8β-hydrocarbyl-substituted estratrienes for use as selective estrogens

1. A 8β-Substituted estra-1,3,5(10)-triene compound of formula I

in which

R 2 means a hydrogen atom, a halogen atom:

a radical R 18 — or R 18 —O—, in which R 18 means a hydrogen atom or a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 6 carbon atoms, or a trifluoromethyl group;

a group R 19 SO 2 —O—, in which R 19 is an R 20 R 21 N group, in which R 20 and R 21 , independently of one another, mean a hydrogen atom, a C 1 -C 5 -alkyl radical, a group C(O)R 22 , in which R 22 represents an optionally substitued, straight-chain or branched-chain, saturated or unsaturated in up to three places, an optionally partially or completely halogenated hydrocarbon radical with up to 10 carbon atoms, an optionally substituted C 3 -C 7 -cycloalkyl radical, an optionally substituted C 4 -C 15 -cycloalkalkyl radical or an optionally substituted aryl, heteroayl or aralkyl radical, or R 20 R 21 N means a polymethylenimino radical with 4 to 6 C atoms or a morpholino radical;

R 3 means a group R 18′ —O—, R 19 SO 2 —O— or —O—C(O)R 22 , in which R 18′ is a hydrogen atom or a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 6 carbon atoms, a trifluoromethyl group, or an aryl, heteraryl or aralkyl radical;

R 6 and R 7 each mean a hydrogen atom or together an additional bond;

R 6′ and R 7′ , are each independently a hydrogen atom, a halogen atom, a group R 18 —O—, R 19 SO 2 —O— or —R 22 ;

R 8 means a branched-chain, optionally partially or completely halogenated alkyl radical with up to 5 carbon atoms, or a straight chain or branched chain, optionally partially or completely halogenated alkenyl radical with up to 5 carbon atoms, an ethinyl or prop-1-inyl radical;

R 9 means a hyrogen atom, a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 5 carbon atoms, or together with R 11 means an additional bond;

R 11 means a hydrogen atom or together with R 9 or together with R 12 means an additional bond;

R 11′ means a hydrogen atom, a halogen atom, a saturated or unsaturated, optionally partially or completely halogenated (F, Cl) hydrocarbon radical, which has a maximum linear chain length of 4 carbon atoms, or a group —X—R 18″ , in which X is an oxygen or sulfur atom, and R 18″ is an alkyl radical with 1 to 3 carbon atoms;

R 12 means a hydrogen atom or together with R 11 means an additional bond;

R 14 means a hydrogen atom or together with R 15 means an additional bond;

R 15 means a hydrogen atom or together with R 14 or togehter with R 16 means an additional bond;

R 16 means a hydrogen atom or together with R 15 means an additional bond;

R 15 and R 16′ , independently of one another, mean a hydrogen atom, a halogen atom, a group R 18 —O—, R 19 SO 2 —O— or —R 22 ;

R 17 and R 17′ each mean a hydrogen atom; a hydrogne atom and a halogen atom; a hydrogen atom and a benzyloxy group; a hydrogen atom and a group R 19 SO 2 —O—; a group R 18 and a group —C(O)R 22 or —O—C(O)R 22 ; a group R 18 —O— and R 18 —; a group R 18 —O— and a group —O—C(O)R 22 ; or

R 17 and R 17′ togehter mean a group ═CR 23 R 24 , in which R 23 and R 24 , independently of one another, represent a hydrogen atom and a halogen atom, or together an oxygen atom;

excluding the compounds of formula I, in which

R 3 is a hydroxy, methoxy or acetyloxy group, and simultaneously

R 2 represents a hydrogen atom,

R 6 , R 6′ , R 7 and R 7′ in each case represent a hydrogen atom;

R 9 represents a hydrogen atom or

R 9 and R 11 together represent an additional bond,

R 11′ and R 12 in each case represent a hydrogen atom,

R 14 , R 15 , R 15′ , R 16 and R 16′ in each case represent a hydrogen atom, and

R 17 and R 17′ form a β-hydroxy group and a hydrogen atom; form a β-(2-bromoacetyl)oxy group and hydrogen atom; or form a β-acetyl group and a hydrogen atom; or

R 17 and R 17′ together represent an oxygen atom.

