17 beta -ARYL ESTER CARBOXYLATES OF 4-AZA-5 alpha -ANDROSTANE-3-ONES

Abstract: Described are new 17(beta)-aryl ester carboxylates of 4-aza-5(alpha)-androstan-3-ones and related compounds and the use of such compounds as 5(alpha)-reductase inhibitors for treatment of benign prostatic hyperplasia and other hyperandrogenetic related disorders.

Description: TΓΓLE OF THE INVENTION 17 -aryl ester carboxylates of 4-aza-5σ-androstane-3-ones. BACKGROUND OF THE INVENTION The present invention is directed to new 17β-aryl ester carboxylates of 4-aza-5oc-androstan-3-ones and related compounds and the use of such compounds as 5α-reductase inhibitors. DESCRIPTION OF THE PRIOR ART The art reveals that certain undesirable physiological manifestations, such as acne vulgaris, seborrhea, female hirsutism, male pattern baldness and benign prostatic hyperplasia, are the result of hyperandrogenetic stimulation caused by an excessive accumulation of testosterone or similar androgenic hormones in the metabolic system. Early attempts to provide a chemotherapeutic agent to counter the undesirable results of hyperandrogenicity resulted in the discovery of several steroidal antiandrogens having undesirable hormonal activities of their own. The estrogens, for example, not only counteract the effect of the androgens but have a feminizing effect as well. Non-steroidal antiandrogens have also been developed, for example, 4'-nitro-3'- trifluoro-methylisobutyranilide. See Neri, et al., Endo., Vol. 91, No. 2 (1972). However, these products, though devoid of hormonal effects, are peripherally active, competing with the natural androgens for receptor sites, and hence have a tendency to feminize a male host or the male fetus of a female host. It is now known in the art that the principal mediator of androgenic activity in some target organs, e.g. the prostate, is 5α- dihydrotestosterone, (DHT) and that it is formed locally in the target organ by the action of testosterone-5α-reductase. It is also known that inhibitors of testosterone-5α-reductase will serve to prevent or lessen symptoms of hyperandrogenetic stimulation. For example, a number of 4-aza steroid compounds are known which are 5α-reductase inhibitors. See the following Merck & Co., Inc. patents, U.S. Patent Nos. 4,377,584, 4,220,775, 4,859,681, 4,760,071 and the articles J. Med. Chem. 27, p. 1690-1701 (1984) and J. Med. Chem. 29, 2998-2315 (1986) of Rasmusson, et al., and U.S. Patent 4,845,104 to Carlin, et al., and U.S. Patent 4,732,897 to Cainelli, et al. which describe 4-aza-17β-substituted-5α-androstan-3-ones said to be useful in the treatment of DHT-related hyperandrogenic conditions. Further there is the suggestion in the early prior art that hyperandrogenic diseases are the result of a single 5α-reductase. However, there are later reports regarding the presence of other 5α- reductase isozymes in both rats and humans. For example, in human prostate, Bruchovsky, et al. (See J. Clin. Endocrinol. Metab. 67, 806-816, 1988) and Hudson (see J. Steroid Biochem. 26, p 349-353, 1987) found different 5α-reductase activities in the stromal and epithelial fractions. Additionally, Moore and Wilson described two distinct human reductases with peaks of activities at either pH 5.5 or pH 7-9. (See J. Biol. Chem. 251. 19, p. 5895-5900, 1976.) Recently, Andersson and Russell isolated a cDNA which encodes a rat liver 5cc-reductase (see J. Biol. Chem. 264 pp. 16249-55 (1989). They found a single mRNA which encodes both the liver and prostatic reductases in rats. This rat gene was later used to identify a human prostatic cDNA encoding a 5oc-reductase termed "5α-reductase 1". (See Proc. Nat'l. Acad. Sci. 87, p. 3640-3644, 1990.) More recently, a second, human prostatic reductase (5α- reductase 2) has been cloned with properties identified with the more abundant form found in crude human prostatic extracts. (See Nature, 354. p. 159-161, 1991.) Further, "Syndromes of Androgen Resistance" - The Biology of Reproduction, Vol. 46, p. 168-173 (1992) by Jean D. Wilson suggests that the 5α-reductase 1 enzyme is associated with hair follicles. Thus, the art supports the existence of at least two genes for 5α-reductase and two distinct isozymes of 5cc-reductase in humans. Both isozymes are believed to be present in prostatic tissue in which, 5cc- reductase 2, is the more abundant, while the other isozyme, 5α-reductase 1, is believed to be more abundant in scalp tissue. In the treatment of hyperandrogenetic disease conditions, e.g. benign prostatic hyperplasia (BPH) it would be desirable to have one drug entity which is dually active against both enzymes 1 and 2 to substantially inhibit dihydrotesterone (DHT) production. Alternatively, it would be desirable to have a drug entity which is highly selective for inhibiting the scalp-associated enzyme 5α-reductase 1 for treating diseases of the scalp, e.g. androgenic alopecia. This latter drug could also be used in combination with PROSCAR® (finasteride) which is highly selective for only the prostatic enzyme 5cc-reductase 2 for combination therapy in the treatment of BPH. SUMMARY OF THE INVENTION The present invention discloses novel 17β-aryl ester carboxylate derivatives of 4-aza-5α-androstan-3-one compounds which are useful for inhibiting the 5α-reductase enzyme and isozymes thereof in prostatic tissue. They are also particularly effective in selectively inhibiting the 5α-reductase 1 associated with the scalp or dually inhibiting both isozymes 1 and 2 in