Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Synthesis and Preliminary Pharmacological Evaluation of 2-[4-(Aryl substituted) piperazin-1-yl]-N-phenylacetamides: Potential Antipsychotics

Sushil Kumar¹ , A K Wahi¹, Ranjit Singh²

¹Drug Design and Medicinal Chemistry Research Laboratory, College of Pharmacy, IFTM, Moradabad-244001 (U.P.); ²School of Pharmaceutical Sciences, Shobhit University, Meerut- 250110 (U.P.), India.

For correspondence:- Sushil Kumar Email: sushilmpharm@rediffmail.com Tel:+919412032192

Received: 29 September 2010 Accepted: 23 April 2011 Published: 24 June 2011

Citation: Kumar S, Wahi AK, Singh R. Synthesis and Preliminary Pharmacological Evaluation of 2-[4-(Aryl substituted) piperazin-1-yl]-N-phenylacetamides: Potential Antipsychotics. Trop J Pharm Res 2011; 10(3):265-272 doi: 10.4314/tjpr.v10i3.6

© 2011 The authors.
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Abstract

Purpose: Arylpiperazines have been recognized as the largest and most diverse class of compounds exerting actions on the central nervous system with strong affinity for serotonin and dopamine receptors. We here report the synthesis of some novel arylpiperazines and their evaluation for possible antipsychotic properties.

Methods: The target compounds 2-[4-(aryl substituted) piperazin-1-yl]-N-phenylacetamides (3a-j) were synthesized by first reacting aniline (1) in 2 N sodium hydroxide with chloroacetylchloride in dichloromethane to obtain 2-chloro-N-phenylacetamide (2) and subsequently treating with appropriate phenylpiperazine in acetonitrile in the presence of K₂CO₃ and KI. All the compounds were characterized by analytical and spectroscopic methods. The compounds were evaluated for antipsychotic activity using three animal models.

Results: All the 10 new arylpipeazines showed variable antipsychotic activity with compound 3h being the least effective in the induction of catalepsy. Their effect may involve interaction with 5-HT_2A and D₂ receptors.

Conclusion: A synthetic method and possible antipsychotic effect have been established for 2-[4-(Aryl substituted) piperazin-1-yl]-N-phenylacetamides.

Keywords: N-phenylacetamide, Arylpiperazines, Antipsychotic activity, 5-HT2A, D2 antagonists