eliminate reactivity at the position. A few radiolabeled derivatives of bicalutamide have been developed for potential use as radiotracers in medical imaging. They include [18F]bicalutamide, 4-[76Br]bromobicalutamide, and [76Br]bromo-thiobicalutamide. The latter two were found to have substantially increased affinity for the relative to that of bicautamide. However, none of these agents have been evaluated in humans. 5N-Bicalutamide, or 5-azabicalutamide, is a minor structural modification of bicalutamide which acts as a reversible covalent antagonist of the and has approximately 150-fold higher affinity for the and about 20-fold greater functional inhibition of the relative to bicalutamide. It is among the most potent antagonists to have been developed and is being researched for potential use in the treatment of antiandrogen-resistant prostate cancer. Synthesis A number of chemical syntheses of bicalutamide have been published in the literature. The procedure of the first published synthesis of bicalutamide can be seen below. History Bicalutamide as well as all of the other currently marketed were derived from structural modification of flutamide, which itself was originally synthesized as a bacteriostatic agent in 1967 at Schering Plough Corporation and was subsequently and serendipitously found to possess antiandrogenic activity. Bicalutamide was discovered by Tucker and colleagues at Imperial Chemical Industries (ICI) in the 1980s and was selected for development from a group of over 2,000 synthesized compounds. It was first patented in 1982 and was first reported in the scientific literature in June 1987. Bicalutamide was first studied in a phase I clinical trial in 1987 and the results of the first phase II clinical trial in prostate cancer were published in 1990. The pharmaceutical division of was split out into an independent company called Zeneca in 1993, and in April and May 1995, Zeneca (now AstraZeneca, after merging with Astra AB in 1999) began pre-approval marketing of bicalutamide for the treatment of prostate cancer in the . It was first launched in the in May 1995, and was subsequently approved by the on 4 October 1995, for the treatment of prostate cancer at a dosage of 50 mg/day in combination with a analogue. Following its introduction for use in combination with a analogue, bicalutamide was developed as a monotherapy at a dosage of 150 mg/day for the treatment of prostate cancer, and was approved for this indication in Europe, Canada, and a number of other countries in the late 1990s and early 2000s. This application of bicalutamide was also under