the treatment of benign prostatic hyperplasia, acne, female hirsutism, androgenic alopecia, i.e., male pattern baldness, prostatitis, and the prevention and treatment of prostatic carcinoma. In accordance with the present invention there is provided novel 17β-aryl ester carboxylates of 4-aza-5α-androstan-3-one and related compounds of the formula: wherein: the dashed line can represent a double bond when present; R is selected from hydrogen, methyl, ethyl; Rl can be: 1) oxo; 2) alpha-hydrogen and beta-hydrogen or a beta-substituent selected from: C1-C4 alkyl, C2-C4 alkenyl, CH2COOH, hydroxy, carboxy, COOC1-C4 alkyl esters; CONR3R4, where R3 and R4 are independently H, C1-C4 alkyl, phenyl, benzyl, and R3 and R4 together with the nitrogen can form a 5-6 membered saturated heterocyclic ring, optionally with one other heteroatom; OC1-C4 alkyl, OC3-C6 cycloalkyl, OCOCH3, halo, hydroxy C1-C2 alkyl, halo C1-C2 alkyl, trifluoromethyl, C3-C6 cycloalkyl; 3) =CH-R' where R' is H, C1-C4 alkyl; 4) spiro: where R' is H, C1-C4 alkyl; R2 is independently selected from the following alpha and beta substituents : hydrogen, C 1 -C4 alkyl; and Ar is a C6-C10 aromatic ring substituted with one or more of C1-C4 alkyl, C1-C4 alkoxy, or halo; and pharmaceutically acceptable salts and esters thereof. Also provided are the new intermediates: 7β-methyl-3-oxo- 4-aza-androstane-17β-carboxylic, acid and 7β-methyl-3-oxo-4-aza- androst- 1 -ene- 17 β-carboxylic acid. Also disclosed are processes for their preparation, pharmaceutical formulations comprising the novel compounds as active ingredients and methods of inhibiting 5α-reductases 1 and/or 2 in diseases which occur under hyperandrogenetic conditions, e.g., benign prostatic hyperplasia. DETAILED DESCRIPΗON OF THE INVENTION AND PREFERRED EMBODIMENTS The structure I above encompasses all the 5α-reductase inhibitor compounds of this invention. The dashed line can independently be a double bond and when present, the compound is a delta- 1-ene. By the term "C1-C4 alkyl" is meant linear or branched alkyl; e.g. methyl, ethyl, isopropyl, propyl, n-butyl, isobutyl, sec-butyl and the like. By the term "hydroxy C1-C2 alkyl" is meant monohydroxy C1-C2 alkyl including: hydroxymethyl, 1 -hydroxy- ethyl, 2- hydroxyethyl, and the like. By the term "halo C1-C2 alkyl" is meant mono halogenated C1-C2 alkyl including: fluoromethyl, chloromethyl, 1-fluoroethyl, 2- fluoroethyl, 1-chloroethyl, 2-chloroethyl, and the like. By the term "OC1-C4 alkyl" as used herein is meant to include methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec- butoxy, t-butoxy, and the like. By the term "OC3-C6 cycloalkyl" as used herein is meant to include: cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, and the like. Ar is a C6-C10 aromatic ring including phenyl, and naphthyl and the like. C2-C4 alkenyl includes ethenyl, propenyl, 1- and 2-butyryl and the like. C3- 5 cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. "Halo" includes fluoro, chloro, bromo and preferred is fluoro, chloro. R3 and R4 can also be connected to form a 5-6 membered heterocychc radical, being fully saturated, containing 1-2 nitrogen atoms and 0-1 oxygen atoms, e.g., piperidino, pyrrohdino, morpholino, and the like. The phenyl and benzyl groups in R3 and R4 can be unsubstituted or substituted with one or more of the following substituents providing the substitution leads to a chemically stable, but biologically active 5-alpha reductase inhibitor: The ring substituents include: C1-C4 straight or branched alkyl; C1-C5 alkoxy; and halo; all as defined above. Representative examples of Rl are where the α-substituent (dashed lines) is hydrogen and the beta substituent (wedge) is e.g. methyl, ethyl, propyl, allyl, carboxymethyl, hydroxy, methoxy, ethoxy, cyclopropyloxy, cyclopentyloxy, acetoxy, fluoro, chloro, bromo, trifluoromethyl, trichloromethyl, fluoromethyl, chloromethyl, carboxy, N,N-dimethylcarbamate, hydroxymethyl, methoxymethyl, and the like. Representative examples where Rl is an alkenyl substituent, =CH-R * , includes, e.g. =CH2, =CH-CH3, =CH-CH2CH3, and the like. Representative examples where Rl is the spiro substituent: stereoisomers thereof and the like. Unless otherwise indicated the 17-substituents herein described are assumed to be in the beta configuration. - Representative compounds of the present invention include the following: 2'-Methoxyphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate 3'-Methoxyphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate 4'-Methoxyphenyl-3-oxo-4-methyl-4-aza-5o-androstane-17β-carboxylate 2',5'-dimethoxyphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β- carboxylate 3',4',5'-trimethoxyphenyl-3-oxo-4-methyl-4-aza-5α-androstane- 17β- carboxylate 2'-t-Butylphenyl-3-oxo-4-methyl-4-aza-5 -androstane-17β-carboxylate 3'-t-Butylphenyl-3-oxo-4-methyl-4-aza-5 -androstane-17β-carboxylate 4'-t-Butylphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate 2'-Fluorophenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate 2'-Methoxyphenyl-3-oxo-4-aza-5α-androstane-17β-carboxylate 3'-Methoxyphenyl-3-oxo-4-aza-5α-androstane-17β-carboxylate 4'-Methoxyphenyl-3-oxo-4-aza-5α-androstane-17β-carboxylate 2',6'-Dimethoxyphenyl-3-oxo-4-aza-5 -androstane-17β-carboxylate 3',4',5'-trimethoxyphenyl-3-oxo-4-aza-5α-androstane-17β-carboxylate 2'-t-Butylphenyl-3-oxo-4-aza-5α-androstane- 17β-carboxylate 3'-t-Butylphenyl-3-oxo-4-aza-5 -androstane-17β-carboxylate 4'-t-Butylphenyl-3-oxo-4-aza-5 -androstane-17β-carboxylate 2'-Fluorophenyl-3-oxo-4-aza-5oc-androstane-17β-carboxylate 2'-Methoxyphenyl-3-oxo-5α-androst-l -ene-17β-carboxylate 3'-Methoxyphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate 4'-Methoxyphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate 2',6'-dimethoxyphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate 3',4',5'-trimethoxyphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate 2'-t-Butylphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate 3'-t-Butylphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate 4'-t-Butylphenyl-3-oxo-4-aza-5o-androst-l-ene-17β-carboxylate 2' -Fluorophenyl-3 -oxo-4-aza-5α-androst- 1 -ene- 17β-carboxylate 2'-Methoxyphenyl-3-oxo-4,7β-dimethyl-4-aza-5α-androstane-17β- carboxylate 3'-Methoxyphenyl-3-oxo-4,7β-dimethyl-4-aza-5α-androstane-17β- carboxylate 4'-Methoxyphenyl-3-oxo-7β-ethyl-4-methyl-4-aza-5 -androstane-17β- carboxylate 2',5'-dimethoxyphenyl-3,7-dioxo-4-methyl-4-aza-5α-androstane-17β- carboxylate 3\4 5'-trimemoxyphenyl-4,7β-di-memyl-3-oxo-4-aza-5α-androstane- 17β-carboxylate 2'-t-Butylphenyl-4,7β-di-methyl-3-oxo-4-aza-5α-androstane-17β- carboxylate 3'-t-Butylphenyl-4,7β-di-methyl-3-oxo-4-aza-5α-androstane-17β- carboxylate 4'-t-Butylphenyl-4,7β-di-methyl-3-oxo-4-aza-5α-androstane-17β- carboxylate 2'-Fluorophenyl-4,7β-di-methyl-3-oxo-4-aza-5α-androstane-17β- carboxylate 2'-Methoxyphenyl-7β-methyl-3-oxo-4-aza-5α-androstane-17β- carboxylate 3'-Methoxyphenyl-7β-methyl-3-oxo-4-aza-5 -androstane-17β- carboxylate 4'-Methoxyphenyl-7β-methyl-3-oxo-4-aza-5α-androstane-17β- carboxylate 2',6'-Dimethoxyphenyl-7β-methyl-3-oxo-4-aza-5α-androstane-17β- carboxylate 3 ' ,4' ,5 '-trimethoxypheny l-7β-methy 1-3 -oxo-4-aza-5oc-androstane- 17β - carboxylate 2'-t-Butylphenyl-3,7-di-oxo-4-aza-5 -androstane-17β-carboxylate 3'-t-Butylphenyl-3,7-di-oxo-4-aza-5α-androstane-17β-carboxylate 4'-t-Butylphenyl-3,7-di-oxo4-aza-5α-androstane-17β-carboxylate 2'-Fluorophenyl-3 ,7-di-oxo-4-aza-5α-androstane- 17β-carboxylate 2'-Methoxyphenyl-7β-ethyl-3-oxo-4-aza-5α-androst- 1 -ene- 17β- carboxylate 3'-Methoxyphenyl-7β-ethyl-3-oxo-4-aza-5α-androst-l-ene-17β- carboxylate 4'-Methoxyphenyl-7β-ethyl-3-oxo-4-aza-5α-androst-l-ene-17β- carboxylate 2',6'-dimethoxyphenyl-7-fluoro-3-oxo-4-aza-5α-androst- 1 -ene- 17β- carboxylate 3^4 5'-trimethoxyphenyl-7β-propyl-3-oxo-4-aza-5α-androst-l-ene-17β- carboxylate 2'-t-Butylphenyl-7-methylene-3-oxo-4-aza-5α-androst-l-ene-17β- carboxylate 3'-t-Butylphenyl-7-methylene-3-oxo-4-aza-5α-androst-l-ene-17β- carboxylate 4'-t-Butylphenyl-7-methylene-3-oxo-4-aza-5α-androst-l-ene-17β- carboxylate 2' -Fluorophenyl-7-methylene-3-oxo-4-aza-5α-androst-l -ene-17β- carboxylate and also including the corresponding compounds wherein the 4-hydrogen substituent is replaced by a methyl or an ethyl radical, and a delta-one double bond is present or absent. Also included within the scope of this invention are pharmaceutically acceptable salts, i.e. hydrochloride, hydrobromide, acetate, pamoate, and the like, which can be used as the dosage form for modifying solubility or hydrolysis characteristics or for use as sustained release or prodrug formulations. The novel compounds of formula I of the present invention are prepared by methods discussed below. The compounds and intermediates, their physical properties, and their preparation is illustrated in Examples 1-30. The starting materials for these preparations are: A; 4-methyl-3-oxo-4-aza-5α-androstane-17-carboxylic acid, whose preparation is described in J. Med. Chem. Vol. 27, p. 1690-1701 (1984); B; 3-oxo-4-aza-5oc-androstane-17-carboxylic acid, whose preparation is described in J. Med. Chem. Vol. 29, p. 2998- 2315 (1986); C; 3-oxo-4-aza-5α-androst-l-ene-17β-carboxylic acid, whose preparation is described in J. Med. Chem. Vol. 29, p. 2998- 2315 (1986); D; 7β-methyl-3-oxo-5α-4-aza-androstane-17β-carboxylic acid, E; 4,7β-dimethyl-3-oxo-4-aza-5oc-androstane-17β-carboxylic acid, F; 4,7 β-dimethyl-3-oxo-4-aza-5α-androstane- 1 -ene- 17β- carboxylic acid, G; 7β-methyl-3-oxo-4-aza-5oc-androst-l-ene-17β-carboxylic acid, H; 4-methyl-3,7-dioxo-4-aza-5α-androstane-17β-carboxylic acid, I; 3,7-dioxo-4-aza-5 -androstane-17β-carboxylic acid, J; 7-methoxycarbonylmethyl-4-methyl-3-oxo-4-aza-5α- androstane-17β-carboxylic acid, K; 7-allyl-4-methyl-3-oxo-4-aza-5α-androstane-l 7β-carboxylic acid, Other starting materials can be prepared from the above intermediates by selective 4-N-alkylation, introduction of the 1,2-double bond as described in the above J. Med. Chem. references and by derivitization of the 7-oxo substituent by suitable methods. SCHEME 1 Compounds prepared by this scheme are as follows: SCHEME 2 11 Compounds prepared by this scheme are as follows: 30 25 30 SCHEME 3 21 Compounds prepared by this scheme are as follows: 30 The compounds of the instant invention where R' is other than hydrogen are made by carrying out Reaction Schemes 1-3 but utilizing the following 7-substituted azasteroid intermediates D-K. In general, the 7-substituent is formed first on the intermediate, then reacted with the appropriate phenol to form the 17-acylester. The compounds of the invention are produced by the Reaction Schemes 1-3 shown above. The starting carboxylic acid A, B or C is first reacted with 2- pyridylthiol and triphenylphosphine in toluene overnight at room temperature (r.t.) to produce the corresponding 2-pyridyl-thio keto analogues (e.g. 1, 11, 21). This thio derivative is then reacted with a displacing