AU2006261049A1

AU2006261049A1 - Benzofuranone derivatives as nonsteroidal progesterone receptor modulators

Info

Publication number: AU2006261049A1
Application number: AU2006261049A
Authority: AU
Inventors: Ulrich Bothe; Ulrike Fuhrmann; Carsten Moeller; Norbert Schmees; Anja Schmidt; Wolfgang Schwede
Original assignee: Bayer Schering Pharma AG
Current assignee: Bayer Pharma AG
Priority date: 2005-06-24
Filing date: 2006-06-22
Publication date: 2006-12-28
Also published as: EP1899315A1; GT200600272A; DE102005030294A1; BRPI0612305A2; PE20070170A1; DOP2006000150A; ECSP078043A; NO20080441L; AR057409A1; UY29626A1; JP2008543911A; MX2008000070A; KR20080018275A; TW200738665A; ZA200800689B; IL188022A0; CN101248056A; WO2006136462A1; CA2611900A1; CR9595A

Description

WO 2006/136462 PCT/EP2006/006532 BENZOFURANONE DERIVATIVES AS NONSTEROIDAL PROGESTERONE RECEPTOR MODULATORS This invention relates to nonsteroidal progesterone receptor modulators, a process for their production, the use of progesterone receptor modulators for the production of pharmaceutical agents as well as pharmaceutical compositions that contain these compounds. The steroid hormone progesterone regulates the reproductive process in the female organism in a decisive way. During the cycle and in pregnancy, progesterone is secreted in large amounts from the ovary or the placenta. By interaction with estrogens, progesterone produces cyclic changes of the uterine mucous membrane (endometrium) in the menstrual cycle. Under the influence of elevated progesterone levels after ovulation, the uterine mucous membrane is converted into a state that allows the nidation of an embryo (blastocyte). In pregnancy, progesterone controls the relaxation of the myometrium and retains the function of the decidual tissue. In addition, it is known that progesterone inhibits the endometrial proliferation by the suppression of the estrogen-mediated mitosis in the uterus tissue (K. Chwalisz, R. M. Brenner, U. Fuhrmann, H. Hess-Stumpp, W. Elger, Steroids 65, 2000, 741-751). An important role of the progesterone and the progesterone receptors is also known in pathophysiological processes. Progesterone receptors are detected in foci of endometriosis, but also in tumors of the uterus, the breast and the CNS. In addition, it is known that uterus leiomyomas grow in a progesterone-dependent manner. The actions of progesterone in the tissues of genital organs and in other tissues are carried out by interactions with progesterone receptors, which are responsible for the cellular effects.

WO 2006/136462 PCT/EP2006/006532 2 Progesterone receptor modulators are either pure agonists or partially or completely inhibit the action of progesterone. Consequently, substances are defined as pure agonists, partial agonists (SPRMS) and pure antagonists. According to the ability of the progesterone receptor modulators to influence the action of the progesterone receptor, these compounds have a considerable potential as therapeutic agents for gynecological and oncological indications as well as for obstetrics and birth control. Pure progesterone receptor antagonists completely inhibit the action of progesterone in the progesterone receptor. They have antiovulatory properties as well as the ability to inhibit estrogen effects in the endometrium up to full atrophy. They are therefore especially suitable for intervening in the female reproductive process, e.g., in post-ovulation, to prevent nidation; in pregnancy, to increase the reactivity of the uterus to prostaglandins or oxytocin or to ensure the opening and softening ("maturation") of the cervix as well as to make the myometrium highly prepared for labor. In foci of endometriosis or in tumor tissue, which are (is) equipped with progesterone receptors, an advantageous influence of the disease process is expected after application of pure progesterone receptor antagonists. Special advantages for influencing pathologic conditions, such as endometriosis or uterus leiomyomas, could then be given if in addition an inhibition of the ovulation can be achieved by the progesterone receptor antagonists. When ovulation is inhibited, a portion of the ovarian hormone production and thus the stimulative effect that is due to this portion are also due to the pathologically altered tissue. A large number of analogs with varying degrees of progesterone receptor antagonistic activity followed the first described progesterone receptor antagonist RU 486 (also mifepristone). While RU 486, in addition to the progesterone receptor- WO 2006/136462 PCT/EP2006/006532 3 antagonistic action, also shows an antiglucocorticoidal action, compounds synthesized later are distinguished primarily by a more selective action than progesterone receptor antagonists. From the literature, in addition to steroidal compounds such as onapristone or lilopristone, which are distinguished from progesterone-receptor-antagonistic action to antiglucorticoidal action relative to RU 486 by a better dissociation of action, various nonsteroidal structures, whose antagonistic action on the progesterone receptor is examined, are also known [see, e.g., S. A. Leonhardt and D. P. Edwards, Exp. Biol. Med. 227: 969-980 (2002) and R. Winneker, A. Fensome, J. E. Wrobel, Z. Zhang, P. Zhang, Seminars in Reproductive Medicine, Volume 23: 46-57 (2005)]. Previously known compounds, however, have only moderately antagonistic activity compared to the known steroidal structures. The most effective nonsteroidal compounds are described as having in vitro activities of 10% of the activity of RU 486. The antiglucocorticoidal activity is disadvantageous for a therapeutic application in which the inhibition of the progesterone receptors is a primary focus of therapy. An antiglucocorticoidal activity causes undesirable side effects in the case of therapeutically necessary dosages. This can prevent the application of a therapeutically useful dose or lead to termination of the treatment. The partial or complete reduction of the antiglucocorticoidal properties is therefore an important requirement for the therapy with progesterone receptor antagonists, in particular for those indications that require a treatment lasting weeks or months. In contrast to the pure antagonists, progesterone receptor partial agonists (SPRMs) show a residual agonistic property, which can be strongly pronounced to different degrees. This leads to the fact that these substances show potential agonistic WO 2006/136462 PCT/EP2006/006532 4 actions of the progesterone receptor in specific organ systems (D. DeManno, W. Elger, R. Garg, R. Lee, B. Schneider, H. Hess-Stumpp, G. Schuber, K. Chwalisz, Steroids 68, 2003, 1019-1032). Such an organ-specific and dissociated action can be of therapeutic use for the indications described. It is therefore the object of this invention to make available additional nonsteroidal progesterone receptor modulators. These compounds are to have a reduced antiglucocorticoidal action and are therefore suitable for the therapy and prophylaxis of gynecological diseases such as endometriosis, leiomyomas of the uterus, dysfunctional bleeding and dysmenorrhea. In addition, the compounds according to the invention are to be suitable for the therapy and prophylaxis of hormone-dependent tumors, for example breast, endometrial, ovarian and prostate cancers. In addition, the compounds are to be suitable for use in female birth control and for female hormone replacement therapy. The object is achieved according to this invention by the preparation of non steroidal compounds of general formula I R 2H H

R

4 a R 4 b Ra | 0 0 (I), in which R' and R 2 , independently of one another, mean a hydrogen atom, a straight or nonstraight, branched or unbranched CI-C 5 -alkyl group, also together with the C atom of the chain forming a ring with a total of 3-7 members, WO 2006/136462 PCT/EP2006/006532 5

R

3 means a radical C=C-Ra, whereby Ra means a hydrogen or a Ci-Cs-alkyl, C 2

-C

8 -alkenyl, C 2

-C

8 -alkinyl,

C

3 -CIo-cycloalkyl, or heterocycloalkyl that optionally is substituted in one or more places, in the same way or differently, with K, or an aryl or heteroaryl that optionally is substituted in one or more places, in the same way or differently, with L, K is a cyano, halogen, hydroxy, nitro, -C(O)Rb, CO 2 Rb, -O-Rb, -S-Rb, SO 2 NRCRd, -C(O)-NRcRd, -OC(O)-NRcRd, or -C=NORb -NRcRd or a C 3 -Cio-cycloalkyl that optionally is substituted in one or more places, in the same way or differently, with M, heterocycloalkyl, or aryl or heteroaryl that optionally is substituted in one or more places with L, L means CI-Cs-alkyl, C 2

-C

8 -alkenyl, C 2

-C

8 -alkinyl, CI-C 6 perfluoroalkyl, Ci-C 6 -perfluoroalkoxy, C 1

-C

6 -alkoxy-Ci

C

6 -alkoxy, (CH 2 )p-C 3 -Cio-cycloalkyl, (CH 2 )p heterocycloalkyl, (CH 2 )pCN, (CH 2 )pHal, (CH 2 )pNO 2 , bb

