RU96105421A - 15,15-DIALKYL SUBSTITUTION DERIVATIVES OF ESTRADIOL - Google Patents

Claims (16)

1. 15,15-Dialkylsteroid compounds of formula I

where R ¹ and R ² , independently of each other, are each hydrogen, unbranched alkanoyl containing from 1 to 10 carbon atoms, branched alkanoyl containing from 3 to 10 carbon atoms, alkanoyl containing 3 to 30 carbon atoms and including a cycloaliphatic structure in the form of a 3-6 membered ring of carbon atoms, or a benzoyl group;
R ³ and R ⁴ , independently of one another, are unbranched alkyl containing from 1 to 10 carbon atoms, or branched alkyl containing from 3 to 10 carbon atoms. 2. The compound according to claim 1, where R ¹ is hydrogen. 3. The compound according to claim 1, where R ² is hydrogen. 4. The compound according to claim 2, where R ² is hydrogen. 5. The compound according to claim 1, where R ³ and R ⁴ , independently of each other, represents each methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl. 6. Compounds according to claim 4, wherein R ³ and R ⁴ , independently of each other, are each methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl. 7. The compound according to claim 1, where each of R ³ and R ⁴ represents methyl.  8. The compound according to claim 7, wherein said compound is 15,15-dimethylestra-1,3,5 (10) -thien-3, 17β-diol.  9. Compounds according to claim 6, wherein said compounds are 15β-ethyl-15α-methylestra-1,3,5 (10) -triene-3,17β-diol, 15α-ethyl-15β-methylestra-1,3,5 (10) -triene-3,17β-diol or 15α-isopropyl-15β-methylestra-1,3,5 (10) -triene-3,17β-diol. 10. The method of producing compounds according to claim 1, characterized in that the compounds of formula II

where R ^{1 ′} is unbranched alkyl containing from 1 to 10 carbon atoms, or branched alkyl containing from 3 to 10 carbon atoms;
R ³ and R ⁴ , independently of each other, are each unbranched alkyl containing from 1 to 10 carbon atoms, or branched alkyl containing from 3 to 10 carbon atoms,
splitting the 3-alkyl ether group and, if necessary, the 3-hydroxy group is esterified, and then the 17-hydroxy group is optionally esterified, or the 3- and 17-hydroxyl groups are optionally esterified and the resulting 3,17-diacyloxy compound is selectively saponified to form 3-hydroxy -17-acyloxy compounds. 11. Compounds of formula IIa

where R ^{1 ′} is unbranched alkyl containing from 1 to 10 carbon atoms, or branched alkyl containing from 3 to 10 carbon atoms;
R ³ and R ⁴ independently of each other are each straight-chain alkyl containing from 1 to 10 carbon atoms, or branched alkyl containing from 3 to 10 carbon atoms;
Z is α-hydrogen atom and β-hydroxyl group or keto-oxygen atom.  12. A pharmaceutical composition comprising at least one compound according to claim 1 and a pharmaceutically compatible carrier.  13. The composition according to claim 12, wherein said composition contains 0.001-0.05 mg of said at least one compound.  14. The composition according to claim 12, where the specified composition contains 0.01 - 0.1 mg of the specified at least one compound per 1 ml.  15. The composition according to claim 12, wherein said composition contains 0.1-10 mg of said at least one compound per ml. 16. The method of obtaining the compounds of formula II

where R ^{1 ′} is unbranched alkyl containing from 1 to 10 carbon atoms, or branched alkyl containing from 3 to 10 carbon atoms;
R ³ and R ⁴ independently of each other are each unbranched alkyl containing from 1 to 10 carbon atoms, or branched alkyl containing from 3 to 10 carbon atoms,
involving the interaction of 3-R ^{1 ′} estra-1,3,5 (10), 15-tetraen-17-one compound with LiCuR $\genfrac{}{}{0ex}{}{\text{3}}{\text{2}}$ or an alkyl magnesium halide, where alkyl is R ³ and the halide is Br or I, in the presence of a catalyst (I) containing the catalyst to produce 3- R ^{1 ′} O-15β-R ³ - estra-1,3,5 (10) trien-17-one, chemical transformation of 3-R ^{1 ′} O-15β-R ³ - estra-1,3,5 (10) -trien-17-it in situ by adding chlorotrimethylsilane and then adding palladium (II) acetate with obtaining 3-R ^{1 ′} O-15β-R ³ - estra-1,3,5 (10), 15-tetraen-17-one, interaction 3-R ^{1 ′} O-15β-R ³ - estra-1,3 , 5 (10), 15-tetraen-17-one with LiCuR $\genfrac{}{}{0ex}{}{\text{four}}{\text{2}}$ or an alkyl magnesium halide, where alkyl is R ⁴ and the halide is Br or I, in the presence of a catalyst (I) containing the catalyst to produce 3-R ^{1 ′} O-15β-R ³ -15β-R ⁴ -estra-1,3, 5 (10) -trien-17-one, and the reduction of the C-17 carbonyl of the said 3-R ^{1 ′} O-15β-R ³ -15βR ⁴ estra-1,3,5 (10) -trien-17-one with obtaining compounds of formula II.