17α-ALKYL-17β-OXY-ESTRATRIENES AND INTERMEDIATE PRODUCTS FOR THEIR PRODUCTION, USE OF THE 17α-ALKYL-17β-OXY-ESTRATRIENES FOR THE PRODUCTION OF PHARMACEUTICAL AGENTS AS WELL AS PHARMACEUTICAL PREPARATIONS

1. A 17α-Alkyl-17β-oxy-estratriene of formula I:

in which

Hal stands for F or Cl, and is in 11β-position,

R 3 stands for hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkanoyl or a cyclic C 3 -C 7 -ether with an O atom,

R 17′ stands for hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkanoyl,

R 17″ stands for C 1 -C 4 -alkyl, C 2 -C 4 -alkinyl or for at least partially fluorinated C 1 -C 4 -alkyl, wherein R 17′ —O is in 17β-position and R 17″ is in 17α-position, and

SK stands for U—V—W—X—Y—Z—E, which is bonded via U in 7α-position,

in which U represents either a straight-chain or branched-chain C 1 -C 13 -alkylene- or C 2 -C 13 -alkenylene- or -alkinylene radical or the group A-B, wherein A is bonded in the 7α-position and represents a benzylidene radical that is bonded via —CH 2 — in the 7α-position, a phenylene radical, or a C 1 -C 3 -alkylaryl radical that is bonded via the alkyl group in the 7α-position and B stands for a straight-chain or branched-chain C 1 -C 13 -alkylene-, or C 2 -C 13 -alkenylene- or -alkinylene radical, and wherein A and B are optionally connected to one another via an O atom,

V represents a CH 2 — or a C(O) group,

W is an N(R 6 )— group or an azolidinylene ring wherein the azolidinylene ring or includes at least one C atom of X,

wherein R 6 is H or CH 2 —R 7 or C(O)—R 7 , in which R 7 is

a) hydrogen or

b) a straight-chain or branched-chain, non-fluorinated or at least partially fluorinated C 1 -C 14 -alkyl-, C 2 -C 14 -alkenyl- or -alkinyl radical, any of which can be hydroxylated in one or more places and can be interrupted by one to three of the heteroatoms —O—, —S—and/or —NR 9 —, in which R 9 stands for hydrogen or a C 1 -C 3 -alkyl radical, or

c) an unsubstituted or substituted aryl- or heteroaryl radical or

d) an unsubstituted or substituted C 3 -C 10 -cycloalkyl radical or

e) an unsubstituted or substituted C 4 -C 15 -cycloalkylalkyl radical or

f) an unsubstituted or substituted C 7 -C 20 -aralkyl radical or

g) an unsubstituted or substituted heteroaryl-C 1 -C 6 -alkyl radical or

h) an unsubstituted or substituted aminoalkyl radical or a biphenyl radical,

X is a direct bond between W and Y or is a straight-chain or branched-chain C 1 -C 12 -alkylene-, C 2 -C 12 -alkenylene- or -alkinylene radical,

Y is a direct bond between X and Z or is:

1) R 11 or O—R 11 , wherein R 11 stands for

i) a straight-chain or branched-chain C 1 -C 5 -alkylene-, C 2 -C 5 - alkenylene- or -alkinylene radical or

ii) an unsubstituted or substituted aryl radical or heteroaryl radical or

iii) an unsubstituted or substituted C 3 -C 10 -cycloalkyl radical or

iv) an unsubstituted or substituted C 4 -C 15 -cycloalkylalkyl radical or

v) an unsubstituted or substituted C 7 -C 20 -aralkyl radical or

vi) an unsubstituted or substituted heteroaryl-C 1 -C 6 -alkyl radical,

2) CH═CF or

3) HN—C(O)—NH—R 12 , wherein R 12 stands for an unsubstituted or substituted arylene radical, and—wherein R 12 is bonded to Z,

Z is a direct bond between Y and E or a straight-chain or branched-chain C 1 -C 9 -alkylene-, C 2 -C 9 -alkenylene- or -alkinylene radical, any of which can be partially or completely fluorinated, and

E is a CF 3 group or an at least partially fluorinated aryl group, or a pharmacologically compatible acid addition salt thereof.

