Synthesis, binding affinity and SAR of new benzolactam derivatives as dopamine D3 receptor ligands

A series of new benzolactam derivatives was synthesized and the derivatives were evaluated for their affinities at the dopamine D-1, D-2, and D-3 receptors. Some of these compounds showed high D-2 and/or D-3 affinity and selectivity over the D-1 receptor. The SAR study of these compounds revealed structural characteristics that decisively influenced their D-2 and D-3 affinities. Structural models of the complexes between some of the most representative compounds of this series and the D-2 and D-3 receptors were obtained with the aim of rationalizing the observed experimental results. Moreover, selected compounds showed moderate binding affinity on 5-HT2A which could contribute to reducing the occurrence of extrapyramidal side effects as potential antipsychotics. (C) 2009 Elsevier Ltd. All rights reserved.