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
| Autor: | Jelena Penjišević, Slađana Kostić-Rajačić, Goran Roglić, Deana Andrić, Vladimir Sukalovic, Vukic Soskic |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
030102 biochemistry & molecular biology Ligand Stereochemistry Chemistry Pharmaceutical Science 010402 general chemistry 01 natural sciences Molecular Docking Simulation 0104 chemical sciences 03 medical and health sciences chemistry.chemical_compound Piperazine Docking (molecular) Drug Discovery Structure–activity relationship Moiety Piperidine Binding site |
| Zdroj: | Archiv der Pharmazie. 349:614-626 |
| ISSN: | 0365-6233 |
| DOI: | 10.1002/ardp.201600081 |
| Popis: | 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 were evaluated for their affinity toward D2 DAR in an in vitro competitive displacement assay. The most active one was 1-(2-methoxyphenyl)-4-{[1-(3-nitrophenethyl)piperidin-4-yl]methyl}piperazine (25) with an affinity of Ki = 54 nM. Docking analysis was conducted on all herein described compounds, whereas molecular dynamic simulation was performed on ligand 25 to establish its mode of interaction with D2 DAR. Two possible docking orientations are proposed; the one with a salt bridge between the piperidine moiety and Asp114 of D2 DAR is more stable. |
| Databáze: | OpenAIRE |
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