2. A compound of formula I according to claim 1 , in which

R 2 means a hydrogen or halogen atom or a hydroxy groups;

R 3 means a group R 18 —O—, R 19 SO 2 —O— or —O—C(O)R 22 ,

R 6 and R 7 each mean hydrogen atom;

R 6′ means a hydrogen atom, or a hydroxy group, a group R 22 ;

R 7′ means a hydrogen atom, a halogen atom, a group R 18 —O—, R 19 SO 2 —O— or —R 22 ;

R 8 means a branched-chain, optically partially or completely halogenated alkyl radical with up to 5 carbon atoms, or a straight chain or branched chain, optionally partially or completely halogenated alkenyl radical with up to 5 carbon atoms, an ethinyl or prop-1-inyl radical;

R 9 means a hydrogen atom or together with R 11 an additional bond;

R 11 means a hydrogen atom or together with R 9 an additional bond;

R 11′ means a hydrogen atom, a halogen atom, a saturated or unsaturated, optionally partially or completely halogenated (F, Cl) hydrocarbon radical, which has a maximum linear chain length of 4 carbon atoms, or group —X—R 18″ , in which X is a sulfur atom, and R 18″ is an alkyl radical with 1 to 3 carbon atoms;

R 12 , R 14 , R 15 in each case mean a hydrogen atom;

R 16′ means a hydrogen atom, a halogen atom, a group R 18 —O—, R 19 SO 2 —O— or —R 22 ;

R 17 and R 17′ in each case mean a hydrogen atom, a hydrogen atom and a halogen atom; a hydrogen atom and a benzyloxy group; a hydrogen atom and a group R 19 SO 2 —O—; a group R 18 and a group —C(O)R 22 or —O—C(O)R 22 ; a group R 18 —O— and a group R 18 —; a group R 18 —O— and a group —O—C(O)R 22 ; or

R 17 and R 17′ together mean a group ═CR 23 R 24 , in which R 23 and R 24 , independently of one another, represent a hydrogen atom and a halogenatom, or together an oxygen atom.

3. A compound of formula I according to claim 1 , in which

R 2 means a hydrogen atom or a fluorine atom or a hydroxy group,

R 3 means a group R 18′ —O—, R 19 SO 2 —O— or —O—C(O)R 22

R 6 and R 7 in each case mean a hydrogen atom;

R 6′ means a hydrogen atom or a hydroxy group,

R 7′ means a hydrogen atom, a fluorine or chlorine atom, a group R 18 —O—, R 19 SO 2 —O— or —R 22 ,

R 18 means a hydrogen atom or a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 6 carbon atoms, or a trifluoromethyl group;

R 19 is an R 20 R 21 N group,

R 20 and R 21 , independently of one another, mean a hydrogen atom, a C 1 -C 5 -alkyl radical, a group C(O)R 22 ,

R 22 represents an optionally substituted, straight-chain or branched-chain, saturated or unsaturated in up to three places, an optionally partially or completely halogenated hydrocarbon radical with up to 10 carbon atoms, an optionally substituted C 3 -C 7 -cycloalkyl radical, an optionally substituted C 4 -C 15 -cycloalkylalkyl radical or an optionally substituted aryl, heteroaryl or aralkyl radical,

or R 20 R 21 N means a polymethylenimino radical with 4 to 6 C atoms or a morpholino radical;

R 9 means a hydrogen atom or together with R 11 an additional bond;

R 11′ means a hydrogen atom, a fluorine or chlorine atom, a saturated, straight-chain or branched-chain C 1 -C 4 -alkyl group, a group —X—R 18″ , in which X is a sulfur atom and R 18″ means a saturated, straight-chain or branched-chain C 1 -C 3 -alkyl group, a chloromethyl or chloroethyl group;

R 12 , R 14 , R 15 and R 16 in each case mean a hydrogen atom;

R 16′ means a hydrogen atom, a fluorine or chlorine atom or a group R 18 —O or —R 22 ;

R 17 and R 17′ in each case mean a hydrogen atom; a hydrogen atom and a halogen atom; a hydrogen atom and a benzyloxy group; a hydrogen atom and a group R 19 SO 2 —O—; a group R 18 and a group —C(O)R or —O—C(O)R 22 ; a group R 18 —O— and a group R 18 —; a group R 18 —O— and a group —O—C(O)R 22 ; or

R 17 and R 17′ together mean a group ═CR 23 R 24 , in which R 23 and R 24 , independently of one another, represent a hydrogen atom and a halogen atom, or together an oxygen atom.

