AU2909500A

AU2909500A - 16-hydroxyestratrienes as selective estrogens

Info

Publication number: AU2909500A
Application number: AU29095/00A
Authority: AU
Inventors: Ulf Bomer; Karl-Heinrich Fritzemeier; Christa Hegele-Hartung; Rudolf Knauthe; Dirk Kosemund; Hermann Kunzer; Monika Lessl; Gerd Muller
Original assignee: Schering AG
Current assignee: Bayer Pharma AG
Priority date: 1999-02-09
Filing date: 2000-02-09
Publication date: 2000-08-29
Also published as: HK1046145A1; CZ20012843A3; NO20013860D0; PE20001461A1; EE200100412A; CN1346364A; DE50011908D1; NZ513409A; EA200100828A1; ZA200107388B; WO2000047603A9; DK1144431T3; DE19906159A1; BR0008076A; WO2000047603A2; NO20013860L; BG105804A; PL350360A1; WO2000047603A3; EP1144431A3

Description

PCT WORLD INTELLECTUAL PROPERTY ORGANIZATION International Office INTERNATIONAL APPLICATION PUBLISHED ACCORDING TO THE PATENT COOPERATION TREATY (PCT) (51) International patent classification 7 : C07J A2 (11) International publication number: WO 00/47603 (43) International publication date: August 17, 2000 (8/17/2000) (21) International file number: PCT/EPOO/01073 (22) International application date: February 9, 2000 (2/9/2000) (30) Priority data: 199 06 159.9 February 9, 1999 (2/9/99) DE 71) Applicant (for all designated countries except for the U.S.): SCHERING AKTIENGESELLSCHAFT [DE/DE]; Mullerstr. 178, D-13353 Berlin (DE). 72) Inventors; and 75) Inventors/Applicants (only for the U.S.): K NZER, Hermann [DE/DE]; Turiner Str. 4, D-13347 Berlin (DE). KNAUTHE, Rudolf [DE/DE]; Wilhelmstr. 9, D-13467 Berlin (DE). LESSL, Monika [DE/DE]; Wilhelmstr. 9, D-13467 Berlin (DE). FRITZEMEIER, Karl-Heinrich [DE/DE]; Rabenstr. 5 A, D-13505 Berlin (DE). HEGELE-HARTUNG, Christa [DE/DE]; Woellenbeck 101, D-45740 Malheim a. d. Ruhr (DE). B6MER, Ulf [DE/DE]; Neue Hochstr. 11, D-13347 Berlin (DE). MULLER, Gerd (DE/DE]; Magdelstieg 132, D-07745 Jena (DE). KOSEMUND, Dirk [DE/DE]; Ulan-Bator-Str. 51, D-99091 Erfurt (DE). 81) Designated countries: AE, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CR, CU, CZ, DK, DM, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW, ARIPO Patent (GH, GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW), Eurasian Patent (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European Patent (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OAPI Patent (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG). Published: Without international search report and to be republished after receipt of the report. 54) Title: 16-HYDROXYESTRATRIENES AS SELECTIVELY ACTIVE ESTROGENS 57) Abstract The invention describes new compounds as pharmaceutical ctive ingredients, which have in vitro a higher affinity to strogen receptor preparations from rat prostates than to strogen receptor preparations from rat uteri and preferably in ivo a preferential action on bone rather than the uterus, and/or ronounced action relative to stimulation of the expression of HT2a receptors and transporters, their production, their therapeutic use and pharmaceutical dispensing forms that contain he new compounds. The new compounds are 16u'- and 168-hydroxystra-1,3,5 (10) -estratrienes, which carry additional substituents >n the steroid skeleton and can have one or more additional double bonds in the B-, C- and/or D-rings.

FOR INFORMATION ONLY Codes used for identifying PCT member countries on the head sheets of the publications of international applications according to the PCT. AL Albania AM Armenia AT Austria AU Australia AZ Azerbaijan 3A Bosnia-Herzegovina 3B Barbados BE Belgium 3F Burkina Faso 3G Bulgaria 3J Benin 3R Brazil 3Y Belarus .A Canada 2F Central African Republic 'G Congo 'H Switzerland I Ivory Coast M Cameroon N China U Cuba Z The Czech Republic E Germany K Denmark E Estonia S Spain I Finland R France A Gabon B United Kingdom E Georgia H Ghana N Guinea R Greece U Hungary E Ireland L Israel S Iceland T Italy P Japan E Kenya 3 Kyrgyzstan P Democratic People's Republic of Korea R Republic of Korea Z Kazachstan jC St. Lucia -I Liechtenstein K Sri Lanka 4 R Liberia .S Lesotho T Lithuania U Luxembourg NV Latvia 4C Monaco 4D Republic of Moldova 4G Madagascar 4K the former Yugoslavian Republic of Macedonia 4L Mali 4N Mongolia 4R Mauritania 4W Malawi 4X Mexico 4E Niger 4L The Netherlands 10 Norway 4Z New Zealand ?L Poland ?T Portugal Z0 Romania ZU Russian Federation 3D Sudan 1 E Sweden 'G Singapore sI Slovenia 3K Slovakian Republic 3N Senegal 3Z Swaziland 'D Chad G Togo 7J Tajikistan M Turkmenistan 7R Turkey T Trinidad and Tobago JA The Ukraine JG Uganda iS United States of America JZ Uzbekistan TN Vietnam rU Yugoslavia aW Zimbabwe WO 00/47603 PCT/EPOO/01073 16-Hydroxyestratrienes as Selectively Active Estrogens Field of the Invention This invention relates to new compounds as pharmaceutical active ingredients, which have in vitro a higher affinity to estrogen receptor preparations from rat prostates than to estrogen receptor preparations from rat uteri and in vivo preferably a preferential action on bone rather than the uterus, ind/or pronounced action with respect to stimulation of the xpression of 5HT2a receptors and transporters, their production, .heir therapeutic use and pharmaceutical dispensing forms that ontain the new compounds. The chemical compounds are novel, steroidal, tissue elective estrogens. ackground of the Invention Established estrogen therapies for treatment of hormone eficiency-induced symptoms and the protective action of strogens on bones, brains, vessels and other organ systems. The efficiency of estrogens in the treatment of hormone eficiency-induced symptoms such as hot flashes, atrophy of strogen target organs and incontinence, as well as the uccessful use of estrogen therapies for prevention of bone mass oss in peri- and postmenopausal women, is well documented and enerally accepted (Grady et al. 1992, Ann Intern Med 117: 1016- 1037) . It is also well documented that estrogen replacement therapy in postmenopausal women or in women with ovarian dysfunction that is caused in some other way reduces the risk of cardiovascular diseases compared to non-estrogen-treated women (Grady et al., loc. cit.). In addition, more recent studies confirm a protective action of estrogens against neurodegenerative diseases, such as, e.g., Alzheimer's disease (Henderson 1997, Neurology 48 (Suppl 7): S27-S35; Birge 1997, Neurology 48 (Suppl 7): S36-S41) , a protective action with respect to brain functions, such as memory and learning capacity (McEwen et al. 1997, Neurology 48 (Suppl 7): S8-S15; Sherwin 1997, Neurology 48 (Suppl 7): S21-S26), as well as against hormone-deficiency-induced mood swings (Halbreich 1997, Neurology 48 (Suppl 7): S16-S20). In addition, estrogen replacement therapy has proven effective relative to the reduction of the incidence of colorectal carcinoma (Calle, E. F. et al., 1995, J Natl Cancer Inst 87: 517-523). In conventional estrogen or hormone replacement therapy (= HRT), natural estrogens, such as estradiol, and conjugated estrogens that consist of equine urine are used either by themselves or in combination with a gestagen. Instead of the natural estrogens, derivatives that are obtained by esterification, such as, e.g., 178-estradiol-valerate, can also oe used. Because of the stimulating action of the estrogens that are ised on the endometrium, which results in an increase of the risk :f endometrial carcinoma (Harlap, S. 1992, Am J Obstet Gynecol 166: 1986-1992), estrogen/gestagen combination preparations are preferably used in hormone replacement therapy. The gestagenic component in the estrogen/gestagen combination avoids hypertrophy -f the endometrium, but the occurrence of undesirable intracyclic menstrual bleeding is also linked to the gestagen-containing -ombination. Selective estrogens represent a more recent alternative to :he estrogen/gestagen combination preparations. Up until now, elective estrogens have been defined as those compounds that lave an estrogen-like effect on the brain, bones and vascular ystem, owing to their antiuterotrophic (i.e., antiestrogenic) >artial action, but they do not have a proliferative effect on he endometrium. A class of substances that partially meet the desired rofile of a selective estrogen are the so-called "Selective strogen Receptor Modulators" (SERM) (R. F. Kauffman, H. U. ryant 1995, DNAP 8 (9): 531-539) . In this case, these are artial agonists of estrogen receptor subtype "ERa. " This ubstance type is ineffective, however, with respect to the herapy of acute postmenopausal symptoms, such as, e.g., hot lashes. As an example of a SERM, the raloxifene that was ecently introduced for the indication of osteoporosis can be entioned.

Estrogen Receptor Beta (ERE) Estrogen receptor 8 (ERS) was recently discovered as a second subtype of the estrogen receptor (Kuiper et al. (1996), Proc. Natl. Acad. Sci. 93: 5925-5930; Mosselman, Dijkema (1996) Pebs Letters 392: 49-53; Tremblay et al. (1997), Molecular Endocrinology 11: 353-365). The expression pattern of ERS liffers from that of the ERa (Kuiper et al. (1996), Endocrinology L38: 863-870). ERZ thus predominates over ERa in the rat rostate, while ERa predominates over ERS in the rat uterus. reas in which in each case only one of the two ER-subtypes is xpressed were identified in the brain (Shugrue et al. (1996), teroids 61: 678-681; Li et al. (1997), Neuroendocrinology 6:63-67). ERS is expressed in, i.a., areas that are considered o be important for cognitive processes and "mood" (Shugrue et 1. 1997, J Comparative Neurology 388: 507-525). Molecular targets for ERZ in these brain areas could be the HT2a receptor and the serotonin transporter (G. Fink & . E. H. Sumner 1996 Nature 383:306; B. E. H. Sumner et al. 1999 olecular Brain Research, in press). The neurotransmitter erotonin (5-hydroxytryptamine) is involved in the regulation of considerable number of processes, which can be impaired in menopause. In particular, the effects of menopause on mood and ignition are connected with the serotoninergic system. Estrogen placement therapy has proven effective with respect to ceatment of these estrogen deficiency-produced symptoms, Dssibly by modulation of serotonin receptor and transporter Kpression.

Other organ systems with comparatively higher ERB-expression :omprise the bones (Onoe, Y. et al., 1997, Endocrinology 138: 509-4512), the vascular system (Register, T. C.; Adams, M. R. L998, J Steroid Molec Biol 64: 187-191), the urogenital tract Kuiper, G. J. M. et al. 1997, Endocrinology 138: 863-870), the gastrointestinal tract (Campbell-Thopson 1997, BBRC 240: 478 83), as well as the testis (Mosselmann, S. et al. 1996 Febs Lett 92 49-53) including the spermatides (Shugrue et al. 1998, teroids 63: 498-504). The tissue distribution suggests that strogens regulate organ functions via ERS. The fact that ERB is unctional in this respect also follows by studies in ERa- (ERKO) r ERB-(BERKO)-knockout mice: ovariectomy produces bone mass oss in ERKO-mice, which can be cancelled out by estrogen ubstitution (Kimbro et al. 1998, Abstract OR7-4, Endocrine ociety Meeting New Orleans). Estradiol in the blood vessels of emale ERKO mice also inhibits vascular media and smooth muscle ell proliferation (Iafrati, M. D. et al. 1997, Nature Medicine : 545-548). These protective actions of estradiol are carried ut in the ERKO mouse presumably via ERB. Observations of BERKO mice provide an indication on a unction of ERB in the prostate and bladder: in the case of older male mice, symptoms of prostate and bladder hyperplasia ccur (Krege,- J. H. et al. 1998, Proc Natl Acad Sci 95: 15677 5682). In addition, female ERKO mice (Lubahn, D. B. et al. 993, Proc Natl Acad Sci 90: 11162-11166) and male ERKO mice Hess, R. A. et al. 1997, Nature 390: 509-512) as well as female ERKO mice (Krege, J. H., 1998) have fertility disorders.

Consequently, the important function of estrogens with respect to maintaining testis and ovary functions as well as fertility is confirmed. Westerlind et al., 1998, describe a differential action of 16a-hydroxyestrone on the bones, on the one hand, and reproductive organs of female rats, on the other (Westerlind et al. 1998, J Bone and Mineral Res 13: 1023-1031). Some studies showed that 16a-hydroxyestrone binds three times better to the human estrogen receptor 1 (ERI) than to the human estrogen receptor a (ERa). The RBA value of the substance on the rat prostate estrogen receptor is five times better than the RBA value of the substance on the rat uterus estrogen receptor. According to some findings, the dissociation of the substance that is described by Westerlind can be attributed to their preference for ERS rather than ERa. It was possible to achieve a selective estrogen action on specific target organs by subtype-specific ligands based on the different tissue or organ distribution of the two subtypes of the ERs. Substances with a preference for ERZ compared to ERa in the in vitro receptor binding test were described by Kuiper et al. (Kuiper et al. (1996), Endocrinology 138: 863-870). A selective action of subtype-specific ligands of the estrogen receptor on estrogen-sensitive parameters in vivo was not previously shown. The object of this invention is therefore to provide :ompounds that have in vitro a dissociation with respect to the binding to estrogen receptor preparations from rat prostates and rat uteri and that have in vivo preferably a dissociation with respect to bones rather than the uterus action. The compounds are to have in vitro a higher affinity to estrogen receptor preparations from rat prostates than to estrogen receptor preparations from rat uteri and in vivo preferably a higher potency with respect to protection against hormone-deficiency induced bone mass loss in comparison to uterus-stimulating action and/or pronounced action with respect to stimulation of the expression of 5HT2a receptors and transporters. In the broader sense, a structure-action relationship, which allows for access to compounds that have the above-formulated pharmacological profile of better estrogenic action on bones than on the uterus, is to be made available by this invention. According to the invention, the object above is achieved by the provision of 16a- and 16B-hydroxy-estra-1,3,5(10)-trienes of general formula I 2 RR R RR 1B RR HO R R4 (I) Ln which radicals R 1 to R independently of one another, have the following meanings: Ri means a halogen atom, a hydroxyl group, a methyl group, a trifluoromethyl group, a methoxy group, an ethoxy group or a hydrogen atom; R2 means a halogen atom, a hydroxyl group, a straight chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or a hydrogen atom; R4 means a halogen atom, a straight-chain or branched chain, saturated or unsaturated alkyl group with up to 10 carbon atoms, a trifluoromethyl or pentafluoroethyl group, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or a hydrogen atom; R7 means a halogen atom in a- or 9-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms, an optionally substituted aryl or heteroaryl radical or a hydrogen atom;

R

8 means a hydrogen atom in a- or 9-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms ir a- or 1-position, or a cyano group in a- or B-position; R9 means a hydrogen atom in a- or 9-position, a methyl, ethyl, trifluoromethyl or pentafluoroethyl group in a or 9-position; R11 means a nitrooxy group in a- or 1-position, a hydroxyl or mercapto group in a- or I-position, a halogen atom in a- or S-position, a chloromethyl group in a- or 9 position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms, an optionally substituted aryl or heteroaryl radical or a hydrogen atom; R 13means a methyl, ethyl, trifluoromethyl or pentafluoroethyl group in a- or 1-position; and either R 14means a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position or a hydrogen atom in a- or S-position and

R

15 means a halogen atom in a- or S-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or B-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR 15 ' (R1 5 ' = hydrogen atom, methyl, ethyl, propyl, i-propyl) or a hydrogen atom or

R

14 and R 1 5 together mean a 14a,15a-methylene or 148,158 methylene group that is optionally substituted with one or two halogen atoms;

R

16 means a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position, a trifluoromethyl or pentafluoroethyl group, a cyanomethyl group or a hydrogen atom in a- or S-position; R17 means a halogen atom in a- or S-position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position, a hydrogen atom or a hydroxyl group and the dotted lines ------ in rings B, C and D optionally mean one or more double bonds, and the wavy lines mean the arrangement of the respective substituent in a- or 1 position, or the production of a pharmaceutical agent for treatment and rophylaxis of estrogen-deficiency-induced diseases and onditions. According to a variant of the invention, preferably ompounds of general formula I are used, in which radicals R 1 to R , independently of one another, have the following meanings R1 means a fluorine atom, a hydroxyl group, a methyl group, a trifluoromethyl group, a methoxy group, an ethoxy group or a hydrogen atom; R 2 means a fluorine atom, a hydroxyl group, a methoxy or ethoxy group or a hydrogen atom; I 4 means a fluorine atom, a methyl, ethyl, trifluoromethyl, methoxy or ethoxy group or a hydrogen atom; R means a fluorine atom in u- or Z-position, a methyl, ethyl, propyl or i-propyl group in a- or 8-position, a trifluoromethyl group in a- or 8-position or a hydrogen atom; R means a hydrogen atom in u- or 8-position, a methyl or ethyl group in a- or 9-position;

R

9 means a hydrogen atom in u- or Z-position, a methyl, ethyl, trifluoromethyl or pentafluoroethyl group in a or Z-position; R means a nitrooxy group in u- or 9-position, a hydroxyl group in u- or 8-position, a fluorine atom in a- or Z position, a choromethyl group in a- or Z-position, a methyl group in a- or 8-position, a methoxy group in a or Z-position, a phenyl- or 3-methylthien-2-yl radical in a- or 9-position or a hydrogen atom; R means a methyl or ethyl group in a- or Z-position; and either R4 means a hydrogen atom in a- or 9-position or a methyl group in a- or S-position and

R

15 means a fluorine atom in a- or 9-position, a methyl group in a- or S-position, or a hydrogen atom, or

R

14 and R 15 together mean a 14a,15a-methylene group or a 148,158-methylene group; R 16means a methyl, ethyl, ethinyl, propinyl or trifluoromethyl group;

R

17 means a fluorine atom in u- or 1-position, a methyl group, a hydrogen atom or a hydroxyl group, and the dotted lines ----- in rings B, C and D optionally mean an additional double bond between carbon atoms 9 and 11. In addition to the above use of the compounds of general formula I, the invention also relates to the compounds of general formula I' themselves. These are the compounds of general formula I excluding the compounds estra-1,3,5(10)-triene-3,16a diol, estra-1,3,5(10)-triene-3,168-diol, estra-1,3,5(10),7 tetraene-3,16a-diol, estra-1,3,5(10),7-tetraene-3,168-diol, 16a ethinylestra-1,3,5(10)-triene-3,168-diol and 168-ethinylestra 1,3,5(10)-triene-3,16a-diol. These last-mentioned compounds are already known; a selective estrogenic action and its use in the context of this invention has not yet been described, however. 16a-Hydroxy-17-methylene estrogens were described as compounds that have an anti-inflammatory action and that are suitable for the therapy of immunological diseases, especially auto-immune diseases (WO 97/08188). A differentiated action of 16a-hydroxyestrone was already described by Westerling et al., see above, but not a differentiated action between the brain functions and the vascular system, on the one hand, and on the uterus, on the other. 3,16a-Dihydroxy-estratriene was already described by Stack and Gorski as "estrogen that has a short-term effect" (Stack, aorski 1985). Nothing is known to date on a use of this last-mentioned -:ompound as a selective estrogen. 3,16-Dihydroxy-estratrienes, which are substituted in 16 position in addition with an ethinyl group, were described in Patent FR 5099. The 168-ethinyl compound can be used as an agent against an elevated cholesterol level. In the compounds of general formulas I and I' as well as in partial structures II and II' that are described below, a Eluorine, chlorine, bromine or iodine atom can always stand for a halogen atom; a fluorine atom is preferred in each case. The alkoxy groups in the compounds of general formulas I and [' as well as in partial structures II and II' that are described >elow can contain 1 to 6 carbon atoms in each case, whereby nethoxy, ethoxy, propoxy, isopropoxy and t-butyloxy groups are )referred.

As representatives of the alkylthio groups, for example, nethylthio, ethylthio and trifluoromethylthio groups can be nentioned. Within the context of this invention, an aryl radical is a phenyl, 1- or 2-naphthyl radical; the phenyl radical is preferred. Unless expressly indicated, aryl always also includes a aeteroaryl radical. Examples of a heteroaryl radical are the 2-, 3- or 4-pyridinyl, the 2- or 3-furyl, the 2- or 3-thienyl, the 2 -r 3-pyrrolyl, the 2-, 4- or 5-imidazolyl, the pyrazinyl, the 2-, I- or 5-pyrimidinyl or 3- or 4-pyridazinyl radical. As substituents for an aryl or heteroaryl radical, for example, a methyl-, ethyl-, trifluoromethyl-, pentafluoroethyl-, -rifluoromethylthio-, methoxy-, ethoxy-, nitro-, cyano-, halogen (fluorine, chlorine, bromine, iodine), hydroxy-, amino-, mono(C 1 8 Llkyl) or di (C 1 8 alkyl)amino, whereby both alkyl groups are Identical or different, di(aralkyl)amino, whereby both aralkyl groups are identical or different, can be mentioned. As representatives of straight-chain or branched-chain alkyl groups with 1-10 carbon atoms, for example, methyl, ethyl, Dropyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, Lsopentyl, neopentyl, heptyl, hexyl, decyl can be mentioned; methyl, ethyl, propyl and isopropyl are preferred. The alkyl groups can be partially or completely fluorinated >r substituted by 1-5 halogen atoms, hydroxy groups or C -C4 ilkoxy groups.

