Current mainstay treatment for advanced prostate cancer is to reduce serum level of androgens by castration and/or to disrupt binding of androgens to the androgen receptor (AR) by antiandrogens. However, most patient progress to a lethal disease state called castration-resistant prostate cancer (CRPC). Over 30,000 men die from CRPC in Canada and USA each year. Most CRPC cells are still dependent on aberrant AR signaling, but this signaling can not be suppressed by castration and current available antiandrogens due to mutations in AR, androgen-independent activation of the AR via crosstalk, etc. We have discovered one lead compound called SC97 that remains a full antagonist even in the mutant ARs and inhibits additional pathway called NF-kB, which contributes to aberrant AR activation. The funding will allow us to build on the exciting results and synthesize even more efficacious derivatives as novel anti-prostate cancer agents for CRPC. We will synthesize a series of SC97 derivatives by varying the side chains and the core scaffold, and evalute their capability against CRPC.