(CH

2 )p-C 6 -C1 2 -aryl, (CH 2 )p-heteroaryl, -(CH 2 )pPO 3 (R )2,

-(CH

2 )pNRcRd, -(CH 2 )pNReCORb,

-(CH

2 )pNReCSRb, -(CH 2 )pNReS(O)R,

-(CH

2 )pNRCS(O) 2 R , -(CH 2 )pNReCONRRd

-(CH

2 )pNReCOORb, -(CH 2 )pNRCC(NH)NRCRd,

-(CH

2 )pNReCSNRcRd, -(CH 2 )pNReS(O)NRRd,

-(CH

2 )pNR*S(O) 2 NRcRd, -(CH 2 )pCORb, b

-(CH

2 )pCSRb, -(CH 2 )pS(O)R,

-(CH

2 )pS(O)(NH)R , -(CH 2 )pS(O) 2 Rb, WO 2006/136462 PCT/EP2006/006532 6

-(CH

2 )pS(O) 2 NR R , -(CH 2 )pSO 2 ORb,

-(CH

2 )pCO 2 R', -(CH 2 )pCONRcR',

-(CH

2 )pCSNRcRd, -(CH 2 )pORb, -(CH 2 )pSRb,

-(CH

2 )pCRb(OH)-Re, -(CH 2 )p-C=NOR',

-O-(CH

2 )n-O-, -O-(CH 2 )n-CH 2 -, -O-CH=CH or -(CH 2 )n+ 2 -, whereby n = 1 or 2, and the terminal oxygen atoms and/or carbon atoms are linked to directly adjacent ring-carbon atoms, M means Ci-C 6 -alkyl or a group -CORb, CO 2 Rb, -O-Rb, or -NRcRd, whereby Rb means a hydrogen or a Ci-C 6 -alkyl, C 2

-C

8 -alkenyl,

C

2

-C

8 -alkinyl, C 3 -Cio-cycloalkyl, C 6

-C

12 -aryl or Ci

C

3 -perfluoroalkyl, and R' and Rd, independently of one another, mean a hydrogen,

CI-C

6 -alkyl, C 2

-C

8 -alkenyl, C 2

-C

8 -alkinyl, C 3

-CIO

cycloalkyl, C 6

-C

12 -aryl, C(O)R or a hydroxy group, whereby if R' is a hydroxy group, Rd can be only one hydrogen, a

CI-C

6 -alkyl, C 2 -Cs-alkenyl, C 2 -Cs-alkinyl, C 3

-CIO

cycloalkyl or C 6

-C]

2 -aryl and vice versa, and Re means a hydrogen, CI-C 6 -alkyl, C 2

-C

8 -alkenyl,

C

2

-C

8 -alkinyl, C 3 -CIo-cycloalkyl or C6-C 1 2 -aryl, and p can be a number from 0- 6, or WO 2006/136462 PCT/EP2006/006532 7 R3 is a radical C = C-R'Rh, whereby R9 and Rh, independently of one another, are a hydrogen or a C I-C 8 -alkyl,

C

2 -Cs-alkenyl or C 2 -Cs-alkinyl that optionally is substituted in one or more places, in the same way or differently, with X, in which X is a cyano, halogen, hydroxy, nitro, -C(O)Rb, CO 2 Rb, -O-Rb, -C(O)-NRcRd, -NRcRd with the meanings already further mentioned above for Rb, RC and Rd, and

R

4 a and R 4 b, independently of one another, mean a hydrogen atom, a C 1

-C

4 -alkyl, a C 2

-C

4 -alkenyl or together with the ring-carbon atom forming a 3- to 6 membered ring, A means a monocyclic or bicyclic, carbocyclic or heterocyclic aromatic ring, which optionally can be substituted in one or more places with CI Cs-alkyl, C 2

-C

8 -alkenyl, C 2 -Cs-alkinyl, Ci-C 6 -perfluoroalkyl, Ci-C 6 perfluoroalkoxy, CI-C 6 -alkoxy-Ci-C 6 -alkyl, Ci-C 6 -alkoxy-Ci-C 6 -alkoxy,

(CH

2 )p-C 3 -Cjo-cycloalkyl, (CH 2 )p-heterocycloalkyl, (CH 2 )pCN,

(CH

2 )pHal, (CH 2 )pNO 2 , (CH 2 )p-C 6

-CI

2 -aryl, (CH 2 )p-heteroaryl, b bd

-(CH

2 )pPO 3 (R )2, -(CH 2 )pNRcR , -(CH 2 )pNReCOR, -(CH 2 )pNReCSR,

-(CH

2 )pNReS(O)Rb, -(CH 2 )pNReS(O) 2 R , -(CH 2 )pNReCONRcR',

-(CH

2 )pNReCOOR', -(CH 2 )pNReC(NH)NRcRd, -(CH 2 )pNReCSNRcRd,

-(CH

2 )pNReS(O)NRcR d, -(CH 2 )pNReS(O) 2 NRcRd, -(CH 2 )pCORb, bb b

-(CH

2 )pCSRb, -(CH 2 )p S(O)R, -(CH 2 )pS(O)(NH)R , -(CH2)pS(O)2R b b cd

-(CH

2 )pS(O) 2 NRcRd, -(CH 2 )pSO 2 OR , -(CH 2 )pCO 2 R , -(CH 2 )pCONRcR, cd b b d

-(CH

2 )pCSNRcR , -(CH 2 )pOR , -(CH 2 )pSR', -(CH 2 )pCR(OH)-R ,

-(CH

2 )p-C=NORb, -O-(CH 2 )n-O-, -O-(CH 2 )n-CH 2 -, -O-CH=CH- or WO 2006/136462 PCT/EP2006/006532 8

-(CH

2

),+

2 -, whereby n = 1 or 2, and the terminal oxygen atoms and/or carbon atoms are linked to directly adjacent ring-carbon atoms, or A means a radical -CO 2 R', C(O)NRcRd, COR , or 5 6 7 A means an alkenyl group -CR = CR R , whereby 5 6 7 R , R and R are the same or different and, independently of one another, mean hydrogen atoms, halogen atoms, aryl radicals or an unsubstituted or partially or completely fluorinated C,-C-alkyl group, or 5 5 A means an alkinyl group -C=-CR , with the meaning cited above for R , and B means a carbonyl group or a CH 2 group as well as their pharmaceutically acceptable salts. The compounds of general formula I according to the invention can be present as different stereoisomers because of the presence of asymmetry centers. Both the racemates and the separately present stereoisomers are part of the subject of this invention. In addition, this invention comprises the new compounds as pharmaceutical active ingredients, their production, their therapeutic application and pharmaceutical dispensing forms that contain the new substances. The compounds of general formula (I) according to the invention or their pharmaceutically acceptable salts can be used for the production of a pharmaceutical agent, especially for treatment and prophylaxis of gynecological diseases, such as endometriosis, leiomyomas of the uterus, dysfunctional bleeding and dysmenorrhea. In addition, the compounds according to the invention can be used for the treatment and WO 2006/136462 PCT/EP2006/006532 9 prophylaxis of hormone-dependent tumors, such as, for example, for breast, prostate and endometrial cancers. The compounds of general formula (I) according to the invention or their pharmaceutically acceptable salts are suitable for use for female birth control or for female hormone replacement therapy. A process for the production of the compounds of general formula (I), moreover, is also a subject of this invention. Substituent R 3 is introduced to a keto group by selective addition reaction of organometallic compounds such as lithium alkinylene or magnesium haloalkinylene. This results, either directly or after implementing additional modifications, in the compounds of general formula (I) according to the invention.

