show add
hide add

17-Ethers and thioethers of 4-aza-steroids


United States Patent     5,536,727

Witzel, et al.     Jul. 16, 1996

 

17-Ethers and thioethers of 4-aza-steroids. Asteroids as 5A-reductase inhibitors.

 

Inventors:

Graham; Donald W. (Mountainside, NJ); Aster; Susan D. (Teaneck, NJ); Hagmann; William (Westfield, NJ); Tolman; Richard L. (Warren, NJ).

 

Assignee:

Merck & Co., Inc. (Rahway, NJ).

 

Appl. No:

335,792

 

Filed:

Nov. 10, 1984

 

Related U.S. Application Data:

Continuation-in-part of Ser No. 886,021, May 20, 1992, abandoned.

Intl. Cl.: C07D 241/12, A61K 31/495

Current U.S. Cl.: 544/336; 544/405; 544/406; 546/77

Field of Search: 546/77; 514/284, 253; 544/336

 

Abstract:

Described are new 17.beta.-ester, amide and ketone 4-aza-5a-androstan-3-ones and related compounds and their use as 5a-reductase inhibitors for treatment of benign prostatic hyperplasia and other hyperandrogenetic related disorders.

3 Claims, No Drawings

References Cited:

U.S. Patent Documents

4,377,584      Mar., 1983      Rasmusson et al.      514/284

4,732,897      Mar., 1988      Cainelli et al.      514/228.2

4,760,071      Jul., 1988      Rasmusson et al.      514/284

4,859,681      Aug., 1989      Rasmusson      514/284

4,882,319      Nov., 1989      Holt      514/119

4,888,336      Dec., 1989      Holt et al.      546/77

5,049,562      Sept., 1991      Rasmusson et al.      546/77

5,110,939      May, 1992      Holt      548/250

5,116,983      May, 1992      Bhattacharya      546/77

5,120,742      Jun., 1992      Rasmusson et al.      514/284

5,138,063      Aug., 1992      Rasmusson et al.

5,175,155      Dec., 1992      Juniewicz et al.      514/284

5,278,159      Jan., 1994      Bakshi et al.

5,300,294      Apr., 1994      Johnson

5,302,621      Apr., 1994      Kojima et al.

Foreign Patent Documents

0200859      Nov., 1986      EP

93-23051     Nov., 1993     WO

WO93/23420     Nov., 1993     WO

Other References

Stinson, Chem. Eng. News, Jun. 29, ’92 pp. 7-8.

Helliker, Wall Street Jour. 7 Jun. ’91, pp. A1 and A7 (1991).

Diani et al., Jour. of Clin. & Metab. vol. 74 pp. 345-350 (1992).

Rasmusson et al. Jour Med Chem vol. 29 pp. 2298-2315 (1986).

Burger, “Medicinal Chemistry 2d Ed” Interscience N.Y., 1960 p. 42.

Rasmusson et al Jour Med Chem vol. 27 pp. 1690-1701 (1984).

Back, Jour Org Chem vol. 46 pp. 1442-1446 (1981).

Helliker, “Alopecia Sufferers Seek to Suffer Less, and Not in Silence”, Wall Street Journal, 7 Jun. 1991, pp. A1 and A7.

Burger, Medicinal Chem. 2nd Ed Interscience, N.Y. 1960, p. 42.

Geldof, “Consideration of the Use of 17-Beta-N,N-diethyl Carbamoyl-4-Methyl-4-Aza-5-Alpha-Androstan-3-one (4MA) A 5-Alpha Reductase Inhibitor, in Prostate Cancer Therapy”, J. Cancer Res. Clin. Oncol. 118:50-55 (1992).

Liang et al. “Species Differences in Prostatic Steroid 5alpha-reductases of Rat, Dog and Human”, Endocrinology, vol. 117, No. 2, pp. 571-579 (1985).

Rasmusson et al., “Azasteroids, Structure-Activity Relationships for Inhibition of 5-alpha Reductase and of Androgen Receptor Binding”, J. Med. Chem. 29: 2298-2315 (1986).

Back et al., “N-chloroazasteroids: A Novel Class of Reactive Steroid Analogous Preparation, Reaction with Thiols and Photochemical Conversion to Electrophilic N-acyl Imines”, J. Org. Chem. 54: 1904-1910 (1989).

Stinson, “Prostate Drug Proscar Cleared for Marketing”, Chem. Eng. News, 1992, pp. 7-8.

Diani et al., “Hair Growth Effects of Oral Administration of finasteride . . . “, Jour. Clinincal Endoc. & Metab. 74: 345-350 (1992).

Back, “Oxidation of Azasteroid Lactams and Alcohols with Benezene Selenic Anhydride”, J. Org. Chem. 46: 1442-1446 (1981).

Rasmusson et al., “Azasteroids as Inhibitors of Rat Prostate 5-alpha Reductase”, J. Med. Chem. 27: 1690-1701 (1984).
Primary Examiner: Daus; Donald G.
Attorney, Agent or Firm: Giesser; Joanne M., Fitch; Catherine D., Winokur; Melvin




READ THIS NEXT

    Shampoo for Women

    Blonde girl worried about hair loss

    ProTHIK Spray

    Tagamet (Cimetidine)

    Hair Loss Treatment

    man controls hair loss and unhappy gazing at you in the mirror 685775544 bald, baldness, loosing, prevention, hearttrob

    Male Pattern Alopecia

    Pin It on Pinterest

    Share This