As perfluorinated alkyl groups, for example, trifluoromethyl, pentafluoroethyl and nonafluorobutyl can be mentioned. Representatives of partially fluorinated alkyl groups are, for example, 2,2,2-trifluoroethyl, 5,5,5,4,4 pentafluoropentyl, 9,9,9,8,8,7,7,6,6-nonafluorohexyl, etc. Monochloromethylene, monofluoromethylene or :ifluoromethylene can stand for the halogen-substituted 14,15 nethylene group. Other variants of the invention provide one or more conjugated double bonds in rings B, C and D of the estratriene skeleton: A double bond between C atoms 6 and 7 or between C atoms 7 and 8 or between C atoms 8 and 9 or between C atoms 9 and 11 or etween C atoms 8 and 14 or between C atoms 14 and 15 or double Donds between C atoms 6 and 7 and C atoms 8 and 9 or between C atoms 8 and 9 and C atoms 14 and 15 or between C atoms 6 and 7, C itoms 8 and 9 and C atoms 11 and 12 or between C atoms 6 and 7, C itoms 8 and 9 and C atoms 14 and 15 or between C atoms 6 and 7, C itoms 8 and 9, C atoms 11 and 12 and C atoms 14 and 15. One or both hydroxyl groups at C atoms 3 and 16 can be sterified with an aliphatic, straight-chain or branched-chain, aturated or unsaturated C 1

-C

14 mono- or polycarboxylic acid or an aromatic carboxylic acid or with an a- or S-amino acid. Considered as such carboxylic acids for esterification are, or example: Monocarboxylic acids: formic acid, acetic acid, propionic cid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, pivalic acid, lauric acid, myristic acid, acrylic acid, ropiolic acid, methacrylic acid, crotonic acid, isocrotonic acid, oleic acid, elaidic acid. Dicarboxylic acids: oxalic acid, malonic acid, succinic icid, glutaric acid, adipic acid, pimelic acid, suberic acid, izelaic acid, sebacic acid, maleic acid, fumaric acid, muconic icid, citraconic acid, and mesaconic acid. Aromatic carboxylic acids: benzoic acid, phthalic acid, .sophthalic acid, terephthalic acid, naphthoic acid, o-, m- and -toluic acid, hydratropic acid, atropic acid, cinnamic acid, icotinic acid, and isonicotinic acid. As amino acids, the representatives of these classes of ubstances that are known sufficiently to one skilled in the art re suitable, for example, alanine, 9-alanine, arginine, ysteine, cystine, glycine, histidine, leucine, isoleucine, henylalanine, proline, etc. The 16-oxy group in the compounds according to the invention nd the structural parts that are described below can be both in -position and in 1-position. A variant of the invention provides that in compounds of eneral formulas I and I' as well as in the structural parts of ormula II' R7 means a halogen atom in a- or 9-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or Z-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical and R', R 2 , R 4 , R 8 , RI, R", R 14 , R 15 , R 1 6 and R 17 in each case mean a hydrogen atom. According to another embodiment of the invention, in the :ompounds of general formulas I and I'., and in the structural )arts of formula II' R1 means a nitrooxy group in a- or S-position, a hydroxyl or mercapto group in a- or B-position, a halogen atom in a- or S-position, a chloromethyl group in a- or 9 position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical, and

R

1 , R 2 , R 4 , R 7 , R 8 , R 9 , R 14 , R 15 , R 16 and R 17 in each case mean a hydrogen atom. Another configuration of the compounds of general formulas I nd I' as well as the structural parts of formula II' provides hat

R

15 means a halogen atom in a- or S-position or a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR1 5 ' (R 15 ' = hydrogen atom, methyl, ethyl, propyl, i-propyl), and

R

1 , R 2 , R 4 , R 7 , R 8 , R 9 , R", R 14 , R 16 and R 17 in each case mean a hydrogen atom. In another variant of the compounds of general formulas I and I' according to the invention as well as the structural parts of formula II' R 7 means a halogen atom in a- or 1-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or B-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical, and R" means a nitrooxy group in a- or 1-position, a hydroxyl or mercapto group in a- or B-position, a halogen atom in a- or S-position, a chloromethyl group in a- or B position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical, and R', R', R 4 , R 8 , R 9 , R 4 , R 15 , R 16 and R 1 in each case mean a hydrogen atom. In another variant of the compounds of general formulas I and I' according to the invention as well as the structural parts of formula II',

R

7 stands for a halogen atom in a- or B-position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or B-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical, and

R

15 stands for a halogen atom in a- or B-position or a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or B-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR 1 5 ' (R1 5 ' = hydrogen atom,, methyl, ethyl, propyl, i-propyl), and R', R 2 , R 4 , R", R 9 , R 11 , R 14 , R 16 and R 17 in each case stand for a hydrogen atom. According to another embodiment of the compounds of general ormulas I and I' according to the invention and the structural >arts of formula II', R" stands for a nitrooxy group in a- or S-position, a hydroxyl or mercapto group in a- or S-position, a halogen atom in a- or S-position, a chloromethyl group in a- or S-position, a straight-chain or branched chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or B-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical, and

R

15 stands for a halogen atom in a- or S-position or a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR 1 5 ' (R 1 5 ' = hydrogen atom, methyl, ethyl, propyl, i-propyl), and

R

1 , R 2 , R 4 , R , R 8 , R 9 , R 4 , R 16 , and R 17 in each case stand for a hydrogen atom. There are also embodiments of the compounds of general ormulas I and I' according to the invention as well as the tructural parts of formula II', in which

R

7 means a halogen atom in a- or S-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical, R means a nitrooxy group in a- or S-position, a hydroxyl or mercapto group in a- or 1-position, a halogen atom in a- or 1-position, a chloromethyl group in a- or 9 position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical,

R

15 means a halogen atom in a- or B-position, or a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR1 5 ' (R 15 ' = hydrogen atom, methyl, ethyl, propyl, i-propyl), and

R

1 , R 2 , R 4 , R 8 , R 9 , R 14 , R 16 and R 17 in each case mean a hydrogen atom. In the variants of the compounds of general formula I according to the invention that are indicated above as well as the partial structures of general formula III,

R

7 preferably stands for a fluorine atom in a- or 9 position, a methyl, ethyl, propyl or i-propyl group in a- or f-position, a trifluoromethyl group in a- or 9 position or a hydrogen atom;

R

11 preferably stands for a nitrooxy group in a- or i position, a hydroxyl group in a- or 9-position, a fluorine atom in a- or 9-position, a chloromethyl group in a- or Z-position, a methyl group in a- or 8 position, a methoxy group in a- or S-position, a phenyl or 3-methylthien-2-yl radical in a- or 9-position or a hydrogen atom and

R

15 preferably stands for a fluorine atom in a- or 9 position, a methyl group in a- or 9-position or a hydrogen atom. Preferred according to this invention are the compounds below: 14a,15a-Methylen-estra-1,3,5(10) -triene-3,16a-diol 148, 158-Methylen-estra-1, 3,5 (10) -triene-3, 16a-diol 148, 158-Methylen-estra-1, 3,5 (10) , 8 (9) -tetraene-3, 16a-diol, Estra-1,3,5(10),8(9)-tetraene-3,16a-diol, Estra-1,3,5(10),8(14)-tetraene-3,16a-diol, Estra-1,3,5(10),6,8-pentaene-3,16a-diol, 7a-Fluoro-estra-1,3,5(10)-triene-3,16a-diol, 118-Methoxy-estra-1,3,5 (10) -triene-3,16a-diol, 7a-Methyl-estra-1,3,5(10)-triene-3,16a-diol lig-Fluoro-estra-1,3,5(10)-triene-3,16a-diol, 8a-Estra-1, 3,5 (10) -triene-3, 16a-diol Estra-1,3,5(10)-triene-2,3,l1cy-triol 17f-Fluoro-estra-1, 3,5(10) -triene-3, 1Gc-diol, 18a-Homo-estra-1,3,5(10)-triene-3,16u-diol, 18a-Homo-estra-1, 3,5(10) ,8 (9) -tetraene-3, 16uy-diol, 18a-Homo-14u, 15u-methylen-estra-1, 3,5(10) -triene-3, l6a-diol, 18a-Homo-14cY,15a-methylen-estra-1,3,5(10) ,8(9)-tetraene 3,l6u-diol, 18a-Homo-14a,15a-methylen-estra-1,3,5 (10) ,6,8-pentaene ,16a-diol, 14a, 15a-Methylen-estra-1, 3,5 (10) -triene-3, 16I9-diol 14Z, 15I-Methylen-estra-1, 3,5 (10) -triene-3, 161g-diol Estra5-, ,5(0) 8 )-etraene-3(10, 1EI)-iol, e3,69d Estra-1,3,5(10),8(9-etaene-3,16g-diol, 7sta-1or-es1,3(1)-trene-3,1Gg-do 11-thoysr-1,,0 ,,5(lo) en-triene-3i,1g-i 7ai-Methyl-estra-1, 3,5 (10) -triene-3, l6g-dial, 11f9-Fluara-estra-1,3,5(1o)-triene-3,169gda, 8ai-Metra-, 3,5( ,510) triene-3 1613-dia Estr-1, o-sa13,5(10)n2,3a-trial-,6F-il 171-Flura-estra10-, ,5 10)-trien-3,61-dal 18a-Hamoo-estra-1, 3,5(10)-triene-3, 163-dil, 18a-Hama-estra-1,3,5(lo),8(9)-tetraene-3,l69gdiol, 18a-Hamo-14a,15a-methylen-estra-1,3,5(l0) -triene-3,1613-dial, 18a-Hamo-14ai,15a-methylen-estra-l,3,5(10) ,8(9)-tetraene 1613-dial, 18a-Homo-14cv,15c-methylen-estra-1,3,S (10) ,6,8-pentaene 7u-Ethyl-estra-1, 3,5 (10) -trierie-3, 16ou-diol 7cu-Propyl-estra-1,3,5(10)-triene-3,1Eu-diol 7ci-i-Propy1-estra-1, 3,5 (10) -triene-3, 1Gc-diol 7u-i-Propeny1-estra-1,3,s (10) -triene-3,16oa-diol 7Y-Phenyl-estra-1,3,5(10)-triene-3,16a-djol 7cu-Methoxy-estra-1, 3,5 (10) -triene-3, 16cu-dio1 7ca-Thiomethy1-estra-1, 3,5 (10) -triene-3, 16u-dio1 7u-Cyanomethyl-estra-1, 3,5 (10) -triene-3, 16cu-dio1 79-Ethyl-estra-i, 3,5 (10) -triene-3, 16u-diol 719-Propy1-estra-1,3, 5(10) -triene-3, 16u-diol 7i9-i-Propyl-estra-1, 3,5(10) -triene-3, 1Ec-dio1 7I9-i-Propeny1-estra-1,3,5 (10) -triene-3,16y-diol 7i9-Phenyl-estra-1,3,5(10)-triene-3,16ae-diol 71-Methoxy-estra-1,3,5 (10) -triene-3,l6y-diol 71-Thiomethyl-estra-i, 3,5(10) -triene-3, 16u-dio1 7I9-Cyanomethyl-estra-1,3,5(10) -triene-3,16y-diol 7u-Ethy1-estra-1, 3,5(10) -triene-3, 1Gf-dio1 7a-Propyl-estra-1,3,5 (10) -triene-3,1Ei9-dio1 7u-i-Propy1-estra-1, 3,5 (10) -triene-3, 16I?-diol 7o-i-Propenyl-estra-1, 3,5 (10) -triene-3, 1GI-dio1 70f-Phenyl-estra-1, 3,5 (10) -triene-3, 16i9-dio1 7u-Methoxy-estra-1, 3,5 (10) -triene-3, 1Gi-dio1 7u-Thiomethyl-estra-1, 3,5 (10) -triene-3,1l6i-diol 7cY-Cyanomethyl-estra-1,3,s (10) -triene-3,161g-diol 719-Ethy1-estra-1, 3,5 (10) -triene-3, 1Gi-diol 7i8-Propy1-estra-1, 3,5(10) -triene-3, lGJ-diol 719-i-Propy1-estra-1, 3,5 (10) -triene-3, 16Z-diol 7i9-i-Propeny1-estra-1,3,s(10)-triene-3,1i-diol 7i9-Phenyl-estra-1, 3,5 (10) -triene-3, 169-dio1 7iB-Methoxy-estra-1,3,5 (10) -triene-3,16I9-diol 7IB-Thiomethy1-estra-1, 3,5 (10) -triene-3, 1Ei-diol 7S-Cyanomethyl-estra-1, 3,5 (10) -triene-3,1lG9-diol 15a-Methyl-estra-i, 3,5 (10) -triene-3, 16cu-dio1 15cu-Ethy1-estra-1, 3,5 (10) -triene-3,1l6c-diol l5u-Propyl-estra-1, 3,5 (10) -triene-3, 16cu-dio1 15a-Allyl-estra-i, 3,5 (10) -triene-3, 16u-diol l5c-i-Propyl-estra-1,3,5(10)-triene-3,16a-diol 15ou-i-Propenyl-estra-1, 3,5 (10) -triene-3, l6a-diol l1cx-Methoxy-estra-1, 3,5(10) -triene-3, l6a-diol 15a-Thiomethyl-estra-1, 3,5(10) -triene-3, l6a-dial 15a-Methyl-estra-1,3,5(10)-triene-3,16g-diol 15u-Ethyl-estra-1, 3,5 (10) -triene-3, 1EI-dio1 15a-Allyl-estra-1,3,5 (10) -triene-3,1i-dio 15a-i-Proyl-estra-1, 3,5(10) -triene-3, 1-di 15u-i-Propeyl-estra-1, 3,5(10) -triene-3,l6f-dil 15u--ethxy-estra-1, 3,5(10) -triene-3, 16-dil 15a-TiMethy-estra-1,3,5(1) -triene-3,l-dil 15f-Timethyl-estra-1,3,5 (1-triene-3,6-diol 15I9-Ethy1-estra-1, 3,5 (10) -triene-3, l6a-diol l5I9-Propy1-estra-1, 3,5(10) -triene-3, 16a-dial 151-Allyl-estra-1,3,5 (10) -triene-3,l6a-diol 15i9-i-Propy1-estra-1, 3,5 (10) -triene-3, 1Gu-dio1 15i8-i-Propeny1-estra-1, 3,5 (10) -triene-3, 16a-diol 15IZ-Methoxy-estra-i, 3,5 (10) -triene-3, 16ou-dio1 15:9-Thiomethy1-estra-1, 3,5 (10) -triene-3, 16u-diol 15iZ-Propy1-estra-1, 3,5(10) -triene-3, 16i9-diol 1519-A11y1-estra-1, 3,5 (10) -triene-3, l6g-diol 15f>--Propy-estra-1, 3,5(10) -triene-3, l6-dil 15i9-i-Propy-estra-1,3,5(1)-triene-3,1-iol 15-i-toxey-estra-1,3,5(10) -triene-3,1g-diol 15Z-Mthomey-estra-1,3,5(10) -triene-3, 16-diol 7ou-Trifluoromethy1-111g-fluoro-estra-1, 3,5 (10) -triene-3, l6y Liol 7a-Pentafluoroethy1-111g-fluoro-estra-1,3,5 (10) -triene-3,16y liol 7cu-Ethyl-111-fluoro-estra-1,3,5 (10) -triene-3,l1ae-diol 7u-Propyl-11g--fluoro-estra-1, 3,5 (10) -triene-3, 16u-diol 7u-i-Propy1-11fg-fluoro-estra-1, 3,5 (10) -triene-3, 1Ec-dio1 7u-i-Propenyl-11I9-fluoro-estra-1, 3,5 (10) -triene-3, 16u-diol 7u-Pheny1-11g-Fluoro-estra-1, 3,5 (10) -triene-3, l6y-diol 7cu-Methoxy-11g-fluoro-estra-i, 3,5 (10) -triene-3, 1Ea-dio1 7eu-Thiomethy1-11g-fluoro-estra-1,3,s (10) -triene-3,16uy-dio1 7ca-Cyanomethy1-11g-fluoro-estra-1, 3,5 (10) -triene-3,1l6c-diol 79-Ethy1-11g-fluoro-estra-1, 3,5(10) -triene-3, l6a-dial 79-Prapy1-11g-fluara-estra-l, 3,5 (10) -triene-3, l6a-dial 79-i-Prapy1-11g-fluaro-estra-1, 3,5 (10) -triene-3, l6a-dial 7i9-i-Propeny1-11f-fluoro-estra-1,3,s (10) -triene-3,16cu-dio1 7I9-Metoy-11i-fluoro-estra-1,3,s (10) -triene-3,l6c-diol 7Z-Mthomey-11-fuoro-estra-1, 3,5(10) -triene-3, l-dil 7f9-Cyaomethy-11-fluoro-estra-1, 3,5 (10) -triene-3, l6-diol 7a-Ethotyl-11f-fluoro-estra-,(10) (0-triene-3,1--dio 7a-Propyl-11iZ-fluoro-estra-1, 3,5 (10) -triene-3 ,16I-dio1 7u--Propy-11I-fluoro-estra-1, 3,5(10) -triene-3, 1E-dio1 7u-i-Propey-12J9-fluoro-estra-1, 35(1) -triene-3, 1Gi-dio 7u--Peny1119-fluoro-estra-1,3, (1-triene-3,169dio1 7a-Meoy-11I9-fluro-estra-1, 3,5 (10) -triene-3, lG-diol 7u-TiMethy-11-fuoro-estra-1, 3,5(10) -triene-3, 16-dio 7a-Cyanomethyl-11f-fluoro-estra-1,3,s (10) -triene-3,16g-diol 7Iu-Etyn-11ih-lfuoro-estra-1, ,(10 -tien-3, i-di169d 7I9-Proy-11-fluro-estra-i, 3,5 (10) -triene-3, 16I?-dio1 7i--Propy-11i-fluoro-estra-, 3,5 (10) -triene-3, 16-dio 7i>-i-Prpey-11I-fuoro-estra-, 3,5 (10) -triene-3, 16-diol 79i-Peny1-11i-fuoro-estra-1,3, (10)-triene-3,6g-diol 7I>-Mhetoy-11i-fluor-estra-1, 3,5(10) -triene-3, 16i-dio1 7i9-Thethy-11-fuoro-estra-1,3, (10) -triene-3,16-dio 7f9-Cyaomethy-11i9-fluoro-estra-1, 3,5 (10) -triene-3, 16i9-dio1 15-Mey1-11th-i-fuoro-estra-1, 3(10) -triene-3, l6a-dia 15u-Methy-119-fluor-estra-1, 3,5 (10) -trien-3, l6a-dil 15u-Prapyl-11i9-fluoro-estra-1,3,s (10) -triene-3,l6a-diol 15u-Aroly1-119-fluro-estra-1, 3,5 (10) -triene-3, l6a-dil 15u-i-Propy1-11i?>-fluoro-estra-1, 3,5 (10)-triene-3, 16u-dial 15u-i-Propeny1-11:9-fluoro-estra-1,3,s (10) -triene-3,l6a-dial 15cu-Methoxy-11I-fluoro-estra-1, 3,5(10) -triene-3, 1Ec-dio1 15ou-Thiomethy1-11i9-fluoro-estra-1, 3,5(10) -triene-3, 16ca-diol 15u-Methyl-1119-fluoro-estra-1,3,5 (10) -triene-3,16i9-diol 15a-Ethy1-11IZ-fluoro-estra-1, 3,5 (10) -triene-3, 161g-diol 15u-Propy1-11i9-fluoro-estra-1, 3,5 (10) -triene-3, 1Gi-dio1 15a-A11y1-11f9-fluoro-estra-1, 3,5 (10) -triene-3, 169-diol l5c-i-Propyl-111-fluoro-estra-1, 3,5 (10) -triene-3, 1G1-diol 15cu-i-Propenyl-1119-fluoro-estra-1,3,5 (10) -triene-3,16iz-dio1 15cu-Methoxy-1119-fluoro-estra-1, 3,5(10) -triene-3,1l6f-diol 15cu-Thiomethyl-11I9-fluoro-estra-1, 3,5 (10) -triene-3, 16iz-diol 15I9-Methyl-11I!-fluoro-estra-1, 3,5 (10) -triene-3, 1Eo-dio1 15IZ-Ethy1-11I9-fluoro-estra-1, 3,5 (10) -triene-3, 16u-dio1 1518-Propy1-11I-fluoro-estra-1, 3,5 (10) -triene-3, 16u-diol 15iZ-Al1y1-11i9-fluoro-estra-1, 3,5 (10) -triene-3, 16a-dio1 151-i--Propyl-111?-fluoro-estra-1,3,5 (10) -triene-3,16u-dio1 15I-i-Propeny1-11i9-fluoro-estra-1, 3,5 (10) -triene-3, l6a-diol 159-Methoxy-11i9-fluoro-estra-1, 3,5 (10) -triene-3, 16a-diol 1519-Thiomethy1-1I9-fluoro-estra-1,3,5 (10) -triene-3,l6a-diol 15I9-Methy1-11I9-fluoro-estra-1, 3,5 (10) -triene-3, 1EI-dio1 151-Ethyl-11I?-fluoro-estra-1,3,5 (10) -triene-3,161g-diol 15f-Propy1-11i9-fluoro-estra-1, 3,5(10) -triene-3, 16Z-diol 15I?-A1y1-11I9-fluoro-estra-1, 3,5 (10) -triene-3, lEI-diol i5iZ-i-Propy1-11i9-fluoro-estra-1, 3,5 (10) -triene-3, 1EI-dio1 l5I9-i-Propeny1-11i9-fluoro-estra-1, 3,5(10) -triene-3, 161g-diol 15I-Methoxy-11i9-fluoro-estra-1,3,5 (10) -triene-3,1Ei9-dio1 15i?-Thimethy1-111Z-fluoro-estra-1,3,5 (10) -triene-3,161-diol 14ou,15ou-Methylene-7c-pheny1-estra-1,3,5 (10) -triene-3,l1cy dial 14i,15I9-Methylene-7u-phenyl-estra-1,3,s (10) -triene-3,16a dial 14I9,1519-Methylene-7u-phenyl-estra-1,3,s (10) ,8 (9) -tetraene 3' 16u-diol, 7cu-Phenyl-estra-1,3,5(10) ,8(9)-tetraene-3,l1cy-dial, 7cu-Phenyl-estra-1,3,5(10),8(14)-tetraene-3,16a-diol, 7ce-Phenyl-estra-1,3,5(10) ,6,8-pentaene-3,16a-diol, 11I-Methoxy-7u-pheny1-estra-1,3,s (10) -triene-3,16cu-diol, 119-Fluoro-7ou-phenyl-estra-1,3,5(10)-triene-316u-diol, 7u-Phenyl-8u-estra-1, 3,5(10) -triene-3, 16u-diol 7u-Phenyl-estra-i, 3,5 (10) -triene-2, 3, l6a-trial 17l9-Fluora-7u-phenyl-estra-1,3,5(10)-triene-3,1l(a-dial, 18a-Hamo-7u-phenyl-estra-1,3,5(10)-triene-3,l6a-dial, 18a-Homo-7a-phenyl-estra-1, 3,5 (10) ,8 (9) -tetraene-3, l6a-dial, 18a-Hama-14a, 15a-methylene-7a-phenyl-estra-., 3,5(10) -triene ,l6a-dial, 18a-Hama-14a,l5a-methylene-7u-phenyl-estra-l,3,5(10) ,8(9) .etraene-3, l6a-dial, 18a-Hama-14a,15a-methylene-7a-phenyl-estra-1,3,5 (10) ,6,8 entaene-3, 16a-dial, 14a,15a-Methylene-7a-phenyl-estra-l,3,5 (10) -triene-3,lEI9 .iol 141l519-Methylene-7a-phenyl-estra-l, 3,5(10) -triene-3, 16i9 .ial 141, 1iS-Methylene-7cy-pheny1-estra-1, 3,5 (10) ,8 (9) -tetraene 7a-Phenyl-estra-1,3,5(10) ,8(9)-tetraene-3,119-diol, 7u-Phenyl-estra-1,3,5(10),6,8-pentaene-3,1i9-diol, 11IB-Methoxy-7cu-phenyl-estra-1,3,s (10) -triene-3,1E19-diol, 1119-Fluoro-7ou-pheny-estra-1,3,5(10)-triene-3,16g-diol, 7ou-Phenyl-8a-estra-1, 3,5 (10) -triene-3, 1Gi-dio1 7cu-Pheny1-estra-1, 3,5 (10) -triene-2 ,3, 16o-trio1 17i9-Fluoro-7a-phenyl-estra-1,3,5(10)-triene-3,16g-diol, 18a-Homo-7e-phenyl-estra-1,3,5(10)-triene-3,16Z-djol, 18a-Homo-7cu-pheny1-estra-1,3,5(10) ,8(9)-tetraene-3,169-diol, 18a-Homo-14u, 15au-methylene-7ou-pheny1-estra-1, 3,5(10) -triene 18a-Homo-14a,15u-methylene-7cu-pheny1-estra-1,3,s (10) ,8(9) .etraene-3,1lE9-diol, 18a-Homo-14cY,15cu-methylene-7ca-pheny1-estra-1,3,5(10) ,6,8 15naen-Met1-7a ey-eta1i35(0o-ree3,ld 15e-Methyl-7a-phenyl-estra-1, 3,5(10) -triene-3, l6a-dil 15a-Proyl-7a-phenyl-estra-1, 3,5 (10) -triene-3, 16-diol 15a-Allyl-7-phenyl-estra-1,3, (10) -triene-3,16a-diol 15a-i-Pryl-7-phenyl-estra-1, 3,5(10) -triene-3, l-dil 15a-i-Propeyl-7-phenyl-estra-, 3,5 (10) -triene-3, l-dil 15a-Methaxey-7a-phenyl-estra-1, 3,5(10) -triene-3,1ca-dil 15a-Thethy-7-phenyl-estra-1,3, (10) -triene-3,16-dil lSa-Methyl-7a-phenyl-estra-1, 3,5(10) -triene-3, 1EI-dio1 15cY-Ethy1-7uy-pheny1-estra-1, 3,5(10) -triene-3,1lGZ-diol 15-rpl7-hnleta1,,(0-ree31Zdo 15o-A11y1-7a-pheny1-estra-1, 3,5 (10) -triene-3, 161g-diol 15cu-i-Propyl-7cu-phenyl-estra-1, 3,5 (10) -triene-3, 161g-diol 15ou-i-Propenyl-7ca-phenyl-estra-1, 3,5 (10) -triene-3,1lGZ-diol 15ou-Methoxy-7u-phenyl-estra-1, 3,5 (10) -triene-3, 16iZ-diol 15u-Thiomethyl-7ca-pheny1-estra-1, 3,5 (10) -triene-3, l6g-diol 15-ehl7-hnleta1,,(0-ree31udo 151Z-Ethy1-7cu-phenyl-estra-1,3,s (10) -triene-3,16uy-dio1 15-rpl7-hnleta1351)tin-,6ydo 15I?-Allyl-7u-phenyl-estra-1,3,5 (10) -triene-3,l6u-diol 15f9-i-Propyl-7a-pheny1-estra-1,3,5 (10) -triene-3,16uy-diol 151Z-i-Propeny1-7ca-pheny1-estra-1, 3,5 (10) -triene-3, 16a-diol 15IZ-Methoxy-7a-phenyl-estra-1,3,5 (10) -triene-3,16u-dio1 15iZ-Thiomethy1-7u-pheny1-estra-1, 3,5 (10) -triene-3, 16uy-diol 15iZ-Methyl-7Y-pheny1-estra-1,3,5 (10) -triene-3,16iZ-diol 15IZ-Ethyl-7eu-pheny1-estra-1, 3,5 (10) -triene-3, 16IZ-diol 15IZ-Prapy1-7ae-pheny1-estra-1,3,s (10) -triene-3,16iZ-diol 15iZ-A11y1-7a-phenyl-estra-1, 3,5(10) -triene-3, 161>-dio1 159-i-Propyl-7cy-phenyl-estra-1, 315(10) -triene-3,1l6f-diol 159-i-Propenyl-7a-pheny1-estra-1, 3,5 (10) -triene- 3, 1EI-dio1 15S-Methoxy-7at-phenyl-estra-1, 3,5 (10) -triene-3, l6g-diol 15Z-Thiomethyl-7u-phenyl-estra-1, 3,5 (10) -triene-3, l6g-dial 15ci-Methy1-11Z-fluaro-7cu-phenyl-estra-1,3,5 (10) -triene ,l6a dial 15ca-Ethyl-11Z-fluara-7ou-phenyl-estra-1, 3,5 (10) -triene-3, l6y ial 15a-Propyl-11I9-fluoro-7ou-pheny1-estra-1,3,s (10) -triene 3,1Eca dial 15cu-Al1yl-11I9-fluoro-7Y-pheny1-estra-1,3,s (10) -triene 3, l6a-dial 15ae-i-Prapyl-11ig-fluara-7a-phenyl-estra-1, 3,5 (10) -triene 3, 16u-dial 15u-i-Prapenyl-11fg-fluara-7o!-pheny1-estra-l,3,s (10) -triene 3, l6a-dial 15u-Methaxy-1lf9-fluaro-7a-pheny1-estra-1, 3,5 (10) -triene 3, l6e-diol 15u-Thiamethy1-1lig-fluara-7ey-phenyl-estra-1,3,s (10) -triene 3, l6a-dial 15a-Methyl-l119-fluora-7u-pheny1-estra-l, 3,5 (10) -triene 15u-Ethy1-11I9-fluora-7a-pheny1-estra-1, 3,5 (10) -triene-3, 1619 15u-Prapy1-11ig-fluora-7a-pheny1-estra-1, 3,5 (10) -triene 3, 16i9-dial 15a-PAply-1i-fur-7-pheny-estra-1, 3,5(10) -triene 3, 169-diol 15a-i-Propey-l1ig-fur-7-pheny-estra-1,3,5(10) -triene ,161g-dial 15a-Methaxey-i-flur-7-phenyl-estra-1, 3,5(10) -triene ,16I-dio1 15u-hioethy-11-floro-ci-henl-esra-,3,(10) -triene l159-Methy-11I-fluoro-7c-phenyl.estra-1,3,5 (10) -triene 3, l6a-diol 15l-Ethy1-11i-fluoro-7c-pheny-estra-1,3,5 (10) -triene-3, l6a diol lSI9-Propyl-11-fuoro-7-phenylestral3,5 (10) -triene 3, 16a-diol lSI9-Allyl-11iB-fluoro-7a-phenyl-estra.1 3,5 (10) -triene-3, l6a fi 15S9-i-Propyl-lg-fluoro7-pheny-estra-1,3,5 (10) -triene 3, l6a-diol l1l9-i-Propeny1-l1Z-fluoro7-pheny-estra1,3,5(10) -triene , 16ay-diol lSJ9-Methoxy-11I9-fluoro-7a-phenyl-estra-1,3,5 (10) -triene l16a-dial 15-hoehl11-loo7 hey-sr-,,(10) -triene 16u-dial l1l9-Methy-11I-flur-7-pheny-estra13,5(10) -triene 169- dial lSIS-Ethyl-11i-flur-7-phenyl-estra1l3,5(10) -triene-3,16g il l1l9-Prapyl-11iZ-fluro-7a-phenyl-estra-1,3,5 (10) -triene ,169-dial 15-ly-i-fur upenleta13,5(10) -triene-3, 1E9 ial l59i-Mtoy-1118-fluoro-7-pheny-estra1,3,5(0) -triene l59i-Tiomety-11-fluoro-7-pheny-estra13,5(10) -triene 3' l69-diol 111: -e(3x-ehithien) o-yl) e-estra-1,3,5 ( 10)-rin-3,16ae-d ,16f- [-(-ehytin y) eta135 1)-ree-,6gd 13a-ETra-1, li-lur-u-hny-sta13,5(10) -tiee-3 lng-io 3 14-Esr-,5(0itree316ldo 11I-[(-Methy ltn)y)estra-1,3, (10) -triene-3,16e-diol 111i-MEthylestra-1, 3,5 (10)-riene-3,1io-l 11Iu-MEthy-18a-omesra-,3 (0)-triene-3,16o-dio1 11i9-MEthy-18ahooetr-115(0)-triene-3,1Gi-dio 11S-Etylestra-1 3,5 (10)-riene-,1Go-i 119-Methyestra-1,3,5(10) -triene-3, 16u-dio 11-ehlsr-,,(0-ree319do 11B-Methy1-18a-homoestra-1, 3,5 (10) -triene-3, 1u-diol 11I9-Vinylestra-1,3,5 (10) -triene-3,l6a-diol 11I9-Vinylestra-1,3,5 (10) -triene-3,169-dio1 l1I9-Vtny1-18a-homoestra-1, 3,5 (10) -triene-3, 16u-dio1 111-Vinyl-18a-homoestra-1, 3,5 (10) -triene-3, 16i!-diol 11i9-Ethinylestra-1, 3,5 (10) -triene-3, 16ce-diol 111-Ethinylestra-1, 3,5 (10) -triene-3, 16Z-diol 11I9-Ethiny1-18a-homoestra-1, 3,5 (10) -triene-3, 1G1-diol 19-MEthiy1esta-, 35 (0) tr135)tiene-3, 169-dio 9ou-Methylestra-1, 3,5 (10) -triene-3, 1Gi-diol 9a-Methyl-18ra-homoestra-, 3,5 ( 1-tri-,16l do 9u-Methyl-18a-homoestra-1,3,5(10) -triene-3,16iu-diol 7a-Methyl-18a-homoestra-1, 3,5 (10) -triene-3, 169-dio1 7cu-Methyl-18a-homoestra-1, 3,5 (10) -triene-3,1lGu-diol 7a-Methy1-18a-homoestra-1, 3,5 (10) -triene-3, 16-diol 7u-Ethy1-18a-homoestra-1, 3,5 (10) -triene-3, 16I?-diol 7a-E11I-1mehymestra-1,3,5 (10)-triene-3,6a-diol 70!,l11I-Dimethylestra-1, 3,5 (10) -triene-3, 16R,-diol 7u,11I9-Dimethy1-1a-omsa-1,,(0-,3,(10)-tr19i-3l~ad 7a, 11B-Dimethy1-18a-homoestra-1, 3,5(10) -triene-3, 160!-diol 71G-tiney-18a-homoestra-1, 3(1 -trine-3, l6a-dial l6a-Ethinyl-18a-homoestra-1,3,5 (10) -triene-3,161g-diol 7-Ethiy-1-hinyestra-1,3,5 (10) -triene-3,160-diol 7a-Methyl-16a-ethinylestra-1,3,5 (10) -triene-3,16E.-diol 7u-Methyl-16Iu-ethinyl-18a-omoestra- 3,5 ( 1 -tri-l~ 7a-Methy1-1Ea-ethiny1-18a-hamestra-1,3,5(10)-trene-3,1Ia 111-Methyl-1E1-ethinylestra-1, 3,5 (10) -triene-3, 16a-dial 11IB-Methyl-1Ea-ethinylestra-1,3,5 (10) -triene-3,l1ig-dial 11IB-Methyl-1EIB-ethiny1-18a-homaestra-1, 3,5 (10) -triene-3, l6a dial 118-Methyl-16a-ethinyl-18a-homoestra-1,3,5 (10) -triene-3,168 diol and of the latter in turn especially the compounds 7a-Fluoro-estra-1,3,5 (10) -triene-3,l16a-diol, 7ai-Methyl-estra-1,3,5(10)-triene-3,168-diol 7a-Methyl-estra-1, 3,5 (10) -triene-3, 16a-diol 18a-Homo-estra-1, 3, 5(10) -triene-3, 16a-diol, 7a-Phenyl-estra-1, 3,5 (10) -triene-3, 168-diol 78-Phenyl-estra-1,3,5(10)-triene-3,168-diol 78-Phenyl-estra-1, 3,5 (10) -triene-3, 16a-diol 7a-Ethyl-estra-1,3,5(10)-triene-3, 168-diol 78-Ethyl-estra-1, 3, 5(10) -triene-3, 16a-diol 78-Ethyl-estra-1,3,5(10)-triene-3,168-diol. Another aspect of this invention relates to the use of the structural part of formula II W-0 s a component of the total structure of compounds that have a issociation in favor of their estrogenic action on bone rather han the uterus.