RIR

9 H

R

3 -Li oder R 3 -MgHal R1 2 H R4a A~ ~~~~ BB______ ~ 00 [or] The production of the compounds according to the invention is carried out by selective addition of organometallic compounds to ketoamides, which were described in, e.g., laid-open specifications WO 200375915 and WO 9854159. The organometallic compounds can be, for example, lithium alkinyl compounds or magnesium haloalkinyl compounds. The latter are produced by, e.g., reaction of the corresponding alkines with butyllithium or Grignard compounds. Analogously to this, the corresponding WO 2006/136462 PCT/EP2006/006532 10 organometallic alkenyl compounds can also be produced. The reactivity of the keto group in comparison to amidocarbonyl or to phthalide is in this case significantly higher, such that with suitable selection of the reaction conditions, a selective addition is achieved. As an alternative, the alkinyl or alkenyl radicals that are introduced as R 3 can also be further modified later. For these modifications, reactions that have become known to one skilled in the art, such as oxidation, reduction, substitution, alkylation, or palladium-catalyzed reaction, are suitable. Optionally present protective groups are cleaved off at a suitable time. The nonsteroidal compounds of general formula I according to the invention have a strongly antagonistic or strongly partially agonistic action on the progesterone receptor. They exhibit a strong dissociation of action with respect to their bonding strength on the progesterone receptor and on the glucocorticoid receptor. While known progesterone receptor antagonists, such as Mifepristone (RU 486), in addition to the desired high binding affinity for the progesterone receptor likewise show a high affinity for the glucocorticoid receptor, the compounds according to the invention are distinguished by a very low glutocorticoid receptor bond with simultaneously present high progesterone receptor affinity. The substituents of the compounds of general formula I according to the invention that are defined as groups can have the meanings below in each case:

CI-C

5 -, CI-C 6 - or CI-C 8 -alkyl groups are defined as straight or nonstraight, branched or unbranched alkyl radicals. In this case, for example, this is a methyl, ethyl, n-propyl, iso-propyl, n-, iso-, tert-butyl, an n-pentyl, 2,2-dimethylpropyl, 3-methylbutyl, hexyl, heptyl or octyl group. In terms of Ra, in this case, the methyl, ethyl, n-propyl or n-butyl group as well as an n-pentyl group are preferred.

WO 2006/136462 PCT/EP2006/006532 11 In terms of R' and R2, methyl or ethyl is preferred. According to the invention, a hydrogen is preferred for R4a and R4b. Alkenyl is defined as straight or nonstraight, branched or unbranched alkenyl radicals. In terms of the invention, a C 2

-C

8 -alkenyl group is defined, for example, as follows: vinyl, allyl, 3-buten-1-yl- or 2,3-dimethyl-2-propenyl. If aromatic compound A is substituted with a C 2

-C

8 -alkenyl radical, this is preferably a vinyl group. Alkinyl is defined as straight or nonstraight, branched or unbranched alkinyl radicals. For example, an ethinyl, propinyl, butinyl, pentinyl, hexinyl or octinyl group, but preferably an ethinyl or propinyl group, is to stand for a C 2

-C

8 -alkinyl radical. For C 3 -Cio-cycloalkyl, for example, cyclopropane, cyclobutane, cyclopentane and cyclohexane can be mentioned. Cyclopropyl, cyclopentyl and cyclohexyl are preferred. In terms of R a, K or L, heterocycloalkyl is defined as 3- to 8-membered heterocycloalkyl radicals. Examples of heterocycloalkyl are morpholine, tetrahydrofuran, pyran, piperazine, piperidine, pyrrolidine, oxirane, oxetane, aziridine, dioxolane and dioxane. In this case, the position of the heteroatom in relation to the point of linkage can be any chemically possible position. For example, methoxymethoxy, ethoxymethoxy or 2-methoxyethoxy can stand for a C 1

-C

6 -alkoxyl-CI-C 6 -alkoxy group. In terms of the invention, a radical ORb is a hydroxy, methoxy, ethoxy, n propoxy, iso-propoxy, n-, iso-, or tert-butoxy group, or an n-pentoxy, 2,2 dimethylpropoxy or 3-methylbutoxy group. Hydroxy, methoxy and ethoxy are preferred. For a partially or completely fluorinated CI-C 5 -alkyl group, the perfluorinated alkyl groups that appear above are considered. Of the latter, primarily the WO 2006/136462 PCT/EP2006/006532 12 trifluoromethyl group or the pentafluoroethyl group as well as as partially fluorinated alkyl groups, for example the 5,5,4,4-pentafluoropentyl group or the 5,5,5,4,4,3,3 heptafluoropentyl group, are preferred. A fluorine, chlorine, bromine or iodine atom can stand for a halogen atom. Preferred here is fluorine, chlorine or bromine. If Ri and R 2 together with the C atom of the chain form a 3- to 7-membered ring, this is, for example, a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl ring. The cyclopropyl ring as well as the cyclopentyl ring are preferred. The monocyclic or bicyclic carbocyclic aromatic ring A, which can be substituted in several places, is a carbocyclic or heterocyclic aryl radical. In the first case, it is, for example, a phenyl or naphthyl radical, preferably a phenyl radical. As a heterocyclic radical, for example, a monocyclic heterocyclic radical, for example the thienyl, furyl, pyranyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazolyl, oxazolyl, furazanyl, pyrrolinyl, imidazolinyl, pyrazolinyl, thiazolinyl, triazolyl, or tetrazolyl radical, and specifically all possible isomers relative to the positions of the heteroatoms, can be used. In terms of R 3 , an aryl radical is an optionally substituted phenyl, 1- or 2 naphthyl radical, whereby the phenyl radical is preferred. Examples of a heteroaryl radical are the 2-, 3- or 4-pyridinyl radical, the 2- or 3-furyl radical, the 2- or 3-thienyl radical, the 2- or 3-pyrrolyl radical, the 2-, 4- or 5-imidazolyl radical, the pyrazinyl radical, the 2-, 4- or 5-pyrimidinyl radical or the 3- or 4-pyridazinyl radical. The number p for the (CH 2 )p radical can be a number from 0 to 6, preferably 0 to 2. "Radicals" are defined according to the invention as all functional groups that are presented in connection with (CH 2 )p.

WO 2006/136462 PCT/EP2006/006532 13 In the case that the compounds of general formula I (B = -CH 2 -) are present as salts, this can be, for example, in the form of hydrochloride, sulfate, nitrate, tartrate, citrate, fumarate, succinate or benzoate. If the compounds according to the invention are present as racemic mixtures, they can be separated into the pure, optically active forms according to methods of racemate separation that are familiar to one skilled in the art. For example, the racemic mixtures can be separated into pure isomers by chromatography on an even optically active carrier material (CHIRALPAK AD®). It is also possible to esterify the free hydroxy group in a racemic compound of general formula I with an optically active acid and to separate the diastereomeric esters that are obtained by fractionated crystallization or by chromatography and to saponify the separated esters in each case to form the optically pure isomers. As an optically active acid, for example, mandelic acid, camphorsulfonic acid or tartaric acid can be used.

WO 2006/136462 PCT/EP2006/006532 14 The compounds that are mentioned below as well as the use thereof are preferred according to the invention: No. Racemic or R3 3 Enantiomer OH 1 rac H H 2 +N 3 - 0 4 rac 5 + 6 7 rac 8 + 9 10 rac 11 + 4 12 13 rac OH 14 + 15 16 rac OH 17 + 18 19 rac OH 20 + 21 22 rac 23 + 24 25 rac 26 + OH 27 28 rac

OH

29 + 30 31 rac 32 + 33 34 rac 35 + 36 37 rac 38 + C 39 40 rac 41 + WO 2006/136462 PCT/EP2006/006532 15 42 43 rac 44 + 45 46 rac 47 + 48 49 rac NO, 50 + 51 52 rac 53 + 54 55 rac 56 + 57 58 rac 0 59 + 60 1 No. Racemic or R3 Enantiomer 3 61 rac H OH 62 + H 63 N | O 64 rac o 65 + 9; 0 66 67 rac 68 + 69 70 rac 71 + 72 73 rac OH 74 + 75 76 rac OH 77 + 78 79 rac OH 80 + 81 82 rac 83 + 84 WO 2006/136462 PCT/EP2006/006532 16 85 rac 86 + OH 87 88 rac

OH

89 + 90 91 rac 92 + 93 94 rac 95 + 96 97 rac 98 + C 99 100 rac 101 + 102 103 rac 0 104 + 105 106 rac 107 + 108 109 rac N 110 +N 111 112 rac 113 + 114 115 rac OH 116 + 117 118 rac 0 119 + OH 120 No. Racemic or R3 Enantiomer

R

3 121 rac H OH 122 + H 123 N 124 rac 0 125 + 126 127 rac WO 2006/136462 PCT/EP2006/006532 17 128 + 129 130 rac 131 + // 132 133 rac OH 134 + 135 -OH 136 rac 137 + 138 139 rac OH 140 + 141 142 rac 143 + 144 145 rac 0 146 + OH 147 148 rac - OH 149 + 150 151 rac 152 + 153 154 rac 155 + 156 157 rac 158 + 159 160 rac 161 + 162 163 rac 0 164 + 165 166 rac 167 + 168 169 rac - NO, 170 + 171 172 rac 173 + 174 WO 2006/136462 PCT/EP2006/006532 18 175 rac H 176 + 177 178 rac 0 179 + 180 1 No. Racemic or R3 Enantiomer

