Claims
- 1. A 17α-Fluoroalkyl steroid of general formula I in whichR1 stands for a methyl or ethyl group, R2 stands for a radical of formula CnFmHo wherein n is 2, 3, 4, 5 or 6, m>1 and m+o=2n+1, R3 stands for a free, etherified or esterified hydroxy group, R4 and R5 each stand for a hydrogen atom, together form an additional bond or a methylene group, St stands for a steroidal ABC-ring system of partial formula A, B or C in whichR6 means a hydrogen atom, a straight-chain C1-C4 alkyl group or branched C3-C4 alkyl group or a halogen atom, R7 means a hydrogen atom, a straight-chain C1-C4 alkyl gyroup or a branched C3-C4 alkyl group, or if St stands for a steroidal ABC-ring system A or B, in addition R6 and R7 together mean an additional bond, X means an oxygen atom, a hydroxyimino grouping ═N—OH or two hydrogen atoms, R8 means a radical Y wherein Y is a hydrogen atom, a halogen atom, an —OH, —NO2, —N3, —CN, —NHSO2R9, —CO2R9, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkanoyloxy, benzoyloxy, C1-C10 alkanoyl, C1-C10 hydroxyalkyl or benzoyl group, or R8 means an aryl radical that is optionally substituted with Y′, wherein Y′ is a hydrogen atom, a halogen atom, an —OH, —NO2, —N3, —NR9aR9b, —CN, —NHSO2R9, —CO2R9, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkanoyloxy, benzoyloxy, C1-C10 alkanoyl, C1-C10 hydroxyalkyl or benzoyl group, and R9a and R9b are the same or different and represent a hydrogen atom or a C1-C10 alkyl group, and R9 is a hydrogen atom or a C1-C10 alkyl group, or for a —NR9aR9b radical, also a physiologically compatible salt thereof with an acid, or for a —CO2R9 radical in which R9 is hydrogen, also a physically compatible salt thereof with a base.
- 2. A 17α-Fluoroalkyl steroid according to claim 1, in which St stands for a steroidal ring system of partial formula A.
- 3. A 17α-Fluoroalkyl steroid according to claim 1, in which St stands for a steroidal ring system of partial formula B.
- 4. A 17α-Fluoroalkyl steroid according to claim 1, in which St stands for a steroidal ring system of partial formula C.
- 5. A 17α-Fluoroalkyl steroid according to claim 4, in which Y stands for a C1-C10 alkanoyl group.
- 6. A 17α-Fluoroalkyl steroid according to claim 1, in which n=2, 3 or 4.
- 7. A 17α-Fluoroalkyl steroid according to claim 6, in which o=0.
- 8. A 17α-Fluoroalkyl steroid according to claim 7, in which n=2.
- 9. A 17α-Fluoroalkyl steroid according to claim 1, in which R3 is a free hydroxy group.
- 10. A 17α-Fluoroalkyl steroid according to claim 1, in which R8 stands for radical Y.
- 11. A 17α-Fluoroalkyl steroid according to claim 10, in which Y stands for a C1-C10 alkanoyl group.
- 12. A 17α-Fluoroalkyl steroid according to claim 11, in which Y stands for a formyl, acetyl or propionyl group.
- 13. A 17α-Fluoroalkyl steroid according to claim 10, in which Y stands for a C1-C10 hydroxyalkyl group.
- 14. A 17α-Fluoroalkyl steroid according to claim 13, in which y stands for a hydroxymethyl or hydroxyethyl group.
- 15. A 17α-Fluoroalkyl steroid according to claim 10, in which Y stands for a hydroxy group.
- 16. A 17α-Fluoroalkyl steroid according to claim 10, in which Y stands for an acetyloxy group.
- 17. A 17α-Fluoroalkyl steroid according to claim 10, in which Y stands for a methoxycarbonyl group.
- 18. A 17α-Fluoroalkyl steroid according to claim 1, in which R8 stands for an aryl radical that is substituted with a group Y′.
- 19. A 17α-Fluoroalkyl steroid according to claim 18, in which the aryl radical is a phenyl, naphthalinyl, furanyl, benzofuranyl, thienyl or pyridinyl radical.
- 20. A 17α-Fluoroalkyl steroid according to claim 19, in which R8 is a 4-cyanophenyl radical.
- 21. A 17α-Fluoroalkyl steroid according to claim 19, in which R8 is a 4-halophenyl radical.
- 22. A 17α-Fluoroalkyl steorid according to claim 21, in which R8 is a 4-fluorophenyl radical.
- 23. A 17α-Fluoroalkyl steroid according to claim 1, in which R4 and R5 each stand for a hydrogen atom.
- 24. A 17α-Fluoroalkyl steroid according to claim 1, in which R4 and R5 together stand for an additional bond.
- 25. A 17α-Fluoroalkyl steroid according to claim 1, in which R6 and R7 are each a hydrogen atom.
