Bicalutamide is an arylpropionamide analog, seen in figure 6. It has replaced flutamide and nilutamide as the first choice antiandrogen for prostate cancer treatment. Bicalutamide is not as hepatotoxic as flutamide and nilutamide and has a longer half-life, of 6 days in humans, that allows once a day administration at lower dosage. Bicalutamide shares the amide bond structure with flutamide. Even so, the amide bond hydrolysis was discovered in rats, not in humans, which could explain the prolonged half life of bicalutamide in humans.
Bicalutamide has a cyano group at the para position instead of a nitro group like flutamide and nilutamide. This change in groups avoids the nitro reduction observed in nilutamide. Bicalutamide has a chiral carbon in its structure (labeled with an asterisk in figure 6), which is connected to the hydroxyl and methyl groups . It is therefore administered as a racemate. Post-approval investigation revealed that its antiandrogenic activity resides almost entirely in the (R)-enantiomer. (R)-bicalutamide has an almost fourfold higher affinity for the prostate AR than hydroxyflutamide and has a better side-effect profile compared to other antiandrogens.