R

3 181 rac H OH 182 + H 183 N | 0 184 rac 0 185 + 0 186 187 rac 188 + / 189/ 190 rac 191 + 192 193 rac OH 194 + 195 196 rac OH 197 + 198 199 rac OH 200 + 201 202 rac 203 + 204 205 rac 0 206 + OH 207 208 rac -OH 209 + 210 211 rac 212 + 213 214 rac 215 + 216 217 rac CF 218 + CF WO 2006/136462 PCT/EP2006/006532 19 219 220 rac 221 +N 222 223 rac 224 + 225 226 rac 227 + 228 229 rac NO, 230 + 231 232 rac 233 + 234 - Om 235 rac 236 + 237 238 rac 0 239 + OH 240 No. Racemic or R3 Enantiomer R O 241 rac H 242 + 243 244 rac 245 + 0 246 247 rac 248 + 249 250 rac 251 + 252 253 rac OH 254 + 1 255 256 rac OH 257 + 258 259 rac OH 260 + WO 2006/136462 PCT/EP2006/006532 20 261 262 rac 263 + 264 265 rac 266 + OH 267 268 rac OH 269 + 270 271 rac 272 + 273 274 rac 275 + 276 277 rac 278 + CF 279 280 rac 281 + 282 283 rac 284 + 285 286 rac 287 + 288 NO, 289 rac 290 + 291 292 rac 293 + 294 295 rac H 296 + 297 298 rac 299 + 300 No. Racemic or R3 Enantiomer R 3 301 rac OH 302 + H 303 0 0 c0 0 WO 2006/136462 PCT/EP2006/006532 21 304 rac 305 + 306 307 rac 308 + 309 310 rac 311 + 312 313 rac OH 314 + 315 316 rac OH 317 + 318 319 rac OH 320 + 321 322 rac 323 + 324 325 rac 0 326 + OH 327 OH 328 rac 329 + 330 331 rac 332 + 333 334 rac 335 + 336 337 rac 338 + 339 340 rac 341 + 342 343 rac 344 + 345 346 rac 347 + 348 349 rac - NO, 350 + WO 2006/136462 PCT/EP2006/006532 22 351 352 rac 353 + 354 355 rac 356 + 357 358 rac 0 359 + 360 No. Racemic or R3 Enantiomer

R

3 361 rac H OH 362 + 0 H 363 N O 364 rac 0 365 + 366 367 rac 368 + 369 370 rac 371 + 372 373 rac OH 374 + 375 376 rac OH 377 + 378 379 rac OH 380 + 381 382 rac 383 + 384 385 rac 0 386 + OH 387 388 rac OH 389 + 390 - WO 2006/136462 PCT/EP2006/006532 23 391 rac 392 + 393 394 rac 395 + 396 397 rac CF3 398 + 399 400 rac 401 + 402 403 rac 404 + 405 406 rac 407 + 408 409 rac NO 410 + 411 412 rac 413 + 414 415 rac OH 416 + 417 418 rac O 419 + 420 No. Racemic or R3 Enantiomer

R

3 421 rac H OH 422 + H 423 N 424 rac - 0 425 + 0 426 427 rac 428 + 429 430 rac 431 + 432 433 rac OH WO 2006/136462 PCT/EP2006/006532 24 434 + 435 436 rac OH 437 + 438 439 rac H 440 + 441 442 rac 443 + 444 445 rac 446 + OH 447 448 rac OH 449 + 450 451 rac 452 + 453 454 rac 455 + 456 457 rac CF, 458 + C 459 460 rac 461 + 462 463 rac 464 + 465 466 rac 467 + 468 469 rac 470 + 471 472 rac 473 + 474 475 rac / ON 476 + 477 478 rac 479 + 480 WO 2006/136462 PCT/EP2006/006532 25 No. Racemic or R3 Enantiomer R 481 rac H OH 482 + 0 H 483 N O 0 484 rac Br 485 + 0 486 487 rac 488 + 489 490 rac 491 + 492 493 rac OH 494 + 495 496 rac OH 497 + 498 499 rac OH 500 + 501 502 rac 503 + 504 505 rac 506 + OH 507 508 rac OH 509 + 510 511 rac 512 + 513 214 rac 515 + 516 517 rac 518 + 519 520 rac 521 +N 522 523 rac 524 + 525 526 rac WO 2006/136462 PCT/EP2006/006532 26 227 + 528 529 rac - NO2 530 + 531 532 rac 533 + 534 535 rac 536 + 537 538 rac 539 + 540 No. Racemic or R3 Enantiomer R3 OH 541 rac H 542 + N 543 544 rac 545 + 0 546 547 rac 548 + 549 550 rac 551 + 552 553 rac OH 554 + 555 556 rac H 557 + 558 559 rac OH 560 + 561 562 rac 563 + 564 565 rac 0 566 + OH 567 568 rac OH 569 + 570 - WO 2006/136462 PCT/EP2006/006532 27 571 rac 572 + 573 574 rac 575 + 576 577 rac 578 + 579 580 rac 581 +N 582 583 rac 0 584 + 585 586 rac 587 + 588 589 rac NO, 590 + 591 592 rac 593 + 594 595 rac OH 596 + 597 598 rac 0 599 + 600 No. Racemic or R3 Enantiomer R 3 601 rac H OH 602 + H 603 - 0 604 rac 0 605 + CF 3 0 606 607 rac 608 + 609 610 rac 611 + 612 WO 2006/136462 PCT/EP2006/006532 28 613 rac OH 614 + 615 616 rac OH 617 + 618 619 rac OH 620 + 621 622 rac 623 + 624 625 rac 0 626 + OH 627 628 rac OH 629 + 630 631 rac 632 + 633 634 rac 635 + 636 637 rac 638 + 639 640 rac 641 + 642 643 rac 644 + 645 646 rac 647 + 648 649 rac NO 650 + ~ 651 652 rac 653 + 654 655 rac -O 656 + 657 658 rac 659 + 660 - WO 2006/136462 PCT/EP2006/006532 29 No. Racemic or R3 Enantiomer R 661 rac H OH 662 + 0 H 663 NO 664 rac 0 665 + F 0 666 667 rac 668 + 669 670 rac 671 + 672 673 rac OH 674 + 675 676 rac OH 677 + 678 679 rac OH 680 + 681 682 rac 683 + 684 685 rac 686 + OH 687 688 rac -OH 689 + 690 691 rac 692 + 693 694 rac 695 + 696 697 rac CF, 698 + CI 699 700 rac 701 + 702 703 rac 704 + 705 WO 2006/136462 PCT/EP2006/006532 30 706 rac 707 + 708 709 rac - NO2 710 + 711 712 rac 713 + 714 715 rac OH 716 + 717 7 18 rac 0 719 + 720 No. Racemic or R3 Enantiomer R 721 rac OH 722 + H 7 2 3 -_N_|_0 O 724 rac o 0 / 725 + 0 726 727 rac 728 + 729 730 rac 731 + 732 733 rac OH 734 + 735 736 rac OH 737 + 738 739 rac OH 740 + 741 742 rac 743 + 744 1 745 rac 746 + OH WO 2006/136462 PCT/EP2006/006532 31 747 748 rac

OH

749 + 750 751 rac 752 + 753 754 rac 755 + 756 757 rac F3 758 + 759 760 rac 761 + 762 763 rac 764 + 765 766 rac 767 + 768 769 rac NO 770 + 771 772 rac 773 + 774 775 rac 776 + 'S 777 778 rac 0 779 + OH 780 No. Racemic or R3 R OH Enantiomer H 781 raC HF O N O 782 + 0 0 783 F 784 rac CF 3 0 785 + 786 787 rac 788 + WO 2006/136462 PCT/EP2006/006532 32 789 790 rac 791 + 792 793 rac OH 794 + 795 796 rac OH 797 + 798 799 rac OH 800 + 801 802 rac 803 + 804 805 rac 0 806 + OH 807 808 rac OH 809 + 810 811 rac 812 + 813 814 rac 815 + 816 817 rac 818 + 819 820 rac 821 + 822 823 rac 824 + 825 826 rac 827 + 828 829 rac NO2 830 + 831 832 rac 833 + 834 835 rac O 836 + 837 WO 2006/136462 PCT/EP2006/006532 33 838 rac 839 + 840 No. Racemic or R3

