OROPHENYL)PIPERAZIN-1-YL]ETHYL]-3-METHOXYBENZAMIDE - A POTENT AND SELECTIVE DOPAMINE D-4 LIGAND

A series of new 1-aryl-4-alkylpiperazines containing a terminal benzam ide fragment or a tetralin-1-yl nucleus on the alkyl chain were synthe sized and tested for binding at cloned human dopamine D-4 and D-2 rece ptor subtypes. A SAFIR (structure-affinity relationship) study on this series is herein discussed. The most relevant D-4 receptor affinities were displayed by ega-[4-arylpiperazin-1-yl]alkyl]-methoxybenzamides (compounds 5, 16-20), their IC50 values ranging between 0.057 and 7.8 nM. Among these, orophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (1 7) emerged since it exhibited very high affinity for dopamine D-4 rece ptor (IC50 = 0.057 nM) with selectivity of >10 000 for the D-4 versus the D-2 receptor; compound 17 was also selective versus serotonin 5-HT 1A and adrenergic alpha(1) receptors.