Abstract
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 D(1)R, D(2)R and D(5)R. As is typical of the 1-phenylbenzazepine scaffold, the compounds displayed selectivity towards D(1)R and D(5)R; analogs generally lacked affinity for D(2)R. Interestingly, 2',6'-dichloro substituted analogs showed modest D(5)R versus D(1)R selectivity whereas this selectivity was reversed in compounds with a 2'-halo substitution pattern. Compound 10a was identified as a D(1)R antagonist (K(i) = 14 nM; IC(50) = 9.4 nM).