2. An estratriene according to claim 1 , wherein R 3 stands for hydrogen, CH 3 , CH 3 CO or C 5 H 10 O.

3. An estratriene according to claim 1 , wherein R 17′ stands for hydrogen, CH 3 or CH 3 CO, and wherein R 17″ stands for methyl, ethinyl or trifluoromethyl.

4. An estratriene according to claim 1 , wherein Hal stands for fluorine.

5. An estratriene according to claim 1 , wherein U stands for (CH 2 ) p , wherein p is an integer of 2 to 10.

6. An estratriene according to claim 5 , wherein p=4.

7. An estratriene according to claim 1 , wherein V stands for CH 2 .

8. An estratriene according to claim 1 , wherein W stands for N(R 6 )—, wherein R 6 is hydrogen or a C 1 -C 3 -alkyl radical.

9. An estratriene according to claim 1 , wherein R 6 stands for methyl.

10. An estratriene according to claim 1 , wherein X stands for (CH 2 ) q , wherein q=0 or is an integer of 1 to 12.

11. An estratriene according to claim 1 , wherein Y is a direct bond between X and Z.

12. An estratriene according to claim 1 , wherein Z is a straight-chain or branched-chain C 1 -C 7 -alkylene radical, which is at least partially fluorinated.

13. An estratriene according to claim 1 , wherein E stands for CF 3 or pentafluorophenyl.

14. An estratriene according to claim 1 , wherein Z—E stands for C 2 F 5 , C 3 F 7 , C 4 F 9 or C 6 F 5 .

15. An estratriene according to claim 1 , which is a salt of a compound of formula 1.

16. An estratriene according to claim 1 , wherein R 17 ′ stands for methyl, ethyl, n-propl, iso-propyl, n-butyl, iso-butyl, ethinyl, 1-propinyl, 1-butinyl, 2-butinyl, 3-butinyl, trifluoromenthyl, pentaflouroethyl, heptafluoropropyl or nonafluorobutyl.

17. An estratriene which is

11β-Fluoro- 7α-{ 5-[methyl(7,7,8,8,9,9,9-heptafluorononyl)amino]pentyl}-17α- methylestra-1,3,5(10)-triene-3, 17-β-diol N-oxide

11β-Fluoro-7α-{5-[methyl(8,8,9,9,10,10,10-heptafluorodecyl)amino]pentyl}-17α- methylestra-1,3,5(10)-triene-3, 17β-diol N-oxide

(RS)-11β-Fluoro-7α-{5-[methyl(7,7,8,8,9,9,10,10,10-nonafluorodecyl)amino]-pentyl}- 17α-methylestra-1,3,5(10)-triene-3,17β-diol N-oxide

11β-Fluoro-7α-{5-[methyl(8,8,9,9,9-pentafluorononyl)amino]pentyl}-17α-methylestra- 1,3,5(10)-triene-3,17β-diol N-oxide

11β-Fluoro-7α-{5-[methyl(9,9,10,10,10-pentafluorodecyl)amino]pentyl-17α-methylestra- 1,3,5(10)-triene-3,17β-diol N-oxide

11β-Fluoro-7α-{5-[methyl(8,8,9,9,9-pentafluorononyl)amino]pentyl}-17α-methylestra- 1,3,5(10)-triene-3,17β-diol

11β-Fluoro-7α-{5-[methyl(7,7,8,8,9,9,10,10,10-nonafluorodecyl)amino]pentyl}-17α- methylestra-1,3,5(10)-triene-3,17α-diol

11β-Fluoro-7α-{5-[methyl(7,7,8,8,9,9,9-heptafluorononyl)amino]pentyl}-17α- methylestra-1,3,5(10)-triene-3,17α-diol

17α- Ethinyl-11β-fluoro-7α-{5-[methyl(7,7,8,8,9,9,10,10,10- nonafluorodecyl)- amino]pentyl}-estra-1,3,5(10)-triene-3,17β-diol

