Remote functionalization of SCH 39166: Discovery of potent and selective benzazepine dopamine D1 receptor antagonists

A series of novel benzazepine derived dopamine D-1 antagonists have been discovered. These compounds are highly potent at D1 and showed excellent selectivity over D-2 and D-4 receptors. SAR studies revealed that a variety of functional groups are tolerated on the D-ring of known tetracyclic benzazepine analog 2, SCH 39166, leading to compounds with nanomolar potency at D-1 and good selectivity over D-2-like receptors. Published by Elsevier Ltd.