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, representing heterocyclic analogs of the selective dopamine D-1 receptor ligands of the 3-phenylbenzazepine class, were synthesized starting from the indole-4-carboxylate 7. Receptor binding studies employing bovine striatal membranes demonstrated that the test compounds 5, 10, and 11 are able to displace the D-1 selective radioligand [3H]-SCH 23390 as well as the D-2 antagonist [3H]-spiperone. Compound 5b turned out to be the most potent and selective ligand (ki = 1.8 microM for D-1 and ki = 8.9 microM for D-2). It is assumed that the moderate selectivity of 5b is due to the conformational inequality of the 7-membered rings when compared to the benzazepines. This results in a spatial arrangement of the phenyl substituent which is not able to interact with a 'subtype selectivity-inducing site'.
Gmeiner
P
P
Pharmazeutisches Institut, Universität Bonn, Germany.
Sommer
J
J
Höfner
G
G
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology; D002417:Cattle; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011869:Radioligand Assay; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors
D001381:Azepines; D015259:Dopamine Agents; D065127:Dopamine D2 Receptor Antagonists; D007211:Indoles; D017447:Receptors, Dopamine D1