The possible substituents in carbon atoms 7, 8, 9, 11, 13, 14, 15 and 17 can be respectively in a- or 8-position. The dotted lines ----- in rings B, C and D stand for one or more possible double bonds between the corresponding carbon atoms. This invention preferably relates to those structural parts of general formula II' R

--

R R2R R R R 1 6-O R7 R4 (II') in which radicals Rl' to R', independently of one another, have the following meanings:

R

1 ' means a halogen atom, a hydroxyl group, a methyl group, a trifluoromethyl group, a methoxy group, an ethoxy group or a hydrogen atom; R2' means a halogen atom, a hydroxyl group, a straight chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or a hydrogen atom; R'' means a halogen atom, a straight-chain or branched chain, saturated or unsaturated alkyl group with up to 10 carbon atoms, a trifluoromethyl or pentafluoroethyl group, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or a hydrogen atom; R' means a halogen atom in a- or S-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms, an optionally substituted aryl or heteroaryl radical or a hydrogen atom;

R

8 ' means a hydrogen atom in a- or 9-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 8-position or a cyano group in a- or B-position; R9' means a hydrogen atom in a- or S-position, a methyl, ethyl, trifluoromethyl or pentafluoroethyl group in a or 1-position; R means a nitrooxy group in a- or 9-position, a hydroxyl or mercapto group in a- or 9-position, a halogen atom in a- or 1-position, a chloromethyl group in a- or 1 position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 1-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms, an optionally substituted aryl or heteroaryl radical or a hydrogen atom;

R

13 ' means a methyl, ethyl, trifluoromethyl or pentafluoroethyl group in a- or f-position; and either R 14 means a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 1-position or a hydrogen atom in a- or 1-position and R15' means a halogen atom in a- or 1-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 8-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR 1 5 ' (R1 5 ' = hydrogen atom, methyl, ethyl, propyl, i-propyl) or a hydrogen atom or

R

14 ' and R 15 ' together mean a 14a,15a-methylene group or a 148,158-methylene group that is optionally substituted with one or two halogen atoms; R16' means a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in u- or 1-position, a trifluoromethyl or pentafluoroethyl group, a cyanomethyl group or a hydrogen atom in a- or 8-position; R17' means a halogen atom in a- or S-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or Z-position, a hydrogen atom or a hydroxyl group, and the dotted lines ---- in rings B, C and D optionally nean one or more double bonds, and the wavy lines mean :he arrangement of the respective substituent in a- or Z )osition. In this patent application, novel structures for selective strogens are described, which have in vitro dissociation with respect to binding to estrogen receptor preparations of rat >rostates and rat uteri and which preferably have in vivo issociation with respect to bone action rather than uterus ction: the substances act in a bone-protective manner over a ide dose range without stimulating the uterus. In the same dose ange, their liver action is small. In addition, the substances xert estrogen-like action on the vascular system and brain unctions. The invention also relates to pharmaceutical preparations hat contain at least one compound of general formula I (or physiologically compatible addition salts with organic and organic acids thereof) and the use of these compounds for the roduction of pharmaceutical agents, especially for the indications below.

The compounds can be used for the following indications both after oral and parenteral administration. The novel selective estrogens that are described in this patent can be used as individual components in pharmaceutical preparations or in combination especially with antiestrogens or gestagens. Especially preferred is the combination of selective estrogens with ERa-selective antiestrogens, or with antiestrogens that are peripherally-selectively active, i.e., that do not pass through the blood-brain barriers. The substances and the pharmaceutical agents that contain them are especially suitable for the treatment of peri- and postmenopausal symptoms, especially hot flashes, sleep disturbances, irritability, mood swings, incontinence, vaginal atrophy, and hormone-deficiency-induced emotional diseases. The substances for hormone substitution and therapy of hormone deficiency-induced symptoms in the case of surgical, medicinal or Dvarian dysfunction that is caused in some other way are also suitable. Prevention of bone mass loss in postmenopausal wcmen, _n women who have undergone hysterectomies or in women who were :reated with LHRH agonists or LHRH antagonists is also part of :his. The compounds are also suitable for alleviating symptoms of nale menopause and female menopause, i.e., for male and female hormone replacement therapy (HRT), specifically both for prevention and for treatment, in. addition for treatment of symptoms that are accompanied by a dysmenorrhea as well as for reatment of acne.

In addition, the substances can be used for prophylaxis against hormone-deficiency-induced bone mass loss and osteoporosis, for prevention of cardiovascular diseases, especially vascular diseases such as arteriosclerosis, for prevention of the proliferation of arterial smooth muscle cells, for treatment of primary pulmonary high blood pressure and for prevention of hormone-deficiency-induced neurodegenerative diseases, such as Alzheimer's disease, as well as hormone deficiency-induced impairment of memory and learning capacity. In addition, the substances can be used for treatment of inflammatory diseases and diseases of the immune system, especially auto-immune diseases, such as, e.g., rheumatoid arthritis. In addition, the compounds can be used for the treatment of nale fertility disorders and prostatic diseases. The compounds can also be used in combination with the natural vitamin D3 or with calcitriol analogues for bone ormation or as supporting therapies to therapies that ause bone mass loss (for example, therapy with glucocorticoids, hemotherapy). Finally, the compounds of general formula I can be used in onnection with progesterone receptor antagonists, specifically specially for use in hormone replacement therapy and for reatment of gynecological disorders. A therapeutic product that contains an estrogen and a pure ntiestrogen for simultaneous, sequential or separate use for the selective estrogen therapy of perimenopausal or postmenopausal conditions is already described in EP-A 0 346 014. The amount of a compound of general formula I that is to be administered varies within a wide range and can cover any effective amount. On the basis of the condition that is to be treated and the type of administration, the amount of the compound that is administered can be 0.01 pg/kg - 10 mg/kg of body weight, preferably 0.04 pg/kg - 1 mg/kg of body weight, per day. In humans, this corresponds to a dose of 0.8 pg to 800 mg, preferably 3.2 pg to 80 mg, daily. According to the invention, a dosage unit contains 1.6 pg to 200 mg of one or more compounds of general formula I. The compounds according to the invention and the acid addition salts are suitable for the production of pharmaceutical compositions and preparations. The pharmaceutical compositions or pharmaceutical agents contain as active ingredient one or more of the compounds according to the invention or their acid addition salts, optionally mixed with other pharmacologically or pharmaceutically active substances. The production of the pharmaceutical agents is carried out in a known way, whereby the known and commonly used pharmaceutical adjuvants as well as other commonly used vehicles and diluents can be used. As such vehicles and adjuvants, for example, those are suitable that are recommended or indicated in the following bibliographic references as adjuvants for pharmaceutics, cosmetics and related fields: Ullmans Encyklop&die der technischen Chemie [Ullman's Encyclopedia of Technical Chemistry], Volume 4 (1953), pages 1 to 39; Journal of Pharmaceutical Sciences, Volume 52 (1963), page 918 ff., issued by Czetsch-Lindenwald, Hilfsstoffe fnr Pharmazie und angrenzende Gebiete [Adjuvants for Pharmaceutics and Related Fields]; Pharm. Ind., Issue 2, 1961, p. 72 and ff.: Dr. H. P. Fiedler, Lexikon der Hilfsstoffe fir Pharmazie, Kosmetik und angrenzende Gebiete [Dictionary of Adjuvants for Pharmaceutics, Cosmetics and Related Fields], Cantor KG, Aulendorf in Wirttemberg 1971. The compounds can be administered orally or parenterally, for example intraperitoneally, intramuscularly, subcutaneously or percutaneously. The compounds can also be implanted in the tissue. For oral administration, capsules, pills, tablets, coated tablets, etc., are suitable. In addition to the active ingredient, the dosage units can contain a pharmaceutically compatible vehicle, such as, for example, starch, sugar, sorbitol, gelatin, lubricant, silicic acid, talc, etc. For parenteral administration, the active ingredients can be dissolved or suspended in a physiologically compatible diluent. As diluents, very often oils with or without the addition of a solubilizer, a surfactant, a suspending agent or an emulsifying agent are used. Examples of oils that are used are olive oil, peanut oil, cottonseed oil, soybean oil, castor oil and sesame oil.

