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 17β-Alkyl-17β-oxy-estratrienes of formula I

in which

Hal stands for F or C1, 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 the 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 1 -C 4 -alkinyl, C 1 -C 4 -alkinyl as for at least partially fluorinated C 1 -C 4 -alkyl,

wherein R 17′ —O in 17β-position and R 17″ in 17α-position

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

U represents either a straight-chain or branched-chain C 1 -C 13 -alkylene- alkenylene- or -alkinylene radical or the group A-B, whereby 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 N + (O − )(R 6 ) group or an azolidinylene ring or an azolidinylene-N-oxide ring, wherein the azolidinylene ring or azolidinylene-N-oxide ring includes at least one C atom of grouping X,

R 6 is either H or CH 2 —R 7 or C(O)—R 7 ,

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, in which

Y is

1) a direct bond between X and Z, or

2) when W is an N + (O − )(R 6 ) group or an azolidinylene—N—oxide ring an SO n —R 10 group, wherein n=0, 1 or 2,

wherein R 10 represents a direct bond between SO n and Z or a straight-chain or branched-chain C 1 -C 6 -alkylene-, C 2 -C 6 -alkenylene- or -alkinylene radical, or

3) 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 for

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

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

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

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

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

4) CH═CF or

5) 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 6 -alkenylene- or -alkinylene radical, which is optionally partially or completely fluorinated,

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

or a pharmacologically compatible acid addition salt or ester thereof.

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

3. An estratrienes 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 estratrienes according to claim 1 , wherein Hal stands for fluorine.

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

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

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

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

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

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

11. An estratrienes according to claim 1 , wherein Y is a direct bond between X and Z or an SO n group, whereby n=0, 1 or 2.

12. An estratrienes 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 estratrienes according to claim 1 , wherein E stands for CF 3 or for pentafluorophenyl.

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

15. An estratrienes, which is

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

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

16. A compound according to claim 1 , wherein 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 grouping X.

17. A compound according to claim 16 , wherein Y is an SO n -R 10 group.

18. A compound according to claim 1 , wherein V is a C(O) group.

19. A compound according to claim 1 , wherein W is an azolidinylene ring.

20. A compound according to claim 1 , which is a salt of said compound.

21. An estratriene according to claim 1 , which is

or a pharmacologically compatible acid addition salt or ester thereof.

22. A estratriene according to claim 1 , which is

or a pharmacologically compatible acid addition salt thereof.

23. A compound according to claim 1 , which is a salt of said compound.

24. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

25. 17β-Oxy-estratrienes of formula II

in which

Hal stands for F or C1 and is bonded 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 the O atom,

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

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

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 grouping X,

R 6 is either H or CH 2 -R 7 or C(O)-R 7 ,

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 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 , R-, 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 13 -cycloalkylalkyl radical or

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

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

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

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-chained 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,

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, in which

Y is

1) a direct bond between X and Z, or

2) when W is an N 30 (O − )(R 6 ) group or an azolidinylene-N-oxide ring an SO n -R 10 group, wherein n=0, 1 or 2,

wherein R 10 represents a direct bond between SO n and Z or a straight-chain or branched-chain C 1 -C 6 -alkylene-, C 2 -C 6 -alkenylene- or -alkinylene radical, or

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

i) a straight-chain or branched-chain C 1 -C 3 -alkylene-, C 2 -C 3 -alkenylene, or -alkinylene radical or for

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

for

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

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

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

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

4) CH═CF or

5) 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, which is optionally partially or completely fluorinated, and

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

26. An 17-Oxo-estratrienes with general formula III

in which

Hal stands for F or Cl and is bonded 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,

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

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 grouping X,

R 6 is either H or CH 2 -R 7 or C(O)-R 7 ,

R 7 is

q) hydrogen or

r) 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 , R-, in which R 9 stands for hydrogen or a C 1 -C 3 -alkyl radical, or

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

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

u) an unsubstituted or substituted C 4 -C 13 -cycloalkylalkyl radical or

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

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

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

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-chained 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,

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, in which

Y is

1) a direct bond between X and Z, or

2) when W is an N 30 (O − )(R 6 ) group or an azolidinylene-N-oxide ring an SO n -R 10 group, wherein n=0, 1 or 2,

wherein R 10 represents a direct bond between SO n and Z or a straight-chain or branched-chain C 1 -C 6 -alkylene-, C 2 -C 6 -alkenylene- or -alkinylene radical, or

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

i) a straight-chain or branched-chain C 1 -C 3 -alkylene-, C 2 -C 3 -alkenylene, or -alkinylene radical or for

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

for

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

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

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

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

4) CH═CF or

5) 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, which is optionally partially or completely fluorinated, and

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

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

in which

Hal stands for F or C1, 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 the 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 1 -C 4 -alkinyl, C 1 -C 4 -alkinyl as for at least partially fluorinated C 1 -C 4 -alkyl,

wherein R 17′ —O in 17β-position and R 17″ in 17α-position

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

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

R 6 is either H or CH 2 —R 7 or C(O)—R 7 ,

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, in which

Y is

1) a direct bond between X and Z, or

2) when W is an N + (O − )(R 6 ) group or an azolidinylene—N—oxide ring an SO n —R 10 group, wherein n=0, 1 or 2, wherein R 10 represents a direct bond between SO n and Z or a straight-chain or branched-chain C 1 -C 6 -alkylene-, C 2 -C 6 -alkenylene- or -alkinylene radical, or

3) 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 for

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

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

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

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

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

4) CH═CF or

5) 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 6 -alkenylene- or -alkinylene radical, which is optionally partially or completely fluorinated,

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

or a pharmacologically compatible acid addition salt or ester thereof.