Pyrmidine derivitives as androgen receptor inhibitors (Otsuka Pharmaceuticals)

United States Patent     5,420,128

Kiyokawa, et. al.     May 30, 1995


17.beta.-substituted 4-aza-5.alpha.-androstan-3-one derivatives



Panzeri; Achille (Merate, IT); Nesi; Marcella (Milan, IT); di Salle; Enrico (Milan, IT).



Farmitalia Carlo Erba S.R.L. (Milan, IT).


Appl. No:




Jul. 29, 1993


Foreign Application Priority Data:

Jul. 31, 1992 [GB]     9216329

Intl. Cl.: A61K 31/58

U.S. Cl.: 514/284; 546/ 77; 544/125; 544/361

Field of Search: 514/284; 546/77



A compound of formula (I): ##STR1## wherein R is a hydrogen atom or a C(1) -C(4) alkyl group;

  • A is a single bond or a straight or branched C(1) -C(6) alkylene chain;
  • R(1) is a hydrogen atom or a C(1) -C(6) alkyl group;
  • R(2) is a C(1) -C(6) alkyl group, a C(5) -C(7) cycloalkyl or a C(6) -C(10) cycloalkylalkyl group, aryl or a C(7) -C(10) arylalkyl group, or a C(6) -C(10) heterocyclylalkyl group;
  • R(3) is hydrogen, a C(1) -C(4) alkyl group or an aryl or a C(7) -C(10) arylalkyl group;
  • Z is a C(1) -C(6) alkyl group, an –OR(5) group wherein R(5) is a C(1) -C(6) alkyl group, ##STR2## group wherein each of R(6) and R(7) is hydrogen, C(1) -C(6) alkyl, C(5) -C(7) cycloalkyl, phenyl or R(6) and R(7) taken together with the nitrogen to which they are linked form a pentatomic or hexatomic saturated heteromonocyclic ring; and the symbol represents a single or a double bond, is a testosterone 68 5.alpha.-reductase inhibitor and is therapeutically useful in benign prostatic hyperplasia, prostatic and breast cancers, seborrhoea, female hirsutism and male pattern baldness.

4 Claims, No Drawings

References Cited:

U.S. Patent Documents

5,155,107     Oct, 1992     Panzeri et al.     546/77

5,302,621     Apr, 1994     Kojima et al.     514/284

Foreign Patent Documents

0155096     Sept, 1985     EP

0200859     Nov, 1986     EP

0271220     Jun, 1998     EP

0484094     May, 1992     EP

Other References

Liang et al. J. Steroid Biochem. vol. 19 No. 1 pp. 385-390 (1983).

Lamb et al. The Prostate vol. 21 pp. 15-34 (1992).

Stinson, Chem. and Eng. News, Jun. 29, 1992 pp. 7 and 8.

Journal of Medicinal Chemistry, vol. 29, No. 11, Nov. 1, 1986, Gary H. Rasmusson, et al., “Azasteroids: Structure-Activity Relationships for Inhibition of 5-.alpha.-Reductase and of Androgen Receptor Binding”, pp. 2298-2315.

Journal of Medicinal Chemistry, vol. 27, No. 12, Dec. 1984, Gary H. Rasmusson, et al., “Azasteroids as Inhibitors of Rat Prostatic 5-.alpha.-Reductase”, pp. 1690-1701.
Primary Examiner: Daus; Donald G.
Attorney, Agent or Firm: Oblon, Spivak, McClelland, Maier & Neustadt