4. A compound of formula I according to claim 1 , in which

R 6′ , R 7′ , R 9 , R 11 , R 14 , R 15 , R 15′ and R 16 in each case stand for a hydrogen atom or R 6′ , R 7′ , R 14 , R 15 , R 15′ and R 16 in each case stand for a hydrogen atom and R 9 and R 11 together stand for an additional bond, and all other substituents have the meanings that are indicated in claim 1 .

5. A compound of formula I according to claim 1 , which have a double bond in position 9(11), 14(15) or 15(16) or two double bonds in positions 9(11) and 14(15) or 15(16).

6. A compound of general formula I according to claim 1 , in which

R 17 and R 17′ are a group R 18 —O— and a group R 18 —; a group R 18 — and a group —O—C(O)R 22 .

7. A compound of formula I according to claim 6 , in which

R 17 and R 17′ are a hydroxy group and a hydrogen atom, a C 1 -C 4 -alkyl group or C 2 -C 4 -alkinyl group.

8. A compound of formula I according to claim 7 , in which

R 17 and R 17′ are a hydroxy group and a hydrogen atom, a methyl, ethinyl, or prop-1-inyl group.

9. A compound of formula I according to claim 1 , in which

R 16′ stands for a group R 18 —O— or R 19 SO 2 —O—, and R 17 and R 17′ each stand for a hydrogen atom.

10. A compound of formula I according to claim 1 , which is

8β-Vinyl-estra-1,3,5(10),9(11)-tetraene-3,17β-diol

3-methoxy-8β-vinyl-estra-1,3,5(10),9(11)-tetraen-17β-ol

8β-(2′,2′-difluorovinyl)-estra-1,3,5(10),9(11)-tetraene-3,17β-diol

8-(2′,2′-difluorovinyl)-3-methoxy-estra-1,3,5(10),9(11)-tetraen-17β-ol

8β-vinyl-estra-1,3,5(10)-triene-3,17β-diol

3-methoxy-8β-vinyl-estra-1,3,5(10)-trien-17β-ol

8β-(2′,2′-difluorovinyl)-estra-1,3,5(10)-triene-3,17β-diol

8β-(2′,2′-difluorovinyl)-3-methoxy-estra-1,3,5(10)-trien-17β-ol

8β-vinyl-estradiol-3-sulfamate

8β-vinyl-estradiol-3,17-disulfamate

8β-vinyl-estradiol-3-(N-acetyl)-sulfamate

8β-vinyl-estrone-3-sulfamate

8β-vinyl-estron-3-acetate

8β-vinyl-estriol

8β-vinyl-estriol-3-sulfamate

8β-(prop-(Z)-enyl)-estradiol

8β-ethinyl-estradiol

17α-ethinyl-8β-vinyl-estra-1,3,5(10)-triene-3,17β-diol

17α-methyl-8β-vinyl-estra-1,3,5,(10)-triene-3,17β-diol

8β-vinyl-estra-1,3,5(10)-triene-3,17α-diol

8β-vinyl-estradiol-diacetate

8β-vinyl-estradiol-17-valerianate or

17β-acetoxy-8β-vinyl-estra-1,3,5(10)-trien-3-ol.

11. A method for

in-vitro treatment of male infertility;

in-vivo treatment of male infertility;

in-vitro treatment of female infertility;

in-vivo treatment of female infertility;

hormone replacement therapy in a patient in need of replacement of estrogen;

therapy of osteoporosis; treatment of arteriosclerosis: or treatment of benign prostate hyperplasia;

comprising administering to a subject in need thereof an effective amount of an 8β-substituted estra-1,3,5(10)-triene compound of formula I′

in which

R 2 means a hydrogen atom, a halogen atom;

a radical R 18 — or R 18 —O—, in which R 18 means a hydrogen atom or a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 6 carbon atoms or, a trifluoromethyl group;

a group R 19 SO 2 —O—, in which R 19 is an R 20 R 21 N, in which R 20 and R 21 , independently of one another, mean a hydrogen atom, a C 1 -C 5 -alkyl radical, a group C(O)R 22 , in which R 22 represents an optionally substituted, straight-chain or branched-chain, saturated or unsaturated in up to three places, an optionally partially or completely halogenated hydrocarbon radical with up to 10 carbon atoms, an optionally substituted C 3 -C 7 -cycloalkyl radical, an optionally substituted C 4 -C 15 -cycloalkylalkyl radical or an optionally substituted aryl, heteroaryl or aralkyl radical, or R 20 R 21 N means a polymethylenimino radical with 4 to 6 C atoms or a morpholino radical;

