Phenylpiperazinylmethylheterocycle Derivatives: Synthesis and Dopamine Receptor Binding Profiles

Four series of phenylpiperazinylmethylimidazo[1, 2‐ a ]pyridine, phenylpiperazinylmethylpyrrole, phenylpiperazinylmethylbenzofuran, and phenylpiperazinylmethylbenzothiophene derivatives were synthesized and investigated for their in vitro binding profiles for the dopamine receptor subtypes D 1 , D 2long , D 2short , D 3 and D 4 . All tested compounds showed selectivity towards the D 4 receptor subtype. Affinity and selectivity for D 4 follows the order imidazo[1, 2‐ a ]pyridine > benzofuran > benzothiophene > pyrrole derivatives. The D 4 ‐related affinity and selectivity pattern seems to be dependent on the presence of a region of negative molecular electrostatic potential below the heterocyclic moiety.