Structural manipulation on the catecholic fragment of dopamine D 1 receptor agonist 1-phenyl- N -methyl-benzazepines

Abstract A series of new benzazepines with modification on the catecholic fragment were designed. The 8-hydroxyl group, other than the 7-hydroxyl was confirmed crucial to the interaction with the dopamine D 1 receptor. Subsequent replacement of the 7-hydroxyl with benzylamino groups was found tolerable. 7-( m -Chlorophenyl)methylamino- and 7-( m - or o -tolyl)methylamino-substituted benzazepines 13b – d displayed K i values of 270–370 nM at the D 1 receptor, which were slightly more potent than that of parent compound 1 . In addition, 7-(arylmethyl)amino-benzazepines 13a – c were found possessing high binding affinities less than 10 nM at the 5-HT 2A receptor. Among them, the non-substituted 7-benzylamino analogue 13a was the most potent showing a K i values of 4.5 nM at the 5-HT 2A receptor and a 5-HT 2A /D 1 selectivity of 147.