SYNTHESIS AND DOPAMINE-RECEPTOR BINDING OF 3-PHENYLAZEPINO[5,4,3-C,D]INDOLE DERIVATIVES

The 3-phenylazepino[5,4,3-c,d]indole derivatives 5 and 9-11, represent ing heterocyclic analogs of the selective dopamine D-1 receptor ligand s of the 3-phenylbenzazepine class, were synthesized starting from the indole-4-carboxylate 7. Receptor binding studies employing bovine str iatal membranes demonstrated that the test compounds 5, 10, and 11 are able to displace the D-1 selective radioligand [H-3]-SCH 23390 as wel l as the D-2 antagonist [H-3]-spiperone. Compound 5b turned out to be the most potent and selective ligand (k(i) = 1.8 mu M for D-1 and k(i) = 8.9 mu M for D-2). It is assumed that the moderate selectivity of 5 b is due to the conformational inequality of the 7-membered rings when compared to the benzazepines. This results in a spatial arrangement o f the phenyl substituent which is not able to interact with a 'subtype selectivity-inducing site'.