Synthesis of 6-substituted 1-phenylbenzazepines and their dopamine D1 receptor activities

A series of racemic 6-aryl substituted 1-phenylbenzazepines 7a–e, and 17a,b were prepared. All these compounds showed binding potencies compatible to or much higher than that of the prototypic (±)-SKF-38393 ((±)-1) and (±)-SKF-83959 (3) for the D1 receptor. Among analogs of (±)-SKF-38393, compounds 7b, 7c and 7e possess 10-, 2- and 7-fold enhancement in binding for the D1 receptor, respectively. Lower but compatible potency to that of (±)-1 was observed for compounds 7a and 7d. The optimal 6-substituents (m-tolyl, and 2′-naphthyl) were applied to the skeleton of (±)-SKF-83959 (3). The resulting compounds 17a,b displayed high affinity at the D1 receptor, only slightly lower than that of 3. These two compounds also showed good binding at the D2 receptor.

A series of 6-substituted analogs of (±)-SKF-38393 ((±)-1) was synthesized, and their binding affinity for dopamine receptors (D1, D2) and serotonin receptors (5-HT1A, 5-HT2A) were evaluated.Figure optionsDownload as PowerPoint slide