Synthesis, pharmacological evaluation and QSAR study of 6- [3-(4-substituted phenylpiperazin-1-yl)propoxy]benzo[d][1,3] oxathiol-2-ones as potential antipsychotics

In a search towards new and efficient agents to treat mental disorders such as schizophrenia 6-[3-(4-substitutedphenylpiperazin-1-l)propoxy]benzo[d][1,3]oxathiol-2-ones were designed, synthesized and evaluated in vivo for their ability to inhibit apomorphine induced climbing behaviour and inhibition of 5-HTP induced head twitches representing antidopaminergic and antiserotonergic action respectively in albino mice. The pharmacological screening revealed that the compounds 6-(3-(4-(2,3-dichlorophenyl)piperazin-1-l)propoxy)benzo[d][1,3]oxathiol-2-one 3l and 6-(3-(4-(2,3-dimethylphenyl)piperazin-1-yl)propoxy)benzo[d][1,3]oxathiol-2-one 3n showed better antipsychotic potential with lower potency of catalepsy induction. To understand the structural activity relationship QSAR model was generated for antipsychotic activity. The resulting study produced highly predictive model that comprised various descriptors like dip²/V, WPSA. These descriptors highlight the important characteristic of antipsychotic potential of title compounds in relation to affinity towards target through electrostatic and steric interaction.