Enantioselectivity of aromatase inhibitors: Substituted 3-(4-aminophenyl)pyrrolidine-2,5-diones

Autor:	Chris Pepper, Massoud Ahmadi, H. John Smith, Paul J. Nicholls, Kevin J. Barrell
Rok vydání:	1995
Předmět:	Pharmacology biology Stereochemistry Organic Chemistry Substrate (chemistry) Catalysis Pyrrolidine Analytical Chemistry chemistry.chemical_compound chemistry Drug Discovery Ic50 values biology.protein medicine Aromatase Binding site Enantiomer IC50 Spectroscopy Aminoglutethimide medicine.drug
Zdroj:	Chirality. 7:376-380
ISSN:	1520-636X 0899-0042
DOI:	10.1002/chir.530070511
Popis:	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.
Databáze:	OpenAIRE
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