17alpha-substituted 4-(3-oxoestra-4,9-dien-11beta-yl)-benzoic acid, its derivatives and process for its production

1 . 17α-Substituted 4-(3-oxoestra-4,9-dien-11β-yl)-benzoic acid of general formula (I)

in which

R means a hydrogen atom or an alkyl radical with 1-4 carbon atoms,

R 1 means a hydrogen atom or an alkyl radical with 1-4 carbon atoms,

R 2 means a hydrogen atom or an alkyl radical with 1-4 carbon atoms, as well as the pharmaceutically acceptable salts thereof.

2 . 17α-Substituted 4-(3-oxoestra-4,9-dien-11β-yl)-benzoic acid according to claim 1 , namely

1) 4-[17β-Hydroxy-(17α-(methoxymethyl)-3-oxoestra-4,9-dien-11β-yl]-benzoic acid

2) 4-[17β-Methoxy-(17α-(methoxymethyl)-3-oxoestra-4,9-dien-11β-yl]-benzoic acid

3) 4-[17β-Hydroxy-(17α-(hydroxymethyl)-3-oxoestra-4,9-dien-11β-yl]-benzoic acid

4) 4-[17α-(Acetoxymethyl)-17β-hydroxy 3-oxoestra-4,9-dien-11β-yl]-benzoic acid

5) 4-[17β-Methoxy-(17α-(methoxymethyl)-3-oxoestra-4,9-dien-11β-yl]-benzoic acid methyl ester

6) 4-[17β-Methoxy-(17α-(methoxymethyl)-3-oxoestra-4,9-dien-11β-yl]-benzoic acid ethyl ester

3 . Process for the production of 17α-substituted 4-(3-oxoestra-4,9-dien-11β-yl)-benzoic acid of general formula (I), characterized in that 11β-substituted estra-4,9-dien-3-ones of general formula (II)

in which

R 1 means a hydrogen atom or an alkyl radical with 1-4 carbon atoms,

R 2 means a hydrogen atom, an alkyl radical with 1-4 carbon atoms, a

tetrahydropyranyl radical, a silylalkyl radical with 3-6 carbon atoms or an acyl radical with 1-3 carbon atoms,

are oxidized under acidic, neutral or alkaline conditions to form the corresponding 11β-benzoic acid.

4 . Process according to claim 3 , wherein corresponding 11-substituted derivatives of estra-4,9-dien-3-ones are reacted to form compounds of general formula (II).

5 . Process according to claim 4 , wherein 11-benzaldehyde oximes, 11-benzaldehyde hydrazones or 11β-formylphenyl acetals of estra-4,9-dien-3-ones are reacted to form compounds of general formula (II).

6 . Process according to claim 3 , wherein the oxidation is performed to form corresponding 11β-benzoic acid under acidic conditions.

7 . Process according to claim 6 , wherein the acidic oxidation is performed to form corresponding 11β-benzoic acid with chromium trioxide in sulfuric acid and acetone (Jones oxidation).

8 . Process according to claim 3 , wherein the oxidation is performed to form corresponding 11β-benzoic acid under neutral conditions.

9 . Process according to claim 8 , wherein the oxidation is performed to form the corresponding 11β-benzoic acid under neutral conditions with pyridinium chlorochromate in dimethylformamide.

10 . Process according to claim 3 , wherein the oxidation is performed to form the corresponding 11β-benzoic acid under alkaline conditions.

11 . Process according to claim 10 , wherein the oxidation is performed to form the corresponding 11β-benzoic acid under alkaline conditions with silver nitrate in aqueous NaOH or with hexafluoroacetone and H 2 O 2 in the presence of Na 2 CO 3 or with tetrabutylammonium permanganate in pyridine.

12 . Process according to claim 1 , wherein optionally still present protective groups on the D ring are hydrolyzed under acidic or alkaline conditions to form R 1 and/or R 2 .

13 . 17α-Substituted 4-(3-oxoestra-4,9-dien-11β-yl)-benzoic acid according to claim 1 for use as a pharmaceutical agent.

14 . Pharmaceutical compositions that contain at least one compound according to claim 1 .

15 . Use of the compounds according to claim 1 for the production of a pharmaceutical agent for treatment and prophylaxis of gynecological diseases such as endometriosis, leiomyomas of the uterus, dysfunctional bleeding and dysmenorrhea.

16 . Use of the compounds according to claim 1 for female birth control.

17 . Use of the compounds according to claim 1 for the production of a pharmaceutical agent for female hormone replacement therapy.