ABSTRACT
The present work involves the synthesis of three series of novel fluoxetine derivatives in order to evaluate their potential as antidepr ess ants. The first series consists of 1 -methyl- 1-[3-phenyl-3-[4-trifluoromethylphenoxy]propyl]-3-substituted ureas 2a-c and thioureas as their bioisosters 3a-m which were prepared by reacting fluoxetine 1a with different isocyanates and isothiocyanates respectively. The second series N-acyl/aroyl-N-methyl-3-phenyl-3-[4-trifluoromethylphenoxy]-propylamines 4a-d were synthesized by refluxing 1a with acyl/aroyl chloride and trifluoroacetic anhydride. The third one, N-chloroacyl-fluoxetine 5a-c was obtained via the reaction of la with chloroacyl chloride. In addition to a propionitrile derivative 8 which was achieved by refluxing 1a with acrylonitrile. The twenty four final compounds were biologically screened throughout the work for their potential as serotonin reuptake inhibitors by measuring potentiation of 5-HTP induced neurotoxity and some as norepinephrine reuptake inhibitor by measuring yohimbine-induced mortality in mice to calculates-HTP/NE ratio as a parameter for selectivity to inhibit serotonin reuptake. Four compounds [3e, 3h, 3i, 5b] were found to be as potent as fluoxetine