Synthesis and Pharmacological Screening of Novel (2-(4-Methyl-2-oxo-2H-chromen-7- yloxy)-N-(benzo[d]thiazol-2-yl))acetamide Derivatives

Abstract

A new series of 2-(4-methyl-2-oxo-2H-chromen-7-yloxy)-N-(benzo[d]thiazol-2-yl)acetamide derivatives (4a-k) was synthesized and evaluated for their D₂ and 5HT₂ antagonistic activity as a measure of atypical antipsychotic property. Compounds (4a-k) were synthesized by refluxing various N-(benzothiazol-2-yl)-2-chloroacetamides substituted derivatives (3a-k) with 7-hydroxy- 4 methyl-2H-chromen-2-one (1) in acetonitrile and anhydrous K₂CO₃. N-(Benzothiazol-2-yl)- 2-chloroacetamides substituted derivatives (3a-k) were prepared from the chloroacetyl chloride with various 2-amino benzothiazole substituted derivatives (2a-k). The synthesized compounds were characterized with the help of spectral and analytical data. Most of these compounds showed dopamine D₂ receptor antagonistic activity from moderate to high affinity along with serotonin 5-HT₂ receptor blockage activity: a property that has been suggested as necessary for atypicality. The D2 and 5-HT₂ receptor blockage activity was evaluated by inhibition of apomorphineinduced climbing behaviour and 5HTP induced head twitches in mice, respectively.