Abstract <p>A new series of indole-oxazole-benzamide conjugates in a multi-step method. The synthesized compound structures were confirmed with ¹H, ¹³C NMR, and mass spectroscopy methods. The synthesized compounds were further screened for their anticancer activity on selected breast cancer cells such as MCF-7 and MDA-MB231, and the standard drug erlotinib was used as a reference drug. The activity results showed that three compounds, namely <i>N</i>-{4-[(1<i>H</i>-indol-1-yl)methyl]oxazol-2-yl}-4-methoxybenzamide, <i>N</i>-{4-[(1<i>H</i>-indol-1-yl)methyl]oxazol-2-yl}-3-methoxybenzamide, and <i>N</i>-{4-[(1<i>H</i>-indol-1-yl)methyl]oxazol-2-yl}-3,5-dimethoxybenzamide, showed higher activity than the standard drug. The in vitro tyrosine kinase EGFR inhibitory activity results indicate that two compounds, <i>N</i>-{4-[(1<i>H</i>-indol-1-yl)methyl]oxazol-2-yl}-3-methoxybenzamide and <i>N</i>-{4-[(1<i>H</i>-indol-1-yl)methyl]oxazol-2-yl}-3,5-dimethoxybenzamide exhibited more activity than the standard drug erlotinib. Furthermore, three compounds in silico pharmacokinetic profiles were conducted using SWISS, ADME, and pkCSM. These compounds complied with five major filters (Lipinski’s rule, Ghose rule, Veber rule, Egan rule, and Muegge rule) without any violations.</p>