R 3 means a group R 18′ —O—, R 19 SO 2 —O— or —O—C(O)R 22 , in which R 18′ is a atom or a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 6 carbon atoms, a trifluoromethyl group, or an aryl heteroaryl or aralkyl radical;

R 6 and R 7 each mean a hydrogen atom or together an additional bond;

R 6′ and R 7′ , are each independently a hydrogen atom, a halogen atom, a group R 18 —O—, R 19 SO 2 —O— or —R 22 ;

R 8 means a branched-chain, optionally partially or completely halogenated alkyl radical with up to 5 carbon atoms, or a straight chain or branched chain, optionally partially or completely halogenated alkenyl radical with up to 5 carbon atoms, an

R 9 means a hydrogen atom, a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 5 carbon atoms, or together with R 11 means an additional bond;

R 11 means a hydrogen atom or together with R 9 or together with R 12 means an additional bond;

R 11′ means a hydrogen atom, a halogen atom, a saturated or unsaturated, optionally partially or completely halogenated (F, Cl) hydrocarbon radical, which has a maximum linear chain length of 4 carbon atoms, or a group —X—R 18″ , in which X is an oxygen or sulfur atom, and R 18″ is an alkyl radical with 1 to 3 carbon atoms;

R 12 means a hydrogen atom or together with R 11 means an additional bond;

R 14 means a hydrogen atom or together with R 15 means an additional bond;

R 15 means a hydrogen atom or together with R 14 or together with R 16 means an additional bond;

R 16 means a hydrogen atom or together with R 15 means an additional bond;

R 15′ and R 16′ , independently of one another, mean a hydrogen atom, a halogen atom, a group R 18 —O—, R 19 SO 2 —O— or —R 22 ;

R 17 and R 17′ each mean a hydrogen atom and a halogen atom; a hydrogen atom and a benzyloxy group; a hydrogen atom and a group R 19 SO 2 —O—; a group R 18 and a group —C(O)R 22 or —O—C(O)R 22 ; a group R 18 —O— and a group R 18 —; a group R 18 —O— and a group —O—C(O)R 22 ; or

R 17 and R 17′ together mean a group ═CR 23 R 24 , in which R 23 and R 24 , independently of one another, represent a hydrogen atom and a halogen atom, or together an oxygen atom,

wherein said administration of the compound of formula I′ achieves a selective effect on estrogen receptor beta.

12. A method according to claim 11 , in which

R 2 means a hydrogen or halogen atom or a hydroxy group;

R 3 means a group R 18′ —O—, R 19 SO 2 —O— or —O—C(O)R 22 ;

R 6 and R 7 each mean a hydrogen atom;

R 6′ means a hydrogen atom, a hydroxy group, or a group R 22 ;

R 7′ means a hydrogen atom, a halogen atom, a group R 18 —O—, R 19 SO 2 —O— or —R 22 ;

R 8 means a branched-chain, optionally partially or completely halogenated alkyl radical with up to 5 carbon atoms, or a straight chain or branched chain, optionally partially or completely halogenated alkenyl radical with up to 5 carbon atoms, an ethinyl or prop-1-inyl radical;

R 9 means a hydrogen atom or together with R 11 an additional bond;

R 11 means a hydrogen atom or together with R 9 an additional bond;

R 11′ means a hydrogen atom, a halogen atom, a saturated or unsaturated, optionally partially or completely halogenated (F, Cl) hydrocarbon radical, which has a maximum linear chain length of 4 carbon atoms, or a group —X—R 18″ , in which X is a sulfur atom, and R 18″ is an alkyl radical with 1 to 3 carbon atoms;

R 12 , R 14 , R 15 and R 16 in each case mean a hydrogen atom;

R 16′ means a hydrogen atom, a halogen atom, a group R 18 —O—, R 19 SO 2 —O— or —R 22 ;

R 17 and R 17′ in each case mean a hydrogen atom; a hydrogen atom and a halogen atom; a hydrogen atom and a benzyloxy group; a hydrogen atom and a group R 19 SO 2 —O—; a group R 18 and a group —C(O)R 22 or —O—C(O)R 22 ; a group R 18 —O— and a group R 18 —; a group R 18 —O— and a group —O—C(O)R 22 ; or

R 17 and R 17′ together mean a group ═CR 23 R 24 , in which R 23 and R 24 , independently of one another, represent a hydrogen atom and a halogen atom, or together an oxygen atom.

