Synthesis, Characterization, and In Vivo Evaluation of Escitalopram Analogues for Depression.

Escitalopram, (S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile, is a highly selective and potent serotonin reuptake inhibitor that is used to treat depression. Herein, we report the synthesis of ester analogues of escitalopram having π-systems in their structures where the ester groups including allyl, propargyl, methoxyethyl, benzyl and ρ-tolyl replaced the cyano group in escitalopram. The analogues were designed to test the possibility of binding such groups to the phenyl in Phe341 amino acid that is in close proximity to the cyano group in human serotonin transporter (hSERT). In vivo antidepressant evaluation showed good activity for the analogues compared to escitalopram. [ABSTRACT FROM AUTHOR]