Synthesis of heteroarylpiperazines and heteroarylbipiperidines with a restricted side chain and their affinities for 5-HT1A receptor.

Abstract

Heteroarylpiperazine and heteroarylbipiperidine derivatives, bearing a 4-piperidine ring instead of an alkylamino side chain to give the semi-rigidity, were prepared and evaluated for their abilities to displace [(3)H]8-OH-DPAT binding to the rat hippocampal synaptic membranes. These compounds showed low to moderate affinities for 5-HT(1A) receptor, with Ki values ranging from 6912 nM to 232 nM. Of these compounds, 8b and 15e exhibited the best affinities for 5-HT(1A) receptor with Ki values of 232 nM and 338 nM, respectively.