Nonsteroid Androgen Antagonists

Antiandrogens have proven to be very useful in treating benign prostatic hypertrophy, an aU too frequent accompaniment of aging. These agents, in addition, have a minor place in the treatment of prostatic cancer. They are also, on a more trivial note, used to 

The scheme used to produce a somewhat more complex 5-a-reductase inhibitor relies on a chiral auxiliary to yield the final product as a single enantiomer. The first step in a sequence similar to that above starts with the reaction of bromotetralone (23-1) with R-a-phenethyl amine (23-2) to afford the enamine (23-3). Reaction with methyl iodide adds the methyl group at what will be a steroid-like AB ring junction 

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Several other aromatase inhibitors are undergoing clinical trials in patients with breast cancer. Fadrozole is an oral nonsteroidal (triazole) inhibitor of aromatase activity. These compounds appear to be as effective as tamoxifen. In addition to their use in breast cancer, aromatase inhibitors have been successfully employed as adjuncts to androgen antagonists in the treatment of precocious puberty and as primary treatment in the excessive aromatase syndrome. 

An irreversible nonsteroidal antiandrogen agent useful in the treatment of prostate cancer was prepared by Miller (2) by modifying the androgen antagonist, Casodex, (III), through A-haloacylation, (IV). 

The photochemical electrocychzation was also applied as key step in the synthesis of nitrogen-containing heterocycles possessing pharmaceutical activity such as, for example, the 5-HT2Q2b Receptor Antagonist 49- or the nonsteroidal androgen receptor agonist 50 (Scheme 8). ... 

Flutamide Flutamide, 4 -nitro-3 -trifluoromethylisobutyranilide (29.2.15), a nonsteroid antagonist of androgens, is made by acylating 4-nitro-3-trifluoromethylaniline with isobu-tyric acid chloride [13-15]. 

Bicalutamide, flutamide and nilutamide are nonsteroidal antiandrogens that are used for the treatment of prostatic carcinoma. They act as competitive antagonists at the androgen receptor. Hutamide also inhibits the formation of dihydrotestosterone from testosterone. 

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

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