Piperidinediones, III. Structure‐Activity Relationships of the Enantiomers of a Series of 2,6‐Piperidinedione Derivatives

Abstract

Among the racemic 2.6-piperidinediones 1-6, compound 6 has the highest anesthetic activity. The enantiomers of 1, 2 , 4 and 5 possess different anesthetic potencies depending on the nature of the aliphatic side chain. The S(-)-enantiomen of the piperidinediones 2, 3 and 5 cause initial CNS stimulation with convulsive symptoms followed by anesthesia. Piperidindione, 3. Mitt.: Struktur-Aktivitiitsbeziehungen der Enantiomere einer Reihe systematisch abgewandelter 2.6-PiperidmdioneVon den racem. 2.6-Piperidindionen 1-6 ist die Verbindung 6 die narkotisch wirksamste Verbindung. Die Enantiomere von 1 , 2 , 4 und 5 besitzen in Abhangigkeit von der aliphatischen Seitenkette eine unterschiedliche narkotische Wirkungsstarke. Die S(-)-Enantiomere der Piperidindione 2,3 und 5 verursachen initial ZNS-Stimulation mit konvulsiven Symptomen, gefolgt von Narkose.The racemates and the enantiomers of the 2.6-piperidinediones 1-6 (tab. l), structurally related to the sedative-hypnotic glutethimide (Doriden@), were synthesized') and their absolute configuration was deduced') (tab. 1).Earlier investigations showed that the enantiomers of N-methylated barbituric acids stereoselectively produce manifold different pharmacodynamic and pharmacokinetic effects%').