13. A method according to claim 11 , in which

R 2 means a hydrogne atom or a fluorine atom or a hydroxy group,

R 3 means a group R 18′ —O—, R 19 SO 2 —O— or —O—C(O)R 22 ,;

R 6 and R 7 in each case mean a hydrogen atom;

R 6′ means a hydrogen atom or a hydroxy group,

R 7′ means a hydrogen atom, a fluorine or chlorine atom, a group R 18 —O—, R 19 SO 2 —O— or —R 22 ;

R 18 means a hydrogen atom or a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 6 carbon atoms, or a trifluoromethyl group;

R 19 is an R 20 R 21 N group,

R 20 and R 21 , independently of one another, mean a hydrogen atom, a C 1 -C 5 -alkyl radical, a group C(O)R 22 ,

R 22 represents an optionally substituted, straight-chain or branched-chain, saturated or unsaturated in up to three places, an optionally partially or completely halogenated hydrocarbon radical with up to 10 carbon atoms, an optionally substituted C 3 C 7 -cycloalkyl radical, an optionally substituted C 4 -C 15 -cycloalkylalkyl radical or an optionally substituted aryl, heteraryl or aralkyl radical,

or R 20 R 21 N means a polymethylenimino radical with 4 to 6 C atoms or a morpholino radical;

R 8 means a branched-chain, optionally partially or completely halogenated alkyl radical with up to 5 carbon atoms or a straight chain or branched chain, optionally partially or completely halogenated alkenyl radical with up to 5 carbon atoms, an ethinyl or pro-1-inyl radical;

R 9 means a hydrogen atom or together with R 11 an additional bond;

R 11′ means a hydrogen atom, a fluorine or chlorine atom, a saturated, straight-chain or branched-chain C 1 -C 4 -alkyl group, a group —X—R 18″ , in which X is a sulfur atom and R 18″ means a saturated, straight-chain or branched-chain C 1 -C 3 alkyl group, a chloromethyl or chloroethyl group;

R 12 , R 14 , R 15 and R 16 in each case mean a hydrogen atom;

R 16′ means a hydrogen atom, a fluorine or chlorine atom or a group R 18 —O or —R 22 ;

R 17 and R 17′ in each case mean a hydrogen atom; a hydrogen atom and a halogen atom; a hydrogen atom and a benzyloxy group; a hydrogen atom and a group R 19 SO 2 —O—; a group R 18 and a group —OC(O)R 22 or —O—C(O)R 22 ; a group R 18 —O— and a group R 18 —; a group R 18 —O— and a group —O—C(O)R 22 , in all above cases with R 18 , R 19 and R 22 in each case in the meaning that is indicated under R 2 in claim 11 ; or

R 17 and R 17′ together mean a group ═CR 23 R 24 , in which R 23 and R 24 , independently of one another, represent a hydrogen atom and a halogen atom, or together an oxygen atom.

14. A method according to claim 11 , in which

R 6′ , R 7′ , R 9 , R 11 , R 14 , R 15 , R 15′ and R 16 in each case stand for a hydrogen atom or R 6′ , R 7′ , R 14 , R 15 , R 15′ and R 16 in each case stand for a hydrogen atom and R 9 and R 11 together stand for an additional bond.

15. A method according to claim 11 , wherein the estratrienes have a double bond in position 9(11), 14(15) or 15(16) or two double bonds in positions 9(11) and 14(15) or 15(16).

16. A method according to claim 11 , in which R 17 and R 17′ are a group R 18 —O— and a group R 18 —; a group R 18 — and a group —O—C(O)R 22 .

17. A method according to claim 16 , in which R 17 and R 17′ are a hydroxy group and a hydrogen atom, a C 1 -C 4 -alkyl group or a C 2 -C 4 -alkinyl group.

