Androgen receptor antagonists

Flutamide is an androgen receptor antagonist that achieves peak concentrations approximately 2 to 4 hours after an oral dose. Flutamide is metabolized extensively, with a terminal half-life of about 8 hours. Bicalutamide achieves peak concentrations approximately 6 hours after the dose, with a terminal half-life of 6 to 10 days. Bicalutamide undergoes stereospecihc metabolism, where the S-enantiomer is cleared more rapidly by the liver than the -enantiomer. Nilutamide achieves peak serum concentrations between 1 to 4 hours after an oral dose and has a terminal half-life of 38 to 60 hours. Nilutamide is metabolized extensively, with less than 2% excreted as unchanged drug by the kidney. Side effects common to these agents are hot flashes, gynecomastia, and decreased libido. Flutamide tends to be associated with more diarrhea and requires three-times-daily administration, whereas bicalutamide is dosed once daily. Nilutamide may cause interstitial pneumonia and is associated with the visual disturbance of delayed adaptation to darkness. 

Scheme 1.34 Lipase resolution of a key intermediate in the synthetic route to an androgen receptor antagonist. TBME tert-butyl methyl ether...

Flutamide, an androgen receptor antagonist possessing a different chemical structure, lacks progestin activity. 

Ostby J, Kelce WR, Lambright C, Wolf CJ, Mann P, Gray LE Jr (1999) The fungicide procymidone alters sexual differentiation in the male rat by acting as an androgen-receptor antagonist in vivo and in vitro. Toxicol Ind Health, 15(1-2) 80-93. 

Flutamide and bicalutamide are structurally different androgen receptor antagonists lacking progestin activity. 

As a reproductive and developmental toxicant, linuron works via androgen receptor antagonist activity, that is, it competes with testosterone for binding to the androgen receptor. 

Linuron, a urea derivative herbicide and androgen receptor antagonist, and butyl benyl phthalate, a plasticizer, are two compounds with very different chemical properties, yet in a laboratory animal study, prenatal exposure to a mixture of these produced dose-additive testosterone and other adverse developmental effects. I66 ... 

Nonsteroidal antiandrogen androgen receptor antagonist inhibits testosterone and dihydrotestosterone uptake and binding in prostate cells... 

Saw 1 palmetto Symptomatic treatment ofBPH 5a-reductase inhibitor and androgen receptor antagonist GI pain, decreased libido, j headache, hypertension [... 

Balk, S.P. and Hollenberg, A.N. (2005) The androgen receptor recruits nuclear receptor corepressor (N-CoR) in the presence of mifepristone via its N and C termini revealing a novel molecular mechanism for androgen receptor antagonists. The Journal of Biological Chemistry, 280, 6511-6519. 

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