substituted phenol, e.g. ArOH, in dimethylformamide containing cesium carbonate as catalyst at room temperature over a 4 hour period to yield the new 17-beta-substituted aryl ester. Conventional isolation and purification procedures, e.g.,chromatography, fractional crystallization yields the pure product. Representative examples of phenols used are 2- methoxyphenol, 3-methoxyphenol, 4-methoxyphenol, 2,6-di- methoxyphenol, 3,4,5-trimethoxyphenol, 2-(t-butyl)phenol, 3-(t- butyl)phenol, 4-(t-butyl)-phenol, and 2-fluorophenol, and the like. Accordingly, the present invention is particularly concerned with providing a method of treating the hyperandrogenic conditions of acne vulgaris, seborrhea, female hirsutism as well as benign prostatic hyperplasia, prostatitis, and prostatic carcinoma by oral or parenteral administration of the novel compounds of the present invention. The present invention is thus also concerned with providing suitable topical, oral and parenteral pharmaceutical formulations for use in the novel methods of treatment of the present invention. The compositions containing the compounds of the present invention as the active ingredient for use in the treatment of benign prostatic hypertrophy can be administered in a wide variety of therapeutic dosage forms in conventional vehicles for systemic administration, as, for example, by oral administration in the form of tablets, capsules, solutions, or suspensions, of by intravenous injection. The daily dosage of the products for an adult human/per day may be varied over a wide range varying from 0.5 to 1 ,000 mg. The compositions are preferably provided in the form of scored tablets containing 0.5, 1.0, 2.5, 5.0, 10.0, 15.0, 25.0,and 50.0-milligrams of the active ingredient for the symptomatic adjustment of the dosage to the patient to be treated. An effective amount of the drug is ordinarily supplied at a dosage level of from about 0.002 mg. to about 50 mg./kg. of body weight per day. Preferably the range is from about 0.01 mg. to 7 mg./kgs. of body weight per day. These dosages are well below the toxic dose of the product. Capsules containing the product of this invention can be prepared by mixing an active compound of the present invention with lactose and magnesium stearate, calcium stearate, starch, talc, or other carriers, and placing the mixture in gelatin capsule. Tablets may be prepared by mixing the active ingredient with conventional tableting ingredients such as calciuim phosphate, lactose, com starch or magnesium stearate. The liquid forms in suitably flavored suspending or dispersing agents such as the synthetic and natural gums, for example, tragacanth, acacia, methylcellulose and the like. Other dispersing agents which may be employed include glycerin and the like. For parenteral administration, sterile suspensions and solutions are desired. Isotonic preparations which generally contain suitable preservative are employed when intravenous administration is desired. For the treatment of acne vulgaris, seborrhea, female hirsutism, the compounds of the present invention are administered in the formula of pharmaceutical composition comprising the active compound in combination with a pharmacologically acceptable carrier adapted for topical administration. Parenteral administration is also applicable. These topical pharmaceutical compositions may be in the form of a cream, ointment, gel or aerosol formulation adapted for application to the skin. These topical pharmaceutical compositions containing the compounds of the present invention ordinarily include about 0.1% to 15%, preferably about 5%, of the active compound, in admixture with about 95% of vehicle. The methods of preparing the novel 17β-aryl ester, derivatives of 3-oxo-4-azasteroids of the present invention, already described above in general terms, may be further illustrated by the following examples. EXAMPLE 1 S-2'-pyridyl-3- oxo-4-aza-4-methyl-5α-androstane-17β-thio-carboxylate (intermediate (1 To a solution of 3-oxo-4-methyl-4-aza-5α-androstane-17β- carboxylic acid (7.0 g, 21 mmol) in toluene (300 ml) was added Aldrithiol * (14.7 g, 66.7mmol) and triphenylphosphine (16.49 g, 62.8mmol). After stirring the reaction mixture for overnight at room temperature, the reaction mixture was concentrated under vaccum and purified by column chromatography over silica gel using 10% acetone/methylene chloride to give 6.0g of titled pure product L ♦ Commercially available from the Aldrich Chemical Co. EXAMPLE 2 2'-Methoxyphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate £2) To a solution of S-2'-pyridyl-3-oxo-4-methyl-4-aza-5α- androstane-17β-thiocarboxylate (200 mg, 0.47 mmol) in DMF was added Cs2Cθ3 (326 mg, 1 mmol) and guaiacol (125 μl, 1.13 mmol). After stirring the reaction mixture for 4 hrs, the reaction mixture was diluted with water and extracted with methylene chloride. The organic layer was dried, concentrated, residue purified by HPLC using Partisil M9 10/50 column and 30% acetone/methylene chloride as solvent to give desired titled product 2, Mpl95-197°C. Mass spec. (MS) M+ calculated, 439.58; observed m/e 439 (El). Anal, calcd for C27H37NO4O.3H2O, C 72.87; H 8.50; N 3.14. Found: C 72.79; H 8.54; N 3.05. EXAMPLE 3 3'-Methoxyphenyl-3-oxo-4-aza-4-methyl-5α-androstane-17β-carboxylate ID Employing substantially the same procedure as described in Example 2, but substituting the guaiacol with 3-methoxyphenol, the titled product 3 was obtained. Mp 196-198°C. Mass spec. (MS) calculated 