Indoleamine 2,3-dioxygenase (IDO) is a metabolic enzyme involved in the degradation of tryptophan and a therapeutic target for the treatment of neurodegeneration and, more recently, cancer. Despite IDO's involvement in these important diseases, there are few reports of highly potent inhibitors. We have developed nanomolar-level IDO inhibitors based on the pyranonaphthoquinone skeleton. The design, synthesis and evaluation of these inhibitors will be described.