Synthesis and structure-activity relationships of a new model of arylpiperazines .3. 2-[omega-(4-arylpiperazin-1-yl)alkyl]perhydropyrrolo-[1,2-c]imidazoles and -perhydroimidazo[1,5-a]pyridines: Study of the influence of the terminal amide fragment on 5-HT1A affinity/selectivity

A series of new arylpiperazine derivatives 2, which are devoid of the terminal amide fragment present in related 5-HT1A ligands, was prepared and evaluated for affinity at 5-HT1A and alpha(1) receptors. All the compounds 2 demonstrated high affinity for the 5-HT1A receptor and moderate affinity for alpha(1) receptor binding sites. Structure-activity relationship (SAR) studies suggest that there is influence of electronic factors on the no-pharmacophoric part of the alpha(1) receptor site. However there is no influence of electronic interactions on the stabilization of the 5-HT1A receptor-ligand complex.