Chiral resolution and absolute configuration of the enantiomers of 5-acetyl-2-methyl-4-methylsulfinyl-6-phenyl-3(2H)-pyridazinone and evaluation of their platelet aggregation inhibitory activity
✍ Scribed by Ornella Azzolina; Vittorio Dal Piaz; Simona Collina; Maria Paola Giovannoni; Carla Tadini
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 96 KB
- Volume
- 9
- Category
- Article
- ISSN
- 0899-0042
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✦ Synopsis
In a series of 5-acyl-6-phenyl-2,4-substituted-3(2H)-pyridaziones the derivative 1a, with a sulfur stereogenic center, had the most potent activity as human platelet aggregation inhibitor. The resolution of rac-1a was successfully performed by chiral chromatography on Chiralcel OD-R, OD-H, and Chiralpak AD columns and scaled up to a preparative level. The absolute configuration of (-)-(S)-1a was determined by X-ray crystallographic analysis. In vitro human platelet aggregation inhibitory activity was evaluated. Both the enantiomers showed IC50 values in the same micromolar range, but the (-)-(S) isomer was slightly more potent [(S)/(R) potency ratio was 4/1].