 This suggests that the bisubstitution in the hydroxyflutamide ring is essential for high AR binding affinity.It has also been demonstrated that hydroxyflutamide requires the strong hydrogen bond donor ability of the tertiary hydroxyl group and fixed conformers involved in intramolecular hydrogen binding, to bind effectively to AR.For bicalutamide, the antiandrogenic activities of sulfide and sulfone substitutions of the X-linkage were tested "in vitro".