R

3 OH Enantiomer 0 841 rac H H 842 + 0 843

CF

3 0 844 rac 845 + 846 847 rac 848 + 849 850 rac 851 + 4 852 853 rac OH 854 + 855 856 rac OH 857 + 858 859 rac OH 860 + 861 862 rac 863 + 864 865 rac 866 + OH 867 868 rac 869 + 870 871 rac 872 + 873 874 rac 875 + 876 877 rac F, 878 + CF 879 - WO 2006/136462 PCT/EP2006/006532 34 880 rac 881 + 882 883 rac 884 + 885 886 rac 887 + 888 889 rac NO, 890 + 891 892 rac 893 + 894 OH 895 rac 896 + 897 898 rac 0 899 + 900 1 No. Racemic or R3 Enantiomer

R

3 901 rac H OH 902 + FH 903 N 904 rac 0 905 + CF 3 0 906 907 rac 908 + 909 910 rac 911 + 912 913 rac OH 914 + 915 916 rac OH 917 + 918 919 rac OH 920 + 921 - WO 2006/136462 PCT/EP2006/006532 35 922 rac 923 + 924 925 rac 926 + OH 927 _ 928 rac 929 + // 930 931 rac 932 + 933 934 rac 935 + 936 937 rac CF, 938 + 939 940 rac N 941 + 942 943 rac 944 + 945 946 rac 947 + 948 949 rac NO 950 + 951 952 rac 953 + 954 955 rac O 956 + 957 958 rac 959 + OH 960 No. Racemic or R3 Enantiomer R3 961 rac H OH 962 + a H N

O

WO 2006/136462 PCT/EP2006/006532 36 963 964 rac 965 + 966 967 rac 968 + 969 970 rac 971 + 972 973 rac OH 974 + 975 976 rac OH 977 + 978 979 rac OH 980 + 981 982 rac 983 + 984 0 OH 985 rac OH 986 + 987 988 rac

OH

989 + 990 991 rac 992 + 993 994 rac 995 + 996 997 rac CF, 998 + C 999 1000 rac 1001 + N 1002 1003 rac 1004 + 1005 1006 rac 1007 + 1008 1009 rac NO, WO 2006/136462 PCT/EP2006/006532 37 1010 + 1011 1012 rac 1013 + 1014 1015 rac OH 1016 + 1017 1018 rac 0 1019 + OH 1020 No. Racemic or R3 Enantiomer R 1021 rac H OH 1022 + 0 H 1023 1024 rac 0 1025 + F O 1026 1027 rac 1028 + 1029 1030 rac 1031 + 1032 1033 rac OH 1034 + 1035 1036 rac OH 1037 + 1038 1039 rac OH 1040 + 1041 1042 rac 1043 + 1044 1045 rac 0 1046 + OH 1047 1048 rac OH 1049 + 1050 1051 rac WO 2006/136462 PCT/EP2006/006532 38 1052 + 1053 1054 rac 1055 + 1056 1057 rac F, 1058 + 1059 1060 rac 1061 + 1062 1063 rac * 1064 + 1065 1066 rac 1067 + 1068 1069 rac NO2 1070 + 1071 1072 rac 1073 + 1074 1075 rac OH 1076 + 1077 1078 rac 1079 + N O 1080 No. Racemic or R3 Ra OH Enantiomer o H 1081 rac H N O 1082 + 0 1083 -0Io 1084 rac 1085 + 1086 1087 rac 1088 + 1089 1090 rac 1091 + 1092 1093 rac OH 1094 + WO 2006/136462 PCT/EP2006/006532 39 1095 1096 rac OH 1097 + 1098 1099 rac O" 1100 + 1101 1102 rac 1103 + 1104 1105 rac 1106 + OH 1107 1108 rac

OH

1109 + 1110 1111 rac 1112 + 1113 1114 rac 1115 + 1116 1117 rac 1118 + 1119 1120 rac 1121 + 1122 1123 rac 0 1124 + 1125 1126 rac 1127 + 1128 _ NO, 1129 rac 1130 + 1131 1132 rac 1133 + 0 1134 1135 rac OH 1136 + 1137 1138 rac 1139 + 1140 - WO 2006/136462 PCT/EP2006/006532 40 No. Racemic or R3 Enantiomer

R

3 OH 1141 rac H 0 1142 + 1143 - a 1144 rac 1145 + 1146 1147 rac 1148 + 1149 1150 rac 1151 + 1152 1153 rac OH 1154 + 1155 1156 rac OH 1157 + 1158 1159 rac H 1160 + 1161 1162 rac 1163 + 1164 1165 rac 1166 + OH 1167 1168 rac

OH

1169 + 1170 1171 rac 1172 + 1173 1174 rac 1175 + 1176 1177 rac CF, 1178 + C 1179 1180 rac 1181 + 1182 1183 rac 1184 + 1185 1186 rac WO 2006/136462 PCT/EP2006/006532 41 1187 + 1188 1189 rac - NO, 1190 + 1191 1192 rac 1193 + 1194 1195 rac OH 1196 + 1197 1198 rac 1199 + O 1200 No. Racemic or R3 Enantiomer R 3 1201 rac H OH 1202 + 0 H 1203 - N 1204 rac c 1205 + 1206 1207 rac 1208 + 1209 1210 rac 1211 + 1212 1213 rac OH 1214 + 1215 1216 rac OH 1217 + 1218 1219 rac OH 1220 + 1221 1222 rac 1223 + 1224 1225 rac 1226 + OH 1227 WO 2006/136462 PCT/EP2006/006532 42 1228 rac 1229 + 1230 | 1231 rac 1232 + 1233 1234 rac 1235 + 1236 1237 rac F 1238 + 1239 1240 rac 1241 + 1242 1243 rac 1244 + 1245 1246 rac 1247 + 1248 1249 rac - NO, 1250 + 1251 1252 rac 1253 + 1254 1255 rac OH 1256 + 1257 1258 rac 1259 + OH 1260 No. Racemic or R3 Enantiomer R 1261 rac H OH 1262 + H 1263 N 1264 rac 0 1265 + F 0 1266 1267 rac 1268 + WO 2006/136462 PCT/EP2006/006532 43 1269 ' 1270 rac 1271 + 1272 1273 rac OH 1274 + 1275 1276 rac OH 1277 + 1278 1279 rac OH 1280 + 1281 1282 rac 1283 + 1284 1285 rac 1286 + OH 1287 1288 rac OH 1289 + 1290 1291 rac 1292 + 1293 1294 rac 1295 + 1296 - _ 1297 rac 1298 + 1299 1300 rac 1301 + 1302 1303 rac 0 1304 + 1305 1306 rac 1307 + 1308 1309 rac NO 1310 + 1311 1312 rac 1313 + 1314 1315 rac - H 1316 + 1317 - WO 2006/136462 PCT/EP2006/006532 44 0 1318 rac 1319 + 1320 No. Racemic or R3 Enantiomer 3 1321 rac H OH 1322 + H 1323 N 1324 rac 0 1325 + F 1326 1327 rac 1328 + 1329 1330 rac 1331 + 1332 1333 rac OH 1334 + 1335 1336 rac OH 1337 + 1338 1339 rac OH 1340 + 1341 1342 rac 1343 + 1344 1345 rac 0 1346 + OH 1347 1348 rac 1349 + 1350 1351 rac 1352 + 1353 1354 rac 1355 + 1356 1357 rac CF, 1358 + WO 2006/136462 PCT/EP2006/006532 45 1359 _ 1360 rac 1361 + 1362 0 1363 rac 1364 + 1365 1366 rac 1367 + 1368 1369 rac NO, 1370 + 1371 1372 rac 1373 + 1374 1375 rac O 1376 + 1377 1378 rac 0 1379 + N 1380 No. Racemic or R3

R

3 OH Enantiomer 1381 rac N 1382 + | 0 1383 1384 rac 1385 + 1386 1387 rac 1388 + 1389 1390 rac 1391 + 1392 1393 rac OH 1394 + 1395 1396 rac OH 1397 + WO 2006/136462 PCT/EP2006/006532 46 1398 1399 rac OH 1400 + 1401 1402 rac 1403 + 1404 1405 rac OH 1406 + 1407 1408 rac OH 1409 + 1410 1411 rac 1412 + 1413 1414 rac 1415 + 1416 1417 rac 1418 + 1419 1420 rac 1421 + 1422 1423 rac 0 1424 + 1425 1426 rac 1427 + 1428 1429 rac NO, 1430 + 1431 1432 rac 1433 + 1434 1435 rac -O 1436 + 1437 1438 rac 1439 1440 WO 2006/136462 PCT/EP2006/006532 47 No. Racemic or R3 Enantiomer

