ISSN:
0899-0042
Keywords:
aromatase
;
P450AROM
;
cholesterol side chain cleavage enzyme
;
P450CSCC
;
spectral binding studies
;
inhibition
;
substituted 3-(4-aminophenyl)pyrrolidine-2,5-diones
;
aminoglutethimide
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The (+)-, (-)-, and (±)-forms of 1- and 1,3-substituted 3-(4-aminophenyl)pyrrolidine-2,5-dione have been examined as inhibitors of P450AROM and P450CSCC. The inhibitory potency for P450AROM resided in the (+)-enantiomers of (1), (2), and (4) and the (-)-enantiomers of (3) and (5). These findings have been accommodated within a molecular graphics-derived model for binding of P450AROM inhibitors to the substrate binding site. Crystallography showed that (+)-(2) has the (R)-configuration. Spectral binding studies with human placental P450AROM showed type II binding but although the KS values were in line with the IC50 values for individual compounds there was no overall correlation between KS and IC50 within the series. There was little difference in the inhibitory potency of the enantiomers and racemate of individual compounds toward P450CSCC. © 1995 Wiley-Liss, Inc.
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chir.530070511
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