Structure−Activity Relationship Studies on the 5-HT<INF>1A</INF> Receptor Affinity of 1-Phenyl-4-[ω-(α- or β-tetralinyl)alkyl]piperazines. 4<SUP>1</SUP><BBR RID="jm9604538b00001">

The synthesis of 1-phenylpiperazines, linked in the α or β position of the tetralin moiety on the terminal part of the N-4 alkyl chain, and their radioligand binding affinities for 5-HT<INF>1A</INF>, 5-HT<INF>2A</INF>, D-1, D-2, α<INF>1</INF>, and α<INF>2</INF> receptors along with SAR studies on the 5-HT<INF>1A</INF> receptor are reported. Several changes have been carried out on previous structures of type <BO>2</BO>, by inserting the alkyl chain with variable length in the α or β position of the tetralin moiety and by changing the position of the methoxy group on the aromatic ring of the tetralin nucleus. The highest affinity (IC<INF>50</INF> = 0.50 nM) and selectivity for the 5-HT<INF>1A</INF> receptor were showed by 1-phenylpiperazine <BO>2a</BO> with a three-membered alkyl chain bearing a 5-methoxytetralin-1-yl ring in the ω position.