Abstract
The enantiomers of the aromatase inhibitors 3-(4-aminophenyl)-pyrrolidine-2,5-dione (WSP-3, II), its N-pentyl derivative (III), and the antifungal econazole (IV), all possessing a benzylic proton at the chiral centre, are rapidly racemised in vitro in phosphate buffer (0.01 M) at pH 7.4 and 23 degrees C with t 1/2 values of 7, 6, and 5 h respectively. In vivo studies in rats show that (+)-econazole is racemised after intraperitoneal injection with t 1/2 = 1.24h. The enantiomers of the antifungal 1-[(benzofuran-2-yl)-4-chlorophenylmethyl] imidazole (V) were stable at pH 7.4, attributable to steric hindrance to carbanion formation in the racemisation step.
MeSH terms
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Aniline Compounds / chemistry*
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Aniline Compounds / isolation & purification
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Aniline Compounds / pharmacology
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Animals
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Aromatase Inhibitors
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Buffers
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Econazole / chemistry*
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Econazole / isolation & purification
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Econazole / pharmacology
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Half-Life
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Hydrogen-Ion Concentration
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Kinetics
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Phosphates
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Protons
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Pyrrolidinones / chemistry*
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Pyrrolidinones / isolation & purification
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Pyrrolidinones / pharmacology
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Rats
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Stereoisomerism
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Succinimides / chemistry*
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Succinimides / isolation & purification
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Succinimides / pharmacology
Substances
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1-pentyl-3-(4-aminophenyl)pyrrolidine-2,5-dione
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Aniline Compounds
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Aromatase Inhibitors
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Buffers
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Phosphates
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Protons
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Pyrrolidinones
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Succinimides
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3-(4'-aminophenyl)pyrrolidine-2,5-dione
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Econazole