Synthesis, docking studies and biological evaluation of benzo[b]thiophen-2-yl-3-(4-arylpiperazin-1-yl)-propan-1-one derivatives on 5-HT 1A serotonin receptors

Abstract

A series of novel benzo[b]thiophen-2-yl-3-(4-arylpiperazin-1-yl)-propan-1- one derivatives 6a-f, 7a-f and their corresponding alcohols 8a-f were synthesized and evaluated for their affinity towards 5-HT 1A receptors. The influence of arylpiperazine moiety and benzo[b]thiophene ring substitutions on binding affinity was studied. The most promising analogue, 1-(benzo[b]thiophen-2-yl)-3-(4-(pyridin-2-yl)piperazin-1-yl)propan- 1-one (7e) displayed micromolar affinity (K i = 2.30 μM) toward 5-HT 1A sites. Docking studies shed light on the relevant electrostatic interactions which could explain the observed affinity for this compound.