A series of novel 1,3,5-trisubstituted indole derivatives, namely, N-benzyl 5-phenyl indole-3-imine, N-benzyl-5-(p-fluorophenyl)indole-3-imine and their corresponding amine congeners, were designed and synthesized as pp60(c-Src) tyrosine kinase inhibitors, and their inhibitory activities toward pp60(c-Src) tyrosine kinase were evaluated by in-vitro kinase assay. Pre-screening at two doses of compounds against kinase target revealed that, except for the N-benzyl-5-phenyl indole imine derivatives 7a-7d, all indole derivatives show the target inhibition at varying levels. Consequently, the compounds, 8c, 8f, 8g, and 8h, were selected for prescreening tests. The dose-response curves for up to six concentrations (250 to 7.8 mu M) of the active compounds were obtained by tyrosine kinase assay and the four-parameter logistic analysis of these data resulted in the IC50S of 4.69, 74.79, 75.06, and 84.23 mu M for compounds 8c, 8f, 8g, and 8h, respectively. Therefore, compound 8c, 1-(1-benzyl-5-phenyl-1H-indole-3-yl)-N-(4-fluorobenzyl)methanamine center dot HCl, was the promising inhibitor for pp60(c-Src), followed by compounds 8g and 8h. Under the same conditions, compound 8f did not provide any reasonable inhibition pattern to be considered as active compound. Therefore, among all four active compounds, compound 8f was not found suitable for further analysis.