexylmethyl derivative 1h both proved more potent (greater than 140-fold) than the clinically effective agent aminoglutethimide [3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione, AG]. As with AG and its derivatives, the 1R-(+)-enantiomer of 1h was responsible for the enzyme inhibitory activity. These novel compounds are of interest as potential drugs for endocrine therapy of hormone-dependent tumors, e.g. breast cancer.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Aminoglutethimide Cytochrome P450 19A1 IC 50 (nM) 13000 N/A N/A Details Aminoglutethimide Cytochrome P450 19A1 IC 50 (nM) 1900 N/A N/A Details