Chemistry Bicalutamide

first-generation nsaas including bicalutamide, flutamide, , nilutamide synthetic, nonsteroidal anilide derivatives , structural analogues of each other. bicalutamide diarylpropionamide while flutamide monoarylpropionamide , nilutamide hydantoin. bicalutamide , flutamide, though not nilutamide, can classified toluidides. 3 of compounds share common 3-trifluoromethylaniline moiety. bicalutamide modification of flutamide in 4-fluorophenylsulfonyl moiety has been added , nitro group on original phenyl ring has been replaced cyano group. topilutamide, known fluridil, nsaa closely related structurally first-generation nsaas, but, in contrast them, not used in treatment of prostate cancer , instead used exclusively topical antiandrogen in treatment of androgenic alopecia.

the second-generation nsaas enzalutamide , apalutamide derived , analogues of first-generation nsaas, while second-generation nsaa, darolutamide, said structurally distinct , chemically unrelated other nsaas. enzalutamide modification of bicalutamide in inter-ring linking chain has been altered , cyclized 5,5-dimethyl-4-oxo-2-thioxo imidazolidine moiety. in apalutamide, 5,5-dimethyl groups of imidazolidine ring of enzalutamide cyclized form accessory cyclobutane ring , 1 of phenyl rings replaced pyridine ring.

the first nonsteroidal androgens (the arylpropionamides) discovered via structural modification of bicalutamide. unlike bicalutamide (which purely antiandrogenic), these compounds show tissue-selective androgenic effects , classified selective androgen receptor modulators (sarms). lead sarms of series included acetothiolutamide, enobosarm (ostarine; s-22), , andarine (acetamidoxolutamide or androxolutamide; s-4). close bicalutamide structurally, key differences being linker sulfone of bicalutamide has been replaced ether or thioether group confer agonism of ar , 4-fluoro atom of pertinent phenyl ring has been substituted acetamido or cyano group eliminate reactivity @ position.

a few radiolabeled derivatives of bicalutamide have been developed potential use radiotracers in medical imaging. include [f]bicalutamide, 4-[br]bromobicalutamide, , [br]bromo-thiobicalutamide. latter 2 found have substantially increased affinity ar relative of bicautamide. however, none of these agents have been evaluated in humans.

5n-bicalutamide, or 5-azabicalutamide, minor structural modification of bicalutamide acts reversible covalent antagonist of ar , has approximately 150-fold higher affinity ar , 20-fold greater functional inhibition of ar relative bicalutamide. among potent ar antagonists ever have been developed , being researched potential use in treatment of antiandrogen-resistant prostate cancer.

synthesis

a number of chemical syntheses of bicalutamide have been published in literature. procedure of first published synthesis of bicalutamide can seen below.

where starting material 4-cyano-3-(trifluoromethyl)aniline (also known 4-amino-2-(trifluoromethyl)benzonitrile), dma dimethylacetamide, , mcpba meta-chloroperoxybenzoic acid.