Tetracyclic analogues of [+]-S 14297: Synthesis and determination of affinity and selectivity at cloned human dopamine D3 vs D2 receptors

Article abstract of DOI:10.1016/S0960-894X(97)00126-1

Starting from the structure of the preferential D₃ antagonist S 14297 (1), we have prepared a series of cis and trans tetracyclic derivatives of general formula I in order to improve potency and selectivity for D₃ receptors. The trans oxazino derivative 2c, showed slightly increased affinity at D₃ receptors and double the selectivity for D₃ over D₂ receptors, in comparison to S 14297. Cis derivatives and compounds where R₁ is aralkyl were totally devoid of activity.