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

Molecules

Hernán Pessoa-Mahana¹  Gonzalo Recabarren-Gajardo¹  Jenny Fiedler Temer¹  Gerald Zapata-Torres¹  C. David Pessoa-Mahana¹  Claudio Saitz Barría¹ 

[1] ¹Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1, Chile

关键词: arylpiperazines;    benzo[b]thiophene;    depression;    5-HT_1A receptor;    docking;    microwave Michael addition;   

DOI  :  10.3390/molecules17021388

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.