Design and synthesis of novel androgen receptor antagonists with sterically bulky icosahedral carboranes

We designed and synthesized novel androgen receptor antagonists such as 8 or 9 bearing a carborane moiety. Carboranes (dicarba- closo-dodecaboranes) are a class of carbon-containing polyhedral boron-cluster compounds having remarkable chemical and thermal stability, and hydrophobic character. These features may allow application of carboranes as a new hydrophobic core structure in biologically active molecules that interact hydrophobically with receptors. Here, we report the design and synthesis of novel androgen antagonists bearing a carborane moiety. These compounds, particularly 8a, 8c, and 9d, exhibited anti-androgenic activity similar to that of the well-known anti-androgen flutamide in reporter gene assay using NIH3T3 cells transfected with a human AR expression plasmid. The carborane cage seems to be a privileged hydrophobic pharmacophore for the expression of AR-antagonistic activity.