| 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°C with t½ values of 7, 6, and 5 h respectively. In vivo studies in rats show that (+)-econazole is racemised after intraperitoneal injection with t½ = 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. © 1994 Wiley-Liss, Inc. |