439.58; observed m/e 439. Anal, calcd.for C27H37NO4O.3H2O, C 72.87; H 8.50; N 3.4. Found: C 72.87; H 8.68; N 3.05. EXAMPLE 4 4'-Methoxyphenyl-3-oxo-4-aza-4-methyl-5α-androstane-17β-carboxylate 4) Employing substantially the same procedure as described in Example 2, but substituting the guaiacol with 4-methoxyphenol, the titled product 4 was obtained. Mp 148-150°C. Mass spec. (MS) calculated, 439.58; observed m/e 439. Anal. calcd.for C27H37NO4, C 73.76; H 8.48; N 3.31. Found: C 73.52; H 8.31; N 3.12. EXAMPLE 5 2',5'-dimethoxyphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β- carboxylate (5) Employing substantially the same procedure as described in Example 2, but substituting the guaiacol with 2,5-dimethoxyphenol, the titled product 5 was obtained. Mp 161-162°C. Mass spec. (MS) calculated, 469.60; observed m/e 469. Anal. calcd.C28H39NO5-0.3H20, C 70.82; H 8.43; N 2.85. Found: C 70.82; H 8.43; N 2.95. EXAMPLE 6 3',4',5'-trimethoxyphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β- carboxylate (6) Employing substantially the same procedure as described in Example 2, but substituting the guaiacol with 3,4,5-triimethoxyphenol, the titled product 6 was obtained. Mp 133-135°C. Mass spec. (MS) calculated, 499.63; observed m/e 499. Anal, calcd. C29H4lNO6«0.3H2O, C 68.96; H 8.30; N 2.77. Found: C 68.94; H 8.29; N 2.70. EXAMPLE 7 2'-t-Butylphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate Employing substantially the same procedure as described in Example 2, but substituting the guaiacol with 2-t-butylphenol, the titled product 7 was obtained. Mpl33-135°C. Mass spec. (MS) calculated, 465.68; observed m/e 465. Anal. calcd.for C30H43NO3, C 77.38; H 9.31; N 3.01. Found: C 77.35; H 9.63; N 2.90. EXAMPLE 8 3'-t-Butylphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate : Employing substantially the same procedure as described in Example 2, but substituting the guaiacol with 3-t-butylphenol, the titled product 8 was obtained, Mpl35-136°C. Mass spec. (MS) calculated, 465.68; observed m/e 465. Anal, calcd. for C30H43NO3O.4H2O, C 76.20; H 9.34; N 2.96. Found: C 76.17; H 9.07; N 3.05. EXAMPLE 9 4'-t-Butylphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate £9} Employing substantially the same procedure as described in Example 2, but substituting the guaiacol with 4-t-butylphenol, the titled product 9 was obtained. Mass spec. (MS) calculated, 465.68; observed m/e 465. Anal, calcd. for C30H43NO3, C 77.38; H 9.31; N 3.01. Found: C 77.46; H 9.40; N 2.91. EXAMPLE 10 2'-Fluorophenyl-3-oxo-4-methyl-4-aza-5 -androstane-17β-carboxylate £10) Employing substantially the same procedure as described in Example 2, but substituting the guaiacol with 2-t-fluorophenol, the titled product JO was obtained. Mass spec. (MS) calculated, 427.54; observed m e 427. Anal, calcd. for C26H34NO3F, C 73.04; H 8.01; N 3.28. Found: C 72.79; H 8.05; N 3.09. EXAMPLE 11 S-2'-pyridyl-3- oxo-4-aza-5oc-androstane-17β-thiocarboxylate (11, intermediate To a solution of 3-oxo-4-aza-5α-androstane-17β-carboxylic acid (20.0 g, 62.7 mmol) in toluene (120 ml) was added aldrithiol (28 g, 127 mmol) and triphenylphosphine (32 g, 122 mmol). After stirring the reaction mixture for overnight at room temperature, the titled product 11 precipitated out of solution and was filtered (20 g), Mp 247-249°C. EXAMPLE 12 2'-Methoxyphenyl-3-oxo-4-aza-5 -androstane-17β-carboxylate (12 To a solution of S-2'-pyridyl-3-oxo-4-aza-5α-androstane- 17β-thiocarboxylate (207 mg, 0.5 mmol) in DMF (10 ml) was added Cs2C03 (326 mg, 1 mmol) and guaiacol (125 ml, 1.13 mmol). After stirring the reaction mixture for 4 hrs, the reaction mixture was diluted with water and extracted with methylene chloride. The organic layer was dried, concentrated, residue purified by prep, silica gel TLC (3:1 acetone/methylene chloride) and recrystallized from ether, to yield the above titled product 12, Mp 228-230°C. Mass spec. (MS) M+ calculated, 425.55; observed m/e 425 (El). Anal, calcd for C26H35NO4-0.2H2O, C 72.76; H 8.31; N 3.26. Found: C 72.783; H 8.23; N 3.17. EXAMPLE 13 3 '-Methox vphenyl-3 -oxo-4-aza-5 -androstane- 17 β-carboxylate (13) Employing substantially the same procedure as described in Example 12, but substituting the guaiacol with 3-methoxyphenol, yields the titled product L3. Mp 216-217°C. Mass spec. (MS) calculated, 425.57; observed m/e 425. Anal, calcd. for C26H35NO4-0.2H2O, C 72.76; H 8.31; N 3.26. Found: C 72.71; H 8.22; N 3.28. EXAMPLE 14 4'-Methoxyphenyl-3-oxo-4-aza-5 -androstane-17β-carboxylate (14) Employing substantially the same procedure as described in Example 12, but substituting the guaiacol with 4-methoxyphenol, the titled product 14 is obtained, Mp 299-301°C. Mass spec. (MS) calculated, 425.57; observed m e 425. Anal, calcd. for C26H35N04, C 73.38; H 8.29; N 3.29. Found: C 72.91; H 8.23; N 3.29. EXAMPLE 15 2'.6'-Dimethoxyphenyl-3-oxo-4-aza-5 -androstane-17β-carboxylate (15) Employing substantially the same procedure as described in Example 12, but substituting the guaiacol with 2,6-dimethoxy-phenol, the titled product 15 is obtained. Mp 256-58°C. Mass spec. (MS) calculated, 455.599; observed m/e 455. Anal, calcd. for C27H37NO5, C 71.18; H 8.19; N 3.08. Found: C 71.06; H 8.28; N 2.96. EXAMPLE 16 3 4\5'-trimemoxyphenyl-3-oxo-4-aza-5α-androstane-17β-carboxylate £16) Employing substantially the same procedure as described in Example 12, but substituting the guaiacol with 3,4,5-trimethoxy-phenol, the titled product 16 is obtained. Mp 244-246°C. Mass