The compounds can also be used in the form of a depot injection or an implant preparation, which can be formulated so that a delayed release of active ingredient is made possible. As inert materials, implants can contain, for example, biodegradable polymers, or synthetic silicones such as, for example, silicone rubber. In addition, for percutaneous administration, the active ingredients can be added to, for example, a patch. For the production of intravaginal systems (e.g., vaginal rings) or intrauterine systems (e.g., pessaries, coils, IUDs, virenaR) that are loaded with active compounds of general formula I for local administration, various polymers are suitable, such as, for example, silicone polymers, ethylene vinyl acetate, polyethylene or polypropylene. To achieve better bio-availability of the active ingredient, :he compounds can also be formulated as cyclodextrin clathrates. ?or this purpose, the compounds are reacted with a-, Z-, or y yclodextrin or derivatives of the latter (PCT/EP95/02656). According to the invention, the compounds of general formula can also be encapsulated with liposomes. ethodology strogen Receptor Binding Studies The binding affinity of the new selective estrogens was ested in competitive experiments with use of 3H-estradiol as a igand to estrogen receptor preparations of rat prostates and rat teri. The preparation of prostate cytosol and the estrogen receptor test with prostate cytosol was carried out as described by Testas et al. (1981) (Testas, J. et al., 1981, Endocrinology 109: 1287-1289). The preparation of rat uterus cytosol as well as the receptor test with the ER-containing cytosol were basically performed as described by Stack and Gorski, 1985 (Stack, Gorski 1985, Endocrinology 117, 2024-2032) with some modification as described in Fuhrmann et al. (1995) (Fuhrmann, U. et al. 1995, Contraception 51: 45-52). The substances that are described in this patent have higher binding affinity to the estrogen receptor of rat prostates than to estrogen receptors of rat uteri. In this case, it is assumed that ERB predominates in the rat prostates over ERa, and ERa predominates in rat uteri over ERE. Table 1 shows that the ratio Df the binding to prostate and uterus receptors qualitatively :oincides with the quotient of relative binding affinity (RBA) to auman ERB and ERa of rats (according to Kuiper et al. (1996), Endocrinology 138: 863-870) (Table 1). In addition, the predictability of the 'prostate-ER versus :he uterus-ER test system' was confirmed with respect to tissue gelective action by in vivo studies. Substances with a )reference for prostate-ER are dissociated in vivo with respect :o bone and uterus action in favor of action on bones (Table 2). one Studies Three-month-old female rats are ovariectomized and treated >nce daily with the test compound immediately after the operation for 28 days. The administration is carried out subcutaneously in arachis oil/ethanol. The animals are sacrificed on the day after the last administration, and tibia as well as uteri are removed. The uteri are weighed, fixed and worked up for histological studies. The determination of bone density is carried out ex vivo on prepared long bones by means of pQCT (quantitative computer tomography). The measurements are made at a distance of 4-6 mm from the ball of the joint of the proximal tibia. The ovariectomy reduces the density of the trabecular bone in the measured area by about 400 mg of Ca 2 /cm 3 to about 300 mg of Ca 2 /cm 3 . By treatment with a compound of general formula I according to this invention, the degradation of the bone density is prevented or inhibited. The bone density in the proximal tibia was measured. Table 2 shows the results for the compound estra-1,3,5(10) :riene-3,16a-diol that is to be used according to the invention is well as for the compounds of Examples 3, 4, 9, 10 and the :ompounds 78-ethyl-estra-1,3,5(10)-triene-3,168-diol, 7a-ethyl stra-1,3,5(10)-triene-3,168-diol, 78-phenyl-estra-1,3,5(10) riene-3,168-diol, 7a-phenyl-estra-1,3,5(10)-triene-3,168-diol, 1-phenyl-estra-1,3,5(10)-triene-3,16a-diol, and 78-ethyl-estra ,3,5(10)-triene-3,16a-diol. They show a higher binding affinity to the estrogen receptor f rat prostates than to the estrogen receptor of rat uteri; for he compound estra-1,3,5(10)-triene-3,16a-diol ER(RBA) rat rostate = 50 and ER(RBA) rat uterus = 9. Estra-1,3,5(10) riene-3,16a-diol reflects this in vivo in the greatly different amounts, which produce a 50% bone protection [3 pg/animal] or a 50% uterus stimulation [30 pg/animal], relative to the bone mass loss, which can be measured in ovariectomized, untreated female rats 28 days after the ovariectomy unlike in intact animals that are subjected to sham operations. The vascular action of the estrogens according to the invention is determined in the model of the ApoE-knockout mouse, as described by R. Elhage et al., 1997 (Elhage, R. et al. 1997, Arteriosclerosis, Thrombosis and Vascular Biology 17: 2679 2684). To detect the action of estrogens in the brain function, the :xytocin receptor mRNA expression is used as a surrogate parameter (Hrabovszky, E. et al. 1998, Endocrinology 1339: 2600 2604). Ovariectomized rats are treated for 7 days with the test substance or vehicle (administration: subcutaneous or oral, six timess daily). On day 7 after the first administration, the nimals are decapitated, the uterus weight is determined, and the )xytocin receptor mRNA level is studied by means of in situ hybridization in suitable brain sections. The ED values are determined with respect to stimulation of uterus growth and .nduction of the oxytocin receptor mRNA. Another possibility to demonstrate in vivo the dissociated strogen action of the substances according to the invention onsists in the fact that after a one-time administration of the ubstances in rats, effects on the expression of 5HT2a receptor nd serotonin transporter proteins and mRNA levels in ERS-rich rain areas can be measured. Compared to the effect on the serotonin receptor and transporter expression, the effect on the LH-secretion is measured. Substances with higher binding to the rat prostate -- compared to the rat uterus estrogen receptor are potent with respect to increasing the expression of serotonin receptors and transporters, in comparison to their positive effect on the LH release. The density of serotonin receptors and transporters is determined in brain sections using radioactive ligands, and the corresponding mRNA is determined using in situ hybridization. The method is described in the literature: G. Fink & B. E. H. Sumner 1996 Nature 383: 306; B. E. H. Sumner et al. 1999 Molecular Brain Research. Production of the Compounds According to the Invention For the production of the compounds according to the invention, i.e., modified/substituted derivatives of estra L,3,5(10)-triene-3,16E-diols, mainly two generally applicable synthesis strategies are used. On the one hand, especially 3,16-protected derivatives of astra-1,3,5(10)-triene-3,166-diols can be used, however, >ptionally also the free diols can be used for modifications to individual positions of the skeleton. The synthesis of 11-nitrate esters represents a typical xample. The known diacetate of estra-1,3,5(10)-triene-3,168 liol (J. Biol. Chem. 1955, 213, 343), which first is oxidized in (9) and C(11)-positions according to a method by Sykes et al. Tetrahedron Letters 1971, 3393), forms the starting point. The eductive removal of the benzylic C(9)-hydroxyl group already yields the 11-nitrate ester of estra-1,3,5(10)-triene-3,118,168 triol that is protected as a diacetate. After saponification, the epimeric 11-nitrate ester of estra-1,3,5(10)-triene-3,16ae diol then results from an inversion of the C(16)-hydroxyl group. The synthesis diagram that is outlined above can also run in reverse, if the diacetate of the estra-1,3,5(10)-triene-3,16a diol is selected as a starting point. In this way, the 11 nitrate ester in the 16a-hydroxy series is produced first. Other compounds that result from intermediate products, such as, e.g., 11-nitrate esters of estra-1,3,5(10)-triene-3,9, 118-16 -tetraole are also obtained after cleavage of protective groups at C(3), C(16). On the other hand, corresponding modified estrone analogs, which can be obtained in large numbers in known methods (characteristic but not limiting synthesis processes, which are useful for provision of representative substitution patterns in the estrone skeleton, also in combination in several substituents, are found in, for example: C(1) J. Chem. Soc. (C) 1968, 2915; C(7) Steroids 54, 1989, 71; C(8a) Tetrahedron Letters L991, 743; C(89) Tetrahedron Letters 1964, 1763; Tetrahedron L969, 25, 4011; J. Org. Chem. 1970, 35, 468; C(11) J. Steroid 3iochem. 31, 1988, 549; Tetrahedron 33, 1977, 609 and J. Org. 'hem. 60, 1995, 5316; C(9) DE-OS 2035879, J. Chem. Soc. Perk. 1 L973, 2095; C(15) J. Chem. Soc. Perk. 1 1996, 1269); C(13a) endeleev Commun. 1994, 187; C(149) Z. Chem. 23, 1983, 410 offer ~lexible access to the compounds according to the invention by ransposition of the oxygen functionality (Z. Chem. 1970, 221) of C(17) to C(16) . Novel derivatives of estrone are also suitable for this purpose, however. In the introduction of a substituent into 7-position of the steroid skeleton, in most cases mixtures of the 7a- and 79 positional isomers are produced. These can be separated into indiviudal isomers according to methods that are familiar to one skilled in the art, for example by chromatography. For the case of C(3)-methyl ether of 8a-estra-1,3,5(10) trien-17-one (Bull. Soc. Chim. Fr. 1967, 561), an in-depth typical description is given. After the ketone is converted into a sulfonylhydrazone, in the simplest case by reaction with phenylsulfonyl hydrazide, the formation of the C(16)-C(17) olefin is carried out in a decomposition reaction (Z. Chem. 1970, 10, 221-2; Liebigs Ann. Chem. 1981, 1973-81), on which hypobromide is stored in a regio/stereocontrolled way. Reductive dehalogenation and removal of the protective group at C(3) produce the 169 alcohol, which can be converted into the 16a-epimer according to known methods. Another variant for the introduction of the hydroxyl group to C atom 16 exists in the hydroboration of the 16(17)-double bond with sterically exacting boranes. It is known of this reaction that it results in 16-oxygenated products (Indian J. Chem. 1971, 9, 287-8) . Consequently, the reaction of 3 nethoxyestra-1,3,5 (10), 16-tetraene and 3-methoxy-18a-homoestra 1,3,5 (10) ,16-tetraene with 9-borabicyclo[3.3.1]nonane produces 16a-hydroxyestratrienes after oxidation with alkaline hydrogen peroxide. To a lesser extent, the epimeric 16I-hydroxy steroids are formed in this reaction. After the cleavage of the 3-methoxy group, estra-1,3,5(10)-3,16a-diols are obtained. By inversion of the configuration at C atom 16, e.g., by Mitsunobu reaction (Synthesis 1980, 1), the 169-hydroxyestratrienes are in turn obtained. The broad applicability of the synthesis method that is outlined above is demonstrated in additional examples, thus, for example, for 3-methoxy-7a-methylestra-1,3,5 (10) -trien-17-one (Helv. Chim. Acta 1967, 281) or 1,3-dimethoxy-1,3,5(10)-trien-17 one (J. Org. Chem. 1967, 32, 4078). The production of the central C(16)-C(17) olefinic intermediate stages is not limited to the arylsulfonylhydrazone method. If substituents on the steroid skeleton are not compatible with the basic reaction conditions of olefination, other processes, especially the conversion of the C(17) ketones into vinyl iodide (Tetrahedron 1988, 147) or enol triflates (Tetrahedron Letters 1984, 4821) and their subsequent reduction are suitable as alternatives. If a synthesis pathway that runs through C(16)-keto derivatives, which then are converted into C(16)b-alcohols or, by inversion, into C(16)a-alcohols, is selected, the possibilities for C(17)- -> C(16)-ketotransposition are also selected. For a concrete example, refer to J. Chem. Soc. Perk. 1, 1976, 1350. The introduction of fluorine atoms on carbon atoms 15 and 17 of the 16-hydroxyestratrienes according to the invention is possible by hydroboration of 15-fluoroestra-1,3,5 (10) ,16 tetraenes or 17-fluoroestra-1,3,5 (10) ,16-tetraenes with terically exacting boranes and oxidation with alkaline hydrogen eroxide. The synthesis of 15-fluoroestra-1,3,5 (10) ,16-tetraenes an be carried out from, for example, 15-hydroxyestra-1,3,5(10) :rien-17-ones. First, the secondary hydroxyl group must be ubstituted on carbon atom 15 by a fluorine atom. In this espect, for example, the 15a-hydroxyestrone that is accessible according to US-PS 3375174 is converted with known processes into .58-fluoroestrone, by being reacted with diethylamino sulfur rifluoride or the corresponding 15a-mesylate being reacted with etra-n-butylammonium fluoride (J. Chem. Res. (M) 1979, 4728-55). The thus accessible 15S-fluoroestra-1,3,5 (10) -trien-17-ones re converted into tosyl hydrazones. The .Bamford-Stevens eaction of the 15-fluorinated tosyl hydrazones produces the 15 luoroestra-1,3,5(10),16-tetraenes that are required for the ntroduction of the 16-hydroxyl group. The 17-fluoroestra ,3,5(10),16-tetraenes that are necessary for the synthesis of 7-fluorinated 16-hydroxyestratrienes are accessible according to stablished processes. Corresponding ketones can be converted nto geminal difluorides by reaction with sulfur tetrafluoride J. Org. Chem. 1971, 36, 818-20) or dialkylaminosulfur rifluorides, such as diethylaminosulfur trifluoride (US-PS 976691). Hydrogen fluoride can be eliminated from these geminal ifluorides by heating with aluminum oxide in an inert solvent ccording to US-PS 3413321, whereby fluoro-olefins are obtained. n addition, such fluoro-olefins can be obtained directly from etones, if the ketones are reacted with diethylaminosulfur rifluoride in polar solvents with the addition of strong acids, e.g., fuming sulfuric acid (US-PS 4212815). The 17-fluoroestra 1,3,5(10),16-tetraen-3-ol that is described in US-PS 3413321 can be converted into a 178-fluoroestra-1,3,5 (10) -trien-3,l16a-ol after the reaction with a sterically exacting borane and subsequent oxidation with alkaline hydrogen peroxide. As a further modification, the introduction of double bonds may be useful. In addition to their pharmacological importance as selective estrogens in the context of this invention, these unsaturated derivatives represent valuable intermediate products for the synthesis of novel 16-hydroxyestra-1,3,5(10)-trienes. Below, the procedure for introducing a 9(11)-double bond is explained: A-ring-aromatic steroids are converted into the 9a bydroxy steroids by dimethyl dioxiram; their dehydration results in estra-1,3,5(10),9(11)-tetraenes (Tetrahedron 1994, 50, 10709 20). By action of in-situ-produced dimethyl dioxiram on 18a iomoestra-1,3,5 (10) -triene-3, 16a-diyldiacetate, the corresponding 9a-hydroxy compound can be produced. The dehydration of this :ertiary alcohol results in 18a-homoestra-1,3,5(10),9(11) :etraene-3,16a-diyldiacetate. After saponification, 18a iomoestra-1,3,5(10),9(11)-tetraene-3,16a-diol is obtained. The compounds of general formula I according to the .nvention are produced as. described in the examples. Additional :ompounds of general formula I can be obtained by an analogous rocedure using reagents that are homologous to the reagents that re described in the examples.

Etherification and/or esterification of free hydroxy groups is carried out according to methods that are common to one skilled in the art.

Example 1 8a-Estra-1,3,5(10)-triene-3,16B-diol 3-Methoxy-8oe-estra-1,3,5(10)-trien-17-one-17 phenylsulfonylhydrazone A suspension of 5.68 g (20 mmol) of 3-methoxy-8a-'estra 1,3,5(10)-trien-17-one and 4.30 g (25 mmol) of benzenesulfonic acid hydrazide in 70 ml of ethanol is mixed with 3 drops of concentrated hydrochloric acid and then allowed to react at a bath temperature of 80-90 0 C for three hours while being stirred vigorously. After the reaction solution is cooled, the recipitated product is suctioned off, rewashed with a little ,old ethanol, and the hydrazone is dried in a vacuum. 8.10 g .92%) of product, which melts at 183-185 0 C, is obtained. -Methoxy-8a-estra-1,3,5(10),16-tetraene A suspension of 8.10 g (18.5 mmol) of the above-described ydrazone in 140 ml of dry ether is cooled in an ice bath in a oisture-free environment (argon atmosphere) to 0*C and mixed rop by drop with 36 ml of methyllithium (57 mmol) in ether. fter the addition is completed, the cold bath is removed and tirred for another 3 hours at room temperature. For working-up, he reaction mixture is cooled to 0C and carefully mixed with aturated aqueous ammonium chloride solution (30 ml) while being stirred vigorously. This mixture is mixed with ethyl acetate, he organic phase is washed with water/brine and dried on sodium sulfate. The crude product is chromatographed on silica gel (hexane/ethyl acetate, 95:5) . 3.60 g (72%) of product is obtained. 1 7 a-Bromo-3-methoxy-8a-estra-1,3,5(10) -trien-1618-o1 3.40 g (12.67 mmol) of the olefin in 75 ml of dimethyl sulfoxide is brought into solution, then mixed with 5 ml of water, and 2.80 g of N-bromosuccinimide (15.75 mmol) in one portion is added while being stirred vigorously. For working-up after 4.5 hours of reaction at room temperature, the reaction solution is poured onto water, extracted with ethyl acetate (300 ml), the organic phase is washed first with water, then with brine and dried on sodium sulfate. The crude product is chromatographed on silica gel (toluene/acetone, 9:1), yield 3.50 g (75%) as an oil. 3-Methoxy-8a-estra-1,3,5(10) -trien-161-ol A solution of 3.50 g (9.60 mmol) of 17u-bromo-3-methoxy-8u astra-1,3,5(10)-trien-168-ol, 3.50 g (12.03 mmol) of tributyl tin lydride and 50 mg of azobisisobutyronitrile in 30 ml of dry :etrahydrofuran is refluxed for 2 hours while being stirred in an irgon atmosphere. For working-up, it is allowed to cool, :oncentrated by evaporation in a vacuum in a Rotavapor, and the :esidue is taken up in ethyl acetate (300 ml). After the organic >hase is washed with aqueous hydrochloric acid, water and brine, .t is dried on sodium sulfate. The residue is chromatographed on ilica gel (dichloromethane/ethyl acetate, 9:1), yield 2.70 g 98%).

8a-Estra-1,3,5(10)-triene-3,16B-dio1 (1) A solution of 1.10 g (3.80 mmol) of methyl ether in 35 ml of diisobutyl aluminum/toluene (1.2 molar solution) is refluxed for 4 hours under an argon atmosphere in a moisture-free environment. Then, the reaction mixture is cooled in an ice bath and carefully mixed with ethyl acetate/water while being stirred. The precipitate that is produced is separated by filtration, thoroughly rewashed with ethyl acetate, and the organic phase is concentrated in a vacuum. The crude product is recrystallized from acetone/hexane, yield 679 mg (65%), melting point 181-182 0 C, rotation [a] +13.60 (c 0.52, CH 3 OH). Example 2 8a-Estra-1,3,5(10)-triene-3,16a-diol 3-Methoxy-8a-estra-1,3,5(10)-trien-16a-ol 1.22 ml (7.85 mmol) of azodicarboxylic acid diethyl ester, dissolved in 2 ml of toluene, is slowly added in drops to a mixture of 1.50 g (5.24 mmol) of 3-methoxy-8a-estra-1,3,5(10) trien-168-ol, 2.06 g (7.85 mmol) of triphenylphosphine and 0.3 ml of formic acid in 10 ml of toluene while being stirred. Then, it is allowed to react for two hours at room temperature. For working-up, it is taken up in ethyl acetate (300 ml), the organic phase is washed with water/brine and dried on sodium sulfate. The crude product is chromatographed on silica gel (hexane/acetone, gradient of up to 4:1). 1.40 g of 16a-formate is obtained, which is dissolved in 50 ml of 3% methanolic potassium hydroxide solution for saponification. After one hour at room temperature, it is mixed with aqueous hydrochloric acid, taken up in ethyl acetate (300 ml), the organic phase is washed with water/brine and dried on sodium sulfate. The crude product is chromatographed on silica gel (dichloromethane/ethyl acetate, gradient of up to 7:3), yield 940 mg (63%). 8a-Estra-1,3,5(10)-triene-3,16a-dio1 (2) A solution of 740 mg (2.58 mmol) of methyl ether in 25 ml of diisobutyl aluminum/toluene (1.2 molar solution) is refluxed for 4 hours in a moisture-free environment in an argon atmosphere (bath temperature of 130 0 C). Then, the reaction mixture is cooled in an ice bath and carefully mixed with ethyl acetate/water. The precipitate is separated by filtration, thoroughly rewashed with ethyl acetate, and the organic phase is concentrated in a vacuum. The crude product is recrystallized from acetone/hexane, yield 323 mg (46%), melting point 239-240 0 C, rotation [a]D+19.8 0 (c 0.52, CH 3 0H) Example 3 7a-Methylestra-1, 3, 5(10 ) -triene-3, 168-diol 3-Methoxy-7a-methylestra-1,3,5(10) -trien-17-one-17 phenylsulfonylhydrazone 4.70 g (66%) of the corresponding phenylsulfonylhydrazone, which crystallized out during cooling of the reaction mixture, was produced from 4.70 g (15.75 mmol) of 3-methoxy-7a methylestra-1,3,5(10)-trien-17-one, melting point 167-170 0

C.

3-Methoxy-7a-methylestra-1, 3,5(10) , 16-tetraene 2.35 g (85%) of olefin, which crystallized from ethanol as white scales after chromatography on silica gel (hexane/ethyl acetate, 9:1), resulted from the olefination of 4.40 g (9.72 mmol) of phenylsulfonylhydrazone, melting point 114-116 0 C. 17a -Bromo-3-methoxy-7a-methylestra-1,3,5(10) -trien-16 -ol The bromohydrin formation with 2.00 g (7.08 mmol) of olefin produced 2.14 g (80%) of adduct, melting point 145-146 0 C (ether/pentane), while being decomposed. 3-Methoxy-7a-methylestra-1,3, 5(10) -trien-168-ol 1.40 g (91%) of product, amorphous, was obtained from 1.94 g (5.12 mmol) of bromide by reductive dehalogenation. 7a-Methylestra-1, 3, 5(10 ) -triene -3, 1689-diol (3) The cleavage of 1.40 g (4.66 mmol) of methyl ether provided 1.25 g (92%) of the diol, whose melting point was 209-210 0 C (acetone/hexane), (a]D +73.8* (c 0.50, CH 3 0H) Example 4 7a -Methylestra-1,3,5(10) -triene-3,16a -diol (4) It was possible to obtain 0.434 g (59%) of the 16a derivative from 0.74 g (2.58 mmol) of 3,16I-diol by epimerization/saponification at C(16), melting point 217-219 0 C (acetone/hexane), [a] D + 84.40 (c 0.52, CH 3

OH).

Example 5 1-Methoxyestra-1,3,5(10) -triene-3,168-diol 1,3-Dimethoxyestra-1,3,5(10)-trien-17-one-17 phenylsulfonylhydrazone According to the general instructions for hydrazone formation, 3.14 g (10 mmol) of 1,3-dimethoxyestra-1,3,5(10) trien-17-one yielded 4.0 g (85%) of the 17-benzenesulfonic acid hydrazone, which recrystallized from the ethanolic reaction solution, melting point 200-202 0 C. 1,3-Dimethoxyestra-1,3,5(10) ,16-tetraene The olefination of 4.0 g (8.54 mmol) of hydrazone resulted in 1.96 g (76%) of tetraene, which was recrystallized from ethanol after chromatography, melting point 109-111 0 C. 1,3-Dimethoxyestra-1,3,5(10)-trien-16S-ol 0.872 g (55%) of the 168-alcohol was obtained from 1.50 g (5.03 mmol) of the olefin by bromohydrin formation and lehalogenation. L,3-Dimethoxyestra-1,3,5(10) -trien-16a-ol The inversion of 0.50 g (1.58 mmol) of 168-alcohol yielded ).46 g (92%) of the 16a-epimer.

1-Methoxyestra-1,3,5(10) -triene-3,168-diol (5) 0.25 g (0.79 mmol) of 1,3-dimethoxy derivative was monodemethylated to 0.18 g (75%) of methoxydiol. Melting point after trituration in toluene 90-93 0 C. Example 6 1-Methoxyestra-1,3,5(10) -triene-3,16a-diol (6) The demethylation of 0.35 g (1.11 mmol) of dimethoxy derivative in the 16a-series produced 0.218 g (65%) of monomethylether, melting point 240-242 0 C (acetone/chloroform). Example 7 3,11I8,1618-Trihdroxyestra-1,3,5(10) -triene-11-nitrate ester 3,16I8-Diacetyloxyestra-1,3,5(10) -triene 8.00 g (29.4 mmol) of estra-1,3,5(10)-triene-3,168-diol is introduced at room temperature into 50 ml of pyridine, it is nixed with 10 ml of acetic acid anhydride while being stirred and then allowed to react overnight. For working-up, the reaction mixture is put into ice water (3 1), whereby the reaction product Ls deposited as precipitate. The precipitate is collected on a Erit, washed thoroughly with distilled water, dried, and finally :aken up in dichloromethane (500 ml). The organic phase is washed with dilute bicarbonate solution and water and dried on sodium sulfate. The organic residue is recrystallized from cetone/hexane, yield 8.40 g (80%).

