CHIRAL RESOLUTION AND ABSOLUTE-CONFIGURATION OF THE ENANTIOMERS OF ETHYL-4-METHYLSULFINYL-6-PHENYL-3(2H)-PYRIDAZINONE AND EVALUATION OF THEIR PLATELET-AGGREGATION INHIBITORY ACTIVITY

In a series of -acyl-6-phenyl-2,4-substituted-3(2H)-pyridazinones the derivative 1a, with a sulfur stereogenic center, had the most potent a ctivity as human platelet aggregation inhibitor. The resolution of rac -1a was successfully performed by chiral chromatography on Chiralcel O D-R, OD-H, and Chiralpak AD columns and scaled up to a preparative lev el. The absolute configuration of (-)-(S)-1a was determined by X-ray c rystallographic analysis. In vitro human platelet aggregation inhibito ry activity was evaluated. Both the enantiomers showed IC50 values in the same micromolar range, but the (-)-(S) isomer was slightly more po tent [(S)/(R) potency ratio was 4/1]. (C) 1997 Wiley-Liss, Inc.