spec. (MS) calculated, 485.60; observed m/e 485. EXAMPLE 17 2'-t-Butylphenyl-3-oxo-4-aza-5α-androstane-17β-carboxylate (17) Employing substantially the same procedure as described in Example 12, but substituting the guaiacol with 2-t-butylphenol, the titled product 17 is obtained. Mp 189-91°C. Mass spec. (MS) calculated, 451.63; observed m/e 451. Anal, calcd. for C29H41NO3, C 77.11; H 9.15; N 3.10. Found: C 76.89; H9.35; N 3.01. EXAMPLE 18 3'-t-Butylphenyl-3-oxo-4-aza-5 -androstane-17β-carboxylate (18) Employing substantially the same procedure as described in Example 12, but substituting the guaiacol with 3-t-butylphenol, the titled product 18 is obtained. Mp 228-231°C. Mass spec. (MS) calculated, 451.63; observed m/e 451. Anal, calcd. for C29H41NO3, C 77.11; H 9.15; N 3.10. Found: C 77.09; H9.25; N 3.09. EXAMPLE 19 4'-t-Butylphenyl-3-oxo-4-aza-5α-androstane-l 7β-carboxylate (19) Employing substantially the same procedure as described in Example 12, but substituting the guaiacol with 4-t-butylphenol, the titled product 19 is obtained. Mass spec. (MS) calculated, 451.63; observed m/e 451. Anal, calcd. for C29H41NO3, C 77.11; H 9.15; N 3.11. Found: C 76.94; H9.16; N 3.04. EXAMPLE 20 2'-Fluorophenyl-3-oxo-4-aza-5α-androstane-l 7β-carboxylate (20) Employing substantially the same procedure as described in Example 12, but substituting the guaiacol with 2-fluorophenol, the titled product 20 is obtained. Mass spec. (MS) calculated, 413.52; observed m/e 302 (m-l ll). Anal, calcd. for C25H32NO3F-0.2H2O, C 71.98; H 7.82; N 3.35. Found: C 71.99; H 7.87; N 3.42. EXAMPLE 21 S-2'-pyridyl-3- oxo-4-aza-5α-androst- 1 -ene- 17 β-thiocarboxylate (21 , intermediate) To a solution of 3-oxo-4-aza-5α-androst-l-ene-17β- carboxylic acid (10.0 g, 31.5 mmol) in toluene (60 ml) was added aldrithiol (14 g, 63.5 mmol) and triphenylphosphine (316 g, 61 mmol). After stirring the reaction mixture for overnight at room temperature, the titled product 21 precipitated out of solution and was filtered (8.4 g). EXAMPLE 22 2'-Methoxyphenyl-3-oxo-4-aza-5 -androst-l-ene-17β-carboxylate (22) To a solution of S-2'-pyridyl-3-oxo-4-aza-5 -androst-l-ene- 17β-thiocarboxylate (205 mg, 0.5 mmol) in DMF (10 ml) was added Cs2Cθ3 (326 mg, 1 mmol) and guaiacol (125 ml, 1.13 mmol). After stirring the reaction mixture for 4 hrs, the reaction mixture was diluted with water and extracted with methylene chloride. The organic layer was dried, concentrated, residue purified by prep, silica gel TLC (3:1 acetone/methylene chloride) and recrystallized from ether, to yield the titled product 22. Mp 247-249°C. Mass spec. (MS) M+ calculated, 423.53; observed m/e 423 (El). Anal, calcd for C26H33Nθ4,«0.2H2θ, C 73.08; H 7.75; N 3.18. Found: C 73.10; H 7.88; N 3.38. EXAMPLE 23 3'-Methoxyphenyl-3-oxo-4-aza-5α-androst- 1 -ene- 17 β-carboxylate (23 ) Employing substantially the same procedure as described in Example 22, but substituting the guaiacol with 3-methoxyphenol, the titled product 23 is obtained. Mp 223-229°C. Mass spec. (MS) calculated, 423.53; observed m/e 423. Anal, calcd. for C26H33NO4O.6H2O, C 71.58; H 7.64; N 3.13. Found: C 71.89; H 7.93; N 3.23. EXAMPLE 24 4'-Methoxyphenyl-3-oxo-4-aza-5 -androst-l-ene-17β-carboxylate (24) Employing substantially the same procedure as described in Example 22, but substituting the guaiacol with 4-methoxyphenol, the titled product 24 was obtained. Mp 302-304°C. Mass spec. (MS) calculated, 423.53; observed m/e 423. Anal, calcd. for C26H33Nθ4,'0.3H2θ, C 72.80; H 7.90; N 3.27. Found: C 72.88; H 7.90; N 3.13. EXAMPLE 25 2',6 , -dimethoxyphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxy) £25) Employing substantially the same procedure as des Example 22, but substituting the guaiacol with 2,6-dimethoxy titled product 25 was obtained. Mp 259-261°C. Mass- spec, calculated, 453.58; observed m/e 453. Anal, calcd. for C27H35NO5, C 71.49; H 7.78; N 3.09. Found: C 71.10; H 7.72; N 2.84. EXAMPLE 26 3',4',5'-trimethoxyphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate (26) Employing substantially the same procedure as described in Example 22, but substituting the guaiacol with 3,4,5-trimethoxy-phenol, the titled product 26 was obtained. Mp 238-239°C. Mass spec. (MS) calculated, 483.59; observed m/e 483. Anal, calcd. for C28H37NO6-0.3H20, C 68.77; H 7.75; N 2.87. Found: C 68.81; H 7.49; N 2.92. EXAMPLE 27 2'-t-Butylphenyl-3-oxo-4-aza-5 -androst-l-ene-17β-carboxylate (27) Employing substantially the same procedure as described in Example 22, but substituting the guaiacol with 2-t-butylphenol, the titled product 27 was obtained. Mp 229-231°C. Mass spec. (MS) calculated, 449.61 ; observed m/e 449. Anal, calcd. for C29H39NO3O.3H2O, C 77.46; H 8.74; N 3.12. Found: C 76.53; H 8.61; N 3.03. EXAMPLE 28 3'-t-Butylphenyl-3-oxo-4-aza-5 -androst-l-ene-17β-carboxylate (28) Employing substantially the same procedure as described in Example 22, but substituting the guaiacol with 3-t-butylphenol, the titled product 8 was obtained. Mp 222-225°C. Mass spec: (MS) calculated, 449.61; observed m/e 449. Anal, calcd. for C29H39NO3O.3H2O, C 76.53; H 8.61; N 3.03. Found: C 77.27; H 8.71; N 3.08. EXAMPLE 29 4'-t-Butylphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate (29) Employing substantially the same procedure as described in Example 22, but substituting the guaiacol with 4-t-butylphenol, the titled product 22 was obtained. Mass spec. (MS) calculated, 449.61; observed m/e 449. Anal, calcd. for C29H39NO3, C 77.46; H 8.74; N 3.12. Found: