N-Substituted-2-alkyl- and 2-arylnorapomorphines: Novel,highly active D2 agonists

Two synthesis routes have been elaborated for the preparation of novel N-substituted-2-alkyl- and 2-arylnorapomorphines. The first one utilizes the traditional methodology of N-substitution of morphinans before acid-catalyzed rearrangements into aporphinoids, while our new approach involves the N-substitution directly on the aporphine backbone. The aimed compounds were obtained in similar overall yields in different synthesis routes and were investigated with respect to their binding affinities and activities to dopamine D₂ and D₁ receptors. These studies revealed remarkable affinity and selectivity of some compounds for D₂ over D₁ receptor subtypes. Partial or full agonist properties were confirmed for all tested compounds.