18. A method according to claim 17 , in which R 17 and R 17′ are a hydroxy group and a hydrogen atom, a methyl, ethinyl or prop-1-inyl group.

19. A method according to claim 11 , in which R 16′ stands for a group R 18 —O— or R 19 SO 2 —O—.

20. A method according to claim 11 , wherein the estratriene is

8β-vinyl-estra-1,3,5(10),9(11)-tetraene-3,17β-diol

3-methoxy-8β-vinyl-estra-1,3,5(10),9(11)-tetraen-17β-ol

8β-(2′,2′-difluorovinyl)-estra-1,3,5(10),9(11)-tetraene-3,17β-diol

8β-(2′,2′-difluorovinyl)-3-methoxy-estra-1,3,5(10),9(11)-tetraen-17β-ol

8β-vinyl-estra-1,3,5(10)-triene-3,17β-diol

3-methoxy-8β-vinyl-estra-1,3,5(10)-trien-17β-ol

8β-(2′,2′-difluorovinyl)-estra-1,3,5(10)-triene-3,17β-diol

8β-(2′,2′-difluorovinyl)-3-methoxy-estra-1,3,5(10)-trien-17β-ol

8β-vinyl-estradiol-3-sulfamate

8β-vinyl-estradiol-3,17-disulfamate

8β-vinyl-estradiol-3-(N-acetyl)-sulfamate

8β-vinyl-estrone-3-sulfamate

8β-vinyl-estron-3-acetate

8β-vinyl-estriol

8β-vinyl-estriol-3-sulfamate

8β-(prop-(Z)-enyl)-estradiol

8β-ethinyl-estradiol

17α-ethinyl-8β-vinyl-estra-1,3,5(10)-triene-3,17β-diol

17α-methyl-8β-vinyl-estra-1,3,5,(10)-triene-3,17β-diol

8β-vinyl-estra-1,3,5(10)-triene-3,17α-diol

8β-vinyl-estradiol-diacetate

8β-vinyl-estradiol-17-valerianate or

17β-acetoxy-8β-vinyl-estra-1,3,5(10)-trien-3-ol.

21. A method according for the treatment of hot flashes, sleep disturbances, irritability mood swings, incontinence, or vaginal atrophy comprising administering to a subject in need thereof an effective amount of an 8β-substituted estra-1,3,5(10)-triene compound of formula I′

in which

R 2 means a hydrogen atom, a halogen atom;

a radical R 18 or R 18 —O—, in which R 18 means a hydrogen atom or a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 6 carbon atoms or, a trifluoromethyl group;

a group R 19 SO 2 —O—, in which R 19 is an R 20 R 21 N, in which R 20 and R 21 , independently of one another, mean a hydrogen atom, a C 1 -C 5 -alkyl radical, a group C(O)R 22 , in which R 22 represents an optionally substituted, straight-chain or branched-chain, saturated or unsaturated in up to three places, an optionally partially or completely halogenated hydrocarbon radical with up to 10 carbon atoms, an optionally substituted C 3 -C 7 -cycloalkyl radical, an optionally substituted C 4 -C 15 -cycloalkylalkyl radical or an optionally substituted aryl, heteroaryl or aralkyl radical, or R 20 R 21 N means a polymethylenimino radical with 4 to 6 C atoms or a morpholino radical;

R 3 means a group R 18′ —O—, R 19 SO 2 —O— or —O—C(O)R 22 , in which R 18′ is a hydrogen atom or a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 6 carbon atoms, a trifluoromethyl group, or an aryl, heteroaryl or aralkyl radical;

R 6 and R 7 each mean a hydrogen atom or together an additional bond;

R 6′ and R 7′ , are each independently a hydrogen atom, a halogen atom, a group R 18 —O—, R 19 SO 2 —O— or —R 22 ;

R 8 means a branched-chain, optionally partially or completely halogenated alkyl radical with up to 5 carbon atoms, or a straight chain or branched chain, optionally partially or completely halogenated alkenyl radical with up to 5 carbon atoms, an ethinyl or pro-1-inyl radical;

R 9 means a hydrogen atom, a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 5 carbon atoms, or together with R 11 means an additional bond;

