Design, synthesis, pharmacological evaluation and computational studies of 1-(biphenyl-4-yl)-2-[4-(substituted phenyl)-piperazin-1-yl]ethanones as potential antipsychotics
| Autor: | Radha Charan Dash, Sharad H. Bhosale, K. R. Mahadik, Ashish M. Kanhed, Mugdha R. Suryawanshi |
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| Rok vydání: | 2013 |
| Předmět: |
Pharmacology
Biphenyl Quantitative structure–activity relationship Magnetic Resonance Spectroscopy Chemistry Stereochemistry Aryl Organic Chemistry Quantitative Structure-Activity Relationship General Medicine Piperazines Molecular Docking Simulation Piperazine chemistry.chemical_compound Docking (molecular) Dopamine receptor D2 Drug Discovery Moiety Homology modeling Antipsychotic Agents |
| Zdroj: | European journal of medicinal chemistry. 74 |
| ISSN: | 1768-3254 |
| Popis: | This article describes the design of biphenyl moiety linked with aryl piperazine and syntheses of fourteen 1-(biphenyl-4-yl)-2-[4-(substituted phenyl)-piperazin-1-yl]ethanone derivatives along with their pharmacological evaluation for antipsychotic activity and computational studies including quantitative structure activity relationship (QSAR) and descriptor based similarity study. All compounds were found to exhibit considerable anti-dopaminergic and anti-serotonergic activity in behavioural models. Among all derivatives, compound 1-(biphenyl-4-yl)-2-[4-(2-methoxyphenyl)-piperazin-1-yl]ethanone (3c) and 1-(biphenyl-4-yl)-2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]ethanone (3k) showed impressive antipsychotic profile with lower potency for catalepsy induction. These results were found to be sturdily matching with docking study in designing of compounds with homology model of human dopamine D2 receptor. Also the QSAR study strongly supports the obtained results. |
| Databáze: | OpenAIRE |
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