R

3 OH 1441 rac H 1442 + N 1443 0 1444 rac 1445 + 1446 1447 rac 1448 + 1449 1450 rac 1451 + 1452 1453 rac OH 1454 + 1455 1456 rac OH 1457 + 1458 1459 rac OH 1460 + 1461 1462 rac 1463 + 1464 1465 rac 0 1466 + OH 1467 1468 rac OH 1469 + 1470 1471 rac 1472 + 1473 1474 rac 1475 + 1476 1477 rac 1478 + 1479 1480 rac 1481 + 1482 1483 rac 0 1484 + WO 2006/136462 PCT/EP2006/006532 48 1485 1486 rac 1487 + 1488 1489 rac - NOs 1490 + 1491 1492 rac 1493 + 1494 1495 rac OH 1496 + 1497 1498 rac 1499 + < H 1500 No. Racemic or R3 Enantiomer R 1501 rac H OH 1502 + H 1503 1504 rac 0 1505 + 0 1506 1507 rac 1508 + 1509 1510 rac 1511 + 1512 1513 rac OH 1514 + 1515 1516 rac OH 1517 + 1518 1519 rac OH 1520 + 1521 1522 rac 1523 + 1524 1525 rac 1526 + 1527 1528 rae

ILOH

WO 2006/136462 PCT/EP2006/006532 49 1529 + 1530 1531 rac 1532 + 1533 1534 rac 1535 + 1536 1537 rac 1538 + CF 1539 1540 rac 1541 + 1542 1543 rac 1544 + 1545 1546 rac 1547 + 1548 ,NO, 1549 rac 1550 + 1551 1552 rac 1553 + 1554 1555 rac OH 1556 + 1557 1558 rac 1559 + OH 1560 No. Racemic or R3 Enantiomer

R

3 1561 rac OH 1562 + 0 H 1563 - N 1564 rac 0 1565 + 0 1566 1567 rac 1568 + 1569 1570 rac

A,

WO 2006/136462 PCT/EP2006/006532 50 1571 + 1572 | 1573 rac OH 1574 + 1575 1576 rac OH 1577 + 1578 1579 rac OH 1580 + 1581 1582 rac 1583 + 1584 1585 rac 0 1586 + OH 1587 1588 rac H 1589 + 1590 1591 rac 1592 + 1593 1594 rac 1595 + 1596 1597 rac F 1598 + 1599 1600 rac 1601 + 1602 1603 rac 0 1604 + 1605 1606 rac 1607 + 1608 1609 rac NO 1610 + 1611 1612 rac 1613 + 1614 1615 rac OH 1616 + 1617 WO 2006/136462 PCT/EP2006/006532 51 1618 rac 0 1619 + 1620 WO 2006/136462 PCT/EP2006/006532 52 Biological Characterization of the Compounds According to the Invention The identification of progesterone receptor modulators can be performed using simple methods, test programs that are known to one skilled in the art. To this end, for example, a compound that is to be tested can be incubated together with a gestagen in a test system for progesterone receptors, and it can be examined whether the progesterone mediated action in this test system is altered in the presence of modulators. The substances of general formula I according to the invention were tested in the following models: Progesterone Receptor Binding Test Measurement of the Receptor Binding Affinity: The receptor binding affinity was determined by competitive binding of a specifically binding 3 H-labeled hormone (tracer) and the compound to be tested on receptors in the cytosol from animal target organs. In this case, receptor saturation and reaction equilibrium were sought. The tracers and increasing concentrations of the compound to be tested (competitor) were co-incubated with the receptor-containing cytosol fraction at 0-4*C over 18 hours. After separation of the unbonded tracer with carbon-dextran suspension, the receptor-bonded tracer portion was measured for each concentration, and the IC 5 0 was determined from the concentration sequence. As a quotient of the IC 50 values of the reference substance and the compound to be tested (x 100%), the relative molar binding affinity (RBA) was calculated (RBA of the reference substance = 100%). For the receptor types, the following incubation conditions were selected: WO 2006/136462 PCT/EP2006/006532 53 Progesterone Receptor: Uterus cytosol of the estradiol-primed rabbit, homogenized in TED buffer (20 mmol of Tris/HCl, pH 7.4; 1 mmol of ethylenediamine tetraacetate, 2 mmol of dithiothreitol) with 250 mmol of saccharose; stored at -30*C. Tracer: 3 H-ORG 2058, 5 nmol; reference substance: progesterone. Glucocorticoid Receptor: Thymus cytosol of the adrenalectomized rat, thymi stored at -30*C; buffer: TED. Tracer: 3 H-Dexamethasone, 20 nmol; reference substance: dexamethasone. The relative receptor binding affinities (RBA values) of the compounds of general formula (I) according to the invention on the progesterone receptor are between 3 and 100% relative to the progesterone. On the glucocorticoid receptor, the RBA values are in the range of 3 to 30% relative to dexamethasone. The compounds according to the invention accordingly have a high affinity to the progesterone receptor but only a low affinity to the glucocorticoid receptor. Antagonism of Progesterone Receptor PR-B The transactivation assay is performed as described in WO 02/054064. Agonism of Progesterone Receptor PR-B The transactivation assay is performed as described in Fuhrmann et al. (Fuhrmann ,U.; Hess-Stump, H.; Cleve, A.; Neef, G.; Schwede, W.; Hoffmann, J.; Fritzemeier, K.-H., Chwalisz, K.; Journal of Medicinal Chem., 43, 26, 2000, 5010 5016).

WO 2006/136462 PCT/EP2006/006532 54 No. Antagonistic activity Agonistic activity

IC

50 [nM] Efficacy [%] EC 50 [nM] Efficacy [%] 9 3 96 n.b. 3 13 3 92 n.b. 7 3b 0,4 97 n.b. 2 7 4 82 2 11 Dosage For use according to the invention, the progesterone receptor modulators can be administered orally, enterally, parenterally or transdermally. In general, satisfactory results can be expected in the treatment of the above mentioned indications if the daily doses encompass a range of 1 Ig to 500 mg of the compound according to the invention. Suitable dosages of the compounds according to the invention in humans for the treatment of endometriosis, leiomyomas of the uterus and dysfunctional bleeding as well as for use in birth control as well as for hormone replacement therapy are 50 pg to 500 mg per day, depending on age and constitution of the patient, whereby the necessary daily dose can be administered one or more times. For treatment of breast cancer, the dosage range for the compounds according to the invention comprises 10 mg to 1000 mg daily. The formulation of the pharmaceutical preparations based on the new compounds is carried out in a way that is known in the art, by the active ingredient being processed with the vehicles, fillers, substances that influence decomposition, binding agents, moisturizers, lubricants, absorbents, diluents, flavoring correctives, dyes, etc., that are commonly used in galenicals and being converted into the desired form of administration.

WO 2006/136462 PCT/EP2006/006532 55 In this case, reference is made to Remington's Pharmaceutical Science, 15' Ed. Mack Publishing Company, East Pennsylvania (1980). For oral administration, in particular tablets, film tablets, coated tablets, capsules, pills, powders, granulates, lozenges, suspensions, emulsions or solutions are suitable. For parenteral administration, injection and infusion preparations are possible. For intraarticulate injection, correspondingly prepared crystal suspensions can be used. For intramuscular injection, aqueous and oily injection solutions or suspensions and corresponding depot preparations can be used. For rectal administration, the new compounds can be used in the form of suppositories, capsules, solutions (e.g., in the form of enemas) and ointments both for systemic therapy and for local therapy. In addition, agents for vaginal application can also be mentioned as preparations. For pulmonary administration of the new compounds, the latter can be used in the form of aerosols and inhalants. For transdermal administration, patches are possible, or for topical application, formulations in gels, ointments, fatty ointments, creams, pastes, powders, milk and tinctures are possible. The dosage of the compounds of general formula I should be 0.0 1% - 20% in these preparations to achieve an adequate pharmacological action. Corresponding tablets can be obtained by, for example, mixing active ingredient with known adjuvants, for example inert diluents such as dextrose, sugar, sorbitol, mannitol, polyvinylpyrrolidone, explosives such as corn starch or alginic acid, binders such as starch or gelatin, lubricants such as magnesium stearate or talc and/or agents for achieiving a depot effect such as carboxylpolymethylene, carboxyl methyl cellulose, WO 2006/136462 PCT/EP2006/006532 56 cellulose acetate phthalate or polyvinyl acetate. The tablets can also consist of several layers. Accordingly, coated tablets can be produced by coating cores, produced analogously to the tablets, with agents that are commonly used in tablet coatings, for example polyvinylpyrrolidone or shellac, gum arabic, talc, titanium oxide or sugar. In this case, the coated tablet shell can also consist of several layers, whereby the adjuvants that are mentioned above in the tablets can be used. Solutions or suspensions of the compounds of general formula I according to the invention can contain additional taste-improving agents such as saccharine, cyclamate or sugar, as well as, e.g., flavoring substances, such as vanilla or orange extract. In addition, they can contain suspending adjuvants such as sodium carboxy methyl cellulose or preservatives such as p-hydroxybenzoates. The capsules that contain compounds of general formula I can be produced by, for example, the compound(s) of general formula I being mixed with an inert vehicle such as lactose or sorbitol and encapsulated in gelatin capsules. Suitable suppositories can be produced by, for example, mixing with vehicles that are provided for this purpose, such as neutral fats or polyethylene glycol, or derivatives thereof. The compounds of general formula (I) according to the invention or their pharmaceutically acceptable salts can be used based on their antagonistic or partial agonistic action for the production of a pharmaceutical agent, in particular for treatment and prophylaxis of gynecological diseases, such as endometriosis, leiomyomas of the uterus, dysfunctional bleeding and dysmenorrhea. In addition, they can be used to counteract hormonal irregularities, to trigger menstruation and alone or in combination with prostaglandins and/or oxytocin to induce birth.

