<unk>  is a racemic mixture consisting of equal proportions of enantiomers (R)-bicalutamide (dextrorotatory) and (S)-bicalutamide (levorotatory). Its systematic name () is (RS)-N-4-cyano-3-(trifluoromethyl)phenyl-3-(4-fluorophenyl)sulfonyl-2-hydroxy-2-methylpropanamide. The compound has a chemical formula of C18H14F4N2O4S, a molecular weight of 430.373 g/mol, and is a fine white to off-white powder. The acid dissociation constant (pKa') of<unk>  is approximately 12. It is a highly lipophilic compound (log P = 2.92). At 37 °C (98.6 °F), or normal human body temperature,<unk>  is practically insoluble in water (4.6 mg/L), acid (4.6 mg/L at pH 1), and alkali (3.7 mg/L at pH 8). In organic solvents, it is slightly soluble in chloroform and absolute ethanol, sparingly soluble in methanol, and freely soluble in acetone and tetrahydrofuran.<unk>  is a synthetic and nonsteroidal compound which was derived from flutamide. It is a<unk> yclic compound (has two rings) and can be classified as and has variously been referred to as an anilide (N-phenylamide) or aniline, a diarylpropionamide, and a toluidide. Analogues First-generation including<unk> , flutamide, and nilutamide are all synthetic, nonsteroidal anilide derivatives and structural analogues of each other.<unk>  is a diarylpropionamide while flutamide is a monoarylpropionamide and nilutamide is a hydantoin.<unk>  and flutamide, though not nilutamide, can also be classified as toluidides. All three of the compounds share a common 3-trifluoromethylaniline moiety.<unk>  is a modification of flutamide in which a 4-fluorophenylsulfonyl moiety has been added and the nitro group on the original phenyl ring has been replaced with a cyano group. Topilutamide, also known as fluridil, is another that is closely related structurally to the first-generation , but, in contrast to them, is not used in the treatment of prostate cancer and is instead used exclusively as a topical antiandrogen in the treatment of pattern hair loss. The second-generation enzalutamide and apalutamide were derived from and are analogues of the first-generation , while another second-generation , darolutamide, is said to be structurally distinct and chemically unrelated to the other . Enzalutamide is a modification of<unk>  in which the inter-ring linking chain has been altered and cyclized into a 5,5-dimethyl-4-oxo-2-thioxo imidazolidine moiety. In apalutamide, the 5,5-dimethyl groups of the imidazolidine ring of enzalutamide are cyclized to form an accessory cyclobutane ring and one of its phenyl rings is replaced with a pyridine ring. The first nonsteroidal androgens, the arylpropionamides, were discovered via structural modification of<unk> . Unlike<unk>  (which is purely antiandrogenic), these compounds show tissue-selective androgenic effects and were classified as selective androgen receptor modulators (SARMs). Lead of this series included acetothiolutamide, enobosarm (ostarine; S-22), and andarine (acetamidoxolutamide or androxolutamide; S-4). They are very close to<unk>  structurally, with the key differences being that the linker sulfone of<unk>  has been replaced with an ether or thioether group to confer agonism of the and the 4-fluoro atom of the pertinent phenyl ring has been substituted with an acetamido or cyano group to eliminate reactivity at the position. A few radiolabeled derivatives of<unk>  have been developed for potential use as radiotracers in medical imaging. They include 18Fbicalutamide, 4-76Brbromobicalutamide, and 76Brbromo-thiobicalutamide. The latter two were found to have substantially increased affinity for the relative to that of<unk> . However, none of these agents have been evaluated in humans. 5N-Bicalutamide, or 5-azabicalutamide, is a minor structural modification of<unk>  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<unk> . 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<unk>  have been published in the literature. The procedure of the first published synthesis of<unk>  can be seen below.
Bicalutamide
Darolutamide
Topilutamide
Apalutamide
Nilutamide
Acetothiolutamide
Flutamide
Enzalutamide