17α-Ethinyl-11β-fluoro-3-(2-tetrahydropyranoyloxy)-7α-{5- [methyl(7,7,8,8,9,9,10,10,10-nonafluorodecyl)amino[pentyl}-estra-1,3,5(10)-trien-17β-ol

11β-Fluoro-3-(2-tetrahydrophyranyloxy)-7α-{5-methyl(7,7,8,8,9,9,10,10,10- nonafluorodecyl)amino]pentyl}-17α-methylestra-1,3,5(10)-trien-17β-ol

11β-Fluoro-7α-{5-[methyl(7,7,8,8,9,9,10,10,10-nonafluorodecyl)amino]pentyl}-17α- trifluoromethylestra-1,3,5(10)-triene-3,17β-diol

11β-Fluoro-7α-{5-[methyl(6,6,7,7,8,8,8-heptafluorooctyl)amino[pentyl}-17α- methylestra-1,3,5(5-triene-3,17β-diol

11β-Fluoro-7α-{5-[methyl(8,8,9,9,10,10,10-heptafluorodecyl)amino[pentyl}-17α- methylestra-1,3,5(10)-triene-3,17β-diol

11β-Fluoro-7α-{5-[methyl(6,6,7,7,8,8,9,9,10,10,10-undecafluorodecyl)amino]-pentyl}- 17α-methylestra- 1,3,5( 10)-triene-3, 17β-diol

11β-Fluoro-7α-{5-[methyl(5,5,6,6,7,7,8,8,8-nonafluorooctyl)aminopentyl}-17α- methylestra-1,3,5(10)-triene-3,17β-diol

11β-Fluoro-7α-{5-[methyl(9,9,10,10,11,11,11-heptafluoroundecyl)amino[pentyl}-17α- methylestra-1,3,5(10)-triene-3,17β-diol or

11β-7α-{5-[methyl(9,9,10,10,10-pentafluorodecyl)amino]pentyl}-17α- methylestra-1,3,5( 10 )-triene-3,17β-diol.

18. A 17β-Oxy-estratriene formula II

in which

Hal stands for F or Cl and is in 11β-position,

R 3 stands for hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkanoyl or a cyclic C 3 -C 7 -ether with an O atom, and

R 17 stands for hydrogen, C 1 -C 4 -alkyl or for C 1 -C 4 -alkanoyl and is in 17β-position, and

SK stands for U—V—W—X—Y—Z—E, which is bonded via U in 7α-position and wherein

U represents either a straight-chain or branched-chain C 1 -C 13 -alkylene-, C 2 -C 13 -alkenylene- or -alkinylene radical or the group A-B, wherein A is bonded in the 7α-position and represents a benzylidene radical that is bonded via —CH 2 — in the 7α-position, a phenylene radical, or a C 1 -C 3 -alkylaryl radical that is bonded via the alkyl group in the 7α-position, and B stands for a straight-chain or branched-chain C 1 -C 13 -alkylene-, C 2 -C 13 -alkenylene- or -alkinylene radical, and wherein A and B are optionally connected to one another via an O atom,

V represents a CH 2 — or a C(O) group,

X is a direct bond between W and Y or is a straight-chain or branched-chain C 1 -C 12 -alkylene-, C 2 -C 12 -alkenylene- or -alkinylene radical,

Y is a direct bond between X and Z or is:

1) R 11 or O—R 11 , wherein R 11 stands for

i) a straight-chain or branched-chain C 1 -C 5 -alkylene-, C 2 -C 5 -alkenylene- or -alkinylene radical or

ii) an unsubstituted or substituted aryl radidal or heteroaryl radical or

iii) an unsubstituted or substituted C 3 -C 10 -cycloalkyl radical or

iv) an unsubstituted or substituted C 4 -C 15 -cycloalkylalkyl radical or

v) an unsubstituted or substituted C 7 -C 20 -aralkyl radical or

vi) an unsubstituted or substituted heteroaryl-C 1 -C 6 -alkyl radical,

2) CH═CF or

3) HN—C(O)—NH—R 12 , wherein R 12 stands for an unsubstituted or substituted arylene radical, and wherein R 12 is bonded to Z,

