Nonsteroidal antiandrogens

Lutsky, B.N., Budak, M., and Koziol, P. (1975). The effects of a nonsteroid antiandrogen, flut-amide, on sebaceous gland activity. Journal Investigative Dermatology 64, 412 17. 

Neri, R.O. and Monahan, M. (1972). Effects of a novel nonsteroidal antiandrogen on canine prostatic hyperplasia. Investigative Urology 10, 123-130. 

Bicalutamide -nonsteroidal antiandrogen -endocrine effects -hot flashes -decreased libido -depression -weight gain -constipation... 

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. 

Decensi AU, Boccardo F, Guameri D, Positano N, Paoletti MC, Costantini M, Martorana G, Giuliani L (1991) Monotherapy with nilutamide, a pure nonsteroidal antiandrogen, in untreated patients with metastatic carcinoma of the prostate. The Italian Prostatic Cancer Project. J Urol 146 377-381... 

Neri R, Florance K, Koziol P, Van Cleave S (1972) A biological profile of a nonsteroidal antiandrogen, SCH 13521 (4 -nitro-3 trifluoromethylisobutyranilide). Endocrinology 91 427437... 

Tucker H, Crook JW, Chesterson GJ (1988) Nonsteroidal antiandrogens. Synthesis and structure-activity relationships of 3-substituted derivatives of 2-hydroxypropionanilides. J Med Chem 31 954-959... 

Payen O, Top S, Vessieres A, Brule E, Plamont M, McGlinchey M, Muller-Bunz H, Jaouen G (2008) Synthesis and structure-activity relationships of the first ferrocenyl-aryl-hydantoin derivatives of the nonsteroidal antiandrogen nilutamide. J Med Chem 51 1791-1799... 

Flutamide [FLEW tah mide] is a synthetic nonsteroidal antiandrogen used in the treatment of prostate cancer. It is metabolized to an active hydroxy derivative that binds to the androgen receptor. 

Table 1 Selected 4 -cyano-3 -trifluoromethyl biphenyl derivatives evaluated as nonsteroidal antiandrogen inhibitors. H-NMR for products supplied by author.

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). 

Flutamide and bicalutamide are nonsteroidal antiandrogens available for use in conjunction with the gonadorelins (e.g. goserelin) in the treatment of prostatic carcinoma. Finasteride (p. 544), which inhibits conversion of testosterone to dihydrotestosterone, has localised antiandrogen activity in tissues where dihydrotestosterone is the principal androgen this makes it a useful drug in the treatment of benign prostatic hypertrophy. 

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

Kaisary, A.V. (1994) Current clinical studies with a new nonsteroidal antiandrogen, Casodex. Prostate. Supplement, 5, 27—33. 

Flutamide, a nonsteroidal antiandrogen (250 mg p.o. q. 8 hours), is indicated in the treatment of metastatic prostatic carcinoma in combination with LHRH analogs, such as leuprolide acetate (see also Table 13). 

Furthermore, urea-type pesticides propanil, linuron, and diuron, which arc the main herbicides used throughout the world, have the ability to bind to AR (Cook et ai, 1993 Bauer et al., 1998). Indeed, linuron is strueturally related to the nonsteroidal antiandrogen flutamidc, and its IC50 for competition at the AR is approximately 3.5 limes that of flutamide. The activity of its metabolite, 3,4-dichloroanilinc, is higher than that of linuron. 

---