RU97106107A

RU97106107A - METHOD FOR MINIMIZING THE HYSTEROTROPHIC EFFECT OF TAMOXIFEN AND ANALOGUES OF TAMOXIFEN

Info

Publication number: RU97106107A
Application number: RU97106107/14A
Authority: RU
Inventors: Ульман Брайант Генри; Энтони Фонтана Стивен
Original assignee: Эли Лилли Энд Компани
Priority date: 1994-09-20
Filing date: 1995-09-18
Publication date: 1999-03-27

Claims

1. The method of minimizing the hysterotrophic effect of non-steroidal antiestrogenic compounds of the formula II

where either R ⁴ is H or a lower alkyl radical, and R ⁵ is a lower alkyl radical, or R ⁴ and R ^{5 are} attached to an adjacent nitrogen atom to form a heterocyclic radical;
R ⁶ is H or a lower alkyl radical;
R ⁷ is H, halogen, OH, a lower alkyl radical or is a buta-1,3-dienyl radical, which together with the adjacent benzene ring forms a naphthyl radical;
R ⁸ is H or OH;
n is 2
or a pharmaceutically acceptable salt thereof, when said compound of formula II is administered to a woman for the treatment or prophylaxis of breast cancer, comprising simultaneously or sequentially administering to said woman a compound of formula I

where R ¹ represents —H, —OH, —O (C ₁ –C ₄ alkyl), —OCOC ₆ H ₅ , —OCO (C ₁ –C ₆ alkyl), or —OSO ₂ (C ₄ –C ₆ alkyl);
R ² is —H, —OH, —O (C ₁ -C ₄ alkyl), —OCOC ₆ H ₅ , —OCO (C ₁ -C ₆ alkyl), or —OSO ₂ (C ₄ -C ₆ alkyl);
n is 2 or 3;
R ³ is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino or 1-hexamethyleneimino;
or a pharmaceutically acceptable salt thereof.

2. The method according to claim 1, where the specified compound of formula II is a compound where each of R ⁴ and R ⁵ is methyl, R ⁶ is ethyl, R ⁷ is H, R ⁸ is H, n is 2,
or a pharmaceutically acceptable salt thereof.

3. The method according to claim 1, where the specified compound of formula I is a compound where each of R ¹ and R ² is —OH, R ³ is 1-piperidinyl, n is 2,
or a pharmaceutically acceptable salt thereof.

4. The method according to claim 2, where the specified compound of formula I is a compound where each of R ¹ and R ² is —OH, R ³ is 1-piperidinyl, n is 2,
or a pharmaceutically acceptable salt thereof.

5. The method according to claim 4, where the specified compound of formula I is its hydrochloric acid salt.

6. The method according to any one of claims 1 to 5, wherein said compound of formula I is administered simultaneously with administration of said compound of formula II.

7. The method according to any one of claims 1 to 5, wherein said compound of formula I is administered sequentially with respect to said compound of formula II.

8. A pharmaceutical composition comprising an effective amount of a first component, which is a compound of formula II

where either R ⁴ is H or a lower alkyl radical, and R ⁵ is a lower alkyl radical, or R ⁴ and R ^{5 are} attached to an adjacent nitrogen atom to form a heterocyclic radical;
R ⁶ is H or a lower alkyl radical;
R ⁷ represents H, halogen, OH, a lower alkyl radical or is a buta-1,3-dienyl radical, which together with the adjacent benzene ring forms a naphthyl radical;
R ⁸ is H or OH;
n is 2;
or a pharmaceutically acceptable salt thereof, when said first component is administered to a woman to treat or prevent breast cancer, and an effective amount of the second component, which is a compound of formula I

where R ¹ is —H, —OH, —O (C ₁ –C ₄ alkyl), —OCOC ₆ H ₅ , —OCO (C ₁ –C ₆ alkyl), or —OSO ₂ (C ₄ –C ₆ alkyl);
R ² is —H, —OH, —O (C ₁ -C ₄ alkyl), —OCOC ₆ H ₅ , —OCO (C ₁ -C ₆ alkyl), or —OSO ₂ (C ₄ -C ₆ alkyl);
n is 2 or 3;
R ³ is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino or 1-hexamethyleneimino;
or a pharmaceutically acceptable salt thereof and said second component are administered to minimize the hysterotrophic effect induced by the compound of formula II, together with a pharmaceutically acceptable carrier, excipient or diluent.

9. The pharmaceutical composition of claim 8, wherein said compound of formula II is a compound wherein each of R ⁴ and R ⁵ is methyl, R ⁶ is ethyl, R ⁷ is H, R ⁸ is H, and n is 2,
or a pharmaceutically acceptable salt thereof.

10. The pharmaceutical composition according to claim 9, wherein said compound of formula I is a compound wherein each of R ¹ and R ² is —OH, R ³ is 1-piperidinyl; n is 2
or a pharmaceutically acceptable salt thereof.

11. The pharmaceutical composition according to any one of claims 8 to 10, wherein said pharmaceutically acceptable salt of a compound of formula I is a hydrochloric acid salt.