- 26. A 17α-Fluoroalkyl steroid according to claim 1, which is11β-(4-Acetylphenyl)-17β-hydroxy- 17α-(1,1,2,2,2-pentafluoroethyl)estr-4-en-3-one; 4′-[17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)estr-4-en-11β-yl][1,1′-biphenyl]-4-carbonitrile; 11β-(4′-fluoro[1,1′-biphenyl]-4-yl)- 17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estr-4-en-3-one; 17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-11β-[4-(3-pyridinyl)phenyl]estr-4-en-3-one; 11β-(4-acetylphenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,15-dien-3-one; 4′-[17β-hydroxy-3-oxo- 17α-(1,1,2,2,2-pentafluoroethyl)estra-4,15-dien-11 β-yl][1,1′biphenyl]-4-carbonitrile; 11β-(4′-fluoro[1,1′-biphenyl]-4-yl)-17β-hydroxy-17α-(I 1,1,2,2,2-pentafluoroethyl)estra-4,15-dien-3-one; 17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-11β-[4-(3-pyridinyl)phenyl]estr-4,15-dien-3-one; 11β-(4-acetylphenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-3-one; 4′-[17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-11β-yl][1,1′-biphenyl]-4-carbonitrile; 11β-(4′-fluoro[1,1′-biphenyl]-4-yl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-3-one; 17β-hydroxy- 17α-(1,1,2,2,2-pentafluoroethyl)-11β-[4-(3-pyridinyl)phenyl]estra-4,9-dien-3-one; 11β-(4-acetylphenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9,15-trien-3-one; 4′-117β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9,15-trien- 11β-yl][1,1′-biphenyl]4-carbonitrile; 11β-(4′-fluoro[1,1′-biphenyl]-4-yl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl))estra-4,9,15-trien-3-one; 17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)- 11β-[4-(3-pyridinyl)phenyl]estra-4,9,15-trien-3-one; 6′-acetyl-9,11α-dihydro-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-4′H-naphth[3′,2′,1′:10,9,11]estr-4-en-3-one; 4-[9,11α-dihydro-17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)-4′H-naphth[3′,2′,1′:10,9,11]estr-4-en-6′-yl]benzonitrile; 9,11α-dihydro-6′-(4-fluorophenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-4′H-naphth[3′,2′,1′:10,9,11]estr-4-en-3-one; 9,11α-dihydro-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-6′-(3-pyridinyl)-4′H-naphth[3′,2′,1′:10,9,11]estr-4-en-3-one; 6′-acetyl-9,11, α-dihydro-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-4′H-naphth[3′,2′,1′:10,9,11]estra-4, 15-dien-3-one; 4-[9,11α-dihydro-17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)-4′H-naphth[3′,2′,1′:10,9,11]estra-4,15-dien-6′-yl]benzonitrile; 9,11α-dihydro-6′-(4-fluorophenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-4′H-naphth[3′,2′,1′:10,9,11]estra-4,15-dien-3-one; 9, 11α-dihydro-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-6′-(3-pyridinyl)-4′H-naphth[3′,2′,1′:10,9,11]estra-4,15-dien-3-one; 17β-hydroxy-11β-(4-hydroxyphenyl)-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-3-one; 17β-hydroxy-11β-(4-hydroxyphenyl)-17α-(1,1,2,2,2-pentafluoroethyl)estr-4-en-3-one; 9,11α-dihydro-6′,17β-dihydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-4′H-naphth[3′,2′,1′:10,9,11]estr-4-en-3-one; 11β-[4-(acetyloxy)phenyl]-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-3-one; 11β-[4-(acetyloxy)phenyl]-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estr-4-en-3-one; 6′-acetyloxy-9,11α-dihydro-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-4′H-naphth[3′,2′,1′:10,9,11]estr-4-en-3-one; 17β-hydroxy-11β-[4-(hydroxymethyl)phenyl]-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-3-one; 17β-hydroxy-11β-[4-(hydroxymethyl)phenyl]-17α-(1,1,2,2,2-pentafluoroethyl)estr-4-en-3-one; 9,11α-dihydro-17β-hydroxy-6′-hydroxymethyl-17α-(1,1,2,2,2-pentafluoroethyl)-4′H-naphth[3′,2′,1′:10,9,11]estr-4-en-3-one; 4-[17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-11β-yl]benzaldehyde; 4-[17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)estr-4-en-11β-yl]benzaldehyde; 9,11α-dihydro-17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)-4′H-naphth[3′,2′,1′:10,9,11]estr-4-en-6′-al; 4-[17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-11β-yl]benzoic acid methyl ester; 4[17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)estr-4-en-11β-yl]benzoic acid methyl ester; 9,11α-dihydro-17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)-4′H-naphth[3′,2′,1′:10,9,11]estr-4-en-6′-carboxylic acid methyl ester; 17β3-hydroxy-11β-[4-(1-hydroxyethyl)phenyl]-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-3-one; 17β-hydroxy-11β-[4-(1-hydroxyethyl)phenyl]-17α-(1,1,2,2,2-pentafluoroethyl)estr-4-en-3-one; or 9,11α-dihydro-17β-hydroxy-6′-(1-hydroxyethyl)-17α-(1,1,2,2,2-pentafluoroethyl)-4′H-naphth[3′,2′,1′:10,9,11]estr-4-en-3-one.