C 76.54; H 8.77; N 3.08. EXAMPLE 30 2'-Fluorophenyl-3-oxo-4-aza-5 -androst-l -ene- 17β-carboxy late (30) Employing substantially the same procedure as described in Example 22, but substituting the guaiacol with 2-fluorophenol, the titled product 30 was obtained. Mass spec. (MS) calculated, 412.529; observed m/e 300 (m-112). EXAMPLE 31 7β-Methyl-3-oxo-4-aza-5α-androstane-17β-carboxylate (D) A solution of 5 grams 7β-methyl-3,20-di-oxo-4-aza-5α- pregnane (XI, See following Flowsheet B) in 200 ml. dioxane was treated at 10-15°C with 62.5 ml of a starch solution (prepared from 42 g. NaOH in 360 ml. water treated dropwise with 43 g. of bromine at 0°C, total volume — 400 ml) over a period of 90 minutes. After stirring for an additional 30 minutes thin layer chromatography (1:1 acetone/methylene chloride, 1% HCOOH) indicated a small amount of starting material still left. More starch solution was added (4.5 ml over 10 minutes) and the mixture stirred for 1.5 hours until TLC indicated starting material was absent. Hydrochloric acid (20%) was added until the mixture was about pH 8. Sodium bisulfite was added until a starch iodide test was negative. The mixture was concentrated until the dioxane was largely removed. Dilute hydrochloric acid was added and the mixture was triturated well and the filtered to yield a precipitate. The precipitate was dried to leave 3.2 g. crude solid. The solid was recrystallized from hot methanol to yield the above-titled intermediate D, mp. 311-312°C. Anal. Calc. for C2θH29Nθ3«0.4H2θ MW 333.47 (hydrate), Calc. C 70.51; H 9.41; N 4.11; Found: C 70.52; H 9.33; N 4.07. The following table lists the above compounds made in this invention and their physical properties in terms of the characteristic C-18, C-19 angular methyl groups and other significant proton absoφtion peaks which characterize and identify the specific molecular structures. The term "Ar" represents an aromatic proton(s). TABLE 8 0.816, 0.888 1.2899(t-Bu) 2.91(N-CH3) 9 0.801, 0.887 1.289(t-Bu) 6.96, 7.35(AR) 10 0.82, 0.891 2.91(N-CH3) 7.08-7.19(Ar) 10 11 0.734, 0.902 7.22-7.78,8.59- 8.62(AR) 12 0.839, 0.911 3.79(0-CH3) 6.91-7.23(Ar) 15 13 0.801, 0.902 3.778(0-CH3) 6.59-7.268(Ar) 14 0.800, 0.920 3.777(0-CH3) 20 6.863-6.96(Ar) 15 0.844, 0.911 3.778(0-CH3) 6.578, 7.096(Ar) 25 16 0.82, 0.92 3.8(0-CH3) 17 0.891, 0.906 1.32(t-Bu) 6.93-7.377(Ar) 30 18 0.819, 0.908 1.291 (t-Bu) 6.845-7.296(Ar) 10 15 20 25 30 FLOWSHEETA FLOWSHEET B 30 EX AMPLE 31 2'-Methoxyphenyl-7-methyl-3-oxo-4-aza-5 -androstane- 17β Carboxylate The intermediate XII is reacted with aldrithiol/PPh3 analogously as described above to give the corresponding 2-thiopyridyl ester. This in turn is reacted with guaiacol, DMF, cesium carbonate, analogously as in Example 12 to yield 2'-methoxyphenyl-7β- methyl-3-oxo-4-aza-5α-androstane-17β-carboxylate (31). Similarly, using other substituted phenols, other 7β-methyl- aza-steroid- 17 -substituted phenyl carboxylates can be produced as described herein. Preparation of the Starting Material D As seen in the Flowsheets A and B, pregnenolone-3-acetate (P) is first reduced to the alcohol II by sodium borohydride in ethanol at -10 to 0°C. The alcohol II is then protected by a dimethyl-t-butyl silyl (TBS) group in DMF with TBS chloride and imidazole as a base at room temperature. The protected alcohol is then oxidized to the corresponding 5-en-7-one III by treatment with hydrogen t-butyl peroxide and chromium hexacarbonyl in e.g., acetonitrile, at reflux. The 7-methyl group can be introduced at this point by a Grignard reaction using e.g., methyl magnesium chloride in e.g., anhydrous THF atO to -10°C to produce the 7 -methy 1-7 -hydroxy adduct IV. This is then oxidized with e.g. aluminum isopropoxide and cyclohexanone (Oppenauer oxidation conditions) in refluxing toluene solvent to produce the 7-methyl-4,6-dien- 3-one V. This in turn is reduced via e.g., metal-ammonia, THF and toluene at -78°C to selectively yield the 7-beta-methyl-5-en-3-one VI. In the next step the delta-5-double bond is isomerized to the 4-ene by use of DBU (l,8-diazabicylco-[5.4.01undec-7-ene) in e.g. refluxing tetrahydrofαran (THF) to produce the 7-methyl-4-ene-3-one, VII. The A ring is next cleaved by treatment with e.g. potassium permanganate, sodium periodate in t-butyl alcohol at 80°C to produce the corresponding seco-acid VQ. Treatment of the seco-acid with ammonium acetate in glacial acetic acid at 120°C yields e.g., the 7-methyl-4-aza-pregn-5-en-3- one DC. This is turn is selectively reduced with e.g., Ptθ2, to remove the 5-double bond to produce the 5α-hydrogen compound X. The TBS protecting group is next removed by aqueous HF in acetonitrile at room temperature and then oxidized by tetrapropylammonium perruthenate/4- methylmoφholine N-oxide in methylene chloride at room temperature to yield the 17-acetyl compound XI, mp. 215-217°C. This is treated with sodium hypobromite/sodium hydroxide solution in dioxane at 10-15°C to form the starting intermediate 17-carboxylic acid D, mp. 311-312°C. This is then used as described above to make the 2-thiopyridyl ester and the resulting azasteroidal phenyl carboxylates. The 1,2-double bond in the A ring can be introduced into D by DDQ oxidation (see procedure in US Patent 5,084,574) to produce G, mp 328-330°C. Formation of the 2-thioρyridyl intermediate XII, analogously as described above, and reaction with a methoxy substituted phenols as described above produces the corresponding phenyl carboxylates, XIE.

