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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
Author(s) -
Azzolina Ornella,
Dal Piaz Vittorio,
Collina Simona,
Giovani Maria Paola,
Tadini Carla
Publication year - 1997
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1997)9:7<681::aid-chir8>3.0.co;2-a
Subject(s) - chemistry , enantiomer , absolute configuration , resolution (logic) , stereochemistry , platelet , inhibitory postsynaptic potential , platelet aggregation , artificial intelligence , computer science , immunology , biology , neuroscience
In a series of 5‐acyl‐6‐phenyl‐2,4‐substituted‐3(2H)‐pyridazinones 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 IC 50 values in the same micromolar range, but the (−)‐(S) isomer was slightly more potent [(S)/(R) potency ratio was 4/1]. Chirality 9:681–685, 1997. © 1997 Wiley‐Liss, Inc.