WO 2006/136462 PCT/EP2006/006532 57 In addition, the compounds of general formula (I) according to the invention or their pharmaceutically acceptable salts are suitable for the production of preparations for contraception for women (see also WO 93/23020, WO 93/21927). In addition, the compounds according to the invention or their pharmaceutically acceptable salts can be used alone or in combination with a Selective Estrogen Receptor Modulator (SERM) for female hormone replacement therapy. In addition, the above-mentioned compounds exert an antiproliferative action in hormone-dependent tumors. They are therefore suitable for the therapy of hormone dependent carcinomas, such as, for example, for breast, prostate or endometrial carcinomas. The compounds according to the invention or their pharmaceutically acceptable salts can be used for the treatment of hormone-dependent carcinomas, both in first-line therapy and in second-line therapy, in particular after tamoxifen failure. The compounds of general formula (I) according to the invention that have an antagonistic or partial agonistic action or their pharmaceutically acceptable salts can also be used in combination with compounds that have an antiestrogenic action (estrogen receptor antagonists or aromatase inhibitors) or Selective Estrogen Receptor Modulators (SERM) for the production of pharmaceutical preparations for treating hormone dependent tumors. For the treatment of endometriosis or leiomyomas of the uterus, the compounds according to the invention can also be used in combination with SERMs or an antiestrogen (estrogen receptor antagonists or aromatase inhibitors). In the treatment of hormone-dependent tumors, the progesterone receptor modulator and the antiestrogen (estrogen receptor antagonists or aromatase inhibitors) or the SERM can be provided for simultaneous or else for sequential administration. In sequential administration, preferably first the antiestrogen (estrogen receptor antagonists or aromatase inhibitor) or SERM is administered, and then the progesterone receptor modulator is administered.

WO 2006/136462 PCT/EP2006/006532 58 In this case, in the combination with the nonsteroidal progesterone receptor modulators according to the invention, for example, the following antiestrogens (estrogen receptor antagonists or aromatase inhibitors) or SERMs are considered: tamoxifen, 5-(4-{5-[(RS)-(4,4,5,5,5-pentafluoropentyl)sulfinyl] pentyloxy}phenyl)-6-phenyl-8,9-dihydro-7H-benzocyclohepten-2-o (WO 00/03979), ICI 182 780 (7alpha-[9-(4,4,5,5-pentafluoropentylsulfinyl)nonyl]estra-1,3,5(10)-triene 3,17-beta-diol), 11 beta-fluoro-7alpha-[5-(methyl{3-[(4,4,5,5,5 pentafluoropentyl)sulfanyl]propyl}amino)pentyl]estra-1,3,5(10)-triene-3,17beta-diol (W098/07740), 1 lbeta-fluoro-7alpha-{5-[methyl(7,7,8,8,9,9,10,10,10 nonafluorodecyl)amino]pentyl}estra-1,3,5(10)-triene-3,17beta-diol (WO 99/33855), 11 beta-fluoro- 1 7alpha-methyl-7alpha- {5 -[methyl(8,8,9,9,9-pentafluorononyl) amino]pentyl}estra-1,3,5(10)-triene-3,17beta-diol (WO 03/045972), clomifene, raloxifene as well as other antiestrogenically active compounds, and aromatase inhibitors, such as, for example, fadrozole, formestane, letrozole, anastrozole or atamestane. Finally, this invention also relates to the use of the compounds of general formula I, optionally together with an antiestrogen or SERM, for the production of a pharmaceutical agent. This invention also relates to pharmaceutical compositions that contain at least one compound according to the invention, optionally in the form of a pharmaceutically/pharmacologically compatible salt, without or together with pharmaceutically compatible adjuvants and/or vehicles. These pharmaceutical compositions and pharmaceutical agents can be provided for oral, rectal, vaginal, subcutaneous, percutaneous, intravenous or intramuscular WO 2006/136462 PCT/EP2006/006532 59 administration. In addition to commonly used vehicles and/or diluents, they contain at least one compound according to the invention. The pharmaceutical agents of the invention are produced in a known way with the commonly used solid or liquid vehicles or diluents and the usually used pharmaceutical-technical adjuvants corresponding to the desired type of administration with a suitable dosage. The preferred preparations exist in a dispensing form that is suitable for oral administration. Such dispensing forms are, for example, tablets, film tablets, coated tablets, capsules, pills, powders, solutions or suspensions or else depot forms. The pharmaceutical compositions that contain at least one of the compounds according to the invention are preferably administered orally. Parenteral preparations, such as injection solutions, are also considered. In addition, for example, suppositories and agents for vaginal application can also be mentioned as preparations.

WO 2006/136462 PCT/EP2006/006532 60 The following examples are used for a more detailed explanation of the subject of the invention, without intending that it be limited to these examples. The production of the starting compound 5-{3-[1-(2-fluoro-5 trifluoromethylphenyl)-cyclopropyl]-2-oxopropionylamino}phthalide is described in Patent WO 200375915, and the production of 5-{3-[1-phenyl-cyclopropyl]-2 oxopropionylamino}phthalide is described in WO 9854159. rac-5-{2-Ethinyl-2-hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl] propionylamino}phthalide 1 F HO H 'O N 00 0 CF, Ethinyl magnesium bromide (6 ml, 0.5 M in tetrahydrofuran) was added to an ice-cold solution that consists of 5-{3-[1-(2-fluoro-5-trifluoromethylphenyl) cyclopropyl]-2-oxopropionylamino}phthalide (632 mg) in THF (4 ml). The reaction solution under argon was allowed to come to room temperature within 3 hours. Then, the reaction mixture was poured into ice-cold, saturated ammonium chloride solution. It was extracted with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution and dried on sodium sulfate. The crude product that is obtained was chromatographed on silica gel. 2.2 g of product was obtained. 'H-NMR (ppm, CDCl 3 , 400 MHz): 0.83 (1H), 0.92-1.10 (2H), 2.37 (1H), 2.56 (1H), 2.59 (1H), 3.10 (1H), 5.28 (2H), 7.02 (1H), 7.31 (1H), 7.37 (lH), 7.58 (1H), 7.86 (1H), 7.94 (1H), 8.70 (1H).