Z is a direct bond between Y and E or a straight-chain or branched-chain C 1 -C 9 -alkylene-, C 2 -C 9 -alkenylene- or -alkinylene radical, any of which can be partially or completely fluorinated,

E is a CF 3 group or an at least partially fluorinated aryl group, and

W stands for an N + (O − )(R 6 ) group or for an azolidinylene-N-oxide ring, wherein the azolidinylene-N-oxide ring includes at least one C atom of X, and R 6 is H or CH 2 —R 7 or C(O)—R 7 , in which R 7 is

a) hydrogen or

b) a straight-chain or branched-chain, non-fluorinated or at least partially fluorinated C 1 -C 14 -alkyl-, C 2 -C 14 -alkenyl- or -alkinyl radical, any of which can be hydroxylated in one or more places and can be interrupted by one to three of the heteroatoms —O—, —S— and/or —NR 9 —, in which R 9 stands for hydrogen or a C 1 -C 3 -alkyl radical, or

c) an unsubstituted or substituted aryl- or heteroaryl radical or

d) an unsubstituted or substituted C 3 -C 10 -cycloalkyl radical or

e) an unsubstituted or substituted C 4 -C 15 -cycloalkylalkyl radical or

f) an unsubstituted or substituted C 7 -C 20 -aralkyl radical or

g) an unsubstituted or substituted heteroaryl-C 1 -C 6 -alkyl radical or an unsubstituted or substituted aminoalkyl radical or a biphenyl radical.

19. An estratriene which is:

11β-Fluoro-7α-{5-[methyl(7,7,8,8,9,9-heptaflorononyl)amino]pentyl}-17α- methylestra-1,3,5(10)-triene- 3,17β-diol N-oxide

11β-Fluoro-7α-{5-(methyl{3-[(2,3,4,5,6-pentafluorophenyl)sulfanyl]propyl}-amino}pentyl]estra-1,3,5(10)-triene-3,17β-diol N-oxide

11β-Fluoro-7α-[5-(methyl{3-[(4,4,5,5,5-pentafluoropentyl)sulfanyl]propyl}amino)-pentyl]estra-1,3,5(10)-triene-3,17β-diol N-oxide

11β-Fluoro-7α-[5-(methyl{3-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]propyl}amino)-pentyl]estra-1,3,5(10)-triene-3,17β-diol N-oxide

11β-Fluoro-7α-{5-[methyl(7,7,8,8,9,9,10,10,10-nonafluorodecyl)amino]pentyl}estra-1,3,5 (10)-triene-3,17β-diol N-oxide

(S)-11β-Fluoro-7α-{5-[methyl(7,7,8,8,9,9,10,10,10-nonafluorodecyl)amino]pentyl}-17α-mehylestra-1,3,5(10)-triene-3,17β-diol N-oxide

(R)-11β-Fluoro-7α-{5-[methyl(7,7,8,8,9,9,10,10,10-nonafluorodecyl)amino]pentyl}-17α-mehylestra-1,3,5(10)-triene-3,17β-diol N-oxide or

11β-Fluoro-7α-{5-[methyl(9,9,10,10,10-pentylfluorodecyl)amino]pentyl}estra-1,3,5(10)-triene-3,17β-diol N-oxide

11β-Fluoro-7α-[5-(methyl{3-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]propyl}amino)-pentyl]estra-1,3,5(10)-trien-3-ol-17-one N-oxide

11β-Fluoro-7α-[5-(methyl{3-[(4,4,5,5,5-pentafluoropentyl)sulfanyl]propyl}amino)-pentyl]estra-1,3,5(10)-trien-3-ol-17-one N-oxide or

11β-Fluoro-7α-{5[methyl(7,7,8,8,9,9,10,10,10-nonafluorodecyl)amino]pentyl}estra-1,3,5(10)-trien-3-ol-17one N-oxide.

