Synthesis and evaluation of novel thiazole‐based derivatives as selective inhibitors of DNA‐binding domain of the androgen receptor

A series of thiazole‐based inhibitors selectively targeting DNA‐binding domain of the androgen receptor (AR) were synthesized and evaluated, and the SAR data were summarized. We identified a novel compound SKLB‐C2807 that effectively inhibited the human prostate cancer cell line LNCaP/AR with the IC 50 value of 0.38 μ m without significant antiproliferative effects on other cell lines PC‐3 (AR‐negative), SW620, MCF‐7 (ER‐positive), and L‐O2 (non‐cancerous). This compound also considerably decreased the expression of prostate‐specific antigen. Its binding mode to the AR‐DBD was studied. These efforts lay the foundation for developing the next generation of anti‐androgens.