6533b827fe1ef96bd1287066
RESEARCH PRODUCT
Synthesis, configuration, and calcium modulatory properties of enantiomerically pure 5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylates.
Rose UDräger Msubject
MaleIntrinsic activityGuinea PigsMolecular Conformationchemistry.chemical_elementCalciumQuinolonesMedicinal chemistrychemistry.chemical_compoundX-Ray DiffractionIleumDrug DiscoveryAnimalsHeart AtriaAortaChiral auxiliaryBicyclic moleculeMolecular StructureEnantioselective synthesisAbsolute configurationBiological activityStereoisomerismPapillary MusclesAtrial FunctionCalcium Channel BlockersElectric StimulationchemistryReagentMolecular MedicineFemaleMuscle Contractiondescription
Enantiomerically pure hexahydroquinolinones of the structural type 9 were prepared by a variation of the Hantzsch synthesis in which an optically active acetoacetate served as a chiral auxiliary reagent. Determinations of the de and ee values are described. The absolute configurations of the optically pure products were characterized by single-crystal X-ray analysis. The antipodes 9a and 9b exhibited calcium antagonistic activities on smooth musculature; the (S)-(-)-enantiomer 9b was the more potent compound with regard to the EC50 values which differed by a factor of 100; the intrinsic activity of 9b was 1.2, compared with a value of 0.54 for 9a. On the other hand, R-(+)-9a exerted positive inotropic effects on electrically stimulated atria. The cause of these effects is discussed.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1992-06-01 | Journal of medicinal chemistry |