Evaluation of N-phenyl homopiperazine analogs as potential dopamine D3 receptor selective ligands

A series of N-(2-methoxyphenyl)homopiperazine analogs of our previously published phenylpiperazine compounds was prepared. When compared with their congeners, the homopiperazines showed (a) generally decreased affinity at D2 and D3 dopamine receptors, (b) decreased D3 receptor binding selectivity, and (c) generally increased intrinsic efficacy, measured using a forskolin-dependent adenylyl cyclase inhibition assay. Compound 11a had Ki of 0.7 nM for the D3 receptor with 170-fold D3:D2 selectivity and may be a useful PET tracer.