Pyruvate dehydrogenases kinases (PDKs) have recently emerged as an attractive target for anticancer treatment. Herein, we report the synthesis and biological evaluation of novel PDK1 inhibitors as anticancer agents. Of the newly synthesized compounds, N-(4,6-bis(4-(2-hydroxyacetyl)piperazin-1-yl)-2-methylpyrimidin-5-yl)-2,2-dichloroacetamide (40) is found to inhibit the growth of SF188 cancer cells with an IC value of 8.21 M. Isothermal titration calorimetry (ITC) experiments reveal that compound 40 directly binds to PDK1 with a K value of 14.7 M. Compound 40 inhibits PDK1 activity by 72.5% at a concentration of 40 , meaning it could be a useful compound to explore the pharmacology of PDK1.