Orally Active Oxime Derivatives of the Dopaminergic Prodrug 6-(N,N-Di-n-propylamino)-3,4,5,6,7,8-hexahydro-2H-naphthalen-1-one. Synthesis and Pharmacological Activity

A series of racemic and enantiomerically pure oxime derivatives of the potential anti-Parkinson prodrug 6-(N V-di-n-propylamino)-3,4,5,6,7,8-hexahydro-2H-naphthalen-l-one (1) were synthesized and pharmacologically evaluated. The oximes induced rotational behavior in the Ungerstedt rat rotation model for Parkinson's disease after oral administration. Especially the unsubstituted oxime ((-)-3) and the acetyl-oxime ((-)-10) induced a pronounced and long lasting effect. In this model, large individual differences were observed in responsiveness to treatment between rats. Though less potent than the parent prodrug, the oxime derivatives of (+/-)-l and (-)-l can be orally active, acting as cascade prodrugs.