Synthesis and antidepressant activity of some novel fluoxetine derivatives

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

Synthesis and cytotoxic activity of certain new acridine derivatives structurally related to amsacrine

Some new 9-substituted acridine derivatives were synthesized. The in vitro cytotoxic activity of these compounds against Ehrlich ascites tumor cells in comparison to amsacrine [1], 9-[9- amidinosulphamoylphenyl-aminomethyl] acridine [3a] and melphalan, revealed that they are more active than their drug prototypes and melphalan

Synthesis and in vitro cytotoxic activity of certain new 9-acridinyl and 9-acridinylmethyl derivatives of amino acids

The synthesis of two series of 9-[N-substituted amino] acridines 1a and 9-[N[-substituted] aminomethyl] acridines 1b and their corresponding N-methyl quaternary salts 2a and 2b and N10 oxides 3a and 3b was reported. Preliminary testing for the in vitro cytotoxic activity of 30 representative examples against Ehrlich ascites carcinoma was carried out. The most active derivatives are those of arginine and glutamine. The N10-oxido derivatives have superior activity