title: 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.
abstract: 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].
authors.affiliation: Dipartimento di Chimica Farmaceutica, Università di Pavia, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Azzolina
authors.forename: V
authors.initials: V
authors.lastname: Dal Piaz
authors.forename: S
authors.initials: S
authors.lastname: Collina
authors.forename: M P
authors.initials: MP
authors.lastname: Giovannoni
authors.forename: C
authors.initials: C
authors.lastname: Tadini
mesh_terms: D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D008968:Molecular Conformation; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011724:Pyridazines / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D010975:Platelet Aggregation Inhibitors; D011724:Pyridazines