20. A 17-Oxo-estratriene formula III:

in which

Hal stands for F or Cl and is in 11β-position,

R 3 stands for hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkanoyl or a cyclic C 3 -C 7 -ether with an O atom, and

SK stands for U—V—W—X—Y—Z—E, which is bonded via U in 7α-position and wherein

U represents either a straight-chain or branched-chain C 1 -C 13 -alkylene-, C 2 -C 13 -alkenylene- or -alkinylene radical or the group A-B, wherein A is bonded in the 7α-position and represents a benzylidene radical that is bonded via —CH 2 — in the 7α-position, a phenylene radical, or a C 1 -C 3 -alkylaryl radical that is bonded via the alkyl group in the 7α-position, and B stands for a straight-chain or branched-chain C 1 -C 13 -alkylene-, C 2 -C 13 -alkenylene- or -alkinylene radical, and wherein A and B are optionally connected to one another via an O atom,

V represents a CH 2 — or a C(O) group,

X is a direct bond between W and Y or is a straight-chain or branched-chain C 1 -C 12 -alkylene-, C 2 -C 12 -alkenylene- or -alkinylene radical,

Y is a direct bond between X and Z or is:

1) R 11 or O—R 11 , wherein R 11 stands for

i) a straight-chain or branched-chain C 1 -C 5 -alkylene-, C 2 -C 5 -alkenylene- or -alkinylene radical or

ii) an unsubstituted or substituted aryl radidal or heteroaryl radical or

iii) an unsubstituted or substituted C 3 -C 10 -cycloalkyl radical or

iv) an unsubstituted or substituted C 4 -C 15 -cycloalkylalkyl radical or

v) an unsubstituted or substituted C 7 -C 20 -aralkyl radical or

vi) an unsubstituted or substituted heteroaryl-C 1 -C 6 -alkyl radical,

2) CH═CF or

3) HN—C(O)—NH—R 12 , wherein R 12 stands for an unsubstituted or substituted arylene radical, and wherein R 12 is bonded to Z,

Z is a direct bond between Y and E or a straight-chain or branched-chain C 1 -C 2 -alkylene, C 2 -C 9 -alkenylene- or -alkinylene radical, any of which can be partially or completely fluorinated,

E is a CF 3 group or an at least partially fluorinated aryl group, and

W stands for an N + (O − )(R 6 ) group or for an azolidinylene-N-oxide ring, wherein the azolidinylene-N-oxide ring includes at least one C atom of

X, and R 6 is H or CH 2 —R 7 or C(O)—R 7 , in which R 7 is

a) hydrogen or

b) a straight-chain or branched-chain, non-fluorinated or at least partially fluorinated C 1 -C 14 -alkyl-, C 2 -C 14 -alkenyl- or -alkinyl radical, any of which can be hydroxylated in one or more places and can be interrupted by one to three of the heteroatoms —O—, —S— and/or —NR 9 —, in which R 9 stands for hydrogen or a C 1 -C 3 -alkyl radical, or

c) an unsubstituted or substituted aryl- or heteroaryl radical or

d) an unsubstituted or substituted C 3 -C 10 -cycloalkyl radical or

e) an unsubstituted or substituted C 4 -C 15 -cycloalkylalkyl radical or

f) an unsubstituted or substituted C 7 -C 20 -aralkyl radical or

g) an unsubstituted or substituted heteroaryl-C 1 -C 6 -alkyl radical or

h) an unsubstituted or substituted aminoalkyl radical or a biphenyl radical.

21. A pharmaceutical composition comprising a 17α-alkyl-17β-oxy-estratriene according to claim 1 and a pharmaceutically compatible vehicle.