Claims: WHAT IS CLAIMED IS: 1. A compound of the formula: wherein: the dashed line can represent a double bond when present; R is selected from hydrogen, methyl, ethyl; Rl can be: 1) oxo; 2) alpha-hydrogen and beta-hydrogen or a beta-substituent selected from: C1-C4 alkyl, C2-C4 alkenyl, CH2COOH, hydroxy, carboxy, COOC1-C4 alkyl esters; OCONR3R4, where R and R4 are independently H, C1-C4 alkyl, phenyl, benzyl, and R3 and R4 together with the nitrogen can form a 5-6 membered saturated heterocychc ring, optionally with one other heteroatom; OC1-C4 alkyl, OC3-C6 cycloalkyl, OCOCH3, halo, hydroxy C1-C2 alkyl, halo C1-C2 alkyl, trifluoromethyl, C3-C6 cycloalkyl; 3) =CH-R * where R' is H, C1-C4 alkyl; 4) spiro: ^ ^ " R ' where R' is H, C l -C4 alkyl; R2 is independently selected from the following alpha and beta substituents: hydrogen, C1-C6 alkyl; and Ar is a C6-C10 aromatic ring substituted with one or more of C1-C4 alkyl, C1-C5 alkoxy, or halo; and pharmaceutically acceptable salts and esters thereof. 2. The compound of Claim 1 wherein said Ar is substituted phenyl. 3. The compound of Claim 1 wherein Rl is H or C1-C4 alkyl. 4. The compound of Claim 1 wherein said R is H or CH3 and R2 is H. 5. The compound of Claim 1 being the following: 2'-Methoxyphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate 3'-Methoxyphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate 4'-Methoxyphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate 2',5'-dimethoxyphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β- carboxylate 3 ' ,4' ,5 '-trimethoxyphenyl-3-oxo-4-methyl-4-aza-5α-androstane- 17β- carboxylate 2'-t-Butylphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate 3'-t-Butylphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate 4'-t-Butylphenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate 2'-Fluorophenyl-3-oxo-4-methyl-4-aza-5α-androstane-17β-carboxylate '-Methoxyphenyl-3-oxo-4-aza-5oc-androstane-17β-carboxylate '-Methoxyphenyl-3-oxo-4-aza-5α-androstane-17β-carboxylate '-Methoxyphenyl-3-oxo-4-aza-5α-androstane-17β-carboxylate ',6'-Dimethoxyphenyl-3-oxo-4-aza-5α-androstane-17β-carboxylate ' ,4' ,5 '-trimethoxyphenyl-3 -oxo-4-aza-5α-androstane- 17β-carboxylate '-t-Butylphenyl-3-oxo-4-aza-5α-androstane- 17β-carboxylate '-t-Butylphenyl-3-oxo-4-aza-5α-androstane-17β-carboxylate '-t-Butylphenyl-3-oxo-4-aza-5α-androstane-17β-carboxylate '-Fluorophenyl-3-oxo-4-aza-5α-androstane-17β-carboxylate '-Methoxyphenyl-3 -oxo-4-aza-5α-androst- 1 -ene- 17 β-carboxylate '-Methoxyphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate '-Methoxyphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate ',6'-dimethoxyphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate 4^5'-trimemoxyphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate '-t-Butylphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate '-t-Butylphenyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxylate '-t-Butylphenyl-3-oxo-4-aza-5α-androst-l -ene-17 β-carboxylate 2'-Fluorophenyl-3-oxo-4-aza-5cc-androst-l-ene-17β-carboxylate. 6. The compound, 7β-methyl-3-oxo-4-aza-androstane- 17β-carboxylic acid (D). 7. The compound, 7β-methyl-3-oxo-4-aza-androst-l- ene-17β-carboxylic acid (G). 8. A method for treating the hyperandrogenic conditions of acne, androgemc alopecia, male pattern baldness, female hirsutism, benign prostatic hypeφlasia, prostatitis, treatment and prevention of prostatic cancer, comprising administering to a patient in need of such treatment a therapeutically effective amount of the compound of Claim 1. 9. The method of Claim 8 wherein said compound is a 5α-reductase 1 inhibitor. 10. The method of Claim 8 wherein said compound is a 5α-reductase 2 inhibitor. 11. The method of Claim 8 wherein said compound is a dual inhibitor for both 5oc-reductases 1 and 2. 12. A pharmaceutical composition comprising a therapeutically effective amount of the compound of Claim 1 in a pharmaceutically acceptable vehicle therefor.

Inventors: BAKSHI RAMAN K, PATEL GOOL F, RASMUSSON GARY H, BAKSHI, RAMAN, K., PATEL, GOOL, F., RASMUSSON, GARY, H.
Applicants: MERCK & CO INC, MERCK & CO., INC.
Application year: 1993
Main classification: C07D221
IPC codes: C07J73