- 27. A 17α-Fluoroalkyl steroid of general formula I in whichR1 stands for a methyl or ethyl group, R2 stands for a radical of formula CnFmHo, wherein n is 2, 3, 4, 5 or 6, m>1 and m+o=2n+1, R3 stands for a free, etherified or esterified hydroxy group, R4 and R5 each stand for a hydrogen atom, together form an additional bond or a methylene group, St stands for a steroidal ABC-ring system of partial formula A or B in whichR6 means a hydrogen atom, a straight-chain C1-C4 alkyl group or branched C3-C4 alkyl group or a halogen atom, R7 means a hydrogen atom, a straight-chain C1-C4 alkyl group or a branched C3-C4 alkyl group, or in addition R6 and R7 together can mean an additional bond, X means an oxygen atom, a hydroxyimino grouping ═N—OH or two hydrogen atoms, R8 means a radical Y or an aryl radical that is optionally substituted with Y, wherein Y is a hydrogen atom, a halogen atom, an —OH, —NO2, —N3, —CN, —NR9aR9b, —NHSO2R9, —CO2R9C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkanoyloxy, benzoyloxy, C1-C10 alkanoyl, C1-C10 hydroxyalkyl or benzoyl group, and R9a and R9b are the same or different and represent a hydrogen atom or a C1-C10 alkyl group, and R9 is a hydrogen atom or a C1-10-alkyl group, or for a —NR9aR9b radical, also a physiologically compatible salt thereof with an acid or for a —CO2R9 radical with R9 meaning hydrogen, also a physiologically compatible salt thereof with a base.
- 28. A compound of claim 27 wherein R8 is Y and Y is a hydrogen atom, a halogen atom, an —OH, —NO2, —N3, —CN, —NHSO2R9, —CO2R9, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkanoyloxy, benzoyloxy, C1-C10 alkanoyl, C1-C10 hydroxyalkyl or benzoyl group, and R9a and R9b are the same or different and represent a hydrogen atom or a C1-C10 alkyl group, and R9 is a hydrogen atom or a C1-C10 alkyl group.
- 29. A pharmaceutical composition comprising a 17α-fluoroalkyl steroid of claim 1 and a pharmaceutically compatible vehicle.
- 30. A pharmaceutical composition comprising a 17α-fluoroalkyl steroid of claim 1 and an antiestrogen.
- 31. A pharmaceutical composition of claim 30 further comprising a pharmaceutically acceptable vehicle.
- 32. A pharmaceutical composiiton of claim 31 comprising 11β-(4-Acetylphenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estr-4-en-3-one or 11β-(4-Acetylphenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-3-one as antigestagen, and 11 β-fluoro-7α-(14,14,15,15-pentafluoro-6-methyl-10-thia-6-azapentadecyl)-estra-1,3,5(10)-triene-3,17β-diol, 7α-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]estra-1,3,5(10)-triene-3, 17β-diol or tamoxifen as antiestrogen.
- 33. A pharmaceutical composiiton of claim 32 wherein the antigestagen is 11β-(4-Acetylphenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estr-4-en-3-one and the antiestrogen is 11β- fluoro-7α-(14,14,15,15-pentafluoro-6-methyl-10-thia-6-azapentadecyl)-estra-1,3,5(10)-triene-3,17β-diol.
- 34. A method of achieving an antigestagenic effect in a patient in need thereof comprising administering a compound of claim 1.
Priority Claims (1)
Number |
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197 06 061 |
Feb 1997 |
DE |
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Parent Case Info
This is a continuation of application Ser. No. 09/020.947 filed Feb. 9, 1998 now abandoned.
US Referenced Citations (6)
Foreign Referenced Citations (5)
Number |
Date |
Country |
0310541 |
Oct 1987 |
DE |
3844408 |
Jul 1989 |
DE |
245 170 |
Nov 1987 |
EP |
299 913 |
Jan 1989 |
EP |
369 881 |
May 1990 |
EP |
Non-Patent Literature Citations (2)
Entry |
Bianchi, “1-Pharmacology,” Chemical Abstracts, vol. 123, No. 21 (1995). |
Wang et al., “Trifluoromethylation of steroidal ketones,” Journal of Fluorine Chemistry, 69, pp. 1-3 (1994). |
Continuations (1)
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09/020947 |
Feb 1998 |
US |
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09/516359 |
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