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Indoleamine 2,3-dioxygenase 1 (IDO1) is closely associated with immune escape in many tumor tissues, and is considered to be a valuable therapeutic target in cancer immunotherapy. In this study, the modification of amino sidechain was performed with the hydroxyamidine core kept intact to optimize lead compound Epacadostat. 19 new compounds with hydrazide, thietane or sulfonamide moiety as polar capping group in sidechain were prepared and their IDO1 inhibitory activities were evaluated. Sulfonamide 3a showed potent IDO1 inhibition in bo