3,16S-Diacetyloxy-9,11S-dihydroxyestra-1,3,5 (10) -triene-11 nitrate ester A suspension of 7.85 g (22.0 mmol) of 3,169 diacetyloxyestra-1,3,5(10)-triene in 200 ml of aqueous acetic acid (90%) is mixed for ten minutes in portions with 60.31 g (110 mmol) of cerium ammonium nitrate while being stirred. The steroidal educt goes into solution during the course of the reaction. After five hours, the reaction solution is poured onto ice water (6 1), and the yellow-red-colored precipitate is suctioned off, which is then dried in air. The crude product is then taken up in ethyl acetate (600 ml), the organic phase is washed with water/brine and dried on sodium sulfate. The red brown-colored crude product is chromatographed on silica gel (dichloromethane/ethyl acetate, 9:1), yield 5.10 g (53%), melting point 173-175 0 C (acetone/hexane) . 3, 16E-Diacetyloxyestra-1, 3,5(10) -trien-118-ol-11-nitrate ester 5.0 ml of boron trifluoride-etherate is added in drops to a solution of 2.42 g (5.58 mmol) of 3,168-diacetyloxyestra 1,3,5(10)-triene-9,118-diol-11-nitrate ester and 2.90 ml (18.31 nmol) of triethylsilane in 60 ml of dry dichloromethane that is :ooled to -15 0 C while being stirred. It is allowed to react Eirst for one hour at -15 0 C, then for another hour at 0*C before :he reaction mixture is stirred into bicarbonate-containing ice qater. The product mixture is extracted with dichloromethane, :he organic phase is washed with water and dried on sodium sulfate. The crude product is chromatographed on silica gel (hexane/ethyl acetate, gradient of up to 7:3). Yield 1.58 g (68%), melting point 188-190 0 C (acetone/hexane) . 3,11S,16i8-Trihydroxyestra-1,3,5(10)-triene-11-nitrate ester (7) 1.31 g (3.14 mmol) of the above-described diacetate is taken up in 60 ml of dichloromethane, mixed with 20 ml of methanolic potassium hydroxide solution (3%) and stirred for four hours in a protective gas atmosphere (argon). For working-up, it is mixed with 500 yl of acetic acid, diluted with dichloromethane, the organic phase is washed with water and dried on sodium sulfate. The crude product is recrystallized from dichloromethane, yield 874 mg (83%), melting point 170-171 0 C, while being decomposed. [a] D +68. 9* (c 0. 52, CH 3 OH). Example 8 3,118,16a-Trihydroxyestra-1,3,5(10) -triene-11-nitrate ester (8) 2.26 g (8.62 mmol) of triphenylphosphine and 325 pl of formic acid are added to a solution of 820 mg (2.46 mmol) of 3,168-diol in 25 ml of dry tetrahydrofuran. Then, 1.34 ml (8.62 mmol) of azodicarboxylic acid diethyl ester is slowly added in drops at room temperature to this solution while being stirred. After addition has been completed, it is stirred for another 30 minutes at room temperature before the reaction solution is poured onto water and extracted with ethyl acetate. The organic phase is washed with water/brine and dried on sodium sulfate. Ihe crude product is taken up in 20 ml of dichloromethane, mixed aith 10 ml of methanolic potassium hydroxide solution (3%) and stirred for 2.5 hours at room temperature in an environment devoid of atmospheric oxygen. For working-up, it is acidified with dilute hydrochloric acid, extracted with dichloromethane (200 ml), washed with water and dried on sodium sulfate. The crude product is chromatographed on silica gel (dichloromethane/ acetone, gradient of up to 4:1), yield 704 mg (85%) as a foam; [al D+71.40 (c 0 . 50, CH 3 0H). Example 9 18a-Homoestra-1, 3,5 (10) -triene-3, 16a-diol 3-Methoxy-18a-homoestra-1,3,5(10) -triene-3,16a-diol 7.41 g of 3-methoxy-18a-homoestra-1,3,5(10),16-tetraene is dissolved in 50 ml of anhydrous tetrahydrofuran under protective gas and mixed with 6.4 g of 9-borabicyclo[3.3.llnonane. It is stirred at room temperature until reaction has been completed. Then, it is mixed with 75 ml of water. After gas generation has been completed, 45 ml of 3 M sodium hydroxide solution is added. 45 ml of hydrogen peroxide solution (30%) is then slowly added in drops to the reaction mixture while being cooled. It is stirred for 1 hour at room temperature and extracted with ethyl acetate. The chromatography of the crude product on silica gel (eluant: cyclohexane/ethyl acetate 3+1) yields 6.03 g of 18a-homoestra 1,3,5(10)-triene-3,16a-diol. After recrystallization from methanol, colorless crystals are obtained; flash point 109. . .111 0 C; [a]D = +71* (chloroform, c = 1.02) 18a-Homoestra-1,3,5(10)-triene-3,16a-diol (9) 2 g of 3-methoxy-18a-homoestra-1,3,5(10)-trien-16a-ol is suspended under protective gas in 40 ml of toluene. 26 ml of a solution of diisobutyl aluminum hydride (30% by vol.) in toluene is added in drops to this suspension and refluxed until the reaction has been completed (about 10 hours). 10.6 ml of ethanol and, carefully while being cooled, 32 ml of semiconcentrated hydrochloric acid are added to the cooled batch. After extraction with ethyl acetate, 1.85 g of crude 18a-homoestra 1,3,5(10)-triene-3,16a-diol is obtained. Recrystallization from ethyl acetate yields 1.34 g of colorless crystals; flash point 194...198'C; [a]D = +69* (dioxane, c = 0.99). Example 10 18a-Homoestra-1,3,5(10)-triene-3,16S-diol (10) 0.5 g of 18a-homoestra-1,3,5(10)-triene-3,16a-diol is dissolved in 25 ml of toluene with the addition of 3.66 g of triphenylphosphine and 3.42 g of 4-nitrobenzoic acid. 6.4 ml of diethylazodicarboxylate, solution (40% in toluene) is slowly added in drops to the above. After 48 hours of reaction at room temperature, it is diluted with ethyl acetate, and the organic phase is washed with sodium bicarbonate solution, water and sodium chloride solution. It is dried on magnesium sulfate and :oncentrated by evaporation. The product that is obtained is dissolved in 30 ml of ethanol and mixed with 4.82 g of potassium carbonate. It is stirred at room temperature until saponification has been completed. For working-up, the main amount of methanol is distilled off, and the residue is taken up in ethyl acetate. It is washed with sodium chloride solution and dried on magnesium sulfate. After concentration by evaporation, 0.45 g of crude 18a-homoestra-1,3,5 (10) -triene-3,168-diol is obtained. The recrystallization from ethyl acetate yields 0.26 g of colorless crystals; flash point 210 .. .213*C; [a]l) = +67* (dioxane, c = 1.01). Example 11 18a-Homoestra-1,3,5(10) ,9(11) -tetraene-3,16a-diol 18a-Homoestra-1,3,5(10)-triene-3,16a-diyldiacetate 1 g of 18a-homoestra-1,3,5(10)-triene-3,16a-diol is mixed with 4 ml of pyridine and 4 ml of acetic anhydride and 10 mg of 4-dimethylaminopyridine and allowed to stand overnight. For working-up, it is mixed with ice and extracted with ethyl acetate. The combined extracts are washed with copper sulfate solution (10%) and saturated sodium chloride solution and dried on magnesium sulfate. 1.32 g of 18a-homoestra-1,3,5(10)-triene 3,16a-diyldiacetate is isolated in the form of a colorless foam; [ol D= +50* (chloroform, c = 1.08). 18a-Homoestra-1,3,5(10),9,11-tetraene-3,16a-diyldiacetate 1.32 g of 18a-homoestra-1,3,5 (10) -triene-3,16a-diyldiacetate is added to a mixture that consists of 12 ml of methylene chloride, 18 ml of water, 15 ml of acetone, 5.4 g of sodium bicarbonate and 12 mg of tetra-n-butylammonium hydrogen sulfate.

After temperature equalization to 10 0 C, 11.1 g of potassium monopersulfate (Caroat(R)) is successively added. The reaction mixture was stirred for 4.5 hours at 10 0 C. Then, it was filtered with a frit to separate the salts, and the organic phase of the filtrate was separated. The aqueous phase is subsequently re extracted with methylene chloride, and the combined extracts are dried on magnesium sulfate. After the solvent is evaporated, 1.73 g of crude 9a-hydroxy-18a-homoestra-1,3,5 (10) -triene-3,16 diyldiacetate is obtained. The latter is dissolved in 12 ml of methylene chloride. The solution is temperature-equalized to -10 0 C and mixed with 0.16 ml of sulfuric acid (70%). After the reaction has been completed, it is mixed with saturated sodium bicarbonate, and the organic phase is separated. After the solvent is dried and evaporated, 1.33 g of a brown oil is obtained. The purification on silica gel (eluant: cyclohexane/ethyl acetate 3 + 1) yields 0.63 g of 18a-homoestra 1,3,5(10),9(11)-tetraene-3,16a-diyldiacetate as a colorless foam; [], D= +123' (chloroform; c = 1.02) 18a-Homoestra-1,3,5(10) ,9(11) -tetraene-3,l16a-diol (11) 0.63 g of 18a-homoestra-1,3,5(10),9(11)-tetraene-3,16a diyldiacetate is dissolved in 50 ml of methanol and mixed with 4.72 g of potassium carbonate. It is stirred at room temperature intil saponification has been completed. For working-up, the nain amount of methanol is distilled off, and the residue is taken up in ethyl acetate. It is washed with sodium chloride solution and dried on magnesium sulfate. After concentration by evaporation, 0.49 g of 18a-homoestra-1,3,5(10) ,9(11)-tetraene 3,16a-diol is obtained as a yellowish crystallizate; Flash point 196... 202*C; [ilD = +163' (dioxane; c = 1) Example 12 Estra-1,3,5(10),9(11)-tetraene-3,16a-diol Estra-1, 3, 5(10 ), 9(11) -tetraene-3, 16a-diyldiacetate Analogously to Example 11, 12.69 g (35.8 mmol; 64% of theory) of estra-1,3,5 (10) ,9(11) -tetraene-3,16a-diyldiacetate is obtained starting from 19.9 g (55.82 mmol) of estra-1,3,5(10) triene-3, 16a-diyldiacetate. Estra-1,3,5(10),9(11)-tetraene-3,16a-dio1 (12) Analogously to Example 11, 12.5 g (35.26 mmol) of estra 1, 3,5(10) ,9(11)-tetraene-3,16a-diyldiacetate is saponified. 9.53 g (35.26 mmol; 99% of theory) of estra-1,3,5(10),9(11)-tetraene 3,16a-diol is obtained as almost colorless crystallizate. Recrystallization from ethyl acetate yields colorless crystals; flash point 237 .. .244 0 C; [a] = +163* (dioxane; c = 1.12) . Example 13 13a-Estra-1,3,5(10) -triene-3,16a-diol 3-Methoxy-17-tosylhydrazono-13a-estra-1,3,5(10) -triene 2.5 g (8.79 mmol) of 3-methoxy-13a-estra-1,3,5(10)-trien-17 one and 1.96 g (10.55 mmol) of tosylhydrazide are refluxed in 15 ml of a mixture that consists of ethanol and glacial acetic acid (4 + 1, v/v) for 6 hours. The cooled reaction solution is mixed with saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic phase is washed with saturated sodium bicarbonate solution and with saturated sodium chloride solution and dried on magnesium sulfate. The dark brown oil that is obtained is chromatographed on silica gel (eluant: cyclohexane/ethyl acetate 4 + 1) . 2.49 g of a colorless, amorphous solid is obtained; [a]D = -58* (dioxane, c = 0.99) 3-Methoxy-13a-estra-1,3,5(10),16-tetraene 2.43 g (5.37 mmol) of 3-methoxy-17-tosylhydrazono-13a-estra 1,3,5(10)-triene is suspended in 20 ml of anhydrous methyl-tert butylether. 1.61 ml of a 10 M n-butyllithium solution in hexane is slowly added in drops to this suspension. It is stirred for 1 hour at room temperature. While being cooled, 50 ml of saturated ammonium chloride solution is added in drops. After the organic phase is separated, it is extracted with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution and dried (MgSO 4 ). The crude product (2.1 g of brown oil) is chromatographed on silica gel, whereby 0.81 g of 3-methoxy-13a-estra-1,3,5(10) ,16-tetraene is obtained as a colorless oil; [al] = -6* (chloroform; c = 0.94) 3-Methoxy-13a-estra-1,3,5(10) -trien-16a-ol 0.81 g (3 mmol) of 3-methoxy-13a-estra-1,3,5(10) ,16-tetraene is dissolved under a cover gas in 10 ml of anhydrous tetrahydrofuran and mixed with 0.73 g of 9-bora bicyclo[3.3.1]nonane. It is stirred at room temperature until the reaction is completed. Then, it is mixed with 15 ml of water. After gas generation is completed, 7.8 ml of 3 M sodium hydroxide solution is added. 7.8 ml of hydrogen peroxide solution (30%) is then slowly added in drops to the reaction mixture while being cooled. It is stirred for 1 hour at room temperature and extracted with ethyl acetate. The chromatography of the crude product on silica gel (eluant: cyclohexane/ethyl acetate 4 + 1) yields 604 mg of 3-methoxy-13a-estra-1,3,5(10) trien-16a-ol in the form of a colorless oil. 13a-Estra-1,3,5(10) -triene-3,16a-diol (13) 0.55 g of 3-methoxy-13a-estra-1,3,5(10)-trien-16a-ol is dissolved hot under a cover gas in 10 ml of toluene. A mixture of 2.3 ml of diisobutylaluminum hydride and 5.4 ml of toluene is added in drops to this solution and refluxed until the reaction is completed (about 4 hours). 2.1 ml of ethanol is added to the cooled batch, and 6 ml of semi-concentrated hydrochloric acid is carefully added while being cooled. After extraction with ethyl acetate, the organic phase is washed neutral and dried on magnesium sulfate. 362 mg of 13a-estra-1,3,5(10)-triene-3,16a diol is obtained. The recrystallization from methanol yields colorless crystals; flash point 224 .. .2314C; [a]D = +61* (pyridine, c = 1.13).

Example 14 9E-Estra-1, 3,5(10) -triene-3,16a-dio1 3-Methoxy-17-tosylhydrazono-9E-estra-1,3,5 (10) -triene Produced analogously to Example 13. Colorless foam. 3-Methoxy-9E-estra-1,3,5(10),16-tetraene Produced analogously to Example 13. Colorless oil. 3-Methoxy-98-estra-1,3,5(10)-trien-16a-ol Produced analogously to Example 13. Colorless oil. 9E-Estra-1,3,5(10)-triene-3,16a-diol (14) Produced analogously to Example 13. Colorless crystals; flash point 140 .. .145*C; [a] D = -91* (dioxane; c = 0.98). Example 15 3 ,16a-Bis (benzyloxy) -18a-homoestra-1, 3,5 (10) -trien-11-one 3,16a-Bis(benzyloxy) -18a-homoestra-1,3,5(10) ,9(11) -tetraene 4 g of sodium hydride (80% in paraffin oil, 25.52 mmol) is added under a cover gas to 32 ml of anhydrous N,N dimethylformamide. A solution of 7.67 (26.97 mmol) of 18a homoestra-1,3,5(10)-triene-3,16a-diol in 40 ml of tetrahydrofuran is added in drops to this mixture. After gas generation is completed, 13.84 g (80.91 mmol) of benzyl bromide is added. After the reaction is completed, the reaction solution is slowly added in drops to water (about 1 1). After extraction with ethyl acetate, 14 g of brown oil is obtained. Chromatography on silica gel yields 10.2 g (21.9 mmol; 81.3% of theory) of 3,16a bis(benzyloxy)-18a-homoestra-1,3,5(10),9(11)-tetraene as a colorless oil; [a]D = +110* (chloroform, c = 1.01) 3,16a-Bis(benzyloxy)-18a-homoestra-1,3,5(10)-trien-lla-ol 10 g (21.5 mmol) of 3,16a-bis(benzyloxy)-18a-homoestra 1,3,5(10),9(11)-tetraene is dissolved under a cover gas in 60 ml of anhydrous tetrahydrofuran, and 12.9 g (107.61 mmol) of catechol borane and 0.99 g (43.1 mmol) of lithium borohydride are added. After the reaction is completed, it is carefully hydrolyzed with 100 ml of water. 95 ml of 3N sodium hydroxide solution is then added, and 95 ml of hydrogen peroxide (30%) is added in drops while being cooled. It is stirred for 1 hour at room temperature and subsequently extracted with ethyl acetate. The chromatography of the crude product on silica gel (eluant: cyclohexane/ethyl acetate 4 + 1) yields 8.73 g (18.08 mmol; 84% of theory) of 3,16a-bis(benzyloxy)-18a-homoestra-1,3,5(10)-trien 1la-ol as a colorless foam; [a]D = -48* (chloroform, c = 0.96). 3,16a-Bis(benzyloxy)-18a-homoestra-1,3,5(10)-trien-11-one (15) 0.89 g (1.84 mmol) of 3,16a-bis(benzyloxy)-18a-homoestra 1,3,5(10)-trien-11a-ol is dissolved in 20 ml of methylene chloride and mixed with 0.98 g (4.6 mmol) of pyridium chlorochromate. It is stirred for 4 hours. The reaction mixture is then diluted with tetrachloromethane and filtered on silica gel. The filtrate is concentrated by evaporation and chromatographed on silica gel (eluant: cyclohexane/ethyl acetate 4 + 1). 0.63 g (1.31 mmol; 71% of theory) of 3,16a bis(benzyloxy) -18a-homoestra-1,3,5 (10) -trien-11-one is obtained as a colorless solid; [al D = +1771 (chloroform, c = 0. 96); IR (v C=O) = 1705 cm~. Example 16 3, 16a-Bis (benzyloxy) estra-1, 3,5 (10) -trien-11-one 3,16a -Bis(benzyloxy)estra-1,3,5(10) ,9(11) -tetraene Analogously to Example 15, 12.83 g (28.47 mmol; 88% of theory) of 3,16a -bis(benzyloxy)estra-1,3,5(10) ,9(11)-tetraene is obtained as a colorless oil from 8.7 g (32.17 mmol) of estra 1,3,5(10),9(11)-tetraene-3,16a-diol; [a] = +96* (chloroform, c = 1). 3, 16a-Bis (benzyloxy) estra-1, 3,5(10) -trien-11a-ol Analogously to Example 15, 9.43 g (20.2 mmol; 71% of theory) of 3,16a-bis(benzyloxy)estra-1,3,5 (10) -trien-ll-ol is obtained as a colorless solid from 12.74 g (28.27 mmol) of 3,16a bis(benzyloxy)estra-1,3,5(10) ,9(11)-tetraene; (a] D = -44* (chloroform, c = 1.02). 3,16(a-Bis(benzyloxy)estra-1,3,5(10) -trien-11-one (16) Analogously to Example 15, 1.91 g (4.09 mmol; 64% of theory) of 3,16a-bis(benzyloxy)estra-1,3,5 (10) -trien-l-one is obtained from 3 g (6.4 mmol) of 3,16a-bis(benzyloxy)estra-1,3,5(10)-trien 11a-ol; [a]D = +1970 (chloroform, c = 0. 96) ; IR (v C=O) = 1709 cm- 1

.

Example 17 9ae-Methyl-18a-homoestra-1,3,5(10)-triene-3,16a-diol 3,16a-Bis(benzyloxy)-9a-methyl-18a-homoestra-1,3,5(10)-trien-11 one Under a cover gas, 0.8 g (7.13 mmol) of potassium-tert butylate is dissolved in 6.26 ml of tert-butanol; 0.8 g (1.66 mmol) of 3,16a-bis(benzyloxy)-18a-homoestra-1,3,5(10)-trien-11 one is dissolved in 15.57 ml of methyl iodide and added in drops to the first solution. After 15 minutes, -50 ml of saturated sodium chloride solution is added. The extraction with ethyl acetate yields a yellow foam, which is chromatographed on silica gel (eluant: cyclohexane/ethyl acetate 7 + 1). 0.6 g (1.21 mmol; 73% of theory) of 3,16a-bis(benzyloxy)-9a-methyl-18a-homoestra 1,3,5(10)-trien-11-one is obtained as a colorless foam; [a] = +2160 (chloroform, c = 1.03); IR (v C=O) = 1705 cm 1 . 3,16a-Bis(benzyloxy)-9a-methyl-18a-homoestra-1,3,5(10)-triene 0.76 g (1.54 mmol) of 3,16a-bis(benzyloxy)-9a-methyl-18a homoestra-1,3,5(10)-trien-11-one is introduced into a flask with 5 ml of triethylene glycol. A solution of 2.16 g (38.15 mmol) of potassium hydroxide in 15 ml of triethylene glycol and 1.54 g (30.8 mmol) of hydrazine hydrate are added to this mixture. This mixture is heated for 4 hours to 210 0 C. Then, it is mixed with saturated sodium chloride solution and extracted with ethyl acetate. The organic phases are washed with dilute hydrochloric acid, water and sodium chloride solution. The crude product is chromatographed on silica gel (eluant: cyclohexane/ethyl acetate 14 + 1). In this case, 0.66 g (1.37 mmol; 89% of theory) of 3, 16a-bis (benzyloxy) -9a-methyl-18a-homoestra-1, 3,5 (10) -triene accumulates as a colorless oil; [a] = +471 (chloroform, c = 0.93). 9c-Methyl-18a-homoestra-1,3,5(10) -triene-3,16a-diol (17) 0.65 g (1.37 mmol) of 3,16a-bis(benzyloxy)-9a-methyl-18a homoestra-1,3,5(10)-triene is dissolved in 20 ml of tetrahydrofuran, mixed with 0.65 g of palladium-carbon (10% Pd) and hydrogenated. The catalyst is filtered off, and the filtrate is concentrated by evaporation, whereby 0.4 g (1.33 mmol; 97% of theory) of 9a-methyl-18a-homoestra-1,3,5(10) -triene-3,16a-diol remains. Recrystallization from methanol yields colorless crystals; flash point 210... 215 0 C; [a]D = +720 (dioxane, c = 0.99). Example 18 9a-Methylestra-1, 3,5 (10) -triene-3,16a-diol 3, 16a-Bis (benzyloxy) -9a-methylestra-1, 3,5(10) -trien-11-one Analogously to Example 17, 0.379 g (0.78 mmol; 73% of theory) of 3, 16a-bis (benzyloxy) -9a-methylestra-1,3,5 (10) -trien 11-one is obtained as a colorless foam from 0.497 g (1.06 mmol) :f 3,16a-bis(benzyloxy)estra-1,3,5 (10) -trien-11-one; [a]D = +231* (chloroform, c = 1.03); IR (v C=O) = 1709 cm- .

