HARTMANN, RW and BATZL, C and PONGRATZ, TM and MANNSCHRECK, A (1992) SYNTHESIS AND AROMATASE INHIBITION OF 3-CYCLOALKYL-SUBSTITUTED 3-(4-AMINOPHENYL)PIPERIDINE-2,6-DIONES. JOURNAL OF MEDICINAL CHEMISTRY, 35 (12). pp. 2210-2214. ISSN 0022-2623,
Full text not available from this repository.Abstract
The synthesis of 3-cycloalkyl-substituted 3-(4-aminophenyl)piperidine-2,6-diones is described [cyclopentyl (1), cydohexyl (2)]. The enantiomers of 2 were separated either by using HPLC on optically active sorbent or by crystallization of the brucine salt of the phthalamic acid of 2. The absolute configuration of the (+)- and (-)-enantiomers of 2 were assigned as S and R, respectively, by comparing the CD spectra to those of the enantiomers of aminoglutethimide (AG, 3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione). The compounds were tested in vitro for inhibition of human placental aromatase, the cytochrome P450-dependent enzyme which is responsible for the conversion of androgens to estrogens. Compounds 1 and 2 inhibited aromatase by 50% at 1.2 and 0.3-mu-M, respectively (IC50 AG = 37-mu-M). According to the findings with AG, the (+)-enantiomer of 2 was responsible for the inhibitory activity, being a 240-fold more potent aromatase inhibitor in vitro than racemic AG. On the other hand, (+)-2 displayed a strongly reduced inhibition of desmolase (cholesterol side-chain cleavage enzyme) compared to AG (relative activity = 0.3). Thus (+)-2 is of interest as a potential drug for the treatment of estrogen-dependent diseases, e.g. mammary tumors.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SELECTIVE-INHIBITION; AMINOGLUTETHIMIDE; ANALOGS; CHOLESTEROL; ENANTIOMERS; |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/54502 |
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