Synthesis and Preliminary Pharmacological Evaluation of
2-[4-(Aryl substituted)
piperazin-1-yl]-N-phenylacetamides: Potential
Antipsychotics
Sushil Kumar1*, AK
Wahi1 and 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:
E-mail:
sushilmpharm@rediffmail.com Tel:
+91-9412032192, 5912360817; Fax: +91-591 2360818
Received: 29 September
2010 Revised
accepted: 23 April 2011
Tropical
Journal of Pharmaceutical Research, June 2011;
10(3):
265-272
doi:
10.4314/tjpr.v10i3.6
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-HT2A 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.
