Design, synthesis, pharmacological evaluation and computational studies of 1-(biphenyl-4-yl)-2-[4-(substituted phenyl)-piperazin-1-yl]ethanones as potential antipsychotics

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 quanti...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2014-03, Vol.74, p.358-365
Main Authors: Bhosale, Sharad H., Kanhed, Ashish M., Dash, Radha Charan, Suryawanshi, Mugdha R., Mahadik, K.R.
Format: Article
Language:English
Subjects:
1-(Biphenyl-4-yl)-2-[4-(substituted phenyl)-piperazin-1-yl]ethanones
Antipsychotic
Antipsychotic Agents - chemical synthesis
Antipsychotic Agents - chemistry
Antipsychotic Agents - pharmacology
Descriptor based similarity study
Magnetic Resonance Spectroscopy
Molecular Docking Simulation
Pharmacological evaluation
Piperazines - chemical synthesis
Piperazines - chemistry
Piperazines - pharmacology
QSAR
Quantitative Structure-Activity Relationship
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Summary: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. [Display omitted] •Biphenyl moiety linked with aryl piperazine as anti-psychotic agent is proposed.•Syntheses and pharmacological evaluation for antipsychotic activity is reported.•QSAR, similarity and docking studies were performed.•Two NCES with impressive antipsychotic potential are reported.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2013.12.043