3, 16a-Bis (benzyloxy) -9ax-methylestra-1,3, 5(10) -triene Analogously to Example 17, 0.458 g (0.98 mmol; 66% of theory) of 3,16a-bis (benzyloxy) -9c-methylestra-1,3,5 (10) -triene is obtained as a colorless oil from 0.715 g (1.48 mmol) of 3,16a bis (benzyloxy) -9a-methylestra-1,3,5(10) -trien-11-one; [a] D = +610 (chloroform, c = 1.16). 9a-Methylestra-1,3,5(10) -triene-3,16a-diol (18) Analogously to Example 17, 0.292 g (1 mmol; 99% of theory) of 9a-methylestra-1,3,5(10) -triene-3,16a-diol is obtained from 0.476 g (1.01 mmol) of 3,16a-bis(benzyloxy)-9a-methylestra 1,3,5(10)-triene. The recrystallization yields colorless crystals; flash point 182.. .186 0 C; [a] D = +77* (dioxane, c = 0.99). Example 19 118-Methyl-18a-homoestra-1,3,5(10) -triene-3,l16a-diol 3, 16a-Bis (benzyloxy) -11a-methyl-18a-homoestra-1, 3,5(10) -trien 119-01 0.6 g (1.25 mmol) of 3,16a-bis(benzyloxy)-18a-homoestra 1,3,5(10)-trien-11-one is dissolved under a cover gas in 20 ml of anhydrous tetrahydrofuran. This solution is cooled to -15 0 C and mixed with 4.17 ml of 3M methylmagnesium bromide solution. After the reaction is completed, saturated ammonium chloride solution is added and extracted with ethyl acetate. The crude product is chromatographed on silica gel (eluant: cyclohexane/ethyl acetate 6 + 1), whereby 0.59 g (1.18 mmol; 95% of theory) of 3,16abis (benzyloxy) -1la-methyl-18a-homoestra-1, 3,5 (10) -trien-118-ol accumulates as a colorless oil; [a] = -I (chloroform, c = 0.99). 3,16a-Bis(benzyloxy) -11E-methyl-18a-homoestra-1,3,5(10) -triene 0.5 g (1 mmol) of 3,16a-bis(benzyloxy)-lla-methyl-18a homoestra-1,3,5(10)-trien-118-ol is dissolved under a cover gas in methylene chloride and mixed with 1.75 g (2.4 ml; 15.3 mmol) of triethylsilane. It is cooled to -10 0 C and mixed with 5.69 g (5 ml, 40 mmol) of boron trifluoride ethyl etherate. After the reaction is completed, it is mixed with saturated sodium bicarbonate solution and extracted. The crude product is purified on silica gel (eluant: cyclohexane/ethyl acetate 9 + 1). 0.327 g (0.68 mmol; 68% of theory) of 3,16a-bis(benzyloxy) 118-methyl-18a-homoestra-1,3,5 (10) -triene is isolated as a colorless oil; [a] = +1190 (chloroform, c = 0. 99) 118-Methyl-18a-homoestra-1,3,5(10)-triene-3,16a-diol (19) 0.45 g (0.93 mmol) of 3,16a-bis(benzyloxy)-l1i-methyl-18a homoestra-1,3,5(10)-triene is dissolved in 20 ml of tetrahydrofuran, mixed with 0.45 g of palladium-carbon (10% Pd) and hydrogenated. The catalyst is filtered off, and the filtrate is concentrated by evaporation, whereby 0.264 g (0.87 mmol; 94% of theory) of 11-methyl-18a-homoestra-1,3,5(10)-triene-3,16a diol remains. Recrystallization from ethyl acetate yields colorless crystals; flash point 244.. .251*C; [U] = +197* (dioxane, c = 1.07).

Example 20 11B-Methyl-18a-homoestra-1,3,5(10)-triene-3,16E-diol (20) 0.1 g (0.33 mmol) of 118-methyl-18a-homoestra-1,3,5(10) triene-3,16a-diol is dissolved in toluene with the addition of 0.35 g (1.33 mmol) of triphenylphosphine and 0.22 g (1.33 mmol) of 4-nitrobenzoic acid. 0.6 ml (1.33 mmol) of diethylazodicarboxylate solution (40% in toluene) is slowly added in drops to it. It is heated to 50 0 C until the reaction is completed. Then, it is diluted with ethyl acetate, and the organic phase is washed with sodium bicarbonate solution, water and sodium chloride solution. It is dried on magnesium sulfate and concentrated by evaporation. The product that is obtained is dissolved in 20 ml of methanol and mixed with 0.81 g (5.85 mmol) of potassium carbonate. It is stirred at room temperature until the saponification is completed. For working-up, the main amount of the methanol is distilled off, and the residue is taken up in ethyl acetate. It is washed with sodium chloride solution and dried on magnesium sulfate. The crude product is chromatographed on silica gel (eluant: cyclohexane/ethyl acetate 2 + 1), whereby 0.79 g (0.26 mmol; 78% of theory) of 118-methyl-18a-homoestra 1,3,5(10)-triene-3,168-diol is obtained. The recrystallization from ethyl acetate yields colorless crystals; flash point 175 .. .188 0 C; [a] D = +1480 (dioxane; c = 0. 95) Example 21 11S-Methylestra-1, 3,5(10) -triene-3 , 16a -diol 3, 16a-Bis (benzyloxy) -11a-methylestra-1, 3, 5(10 ) -trien-11B-ol Produced analogously to Example 19. Colorless oil; [al D = +2* (chloroform, c = 0. 92) . 3, 16a-Bis (benzyloxy) -118-methylestra-1,3, 5(10) -triene Produced analogously to Example 19. Colorless oil; [a]D +1124 (chloroform, c = 1) 118-Methylestra-1,3,5(10) -triene-3,l16a-diol (21) Produced analogously to Example 19. Colorless crystals from methyl-tert-butyl ether; flash point 243.. .250*C; [a]D = +1720 (dioxane, c = 0.96). Example 22 118-Methylestra-1,3,5(10) -triene-3,169-diol (22) Produced analogously to Example 20. Colorless crystals from cyclohexane/ethyl acetate; flash point 194 .. .199 0 C; [a] = +177* (dioxane, c = 0.97).

Example 23 118-Ethyl-18a-homoestra-1,3,5(10) -triene-3,16a-diol 3,16a-Bis(benzyloxy) -lla-ethyl-18a-homoestra-1,3,5(10) -trien-118 ol Produced analogously to Example 19. Colorless oil. 3,16a-Bis(benzyloxy) -11I8-ethyl-18a-homo estra-1,3,5(10) -triene Produced analogously to Example 19. Colorless oil. 1118-Ethyl-18a-homoestra-1,3,5(10) -triene-3,l16a-diol (23) Produced analogously to Example 19. Colorless crystals 242 .. .255 0 C; [U)D = +140- (pyridine, c = 0.99). Example 24 11E-Ethyl-18a-homoestra-1,3,5(10) -triene-3,16E-diol (24) Produced analogously to Example 20. Colorless crystals 152 .. .156 0 C; [aI]D = +1480 (dioxane, c = 0. 95) . Example 25 11E -Ethylestra-1, 3,5 (10) -triene-3, 16a -diol 3, 16a-Bis (benzyloxy) -11a-ethylestra-1, 3, 5(10 ) -trien-118-ol Produced analogously to Example 19. Colorless oil; [a] = -30 (chloroform, c = 1) 3,16a-Bis(benzyloxy) -11B-ethylestra-1,3,5(10) -triene Produced analogously to Example 19. Colorless oil; [alD = +970 (chloroform, c = 1) 11B-Ethylestra-1,3,5(10) -triene-3,16a-diol (25) Produced analogously to Example 19. Colorless crystals from ethyl acetate; flash point 245.. .250*C; [a]D = +1040 (dioxane, c = 1). Example 26 11_-Ethylestra-1,3,5(10) -triene-3,16S-diol (26) Produced analogously to Example 20. Amorphous solid. Example 27 11B-Methoxy-estra-1,3,5(10) -triene-3,16ao-dio1 11B-Methoxy-17-tosylhydrazono-estra-1,3, 5(10) -trien-3-ol In a mixture of 6 ml of ethanol and 4 ml of glacial acetic acid, 1 g (3.3 mmol) of 3-hydroxy-1l8-methoxy-estra-1,3,5(10) trien-17-one and 0.7 g (3.8 mmol) of toluene-4-sulfonic acid hydrazide are refluxed. After a reaction time of about 5 hours at boiling heat, the reaction mixture is cooled, and the product is isolated in about 100 ml of water by addition in drops. By boiling the crude product in n-hexane, the water that is contained is azeotropically removed. 1.14 g of product (73% of theory) is obtained.

11B-Methoxy-estra-1, 3, 5(10 ) ,16 -tetraen-3 -ol 469 mg (1 mmol) of 11-methoxy-17-tosylhydrazono-estra 1,3,5(10)-trien-3-ol is introduced into 15 ml of tetrahydrofuran. The solution is mixed at room temperature with 1 ml (10 mmol) of n-butyllithium solution (10 M, n-hexane) under inert gas and while being stirred vigorously. The reaction solution is refluxed. After about 10 minutes of reaction time and cooling, the working-up is carried out by the addition in drops of 20 ml of saturated ammonium chloride solution and 30 ml of ethyl acetate. The organic phase is washed with water/common salt solution and dried on sodium sulfate. The crude product is purified by chromatography on silica gel (cyclohexane/ethyl acetate, 1:1) . Yield 170 mg (60% of theory). 118-Methoxy-3-triethylsilyloxy-estra-1,3,5(10),16-tetraene 284 mg (1 mmol) of 118-methoxy-estra-1,3,5(10),16-tetraen-3 ol is reacted in 10 ml of tert-butylmethyl ether and 1 ml of pyridine with 0.6 ml of triethylbromosilane. After 1 hour, 30 ml of water is added to the reaction suspension. The organic phase is separated, washed, dried and concentrated by evaporation in a vacuum. The oily product that is thus obtained is used immediately in the next stage (hydroboration). Yield: 380 mg (95% of theory) 11S-Methoxy-estra-1,3,5(10) -triene-3,l16a-diol (27) 380 mg (0.95 mmol) of 118-methoxy-3-triethylsilyloxy-estra 1,3,5(10),16-tetraene is dissolved in 20 ml of tetrahydrofuran under inert gas. After 464 mg (3.8 mmol) of 9 borabicyclo[3.3.1]nonane is added, the reaction solution is stirred at room temperature until the reaction is completed. Then, 5 ml of water is added in drops, and after gas generation is completed, 2 ml of 5N sodium hydroxide solution and 2 ml of 30% hydrogen peroxide solution are added in drops. It is stirred for 1 hour at room temperature, and the product that is produced is extracted with ethyl acetate. The crude product that is obtained is purified by chromatography on silica gel (n hexane/chloroform/methanol 45/45/10) and crystallized from ethyl acetate/n-hexane. Colorless crystals are obtained: 230 mg (80% of theory). Melting point 212-222*C; [a] 20 D = +1010 (dioxane, c = 0.53) Example 28 1189-Methoxy-estra-1,3,5(10) -triene-3,16B-dio1 (28) 229 mg (0.76 mmol) of 118-methoxy-estra-1,3,5(10)-triene 3,16a-diol is dissolved in 30 ml of toluene together with 1.8 g (6.8 mmol) of triphenylphosphine and 1.14 g (6.8 mmol) of 4 nitrobenzoic acid. 2.7 ml (6.8 mmol) of azodicarboxylic acid diethyl ester (40% in toluene) is added drop by drop to this solution. After a 24-hour reaction at room temperature, the reaction solution was mixed with ethyl acetate. The organic phase that is thus obtained is extracted with sodium bicarbonate solution, water and sodium chloride solution. The organic phase is concentrated by evaporation, and then the product is taken up in methanol. After 2.5 g of potassium carbonate is added, the suspension is refluxed until saponification is completed. For working-up, the methanol is distilled off, and the crude product is taken up in ethyl acetate, washed with water and sodium chloride solution, and the solution is concentrated by evaporation. After recrystallization from chloroform/ cyclohexane, almost colorless crystals are obtained: 195 mg (85% of theory) ; melting point 195-200*C; [a0] 20 , = +860 (dioxane, c = 1.18). Example 29 11B-Phenyl-estra-1, 3, 5(10) -triene-3, 16a-diol 116-Phenyl-17-tosylhydrazono-estra-1,3,5 (10) -trien-3-ol 590 mg (1.71 mmol) is reacted with toluene-4-sulfonic acid hydrazide as described in Example 28. By cooling the reaction solution, in this case a portion of the product precipitates. The solid product is suctioned off, washed with ethanol and dried. 450 mg of yellowish crystallizate (51% of theory) is obtained. The product that is still contained in the mother liquor can be isolated by extraction and corresponding chromatographic working-up (303 mg, 38% of theory). 11E-Phenyl-estra-1,3,5(10) ,16-tetraen-3-ol 515 mg (1 mmol) of l11-phenyl-17-tosylhydrazono-estra 1,3,5(10)-trien-3-ol is reacted with 1 ml (10 mmol) of n butyllithium solution as in Example 28. 450 mg of crude product is obtained, which is reacted to form triethylsilyl ether in the next stage.

11I-Phenyl-3-triethylsilyl-estra-1,3,5(10) ,16-tetraene Corresponding to Example 28, 450 mg of 1189-phenyl-estra 1,3,5(10),16-tetraen-3-ol (crude product) is reacted to form triethylsilyl ether. The product that is obtained is purified by chromatography on silica gel (cyclohexane/ethyl acetate, 6/1), and the solution is concentrated by evaporation in a vacuum. An oily substance is obtained. Yield 320 mg (72% of theory relative to 515 mg of 118-phenyl-17-tosylhydrazono-estra-1,3, (10) -trien 3-ol). 118-Phenyl-estra-1,3, 5 (10) -triene-3,16a-diol (29) The hydroboration is carried out according to Example 27. 320 mg (0.72 mmol) of 118-phenyl-3-triethylsilyl-estra 1,3,5(10),16-tetraene yielded 183 mg (73% of theory) after working-up and purification by chromatography on silica gel (toluene/ethyl acetate, 70/30) and crystallization from methanol. Melting point 254-261 [a] 2 0 % = -1034 (dioxane, c = 0.09). Example 30 1118-Phenyl-estra-1,3 ,5 (10) -triene-3,166-diol (30) The inversion of the 16-hydroxy group was performed according to Example 28. 36 mg (0.1 mmol) of 1l1-phenyl-estra 1,3,5(10)-triene-3,16a-diol yielded 25 mg (69% of theory) of colorless crystals after chromatography on silica gel (toluene/ethyl acetate, 70/30) and crystallization from toluene. Melting point 241-247* [a] 20 , = -930 (dioxane, c = 0.31) Example 31 16a-Ethinyl-18a-homo-estra-1,3,5(10)-triene-3,161-diol 3-Hydroxy-18a-homoestra-1,3,5(10) -trien-16-one: 2.4 g of 18a-homoestra-1,3,5(10)-triene-3,16a-diol is dissolved in 60 ml of acetone with the addition of 2.5 ml of methylene chloride. This solution is cooled to 10 0 C and mixed drop by drop with 4.2 ml of chromosulfuric acid (8 mol/l of Cr0 3 ) . After the reaction is completed, it is mixed with sodium hydrogen sulfite solution, and the main amount of the acetone is distilled off. About 100 ml of water is added to the remaining residue. Then, the precipitated steroid is suctioned off. After drying, 2.02 g of 3 -hydroxy-18a-homoestra-1,3,5(1o)-trien-16-one is obtained in the form of colorless crystals; flash point 264 .. .266 0 C; [a]D = -115* (pyridine, c = 0.743) 16a-Ethinyl-18a-homo-estra-1,3,5(10) -triene-3,166-diol (31) At a temperature of about 0 0 C, 30 ml of tetrahydrofuran is saturated with ethine. Then, 3.4 ml (8.4 mmol) of n-butyllithium solution (2.5 M, toluene) is added to the solution while being cooled and stirred. The temperature should be about 0 0 C. A solution of 141 mg (0.5 mmol) of 3-hydroxy-18a-homo-estra 1,3,5(10)-trien-16-one in 10 ml of tetrahydrofuran is added to the suspension of lithium acetylide that is thus obtained. After 30 minutes of reaction time at about 0*C, the reaction solution is mixed with dilute hydrochloric acid. After the tetrahydrofuran is distilled off, the organic residue is taken up in toluene, the phases are separated, the organic phase is washed with water, and the crude product is isolated by concentration by evaporation of the solution under vacuum. A purification of the product is achieved by chromatography on silica gel (toluene/acetone, 7/1) and crystallization from toluene. 131 mg (85% of theory) of crystalline substance is obtained. Melting point 197-202 0 C [a] 20 D = +1000 (dioxane, c = 1.06) Example 32 16B-Ethinyl-18a-homo-estra-1,3,5(10) -triene-3,16a-diol (32) The production of 168-ethinyl-18a-homo-estra-1,3,5 (10) triene-3,16a-diol is performed analogously to Example 31. The increase of the reaction temperature to room temperature produced a larger proportion of 168-ethinyl product. By chromatography on silica gel (cyclohexane/ethyl acetate, 3/1), it was possible to isolate the product. Yield: 20% of theory, 213-219 0 C, [a] 20 D = +484 (dioxane, c 1.04). Example 33 1118-Fluoro-7a-methylestra-1,3,5(10)-triene-3,16S-diol 11i8-Fluoro-7a-methylestra-1, 3,5 (10) -triene-3, 16a-diol 118-Fluoro-7a-methylestr-4-ene-3, 17-dione A suspension of 15.2 g (79.8 mmol) of copper iodide in 70 ml of dry tetrahydrofuran is cooled to 04C, mixed with 28.7 g (330 mmol) of lithium bromide and 27.8 ml of DMPU, stirred first for 30 minutes at this temperature and then cooled to -30 0 C. While being stirred, 52 ml of methylmagnesium bromide in diethyl ether (3 molar solution) is then added in drops, stirred for another 30 minutes, and the gray-colored suspension is mixed with a solution that consists of 10.0 g (34.7 mmol) of 118-fluoroestra-4,6-diene 3,17-dione, 24.3 ml of DMPU and 23 ml of trimethylsilyl chloride in 60 ml of dichloromethane. After the addition is completed, it is allowed to stir for another 1.5 hours between -30 -> -10 0 C, the cold bath is removed, and 35 ml of ethyl acetate is carefully added at room temperature while being stirred vigorously. For working-up, the reaction solution is diluted with ethyl acetate, washed with saturated aqueous ammonium chloride solution that is free of copper, and the organic phase is dried on sodium sulfate. The crude product is chromatographed on silica gel (hexane-ethyl acetate, gradient of up to 1:1), yield 3.1 g (30%). 11B-Fluoro-3-hydroxy-7a-methylestra-1, 3,5(10) -trien-17-one 8.3 g (27.2 mmol) of 118-fluoro-7a-methylestr-4-ene-3,17 dione in 260 ml of acetonitrile is mixed with 7.0 g (31.3 mmol) of copper(II) bromide, and the reaction mixture is stirred for 7 hours at room temperature. For working-up, the reaction solution is diluted with ethyl acetate, the organic phase is washed with aqueous ammonium chloride solution, sodium bicarbonate solution, and finally with water and dried on sodium sulfate. The crude product is chromatographed on silica gel (toluene-ethyl acetate, gradient of up to 7:3), yield 3.3 g (40%), [a]D +166.80 (c 0.5 methanol).

3-Acetyloxy-118-fluoro-7a-methylestra-1,3,5(10) -trien-17-one 3.0 g (9.9 mmol) of 118-fluoro-3-hydroxy-7a-methylestra 1,3,5(10)-trien-17-one in 12 ml of pyridine and 6 ml of acetic acid anhydride are dissolved and allowed to react overnight at room temperature. For working-up, the reaction mixture is stirred into ice water, the precipitate is suctioned off, which then is taken up in ethyl acetate. The organic phase is first washed with dilute hydrochloric acid, then with water and dried on sodium sulfate. 3.4 g of product is obtained, which is sufficiently pure for further processing. 3-Acetyloxy-11E-fluoro-7a-methylestra-1,3,5(10),16-tetraene 3.8 g (18.4 mmol) of 2,6-di-tert-butyl-4-methylpyridine is added to a solution of 2.7 g (7.9 mmol) of 3-acetyloxy-118 fluoro-7a-methyletra-1,3,5(10)-trien-17-one in 40 ml of dry dichloromethane, cooled under a cover gas atmosphere (argon) to 0"C, and 2.64 ml (16 mmol) of trifluoromethanesulfonic acid anhydride is added in drops while being stirred. The cold bath is removed, and stirred for 1.5 more hours at room temperature. For working-up, it is diluted with ethyl acetate, the organic phase is washed with water and dried on sodium sulfate. The crude product (6.0 g) is then taken up in 15 ml of dimethylformamide, mixed at room temperature with 5.72 ml of tributylamine, 0.11 g (0.15 mmol) of bis(acetato) bis(triphenylphosphine) palladium, 0.61 ml (16 mmol) of formic acid and stirred for 30 minutes at a bath temperature of 60 0 C (argon atmosphere). For working-up, it is poured into ice water, extracted with ethyl acetate, the organic phase is washed first with dilute hydrochloric acid, then with water and dried on sodium sulfate. The crude product is chromatographed on silica gel (heptane-acetone, gradient of up to 9:1), yield 1.71 g (66%). 118-Fluoro-7a-methylestra-1,3,5(10)-triene-3,16E9-diol (33a) A solution of 1.67 g (5.22 mmol) of 3-acetyloxy-118-fluoro 7a-methylestra-1,3,5(10),16-tetraene in 30 ml of DMSO and 2.4 ml of water is replaced in portions with 1.36 g of N bromosuccinimide while being stirred at 0*C, the cold bath is removed after the addition of NBS is completed, and it is stirred for 45 more minutes at room temperature. For working-up, the reaction mixture is poured into ice water, extracted with ethyl acetate, the organic phase is washed with water and dried on sodium sulfate. The crude bromohydrin (2.3 g) is then taken up in 25 ml of dry tetrahydrofuran, mixed with 5 ml (18.6 mmol) of tributyl tin hydride, a first spatula tip full of AIBN (a total of 200 mg dispersed over the reaction time), and stirred for 10 hours at a bath temperature of 80 0 C under an argon atmosphere. For working-up, it is diluted with ethyl acetate, the organic phase is washed with dilute hydrochloric acid and water and dried on sodium sulfate. For saponification, the crude product is dissolved in 50 ml of methanol and 5 ml of dichloromethane, and it is mixed with 2.0 g of potassium carbonate. The reaction mixture is stirred for 1.5 hours under argon and poured into ice water for working-up. It is made hydrochloric with dilute acid, and it is extracted with ethyl acetate. The organic phase is washed with water and dried on sodium sulfate. The crude product is chromatographed on silica gel (chloroform-tert butylmethylether, gradient of up to 95:5), yield 1.16 g (75%), melting point 239-240 0 C while decomposing, [a]D + 96.80 (c 0.51 methanol). 11S-Fluoro-7a-methylestra-1,3,5(10)-triene-3,16a-diol (33b) A solution of 0.60 g (2.0 mmol) of 118-fluoro-7u methylestra-1,3,5(10)-triene-3,168-diol in 20 ml of dry tetrahydrofuran is mixed with 1.82 g (6.9 mmol) of triphenylphosphine and 0.26 ml of formic acid. Under an argon atmosphere, 1.10 ml of DEAD is then added in drops to this solution while being stirred at room temperature. After a reaction time of 30 minutes, it is mixed with water, extracted with ethyl acetate, the organic phase is washed with water and dried on sodium sulfate. The crude product is chromatographically purified on silica gel (dichloromethane ethyl acetate, gradient of up to 95:5). The formates that are thus obtained are dissolved in 15 ml of dichloromethane, mixed with 7.5 ml of 3% methanolic potassium hydroxide solution, and left for 2 hours at room temperature under argon. For working up, it is mixed with aqueous acetic acid, extracted with ethyl acetate, the organic phase is washed with water and dried on sodium sulfate. The crude product is purified by crystallization from acetone/hexane. Yield: 0.45 g (75%), melting point 221 222 0 C while decomposing, a] D +104.20 (c 0.52 methanol) Analogously to Examples 3 and 4, the compounds below were produced: 7a-Phenyl-estra-1,3,5(10)-triene-3, 16-diol, melting point 239-241 0 C (acetone/hexane) ; 7f-Phenyl-estra-1,3,5(10) -triene-3,168-diol, melting point 171-173 0 C (acetone/hexane); 78-Phenyl-estra-1,3,5(10) -triene-3,16a-diol, amorphous 7a-Ethyl-estra-1,3,5 (10) -triene-3,16a-diol, melting point 192-193 0 C (acetone /hexane) ; 7a-Ethyl-estra-1,3,5 (10) -triene-3,168-diol, amorphous; 78-Ethyl-estra-1,3,5 (10) -triene-3,16a-diol, melting point 187-189 0 C (acetone /hexane) ; 78-Ethyl-estra-1,3,5(10) -triene-3,168-diol, melting point 156-157 0 C (dichloromethane/hexane).

