Synthesis and dopaminergic binding of 2-aryldopamine analogues: phenethylamines, 3-benzazepines, and 9-(aminomethyl)fluorenes.

A series of 2-aryldopamine analogues were synthesized and evaluated for their effects on D1 and D2 dopamine receptors. The 2-phenyldopamine and 6-phenylbenzazepine analogues exhibited weak binding to both D1 and D2 receptors. The 9-(aminomethyl)fluorenes also exhibited weak D2 binding; however, 2,5,6-trihydroxy-9H-fluorene-9-methanamine (4b) exhibited D1 binding comparable to apomorphine. The binding activity has been correlated with the calculated torsion angle of the biphenyl portion of these molecules. Good D1 dopamine binding occurs when the aromatic rings approach coplanarity; poor binding occurs when the aromatic rings are orthogonal.