Synthesis, Biological, and Computational Evaluation of Substituted 1-(2-Methoxyphenyl)-4-(1-phenethylpiperidin-4-yl)piperazines and 1-(2-Methoxyphenyl)-4-[(1-phenethylpiperidin-4-yl)methyl]piperazines as Dopaminergic Ligands.
作者： Jelena Z. Penjišević , Vladimir V. Šukalović , Deana B. Andrić , Goran M. Roglić , Vukić Šoškić
关键词:
摘要: Sixteen new 1-(2-methoxyphenyl)-4-(1-phenethylpiperidin-4-yl)piperazines and 1-(2-methoxyphenyl)-4-[(1-phenethylpiperidin-4-yl)methyl]piperazines were synthesized to be used as probes for mapping the dopamine D2 receptor (D2 DAR) arylpiperazine binding site. All compounds evaluated their affinity toward DAR in an vitro competitive displacement assay. The most active one was 1-(2-methoxyphenyl)-4-{[1-(3-nitrophenethyl)piperidin-4-yl]methyl}piperazine (25) with of Ki = 54 nM. Docking analysis conducted on all herein described compounds, whereas molecular dynamic simulation performed ligand 25 establish its mode interaction DAR. Two possible docking orientations are proposed; a salt bridge between piperidine moiety Asp114 is more stable.
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