Synthesis, configuration, and calcium modulatory properties of enantiomerically pure 5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylates.
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.
Rose
U
U
Institut für Pharmazie, Johannes Gutenberg-Universität Mainz, Federal Republic of Germany.
Dräger
M
M
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D016275:Atrial Function; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008297:Male; D008968:Molecular Conformation; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D014961:X-Ray Diffraction
D002121:Calcium Channel Blockers; D015363:Quinolones; C075254:methyl 2-methyl-4-(3,4-(methylenedioxy)phenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate