Synthesis, Docking Studies and Biological Evaluation of Benzo[b]thiophen-2-yl-3-(4-arylpiperazin-1-yl)-propan-1-one Derivatives on 5-HT1A 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-HT1A 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 (Ki = 2.30 μM) toward 5-HT1A sites. Docking studies shed light on the relevant electrostatic interactions which could explain the observed affinity for this compound.

Keywords

• arylpiperazines
• benzo[b]thiophene
• depression
• 5-HT1A receptor
• docking
• microwave Michael addition