R 11 means a hydrogen atom or together with R 9 or together with R 12 means an additional bond;

R 11′ means a hydrogen atom, a halogen atom, a saturated or unsaturated, optionally partially or completely halogenated (F, Cl) hydrocarbon radical, which has a maximum linear chain length of 4 carbon atoms, or group —X—R 18″ , in which X is an oxygen or sulfur atom, and R 18″ is an alkyl radical with 1 to 3 carbon atoms;

R 12 means a hydrogen atom or together with R 11 means an additional bond;

R 14 means a hydrogen atom or together with R 15 means an additional bond;

R 15 means a hydrogen atom or together with R 14 or together with R 16 means an additional bond;

R 16 means a hydrogen atom or together with R 15 mean an additional bond;

R 15′ and R 16′ , independently of one another, mean a hydrogen atom, a halogen atom, a group R 18 —O—, R 19 SO 2 —O— or —R 22 ;

R 17 and R 17′ each mean a hydrogen atom; a hydrogen atom and a halogen atom; a hydrogen atom and an benzyloxy group; a hydrogen atom and a group R 19 SO 2 O—; a group R 18 and a group —C(O)R 22 or —O—C(O)R 22 ; a group R 18 —O— and a group R 18 —; a group R 18 —O— and a group —O—C(O)R 22 ; or

R 17 and R 17′ together a group ═CR 23 R 24 , in which R 23 and R 24 , independently of one another, represent a hydrogen atom and a halogen atom, or together an oxygen atom,

wherein said administration of the compound of formula I′ achieves a selective effect on estrogen receptor beta.

22. A method according to claim 11 , which is for the in-vitro treatment of male infertility.

23. A method according to claim 11 , which is for the in-vivo treatment of male infertility.

24. A method according to claim 11 , which is for the in-vitro treatment of female infertility.

25. A method according to claim 11 , which is for the in-vivo treatment of female infertility.

26. A method according to claim 11 , which is for the hormone replacement therapy in a patient in need of replacement of estrogen.

27. A method according to claim 11 , which is for the therapy of osteoporosis.

28. A method according to claim 11 , which is for the treatment of arteriosclerosis.

29. A method according to claim 11 , which is for the treatment of benign prostate hyperplasia.

30. A compound having partial formula II or II′

in which R 8 represents a straight-chain or branched-chain, optionally partially or completely halogenated alkyl or alkenyl radical with up to 5 carbon atoms, or an ethinyl- or prop-1-inyl radical, and in addition to the aromatic A-ring, one or more double bonds can be present in the B-, C- and/or D-ring in positions 6(7); 9(11); 11(12); 14(15) and 15(16), and substituents at carbon atoms 6, 7, 11, 15, 16 and 17 can be respectively in α- or β-position.

31. A method of achieving estrogenic action on bone, and not on uterine tissue, comprising administering a compound according to claim 30 .

32. A pharmaceutical composition that contains at least one compound according to claims 1 and a pharmaceutically compatible vehicle.

33. A compound of formula I, according to claim 1 , excluding compounds wherein R 8 is alkyl.

34. A method according to claim 21 , wherein the treatment of hot flashes, sleep disturbances, irritability, mood swings, incontinence, or vaginal atrophy is in a subject undergoing hormone replacement therapy, and wherein said subject is in need of replacement of estrogen.

35. A method for

in-vitro treatment of male infertility;

in-vivo treatment of male infertility;

in-vitro treatment of female infertility;

in-vivo treatment of female infertility;

hormone replacement therapy in a patient in need of replacement of estrogen;

therapy of osteoporosis;

treatment of arteriosclerosis; or

treatment of benign prostate hyperplasia;

comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition according to claim 32 .

36. A method for the treatment of hot flashes, sleep disturbances, irritability, mood swings, incontinence, or vaginal atrophy comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition according to claim 32 .

37. A method according to claim 36 , wherein the treatment of hot flashes, sleep disturbances, irritability, mood swings, incontinence, or vaginal atrophy is in a subject undergoing hormone replacement therapy, and wherein said subject is in need of replacement of estrogen.

38. A method according to claim 21 , wherein mood swings are treated.

39. A method according to claim 21 , wherein incontinence is treated.

40. A method according to claim 36 , wherein mood swings are treated.

41. A method according to claim 36 , wherein incontinence is treated.