Androgen antagonists

Fungicides Vinelozolin Antagonist Effeets on androgen regulated endpoints—AR antagonist ... 

Hormone antagonists (tamoxifen and toremifen bind to the estradiol receptor, flutamide binds to the androgen receptor) are used for treating breast and prostate cancer. 

Soimenschein C, Soto AM. 1998. An updated review of environmental estrogen and androgen mimics and antagonists. J Steroid Biochem Mol Biol 65(1) 143-150. 

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. 

The answer is c. (Hardmanr pp 706-708.) Spironolactone is an aldosterone antagonist that acts on the mineralocorticoid receptor It is a Kksparing diuretic. It can also function as an androgen antagonist, which could explain the gynecomastia and erectile dysfunction. Women with hirsutism are sometimes treated with spironolactone. 

The development of new tests and bioassays is likely to lengthen the list of endocrine disrupters. Recent research on hormonal disruption has not only investigated estrogens and androgens as agonists and antagonists but also considered the development of the individual and the presence of compounds that interfere in other hormonal systems, such as the thyroid system. 

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

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