RU99118008A

RU99118008A - DERIVATIVES 16-HYDROXY-11- (SUBSTITUTED PHENYL) -ESTRA-4,9-DIENA

Info

Publication number: RU99118008A
Application number: RU99118008/04A
Authority: RU
Inventors: Маринус Бернард ГРУН; Рональд ГЕБХАРД
Original assignee: Акцо Нобель Н.В.
Priority date: 1997-01-15
Filing date: 1998-01-13
Publication date: 2001-06-27

Claims

1. The compound of formula I

where R ₁ is C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 alkoxy, triflate, pyridyl or phenyl, where the phenyl group is optionally substituted by one or more substituents selected from cyano, halogen and C _{1- 4-} alkyl;
R ₂ is hydrogen, C _1-6 alkyl, l-oxo C _1-6 alkyl or carboxy-1-oxo C _1-6 alkyl;
R ₃ is hydrogen, halogen or C _1-6 alkyl, optionally substituted with one or more substituents selected from C _1-6 alkoxy and halogen;
R ₄ is hydrogen, C _1-6 alkyl, l-oxo-C _1-6 alkyl or carboxy-1-oxo-C _1-6 alkyl; and
X is (H, OH), O, or NOH; or a pharmaceutically acceptable salt or solvate thereof.

2. The compound according to claim 1, where R ₁ is phenyl, triflate or C _1-6 -alkyl; R ₂ is hydrogen; R ₃ represents hydrogen, halogen, C _1-6 alkyl, optionally substituted C _1-6 alkoxy; R ₄ represents hydrogen or methyl; X represents O, or its pharmaceutically acceptable salt or solvate.

3. The compound according to claims 1-2, where R ₁ is phenyl or C _1-6 -alkyl; R ₂ is hydrogen; R ₃ is C _1-6 alkyl; R ₄ is hydrogen or C _1-6 alkyl; and X is O, or a pharmaceutically acceptable salt or solvate thereof.

4. The compound according to any one of claims 1 to 3, where R ₁ is phenyl, tert-butyl, isopropyl or methyl; R ₂ is hydrogen; R ₃ is methyl; R ₄ represents hydrogen or methyl; and X is O, or a pharmaceutically acceptable salt or solvate thereof.

5. The compound according to any one of claims 1 to 4, selected from:
(11β, 16α, 17β) -11- (4-tert-butylphenyl) -16,17-dihydroxy-17- (1-propynyl) -estra-4,9-diene-3-one;
(11β, 16α, 17β) -11- (4-isopropylphenyl) -16,17-dihydroxy-17- (1-propynyl) -estra-4,9-diene-3-one;
(11β, 16α, 17β) -11- (4-methylphenyl) -16,17-dihydroxy-17- (1-propynyl) estra-4,9-diene-3-one;
(11β, 16α, 17β) -11- (1,1-biphenyl-4-yl) -16,17-dihydroxy-17- (1-propynyl) -estra-4,9-diene-3-one;
(11β, 16α, 17β) -16,17-dihydroxy-11- [4 - [(trifluoromethylsulfonyl) oxy] phenyl] -17- (1-propynyl) estra-4,9-dien-3-one;
or a pharmaceutically acceptable salt or solvate thereof.

6. The compound of formula I or its pharmaceutically acceptable salt or solvate, as described in any one of claims 1 to 5, for use in therapy.

7. The use of a compound of formula I or a pharmaceutically acceptable salt or solvate thereof, as described in any one of claims 1 to 5, for the preparation of a medicament for the treatment or prevention of glucocorticoid-dependent diseases or symptoms.

8. A pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt or solvate thereof as specified in any one of claims 1 to 5, in a mixture with a pharmaceutically acceptable carrier.

9. A method for preparing a compound of formula I as defined in any one of claims 1 to 5, including dehydration and deprotection of a compound of formula II:

where P represents a protected keto group and R ₅ represents a group R ₄ as defined in paragraph 1, or a suitably protected group R ₄ ; optionally followed by treatment with a suitable reducing agent or a suitable oximating agent, and optionally followed by conversion into a pharmaceutically acceptable salt or solvate.

10. The compound of formula II:

where R ₁ , R ₂ and R ₃ are as defined in claim 1, R ₅ represents the group R ₄ as defined in claim 1, or an appropriately protected group R ₄ ; and P represents a protected keto group.