7-[(4-Substituted phenyl-piperazin-1-yl)-alkoxyl]-4-methylchromene-2-ones as potential atypical antipsychotics:Synthesis and pharmacological evaluation

摘要

7-Hydroxy-4-methylchromene-2-one 1 when reacted respectively with 2-bromo-l-chloroethane and 3-bromo-1-chloropropane in acetonitrile and in the presence of anhydrous K_2CO_3 yields 7-alkoxy-4-methylchromcne-2-ones 2a,b.Compounds 2a,b when refluxed with various arylpiperazines in toluene and in the presence of triethylamine yield the title compounds,7-[(4-substituted phenyl-piperazin-1-yl)-alkoxyl]-4-methylchromen-2-ones 3a-j.Their atypical antipsychotic activity have been evaluated by their ability to inhibit apomorphine induced climbing behavior(D_2 antagonism)and to inhibit the 5-HTP induced head twitches in albino mice(5-HT_(2A)antagonism)alongwith catalepsy studies.All the compounds inhibit apomorphine induced climbing behavior and 5-HTP induced head twitches.The SAR studies reveal that methyl group in the phenyl ring of piperazine and the chain length(n=3)gives more dopaminergic and serotonergic antagonistic activity,while dichlorophenyl piperazines have less dopaminergic and serotonergic antagonistic activity.3f and 3g have been found to have significant atypical behaviour.