Synthesis and dopamine receptor pharmacological evaluations on ring C ortho halogenated 1-phenylbenzazepines.

A series of 1-phenylbenzazepines containing bromine or chlorine substituents at the ortho position of the appended phenyl ring (2'-monosubstituted or 2',6'- disubstituted patterns) were synthesized and evaluated for affinity towards dopamine DR, DR and DR. As is typical of the 1-phenylbenzazepine scaffold, the compounds displayed selectivity towards DR and DR; analogs generally lacked affinity for DR. Interestingly, 2',6'-dichloro substituted analogs showed modest DR versus DR selectivity whereas this selectivity was reversed in compounds with a 2'-halo substitution pattern. Compound 10a was identified as a DR antagonist (K = 14 nM; IC = 9.4 nM).