Method of treatment of chronic prostatitis with 17.beta.-N-monosubstituted-carbamoyl-4-aza-5.alpha.-androst-1-en-3-ones

#This application is a 371 of PCT/US93/11155 filed Nov. 18, 1993.

#The present invention is concerned with the use of 17.beta.-N-monosubstituted-carbamoyl-4-aza-5.alpha.-androst-1-en-3-one compounds as testosterone-5.alpha.-reductase inhibitors for the treatment of chronic prostatitis.

#Prostatitis in general constitutes about 10 to 15% of all urological practice. This category of poorly understood syndromes can be characterized by evidence of prostatic inflammation and by the presence or absence of white blood cells in prostatic fluid and/or pain associated with the prostate. Within this group of syndromes, the origins of chronic idiopathic prostatitis, asymptomatic prostatitis, and prostatodynia are problematic and are probably the least understood. The origin of these diseases have been attributed to some undefinable bacterial or viral infection, but this has never been proven. These syndromes do not exist prior to puberty but have a peak incidence between the ages of 18 and 50. It is possible that these three specific entities actually represent the same disease process in different phases or forms. Suggestions as to the origins of these conditions have included a chemical imbalance in the prostate, infection undetected by current microbiological methods, and autoimmunity to the prostate gland itself.

#The method of preparing the novel compounds of the present invention, already described above in general terms, may be further illustrated by the following examples.

#A suspension of 83.7 g of methyl 3-oxo-4-aza-5.alpha.-androstane-17-carboxylate* and 126.5 g of benzeneseleninic anhydride in 2.09 l of chlorobenzene was heated at reflux for 2 hours. The reflux condenser was switched to a distillation head and the mixture was distilled slowly to remove water that had formed in the reaction (2 hours). The solution was evaporated to leave 198 g of wet residue. The residue as a solution in dichloromethane was washed with saturated aqueous NaHCO.sub.3 solution and saturated NaCl solution, then dried and evaporated to leave 172.4 g. This material was chromatographed on 2.56 kg of silica gel eluting first with dichloromethane (5 l) and then with 4:1 dichloromethane acetone. The desired product eluted after 8 l and amounted to 53.4 g. It was rinsed with diethyl ether and dried to leave 49.5 g, of the title compound m.p. 278.degree.-280.degree. C. In a similar fashion the following compounds were converted to their corresponding 1,2-unsaturated derivatives:

#______________________________________ ##STR5## ##STR6## m.p. ______________________________________ 1a R = CONHC(CH.sub.3).sub.3 252-254.degree. C. 1b R = CONHC(CH.sub.3).sub.2 CH.sub.2 C(CH.sub.3).sub.3 224-226.degree. C. ______________________________________