Table 1 Estrogen Struc- hERa hERS ERZ/ Rat Rat prost. ture RBA* RBA* ERa uterus prost. ER/u ER(RBA) ER(RBA) terus ER Estra- - 100 100 1 100 100 1 diol Estrone 60 37 0.6 3 2 0.8 17a- 58 11 0.2 2.4 1.3 0.5 Estra diol Estriol 14 21 1.5 4 20 5 5-Andro- 6 17 3 0.1 5 50 stene diol Geni- 5 36 7 0.1 10 100 steine Coumes- - 94 185 2 1.3 24 18 trol *Cited from: Kuiper et al. (1996), Endocrinology 138: 863-870 Table 2 Compound Structure ER ER (RBA) 50% bone 50% or (RBA) Rat protec- uterus Example Rat prostate tion in stimu uterus [jg/ani- lation mal] in [yg/ani mal] 16u-Es- 9 50 3 30 tradiol 9 5.3 59 10 1 13 79-Ethyl- 0.2 2 estra 1,3,5(10) triene 3,169-diol1 7-Ethyl- * 11 143 estra 1,3,5(10) triene 3,168-diol 78-Phenyl- 0.7 14 estra 1,3,5(10) triene 3,168-diol 7a-Phenyl- 2.9 9 estra 1,3,5(10) triene 3 ,168-diol 78,-Phenyl- 0.2 1.3 estra 1,3,5(10) triene- ,o 3,16a-diol 78-Ethyl- 0.1 2.9 estra 1,3,5(10) triene 3,16a-diol 4 29 200 3 _ 5.6 1 83

Claims

1. 3,16-Dihydroxyestra-1,3,5(10)-triene derivatives of general formula I R 16R R R 2 . ..- -. OH HO R R1 R4 (I) in which radicals R 1 to R 1 , independently of one another, have the following meanings: R1 means a halogen atom, a hydroxyl group, a methyl group, a trifluoromethyl group, a methoxy group, an ethoxy group or a hydrogen atom; R 2 means a halogen atom, a hydroxyl group, a straight chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or a hydrogen atom; R4 means a halogen atom, a straight-chain or branched chain, saturated or unsaturated alkyl group with up to 10 carbon atoms, a trifluoromethyl or pentafluoroethyl group, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or a hydrogen atom; R 7 means a halogen atom in a- or S-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms, an optionally substituted aryl or heteroaryl radical or a hydrogen atom; R 8 means a hydrogen atom in a- or 8-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position or a cyano group in a- or 9-position; R9 means a hydrogen atom in a- or Z-position, a methyl, ethyl, trifluoromethyl or pentafluoroethyl group in a or 8-position; R" means a nitrooxy group in a- or S-position, a hydroxyl or mercapto group in a- or I-position, a halogen atom in a- or S-position, a chloromethyl group in a- or 9 position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms, an optionally substituted aryl or heteroaryl radical or a hydrogen atom; R13 means a methyl, ethyl, trifluoromethyl or pentafluoroethyl group in B-position; and either R 14 means a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position or a hydrogen atom in a- or 1-position and R15 means a halogen atom in a- or S-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR1 5 ' (R 15 ' = hydrogen atom, methyl, ethyl, propyl, i-propyl) or a hydrogen atom or R 14 and R 15 together mean a 14a,15a-methylene or 14Z,158 methylene group that is optionally substituted with one or two halogen atoms; R16 means a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or B-position, a trifluoromethyl or pentafluoroethyl group, a cyanomethyl group or a hydrogen atom in a- or B-position; R17 means a halogen atom in a- or 9-position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or Z-position, a hydrogen atom or a hydroxyl group and the dotted lines ------ in rings B, C and D optionally mean one or more double bonds, and the wavy lines mean the arrangement of the respective substituent in a- or Z-position, excluding the compounds estra-1,3,5(10)-triene-3,16a-diol, estra-1,3,5(10)-triene-3,168-diol, estra-1,3,5(10),7-tetraene 3, 16a-diol, estra-1, 3, 5(10 ), 7-tetraene -3, 1689-diol, 16a ethinylestra-1, 3 ,5(10) -triene-3,168-diol and 169-ethinylestra 1,3,5(10)-triene-3,16a-diol.

2. Compounds according to claim 1, in which radicals R 1 to R 17 , independently of one another, have the following meanings R1 means a fluorine atom, a hydroxyl group, a methyl group, a trifluoromethyl group, a methoxy group, an ethoxy group or a hydrogen atom; R2 means a fluorine atom, a hydroxyl group, a methoxy or ethoxy group or a hydrogen atom; R4 means a fluorine atom, a methyl, ethyl, trifluoromethyl, methoxy or ethoxy group or a hydrogen atom; RI 7 means a fluorine atom in a- or S-position, a methyl, ethyl, propyl or i-propyl group in a- or S-position, an optionally substituted aryl radical, a trifluoromethyl group in a- or S-position or a hydrogen atom; R 8 means a hydrogen atom in a- or B-position, a methyl or ethyl group in a- or S-position; R9 means a hydrogen atom in a- or S-position, a methyl, ethyl, trifluoromethyl or pentafluoroethyl group in a or S-position; R1 means a nitrooxy group in a- or s-position, a hydroxyl group in a- or S-position, a fluorine atom in a- or S position, a choromethyl group in a- or S-position, a methyl group in a- or S-position, a methoxy group in a or S-position, a phenyl- or 3-methylthien-2-yl radical in a- or S-position or a hydrogen atom; R13 means a methyl or ethyl group in a- or S-position; and either R 14means a hydrogen atom in a- or S-position or a methyl group in a- or -position and R 15 means a fluorine atom in a- or S-position, a methyl group in a- or S-position, or a hydrogen atom, or R 14 and R 15 together mean a 14a,15a-methylene group or a 148, 158-methylene group R 16 means a methyl, ethyl, ethinyl, propinyl or trifluoromethyl group; R17 means a fluorine atom in a- or s-position, a methyl group, a hydrogen atom or a hydroxyl group, and the dotted lines ----- in rings B, C and D optionally mean an additional double bond between carbon atoms 9 and

11. 3. Compounds of general formula I according to claim 1, in which R7 means a halogen atom in a- or B-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or B-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms, or an optionally substituted aryl or heteroaryl radical and R 1 , R 2 , R 4 , R 8 , R 9 , R 11 , R 14 , R 15 , R 16 and R 17 in each case mean a hydrogen atom. 4. Compounds of general formula I according to claim 1, in which R1 means a nitrooxy group in a- or 9-position, a hydroxyl or mercapto- group in a- or S-position, a halogen atom in a- or i-position, a chloromethyl group in a- or 9 position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms, or an optionally substituted aryl or heteroaryl radical, and RI, R 2 , R 4 , R 7 , R 8 , R 9 , R 14 , R 15 , R 16 and R 17 in each case mean a hydrogen atom. 5. Compounds of general formula I according to claim 1, in which R 15 means a halogen atom in a- or S-position or a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR 15 ' (R 15 ' = hydrogen atom, methyl, ethyl, propyl, i-propyl), and R 1 , R 2 , R 4 , R, R, R 9 , R 11 , R 14 , R 16 and R 1 in each case mean a hydrogen atom. 6. Compounds of general formula I according to claim 1, in which R 7 means a halogen atom in a- or 9-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical, R means a nitrooxy group in a- or 9-position, a hydroxyl or mercapto group in a- or S-position, a halogen atom in a- or 1-position, a chloromethyl group in a- or 9 position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 8-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical, and RI, R 2 , R 4 , R , R 9 , R 14 , R 15 , R 16 and R 17 in each case mean a hydrogen atom. 7. Compounds of general formula I according to claim 1, in which R 7 means a halogen atom in a- or 9-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical, R 15 means a halogen atom in a- or 9-position or a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR1 5 ' (R 15 ' = hydrogen atom, methyl, ethyl, propyl, i-propyl), and R 1 , R 2 , R 4 , R 8 , R 9 , Ri 1 , R 14 , R 16 and R 17 in each case mean a hydrogen atom. 8. Compounds of general formula I according to claim 1, in which R 11 means a nitrooxy group in a- or 9-position, a hydroxyl or mercapto group in a- or S-position, a halogen atom in a- or 9-position, a chloromethyl group in a- or 9 position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or I-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical, R1 means a halogen atom in a- or S-position or a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or B-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR 15 ' (R 15 ' = hydrogen atom, methyl, ethyl, propyl, i-propyl), and R 1 , R 2 , R 4 , R , R , R 9 , R 14 , R 16 , and R 17 in each case mean a hydrogen atom. 9. Compounds of general formula I according to claim 1, in which R 7 means a halogen atom in a- or 9-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical, R means a nitrooxy group in a- or 9-position, a hydroxyl or mercapto group in a- or B-position, a halogen atom in a- or S-position, a chloromethyl group in a- or I position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or B-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms or an optionally substituted aryl or heteroaryl radical, R15 means a halogen atom in a- or i-position, or a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 1-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR1 5 ' (R1 5 ' = hydrogen atom, methyl, ethyl, propyl, i-propyl), and R 1 , R 2 , R 4 , R 8 , R 9 , R 14 , R 1 6 and R 17 in each case mean a hydrogen atom. 10. Compounds according to claim 1, characterized in that the dotted lines mean one or more conjugated double bonds. 11. Compounds according to claim 1, wherein there is a double bond between C atoms 6 and 7.

12. Compounds according to claim 1, wherein there is a double bond between C atoms 7 and 8.

13. Compounds according to claim 1, wherein there is a double bond between C atoms 8 and 9.

14. Compounds according to claim 1, wherein there is a double bond between C atoms 9 and 11.

15. Compounds according to claim 1, wherein there is a double bond between C atoms 8 and 14.

16. Compounds according to claim 1, wherein there is a double bond between C atoms 11 and 12.

17. Compounds according to claim 1, wherein there is a double bond between C atoms 14 and 15.

18. Compounds according to claim 10, wherein there are double bonds between C atoms 6 and 7 and C atoms 8 and 9.

19. Compounds according to claim 10, wherein there are double bonds between C atoms 8 and 9 and C atoms 14 and 15.

20. Compounds according to claim 10, wherein there are double bonds between C atoms 6 and 7, C atoms 8 and 9 and C atoms 11 and 12.

21. Compounds according to claim 10, wherein there are double bonds between C atoms 6 and 7, C atoms 8 and 9 and C atoms 14 and 15.

22. Compounds according to claim 10, wherein there are double bonds between C atoms 6 and 7, C atoms 8 and 9, C atoms 11 and 12 and C atoms 14 and 15.

23. Compounds according to one of claims 1 to 22, wherein one or both hydroxyl groups is (are) esterified at C atoms 3 and 16 with an aliphatic or aromatic carboxylic acid or with an a- or 1-amino acid.

24. Compounds according to claim 1, namely 14a,15a-Methylen-estra-1,3,5(10)-triene-3,16a-diol 148,158-Methylen-estra-1,3,5(10)-triene-3,16a-diol 148,158-Methylen-estra-1,3,5(10),8(9)-tetraene-3,16a-diol, Estra-1,3,5(10),8(9)-tetraene-3,16a-diol, Estra-1,3,5(10),8(14)-tetraene-3,16a-diol, Estra-1,3,5(10),6,8-pentaene-3,16a-diol, 7a-Fluoro-estra-1,3,5(10)-triene-3,16a-diol,

118-Methoxy-estra-1,3,5(10)-triene-3,16a-diol, 7a-Methyl-estra-1,3,5(10)-triene-3,16a-diol l1-Fluoro-estra-1,3,5(10)-triene-3,16a-diol, 8a-Estra-1,3,5(10)-triene-3,16a-diol Estra-1,3,5(10)-triene-2,3,16a-triol

178-Fluoro-estra-1,3,5(10)-triene-3,16a-diol, 18a-Homo-estra-1,3,5(10)-triene-3,16a-diol, 18a-Homo-estra-1,3,5(10),8(9)-tetraene-3,16a-diol, 18a-Homo-14a,15a-methylen-estra-1,3,5(l0)-triene-3,16a-diol, 18a-Homo-14a,15a-methylen-estra-1,3,5(10),8(9)-tetraene 3,,16a-diol, 1 8 a-Homo-14u,15umethylenestra-1, 3 ,S (10) ,6,8-pentaele 16a-diol, 14u, 15cuMethylef-estra1, 3,5 (10) -triene-3, 1E1-diol 149, 15I9-Methylef-estra1, 3,5 (10) -triene-3,1iGI-diol Estra1l,3,5(1O),G,8Peaee3,1E8()-etane3,6lIil 7otr- ,51uesr-, 3(10) trene-3, 16?-dio, 11ZMetX-e,3 tral0,8(14 (10) -trie-3,1S-di, 8-Estra-1, 3,5(10)6,-ptrene-3, 16-dio, Estlrao3,51tr1,,5e2,3,1Ga trial diol 117i-Fluho-estra-1, 3 S (10) -triene-3,16i-diol, 18-ehom-estral1, 3 ,S (10) -triene-3,16I-diol 118aFHoo-estra1,3,5(1) ,(tetrfe-3,16 diol 8-H O1s io~ehyeltral, 3,5(10) -triene-3,16GI-diQ1, lsta-1Ho ,o1),15mehnenes,6tr13i 1) 8()-ttafe 17Z-Ethy1-estra-1, 3,5(10) -triene-3, i6-dio, 7a-Popy-estra1, 3,5 (10) -triene-3, 16-dio1, 7i~a-Prmopy1r-~1, 3,5 (10)89-trene-3 i6-dio, 7lyai-popeflyu15amy-e sttra1I 3 IS (10)tririene-3,1Ecddill 7cy-phefly-estra-, 3,5 (10) -triere-3, l6-diol 7u-Methoxy-estra-1,3,5(10) -triene-3,16u-diol 7c-Thiomethyl-estra-1, 3,5(10) -triene-3, 16u-diol 7ca-Cyanomethy1-estra-1, 3,5 (10) -triene-3, 16a-diol 7I9-Ethy1-estra-1, 3,5(10) -triene-3,6lea-diol 7i9-Propy1-estra-1, 3,5 (10) -triene-3, l6a-diol 7I9-i-Propy1-estra-1, 3,5 (10) -triene-3,16Ea-diol 7i9-i-Propenyl-estra-1, 3,5 (10) -triene-3, l6a-dial 7Ig-Phenyl-estra-1,3,5(10)-triefe-3,1Ea-diol 7i9-Methoxy-estra-1,3,5 (10) -triene-3,l6u-diol 7f9-Thiamethy1-estra-1,3,5(10) -triene-3,l6a-dial 7f9-Cyanomethy1-estra-1,3,5 (10) -triene-3,l6ea-diol 7a-Ethyl-estra-1, 3,5 (10) -triene-3, 1Ei-dio1 7a-Propyl-estra-1,3,5(10) -triene-3,16I9-dio1 7a-i-Prapyl-estra-1, 3,5(10) -triene-3, 1Ei-diol 7a-i-Propenyl-estra-1, 3,5 (10) -triene-3, l6g-dial 7a-Phenyl-estra-1, 3,5 (10) -triene-3, l6g-dial 7a-Methaxy-estra-1,3,5 (10) -triene-3,l619-dial 7a-Thiamethyl-estra-1,3,5 (10) -triene-3, 161?-dial 7a-Cyanamethyl-estra-1,3,5 (10) -triene-3,1E19-dia1 7I9-Ethyl-estra-1, 3,5 (10) -triene-3, 16I9-dial 71-Prapyl-estra-l, 3,5(10) -triene-3, l6g-dial 7g-i-Prapyl-estra-1,3,5 (10) -triene-3,l6g-dial 71g-iPrpenyl-estra-1,3,5(10)-triene-3,169-dial 7:9-Pheny1-estra-l, 3,5 (10) -triene-3, l6g-dial 7g-Methaxy-estra-1, 3,5(10) -triene-3, 16g-dial 7g-Thiamethyl-estra-1,3,5 (10) -triene-3,l6g-dial 7g-Cyanamethyl-estra-1, 3,5 (10) -triene-3,1l:g-dial 15u-ethy-esta-1,,5(1)-trene-,16 diL l5a-MEthyl-estra-1, 3,5 (10) -triene-3, 16-diol 15u-Ethy-estra-1, 3,5 (10) -triene-3, l6a-dol 15cu-Proy-estra-1, 3,5 (10) -triene-3, l6-diol 15o--y-estra-1, 3,5(10) -triene-3, 1a-dio 15a-i-Propenyl-estra-1, 3,5 (10) -triene-3, 16cu-diol 15u-Methoxy-estra-1,3,5 (10) -triene-3,16u-dio1 15ou-Thiorethy1-estra-1, 3,5 (10) -triene-3, 16u-diol 15ou-Methyl-estra-1, 3,5(10) -triene-3, 16i9-dio1 15u-Proyl-estra-1, 3,5 (10) -triene-3,1l6i-diol 15cu-A1py1-estra-1, 3,5(10) -triene-3,1lG9-diol lc-i-Pryl-estrA-1, 3,5(10) -triene-3, 16-dio i5u-i-Propey-estra-1, 3,5(10) -triene-3, 1-dio 15u--toxey-estra-1,3,5 (10)-triene-3,16-dio lc-MThomey-estra-1, 3,5(10) -triene-3, 16-dio1 15iu-Timethyestra-1, 3,5(1-triene-3, 6y-diol 151-Methyl-estra-1, 3,5 (10) -triene-3, 16u-diol i5i9-Proy-estra-1,3,5 (10) -triene-3,l1o-diol 151-Allyl-estra-1, 3,5 (10) -triene-3, 16u-diol