22. A pharmaceutical composition comprising an estratriene of claim 17 and a pharmaceutically acceptable carrier.

23. A 17α-Alkyl-17β-oxy-estratriene of formula I:

in which

Hal stands for F or Cl, and is in 11β-position,

R 3 stands for hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkanoyl or a cyclic C 3 -C 7 -ether with an O atom,

R 17′ stands for hydrogen, C 1 -C 4 -alkyl or C 1 -C 4 -alkanoyl,

R 17″ stands for C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkinyl or for at least partially fluorinated C 1 -C 4 -alkyl, wherein R 17′ —O is in 17β-position and R 17″ is in 17α-position, and

SK stands for U—V—W—X—Y—Z—E, which is bonded via U in 7α-positon,

in which U represents either a straight-chain or branched-chain C 1 -C 13 -alkylene- or C 2 -C 13 -alkenylene- or -alkinylene radical or the group A-B, wherein A in bonded in the 7α-position and represents a benzylidene radical that is bonded via —CH 2 — in the 7α-position, a phenylene radical, or a C 1 -C 3 -alkylaryl radical that is bonded via the alkyl group in the 7α-position and B stands for a straight-chain or branched-chain C 1 -C 13 -alkenylene- or -alkinylene radical, and wherein A and B are optionally connected to one another via an O atom,

V represents a CH 2 — or a C(O) group,

W is an N(R 6 )— group or an azolidinylene ring wherein the azolidinylene ring includes at least one C atom of X,

wherein R 6 is H or CH 3 —R 7 or C(O)—R 7 , in which R 7 is

i) hydrogen or

j) a straight-chain or branched-chain, non-fluorinated or at least partially fluorinated C 1 -C 14 -alkyl-, C 2 -C 14 -alkenyl- or -alkinyl radical, any which can be hydroxylated in one or more places and can be interrupted by one to three of the heteroatoms —O—, —S— and/or —NR 9 —, in which R 9 stands for hydrogen or a C 1 -C 3 -alkyl radical, or

k) an unsubstituted or substituted aryl- or heteroaryl radical or

l) an unsubstituted or substituted C 3 -C 10 -cycloalkyl radical or

m) an unsubstituted or substituted C 4 -C 15 -cycloalkylalkyl radical or

n) an unsubstituted or substituted C 7 -C 20 -aralky radical or

o) an unsubstituted or substituted heteroaryl-C 1 -C 6 alkyl radical or

p) an unsubstituted or substituted aminoalky radical or a biphenyl radical,

X is a direct bond between W and Y or is a straight-chain or branched-chain C 1 -C 12 -alkylene-, C 2 -C 12 -alkenylene- or -alkinylene radical,

Y is a direct bond between X and Z or is:

1) R 11 or O—R 11 , wherein R 11 stands for

i) a straight-chain or branched-chain C 1 -C 5 -alkylene-, C 2 -C 5 -alkenylene- or -alkinylene radical or

ii) an unsubstituted or substituted aryl radical or heteroaryl radical or

iii) an unsubstituted or substituted C 3 -C 10 -cycloalkyl radical or

iv) an unsubstituted or substituted C 4 -C 15 -cycloalkylalkyl radical or

v) an unsubstituted or substituted C 7 -C 20 -aralkyl radical or

vi) an unsubstituted or substituted heteroaryl-C 1 -C 6 -alkyl radical,

2) CH═CF or

3) HN—C(O)—NH—R 12 , wherein R 12 stands for an unsubstituted or substituted arylene radical, and—wherein R 12 is bonded to Z,

Z is a direct bond between Y and E or a straight-chain or branched-chain C 1 -C 9 -alkylene-, C 2 -C 9 -alkenylene- or -alkinylene radical, any of which can be partially or completely fluorinated, and

E is a CF 3 group or an at least partially fluorinated aryl group, or a pharmacologically compatible acid addition salt thereof or an ester thereof formed in the 3- or 17β-position.

24. An estratriene according to claim 21 , wherein the ester of a compound of formula I is formed with an alkanoic acid.

25. An estratriene according to claim 23 , wherein the ester of a compound of formula I is formed with a C 2 -C 5 alkanoic acid.

26. An estratriene according to claim 23 , wherein the ester is formed with acetic, propionic, butyric, isobutyric, valeric, isovaleric or pivalic acid.

27. An estratriene according to claim 23 , wherein the ester is formed with acetic acid.

28. A pharmaceutical composition comprising an estratriene of claim 21 and a pharmaceutically acceptable carrier.