1519-i-Pry-estra-1, 3,5(10) -triene-3, 16-dio1 15I9-i-Propey-estra-1, 3,5(10) -triene-3, l6-dil 151g-toxey-estra-1,3,5 (10)-triene-3,u-diol 15-MThomty-estra-1, 3,5(10) -triene-3, l-dil 151-Mhethyl-estra-1,3(1 -tre3, lE6g-di 15i>-Methy1-estra-1,3,5 (10) -triene-3,16g-diol i5i>-Propy1-estra-l, 3,5(10) -triene-3, 16I9-diol 15i9-Al1y1-estra-1,3,5 (10) -triene-3,16i9-diol i519-i-Propy1-estra-1, 3,5 (10) -triene-3,1lGZ-diol i5i>-i-Propeny1-estra-1, 3,5 (10) -triene-3, i6i-dio1 151-Methoxy-estra-1,3,5 (10) -triene-3,l6g-diol 7u-Trifluoromethyl-11ig-fluoro-estra-1,3, 5(10) -triene-3, 16a diol 7u-Pentafluoroethy1-11i9-fluor-estral1, 3 iS (10) -triene-3,1cu diol 7c-Ethyl-11i9-fluoro-estra-1,3tS (10) -triene-3,16a-diol 7u-Prapyl-1119-fluoro-estra-1, 3,5 (10) -triene-3,1l6u-diol 7ou-i-Propy1-11i9-fluoro-estra-1,3,5 (10) -triene-3,16u-dio1 7u-i-Propenyl-119-f1uoro-estra-1, 3,5 (10) -triene-3, i6o-dio1 7a-Phenyl11I-F1uoro-estra-1, 315(10) -triene-3, 16cu-dio1 7c--Methoxy-1119-f1uoro-estra-1, 3,5(10) -triene-3, 16u-diol 7a-TCyaomethy-11g-f1uoro-estra1,3,5(10) -triene-3,16ou-diol 71a-Eynom1Ih-11U9r-lutro-1, 3,5(10)-rin-3, 16ce-di16ud 7I-Proy111-f1uoro-estra1,3,5(10) -triene-3, 16c-dio1 7I9iPropy-11i-f1uoro-estra-1, 3,5(10) -triene-3, l6a-dil 79iPoyl19furoet 13,5 (10) -triene-3, l6a-dil 7-i-Proeny-11-f1uoroestra3,3,(10) -triene,l6a-dia 7i9-Methoxy-11i9-fluoro-estra-1,3,5 (10) -triene-3,16a-diol 7ig-Cyanmethy111I-fluoro-estra-1, 3 iS (10) -triene-3,l6a-diol 7u-Ethyl11,-f1uoro-estra-1, 3,5(10) -triene-3, l6ig-diol 7u-Propyl-1l19-f1uoro-estra-1, 3,5(10) -triene-3,1l6i-diol 7a-i-Propey-11-fuoroestra1,3,5(10) -triene-3, 16-dio 7o-i-Poeny11i-fluoroestra 3,5(10)-trne-3, 1-dio 7cu-.Mety-11I-fuoro-estra1, 3 iS(10) -triene-3,lG6-diol 7y-Mthomey-11i-f1Urr-estra, 35 (10) -triene-3, 1E-dio 7(~Yanhomethy-11-f1uoro-estrali, 3 iS(10) -triene-3,16i9-diol 7Z-CaEthy1-i9-fluoro-estra-1 ,(10 -tien-3, 161-diol-io 7i:9Proy-11i-fluoro-estra1,3,5 (10) -triene-3, 6i>-diol 7j9Propy-11fuor-estra1,3,5 (10) -triene-3,16i-dol 7Ig-i-Propfl-11ifluoroestra1,3,5(1) -triene-3,6Z-diol 79-iPeny-11-fluoro-estra-,3,5 (1-tre3, 16zio1 7Z-PMetoy-11-f1uoro-estra1, 3,5 (1)-triene-3, 161-diol 7i9Tiethy-1i?fl fUoestra, 3,5(1) -triene-3, 16-dio1 7i9-Cyaomethy-11i-fuoroestralI, 3 IS(10) -triene-3,161-diol 715Cyanmethy11-fuoro-estra 3 iS (10) -tee3,1Gc9-di 15ofMethy1-11i-fluoro-estra-1, 3,5 (10) -triene-3, i6u-dio 15a-proy1-11-fluoro-estra1,3,5 (10) -triene-3, 160-diol 15u-PA11y-11?-fluoro-estra-1 3,5 (10) -triene-3, i6a-dio 15-ly-1>flooet 1 3,5 (10) -triene-3 ,16-dio 15iiPoyl1: loo-sr- ,(10) -triene-3,16-diol 15aY-Methoxy-111Z-f1uoro-estra1, 3,5 (10) -triene-3, l6c-diol 15y-Thiomethyl11i-f1uoro-estrali, 3 iS(10) -triene-3,16a-diol 15yuMEthy-11-f1uoro-estra1, 3,5 (10) -triene-3, 6i-dio1 15cu-Propy1-11I9-fluoro-estral1, 3 iS (10) -triene-3,16i>-diol 15oe-iPropy-11-f1uoro-estral1, 3 iS (10) -triene-3,1613-diol 15a-i-Propeny-1ig-f1uoro-estra-1, 3,5 (10) -triene-3, 16I9-dio1 15ou-Methoxy-11I-f1uoro-estra-1,3,5 (10) -triene-3,lE6g-diol 15oa-Thiomethy1-1i-f1uoro-estra-1,3,5 (10) -triene-3,1619-diol 159-Methy1-11i9-fluoro-estra-1,3,5 (10) -triene-3,16-dio 15I9-Proy-11i-fluoro-estra-1, 3,5(10) -triene-3, 1Go-dio1 15i9-A11y1-11iZ-fluoro-estra-1,3,5 (10) -triene-3,16-dio 15I-i-Proy-11-f1uoro-estra-1, 3,5(10) -triene-3, 1 -diol 1519-i-Propy-11-fuoro-estra-1, 3,5(10) -triene-3, 1c-dio1 159i-toxey-11-fluro-estra-1,3,5 (10)-triene-3,-diol 159-Mthomty-11-fuoro-estra-1, 3,5(10) -triene-3, 6-diol 15I9-Timethy11-fuorestra-1, 3,5(10)-tee3, 16-diol 15i9-Propy1-11i9-fluoro-estra-1, 3,5(10) -triene-3, 16iZ-dio1 15I-A11y1-11i9-fluoro-estra-1, 3,5 (10) -triene-3, 16i9-dio1 1sI9-Propy-11-fluoro-estra-1, 3,5(10)-triene-3, 16-dio1 15I-i-Propey-11i-fuoro-estra-1, 3,5(10) -triene-3, 16-dio1 15I-Methoxy-11i9-f1uoro-estra-1, 3,5 (10) -triene-3, 161g-diol 15i9-Thiomethyl-11Z-f1uoro-estra-1, 3,5 (10) -triene-3, 161?-diol 14u, 15a~-Methylene-7cY-phefl-estra-1, 3,5 (10) -triene-3, 16ou diol 149, 159-Methylene-7a-phefl-estra-1, 3,5(10) -triene-3, 16cu diol 14g, 159-Methylene-7!-phefl-estra-1, 3,5 (10) ,8 (9) -tetraene 7o-Pheny1-estra-1,3,5(10),8(9)-tetraele-3,16c-diol, 7cuPheny1-estra-1,3,5(1O) ,6,8-pentaefle-3,16c-diol, li-ehx-7-hnlesr-,,(10) -trlene-3,16Y diol, 19-Fluoro-7a-phefylY-estral1, 3 ,S (10) -triene-3,16uy-diol, 7a-Phenyl-8a-estra1, 3,5 (10) -triene-3, l6a-diol 7ou-Phefl-estra-l, 3,5 (10) -triene-2 ,3, 16u-trio1 l7I9-Fuoro-7c-pheny-estra-1I 3 IS(10) -triene-3,16Y-diol, 18a-Homo-7au-pheylY-estra1, 3,5(10) -triene-3, i6c-dio1, l8a-Homo-7u-pheylY-estra-1,3,5(10) ,8(9)-tetraefle-3,16c-diol, 18a-Homo-14u,15 ehyee7-pey eta 3,5 (10) -triene l 8 a-Homo14,15methylene-7uphenyl-estra-1,3,5(10) ,8(9) tetraene-3,1l(a-diol, 1 8 a-Homo14,15methylene7uPheny-estra1,3,5(10) ,6,8 pentaene-3 , l6-diol, 14a, l5a-Methylefl-7apheyl-lestra-1,3,5 (10) -triene-3, 16i9 dial 149, 15 fg-Methylee7&-pheyl-lestra-1,3,5 (10) -triene-3, 1E9 dial 14 j9, 1 5g-Methylene-7cY-pheyl-estralI, 3 IS(10) ,8 (9) -tetraefle 7u-Pheny1-estra-1,3,5(10) ,8(9)-tetraee3,1E9-diol, 7u-Phenyl-estra-1,3,5(lO) ,8(14)-tetraefe-3,16E-diol, 7cy-Phenyl-estra-1,3,5(1O) ,6,8-pentaefle-3,16I-diol, 11 ig-Methoxy-7a-phefyly-estrali, 3 IS(10) -triene-3,16i9-diol, 11-Fur-7a-phefylYestra1, 3,5(10) -triene-3, 16i9-dial, 7a-Phenyl-8u-estra1, 3,5(10) -triene-3, 16iZ-diol 7 a-Phenyl-estra1,3,5(10Y-triene2,3,16u-triol 17i9-Fluoro-7Oa-phefylY-estra-1, 3 tS (10) -triene-3,1619-diol, 18a-Homo-7cu-pheyly-estra-1,3,5(10) -triene-3,1E19-diol, 18a-Homo-7o!-pheyly-estra1, 3,5(10) ,8 (9) -tetraene-3, 1Gi-diol, 18-oo1a1umtyen upey-sr-,,(10) -triene K,169-dial, 1 8 a-Homo-14,15methyle7phenyl-estra-1,3,5(10),86,8 :etaene-3, 16I9-dio1, 15cYHEthy14-7t-mtlne7-phenyl-estra-lii (0 tre3,GY-di6,l oe5ta Proy197dolhfYeta,, 10 tin-,6Yd~ 15u-MAtlyl-7uY-pheflestra-1, 3,5 (10) -triene-3, l6a-dil i5auiEPryl-7a-phellestra, 3 i (10) -triene-3,16-dil l5a-iPral-peflyly7-efltlat, 3,5 10) -tene-3, a-dil 15u-AlMhy-7-pheylestra1, 3,5 (10) -triene-3, l-dil 15a-Tiameyl7apheylestra1, 3 , (10) -triene-3,16-dil 15a-iMeophy-7a-pheylestra 3,5 (1-trne-3, 1Ei-dio 15uMethoy-7-pheny-estra- 3,5 (10) -triene-3, i16-dil 15a-TPrapy-7-pheylestra-1,35(1) -tre3,16fu-do 15u-MAtl-7-phel-estra-, 3,5 (10)-triene-3,169i-dial l5auiEPy-7-phelestra, 3,5 (10) -triene-3,6E-d 1 15u-iPryay-7any-heflY1r 3 iS 10) -iene-3,1Ef--dl 15u-Methopyl-7a-phel-estra, 3,5 (10) -triene-3, 1i-dil 15u-Thiamethy1-7a-phefylestral1, 3 ,S (10) -triene-3,1E19-diol 15IZ-Methy1-7a-pheflyl-estra-1, 3 iS(10) -triene-3,16a-diol 1519-Ethy1-7a-phefl-estra-1, 3 iS (10) -triene-3,16a-dial 1519-Propy1-7Y-phefl-estra-1, 3,5(10) -triene-3, l6a-dial 151-Allyl-7u-pheflyl-estra-1,3,5 (10) -triene-3,l6a-diol 1519-i-Prpy1-7a-phefl-estra-1, 3,5 (10)-triene-3, l6a-dial 151-i-Prapenyl-7a-phelyl-estra-1, 3,5 (10) -triene-3, l6a-diol 15i9-Methoxy.-7u-phefl-estra-1, 3,5(10) -triene-3, l6a-dial 1519-Thiamethyl-7a-phefl-estra-1, 3,5 (10) -triene-3, 16a-dial 15i9-Methy1-7a-phefl-estra-1,3,5 (10) -triene-3,1EI9-dia1 15IZ-Ethy1-7a-phenyl-estra-1, 3,5 (10) -triene-3, 161-diol 15i9-Prapyl-7ay-pheflyl-estra-l,3,5 (10) -triene-3,1Gi9-dial 1519-Allyl-7u-phenyl-estra-1, 3,5 (10) -triene-3,1l6i-dial 15I-i-Prapy1-7a-pheflyl-estra-1, 3,5 (10) -triene-3, 16i9-dio1 15i9-i-Propeny1-7a-pheny1-estra-1, 3,5 (10) -triene-3, l6I-dia1 15f9-Methaxy-7a-pheny1-estra-1,3,5 (10) -triene-3,161g-dial 151!-Thimethyl-7a-pheflyl-estra-1, 3,5 (10) -triene-3, 161g-dial 15a-Methy1-11I9-fluaro-7a-phefl-estra-1,3,S (10) -triene 3, l6a-dial 15a-Ethy1-11i9-f1uoro-7a-pheyly-estra-1,3,S (10) -triene-3,16a dial 15a-Propy1-11I9-fluara-7a-pheny1-estra-1, 3,5 (10) -triene 3' l6a-diol 15a-Al1yl11-fluora-7a-phel-estra-1, 3,5 (10) -triene-3, l6a dial i5a-i-Prapy1-11I9-fluara-7a-phefl-estra-1,3,S (10) -triene 3, 16a-dial 15a-i-Prapenyl-111g-f1uoro-7a-pheylY-estra-1, 3,5(10) -triene 3, l6a-dial 15a-Methoxy-11-fluoro-7a-phenyl-estra-1, 3,5(10) -triene 3,16a-diol 15a-Thiomethyl-118-fluoro-7a-phenyl-estra-1,3,5(10 -triene 3,16a-diol 15a-Methyl-118-fluoro-7a-phenyl-estra-1,3,5(10)-triene 3,168-diol 15a-Ethyl-11-fluoro-7a-phenyl-estra-1, 3,5(10) -triene-3,16f diol 15a-Propyl-11-fluoro-7a-phenyl-estra-1, 3,5(10) -triene 3, 168-diol 15a-Allyl-11-fluoro-7a-phenyl-estra-1, 3,5(10) -triene-3,168 diol 15a-i-Propyl-118-fluoro-7a-phenyl-estra-1,3,5 (10) -triene 3 ,168-diol 15a-i-Propenyl-11-fluoro-7a-phenyl-estra-1, 3,5(10) -triene 3,168-diol 15a-Methoxy-118-fluoro-7a-phenyl-estra-1,3, (10) -triene 3, 168-diol 15a-Thiomethyl-118-fluoro-7a-phenyl-estra-1,3, (10) -triene 3 ,168-diol 158-Methyl-11-fluoro-7a-phenyl-estra-1, 3,5 (10) -triene 3, 16a-diol 153-Ethyl-118-fluoro-7a-phenyl-estra-1,3,5 (10) -triene-3, 16a diol 158-Propyl-111-fluoro-7a-phenyl-estra-1,3,5(10) -triene 3,16a-diol 159-lly-llZ-floro7u-heny-esra-,,(10) -triene-3,16u iol 15--rpl19-loo7-hny sr-,,(10) -triene 16a- dial 15s9-i-PropenyJ-11-l-r7phenyl-estra-1, 3 IS(10) -triene 16cy-diol l1i9-Methoxy-11f1uoro-7uphenyl-estra-1,3,5 (10) -triene l16a-dial l1i9-Thimethy-lgfluor-7u-phenyl-estralI, 3 IS(10) -triene 3,l6a-dial lSI>-Methy111fluoro-7uphenyl-estralI 3,5 (10) -triene 15-ty-i-loo7 pey-sr-,,(10) -triene-3,16I diol 15-rpl19furo7-hnleta13,5 (10) -triene 15.Alllgfuro7-hnleta13,5 (10) -triene-3, l6iz diol 15--rpllgfuro7 hnleta13,5(10) -triene lS9-iMethaeyl-ligf1uoro-7uphenylestra- 3 (10) -triene 3, lEI-dial lS9-Thiamethy111-f1uoro-7aphenyl-estralI 3,5(10) -triene iii9- E2- (3-Methyithien) -yl) -estra-1, 3,5(10) -triene-3, l6a-dial 11Z- [2- (3-Methyithien) -yl) -estra-1, 3,5(10) -triene-3, 1613-diol 13a-Estra-1, 3,5(10) -triene-3, 16a-diol 13cy-Estra-1, 3,5(10) -triene-3, 16i9-dio1 14i9-Estra-1, 3,5(10) -triene-3, l6a-diol 14IZ-Estra-1, 3,5(10) -triene-3, 161g-diol 11I9-Methylestra-1, 3,5 (10) -triene-3, l6a-diol 111?-Methylestra-1, 3,5 (10) -triene-3, 16i9-dio1 11i9-Methyl-18a-homfoestra-1, 3,5 (10) -triene-3, 16a-diol 11iZ-Methy1-18a-homloestra-1, 3,5 (10) -triene-3, 1619-dio1 llig-Ethylestra-1, 3,5(10) -triene-3, l6a-dial 11iZ-Ethylestra-1, 3,5(10) -triene-3, 16E-diol 11i-Vinyl1sta-1,3,5 (-1,510) -triene-3,l6a-dio 11Ig-Vinylestra-1,3,5 (10) -triene-3,161g-diol 1119-Viny1-1a-s mrra1,(0-,3,5 (10)-ren-,9-di al 11i9-Viny1-18a-homoestra-1, 3,5 (10) -triene-3, 1E1-dio1 ll1-Etinylestromsra1, 3,5(10)-rin-3, len-dial-io 11ig-Ethiny1-18ra-hm,5(tra-, 3,5 ( 1-renla-dil 111g-Ethiny1-18ra-hm,5(tra-, 3,5 ( 1-i-,ol~ do 11ZMEthiy18ta-1,3,5(1tr13f5l03,1Eaien-,6udo 9-MEthiyl-tra-1,3,5 (10) (10-triene-3,19 9a-Methy1-18ra-h1m3etr1, 3,5 (-10)-rin-3 u -dil 9a-Methy1-18a-homfoestra-1, 3,5 (10) -triene-3, l6i-diol 7a-Methyl-18a-homolestra-1, 3 1 S (10) -triene-3,l6a-diol 7a-Methyl-18a-homoestral1, 3 1 S (10) -triene-3,16i9-diol 7cy-Ethyl-18a-homoestra-1, 3,5 (10) -triene-3, i6u-diol 7cy-Ethy18a-homoestra-1,3,5(lO) -triene-3,16g-diol 7o 8 11ig-Dimethylestra-1,3,S (10) -triene-3,l1eY-diol 7u, 11i9-Dimethylestra-1, 3,5(10) -triene-3, 16I!-dio1 7ca,ll~gDimethy1-18a-homoestra1, 315 (10) -triene-3, l6a-diol 7a, 11Ig-Dimethy1-18a-homoestra-l, 3,5 (10) -triene-3, 16a-diol

1619-Ethinyl-18a-homoestra-1i 3 iS (10) -triene-3,16a-diol l6a-Ethiny-18a-homoestra-1,3,5(l0)-triene-3,16I-diol 7a-Methyl-16i9-ethinylestra-li 3,5 (10)-triene-3, l6a-diol 7a-Methyl-16a-ethilylestra-li 3 , (10) -triene-3,161Z-diol 7a-Methyl-16I9-ethinyl18ahomoestral1, 3 IS(10) -triene-3,l6u diol 7a-Methyl-16a-ethifyl-18ahomoestral1, 3 IS(10) -triene-3,1f9 dil 11ig.Methy161EI-ethflylestra1, 3 iS (10) -triene-3,l6a-dlo1 11I>-Methyl-16a-ethiflylestrali 3,5 (10) -triene-3, i6i-dio1 11-ehl19-tiy-8-hmeta13,5 (10) -triene-3, l6a diol ll9-Methy1-16a-ethifyl-18a-homoestralI 3,5 (10) -triene-3, 1E9 diol. 25. Compounds according to claim 24, namely 7a-Fluoro-estra-1, 3 , 5(10) -triene-3, l6a-diol, 7a-Methyl-estra-1, 3,5 (10) -triene-3, 1Ei-dio1 7a-Methyl-estra-1,3,5(10)-triee3,16a-diol 18a-Homo-estra-l, 3,5(10) -triene-3,6lE-dial 7a-Phenyl-estra-1, 3,5(10) -triene-3, i61-diol 7i9-Phenyl-estra-1, 3,5(10) -triene-3, 1EZ-dio1 78-Phenyl-estra-1, 3,5(10) -triene-3, 16a-diol 7a-Ethyl-estra-1,3,5(10)-triene-3,168-diol 78-Ethyl-estra-1, 3,5(10) -triene-3, 16a-diol 78>-Ethyl-estra-1, 3,5 (10) -triene-3, 168-diol. 26. Use of the 3,16-dihydroxyestra-1,3,5(10)-triene derivatives of general formula I' Ri w13 R h 2 :R R ..- --. OH HO R RR (W) in which radicals R1 to R independently of one another, have the following meanings: R1 means a halogen atom, a hydroxyl group, a methyl group, a trifluoromethyl group, a methoxy group, an ethoxy group or a hydrogen atom; R2 means a halogen atom, a hydroxyl group, a straight chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or a hydrogen atom; R4 means a halogen atom, a straight-chain or branched chain, saturated or unsaturated alkyl group with up to 10 carbon atoms, a trifluoromethyl or pentafluoroethyl group, a straight-chain or branched-chain, saturated or .L4 £j unsaturated alkoxy group with up to 6 carbon atoms or a hydrogen atom; R7 means a halogen atom in a- or S-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or I-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms, an optionally substituted aryl or heteroaryl radical or a hydrogen atom; R 8 means a hydrogen atom in a- or B-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 1-position or a cyano group in a- or B-position; R9 means a hydrogen atom in a- or 9-position, a methyl, ethyl, trifluoromethyl or pentafluoroethyl group in a or B-position; R" means a nitrooxy group in a- or 1-position, a hydroxyl or mercapto group in a- or S-position, a halogen atom in a- or 9-position, a chloromethyl group in a- or L position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms, an optionally substituted aryl or heteroaryl radical or a hydrogen atom; R13 means a methyl, ethyl, trifluoromethyl or pentafluoroethyl group in a- or S-position; and either R14 means a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position or a hydrogen atom in a- or S-position and R 15 means a halogen atom in a- or S-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR 1 5 ' (R1 5 ' = hydrogen atom, methyl, ethyl, propyl, i-propyl) or a hydrogen atom or R 14 and R 15 together mean a 14a,15a-methylene or 148,1589 methylene group that is optionally substituted with one or two halogen atoms; R 16 means a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position, a trifluoromethyl or pentafluoroethyl group, a cyanomethyl group or a hydrogen atom in a- or 9-position; R 17 means a halogen atom in a- or S-position, a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position, a hydrogen atom or a hydroxyl group and the dotted lines ------ in rings B, C and D optionally mean one or more double bonds, and the wavy lines mean the arrangement of the respective substituent in a- or Z position, -or the production of a pharmaceutical agent for treatment of strogen-deficiency-induced diseases and conditions in women and in men. 27. Use according to claim 26 for the treatment of peri .nd post-menopausal symptoms,. 28. Use according to claim 26 for treatment of peri- and post-male-menopausal symptoms. 29. Use according to claim 27 for prevention and treatment of hot flashes, sleep disturbances, irritability, mood swings, incontinence, vaginal atrophy, and hormone-deficiency-induced emotional diseases. 30. Use according to claim 29 for prevention and treatment of diseases in the urogenital tract. 31. Use according to claim 26 for prevention and therapy of gastrointestinal diseases. 32. Use according to claim 31 for prevention and therapy of ulcers and hemorrhagic diatheses in the gastrointestinal tract. 33. Use according to claim 32 for prevention and therapy of leoplasias. 34. Use according to claim 26 for in-vitro treatment of iale infertility. 35. Use according to claim 26 for in-vivo treatment of male [nfertility. 36. Use according to claim 26 for in-vitro treatment of emale infertility. 37. Use according to claim 26 for in-vivo treatment of -emale infertility. 38. Use according to claim 26 for hormone replacement .herapy (HRT). 39. Use according to claim 26 for the therapy of hormone leficiency-induced symptoms in the case of surgical, medicinal or >varian dysfunction that is caused in some other way. 40. Use according to claim 26 for prophylaxis and therapy Df a hormone-deficiency-induced bone mass loss. 41. Use according to claim 40 for prophylaxis and therapy Df osteoporosis. 42. Use according to claim 26 for prevention and therapy of cardiovascular diseases. 43. Use according to claim 26 for prevention and treatment of vascular diseases. 44. Use according to claim 43 for prevention and treatment of arteriosclerosis. 45. Use according to claim 43 for prevention and treatment >f neointimal hyperplasias. 46. Use according to claim 26 for prevention and treatment f hormone-deficiency-induced neurodegenerative diseases. 47. Use according to claim 26 for prevention and treatment >f Alzheimer's disease and hormone-deficiency-induced impairment >f memory and learning capacity. 48. Use according to claim 26 for treatment of inflammatory diseases and diseases of the immune system. 49. Use according to claim 26 for prevention and treatment >f benign prostate hyperplasia (BPH). 50. Use of the structural part of formula II -O as a component of the total structure of compounds that have a dissociation in favor of their estrogenic action on bone rather than the uterus. 51. Use of the structural part of general formula II' iccording to claim 50 R R R5 .-- O R RR in which radicals Rl' to R 17 ', independently of one another, have the following meanings: R1' means a halogen atom, a hydroxyl group, a methyl group, a trifluoromethyl group, a methoxy group, an ethoxy group or a hydrogen atom; R 2' means a halogen atom, a hydroxyl group, a straight chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or a hydrogen atom; R 4' means a halogen atom, a straight-chain or branched chain, saturated or unsaturated alkyl group with up to 10 carbon atoms, a trifluoromethyl or pentafluoroethyl group, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms or a hydrogen atom; RP' means a halogen atom in a- or S-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy group with up to 6 carbon atoms, an optionally substituted aryl or heteroaryl radical or a hydrogen atom; R8' means a hydrogen atom in a- or B-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in u- or B-position or a cyano group in a- or B-position; R 9' means a hydrogen atom in a- or B-position, a methyl, ethyl, trifluoromethyl or pentafluoroethyl group in a or B-position; R"l' means a nitrooxy group in u- or S-position, a hydroxyl or mercapto group in a- or B-position, a halogen atom in a- or B-position, a chloromethyl group in a- or B position,- a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or B-position, a straight-chain or branched-chain, saturated or unsaturated alkoxy or alkylthio group with up to 6 carbon atoms, an optionally substituted aryl or heteroaryl radical or a hydrogen atom; R 13 ' means a methyl, ethyl, trifluoromethyl or pentafluoroethyl group in a- or 9-position; and either R1 4 ' means a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position or a hydrogen atom in a- or S-position and R 15 ' means a halogen atom in a- or 9-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or 9-position that can be interrupted by one or more oxygen atoms, sulfur atoms, sulfoxide or sulfone groups or imino groups = NR 15 ' (R 15 ' = hydrogen atom, methyl, ethyl, propyl, i-propyl) or a hydrogen atom or R 14 ' and R 15 ' together mean a 14a,15a-methylene group or a 148,158-methylene group that is optionally substituted with one or two halogen atoms; R16 means a straight-chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or f9-position, a trifluoromethyl or pentafluoroethyl group, a cyanomethyl group or a hydrogen atom in a- or 9-position; R 17 ' means a halogen atom in a- or S-position, a straight chain or branched-chain, saturated or unsaturated, optionally partially or completely fluorinated alkyl group with up to 10 carbon atoms in a- or S-position, a hydrogen atom or a hydroxyl group, and the dotted lines ---- in rings B, C and D optionally mean one or more double bonds, and the wavy lines mean the arrangement of the respective substituent in a- or S-position. 52. Pharmaceutical compositions that contain at least one compound according to one of claims 1 to 25 as well as a pharmaceutically compatible vehicle.