WO 2006/136462 PCT/EP2006/006532 61 rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-propinyl propionylamino}phthalide 2 II F HO H 00 O0 CF, Analogously to Example 1, 145 mg of product was obtained from 1 propinylmagnesium bromide (2 ml of 0.5 M solution in tetrahydrofuran) and 210 mg of 6-[4-(2-chloro-4-fluorophenyl)-4-methyl-2-oxovaleroylamino]-4-methyl-2,3 benzoxazin- 1-one. 'H-NMR (ppm, CDCl 3 , 400 MHz): 0.86 (1H), 0.90-1.05 (3H), 1.72 (3H), 2.35 (1H), 2.49 (1H), 2.96 (1H), 5.27 (2H), 7.03 (1H), 7.30 (1H), 7.36 (1H), 7.58 (1H), 7.85 (1H), 7.98 (1H), 8.73 (1H). (+)-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-phenyl propionylamino}phthalide 3a and (-)-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2 (phenylethinyl)-propionylamino}phthalide 3b F HO H 0 0 00 CF, n-Butyllithium (625 pl, 1.6 M in hexane) was added at -78*C to a solution of 110 pl of phenylacetylene in tetrahydrofuran. Stirring was allowed to continue at this temperature for 30 minutes, and then a solution of 5-{3-[1-(2-fluoro-5- WO 2006/136462 PCT/EP2006/006532 62 trifluoromethylphenyl)-cyclopropyl]-2-oxopropionylamino}phthalide (210 mg) in 5 ml of tetrahydrofuran was added in drops. Then, it was allowed to come to 23*C over about 3 hours and then stirred for 10 more hours. Then, the reaction mixture was poured into ice-cold, saturated ammonium chloride solution. It was extracted with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution and dried on sodium sulfate. The crude product was chromatographed on silica gel. The racemic mixture obtained was then separated by preparative chiral HPLC (Chiralpak AD column, 250x10 mm) into enantiomers 3a (46 mg) and 3b (47 mg). 3a and 3b: 'H-NMR (ppm, CDCl 3 , 300 MHz): 0.88 (1H), 0.95-1.11 (3H), 2.46 (1H), 2.65 (1H), 3.10 (1H), 5.27 (2H), 7.00 (1H), 7.24-7.42 (7H), 7.61 (11H), 7.84 (1H), 7.98 (1H), 8.80 (1H). 3a : [a]D 20 : + 12.9' (CHCl 3 , 1.06 g/100 ml; X=589 nM) 3b: [a]D20: - 14.40 (CHCl 3 , 1.03 g100 ml; ?=589 nM) Analogously to Example 3, compounds 4 and 5 were produced from 5-{3-[1-(2 fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-oxopropionylamino}phthalide and the respective lithium aryl acetylide. rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-[(4 trifluoromethylphenyl)ethinyllpropionylamino}phthalide 4 WO 2006/136462 PCT/EP2006/006532 63 CF, F HO 0 I 0 0 CF, 'H-NMR (ppm, CDCl 3 , 300 MHz): 0.92 (1H), 0.99-1.16 (3H), 2.55 (1 H), 2.68 (1H), 3.27 (1H), 5.30 (2H), 7.03 (1H), 7.30-7.52 (4H), 7.55-7.62 (2H), 6.67 (1H), 7.99 (1lH), 8.03 (1H), 8.84 (1H). (+)-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluormethylphenyl)-cyclopropyl]-2-[(4 trifluormethylphenyl)ethinyl] propionylamino}phthalide 4a and (-)-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluormethylphenyl)-cyclopropyl]-2-[(4 trifluormethylphenyl)ethinyl]propionylamino}phthalide 4b The racemic mixture (150 mg) which was described in example 4 was separated by preparative chiral HPLC (column Chiralpak AD 250x10 mm) into the enantiomers 4a (51 mg) and 4b_(62 mg). 4a: [a]D 2 0: + 6.3 (CHC1 3 , 1.07 g/100 ml; ?=589 nM) 4b [a]D 2 0: - 5.3* (CHC1 3 , 1.09 g100 ml; X=589 nM) rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-[(4 methylphenyl)ethinyljpropionylamino}phthalide 5 F HO H 0 0

CF,

WO 2006/136462 PCT/EP2006/006532 64 'H-NMR (ppm, CDCl 3 , 300 MHz): 0.87 (1H), 0.93-1.15 (3H), 2.38 (3H), 2.45 (1H), 2.66 (1H), 3.11 (1H), 5.25 (2H), 6.99 (1H), 7.10 (2H), 7.18-7.38 (4H), 7.61 (1H), 7.86 (1H), 8.00 (1H), 8.80 (1H). (+)-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyll-2-[(4 methylphenyl)ethinyljpropionylamino}phthalide 5a and (-)-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-[(4 methylphenyl)ethinyll propionylamino} phthalide 5b The racemic mixture (109 mg) which was described in example 5 was separated by preparative chiral HPLC (column Chiralpak AD 250x10 mm) into the enantiomers 5a (41 mg) and 5(28 mg). Sa : [a]D20: + 14.80 (CHC1 3 , 1.07 g/100 ml; %=589 nM) 5b: [a]D 2 0: - 16.3' (CHC1 3 , 1.13 g100 ml; ?=589 nM) rac-5-{2-[(4-Acetoxyphenyl)ethinyl]-2-hydroxy-3-[1-(2-fluoro-5 trifluoromethylphenyl)-cyclopropyl]-propionylamino}phthalide 6 0 F HO H 0 0 0 CF, A suspension of the compound (104 mg) described under Example 1, triphenylphosphine (12.2 mg), copper iodide (8.9 mg), 4-iodophenyl acetate (92 mg), palladium acetate (5.3 mg) in THF (5 ml) and triethylamine (5 ml) was reacted for I hour in an ultrasound bath at 25 0 C under argon. Then, it was poured into saturated, aqueous ammonium chloride solution. It was extracted with ethyl acetate and washed with water and saturated sodium chloride solution. The combined organic phases were WO 2006/136462 PCT/EP2006/006532 65 dried on sodium sulfate. After column chromatography of the crude product on silica gel, 55 mg of product was obtained. 'H-NMR (ppm, CDCl 3 , 400 MHz): 0.88 (lH), 0.95-1.10 (3H), 2.29 (3H), 2.45 (1H), 2.63 (1H), 3.17 (1H), 5.29 (2H), 6.97-7.07 (3H), 7.28-7.37 (4H), 7.60 (1H), 7.84 (1H), 7.98 (1H), 8.80 (1H). rac-5-{2-Hydroxy-2-[(4-hydroxyphenyl)ethinyl]-3-[1-(2-fluoro-5 trifluoromethylphenyl)- cyclopropyl]-propionylamino)phthalide 7 OH F HO H 0 0 0 CF, A solution of the compound described under 6 (45 mg) in 5 ml of methanol was mixed with sodium bicarbonate (130 mg). Stirring was continued for 2 more hours at 23*C. Then, the reaction mixture was diluted with ethyl acetate. Then, it was washed twice with saturated sodium chloride solution. After drying on sodium sulfate, the crude product was purified on silica gel by column chromatography. 38 mg of product was obtained. 'H-NMR (ppm, CDCl 3 , 300 MHz): 0.87 (1H), 0.92-1.11 (3H), 2.43 (1H), 2.64 (1H), 3.11 (lH), 5.27 (2H), 5.67 (lH), 6.73 (2H), 6.98 (lH), 7.14 (2H), 7.28-7.38 (2H), 7.60 (lH), 7.85 (1H), 7.97 (1H), 8.84 (lH). rac-5-{2-[(4-Carboxyphenyl)ethinyl]-2-hydroxy-3-[1-(2-fluoro-5 trifluoromethylphenyl)- cyclopropyl]-propionylamino}phthalide 8 WO 2006/136462 PCT/EP2006/006532 66 CO,H F HO H 0 0 CF, Analogously to Example 6, compound 8 was produced from the compound described under Example 1 and 4-iodobenzoic acid. 'H-NMR (ppm, CDCl 3 /MeOD (5%), 400 MHz): 0.82 (1H), 0.89-1.05 (3H), 2.37 (1H), 2.65 (1H), 5.24 (2H), 6.97 (1H), 7.35 (1H), 7.44 (2H), 7.50-7.65 (2H), 7.72 (1H), 7.80 (1H), 7.92 (2H). rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-(pentin 1-yl)-propionylamino}phthalide 9 )7 F HO H NO 0 CF, A solution that consists of 1-pentyne (0.94 ml) in THF (9 ml) was mixed at-78*C with nBuLi (0.6 ml, 1.6 M in hexane). It was allowed to stir for 30 minutes at -78*C, and then a solution of 5-{3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2 oxopropionylamino}phthalide (200 mg) in 3 ml of tetrahydrofuran was added. Then, it was allowed to come to 23*C over about 3 hours, and it was stirred for 10 more hours at this temperature. Then, the reaction mixture was poured into ice-cold, saturated ammonium chloride solution. It was extracted with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution and dried on WO 2006/136462 PCT/EP2006/006532 67 sodium sulfate. The crude product was chromatographed on silica gel. 130 mg of product was obtained. 'H-NMR (ppm, CDCl 3 , 400 MHz): 0.82 (1H), 0.92-1.07 (6H), 1.45 (2H), 2.08 (2H), 2.30 (1H), 2.53 (1H), 2.83 (1H), 5.27 (2H), 7.02 (1H), 7.29 (1H), 7.36 (1H), 7.57 (1H), 7.84 (1H), 7.96 (1H), 8.72 (11H). (+)-5-{2-Hydroxy-3-fl-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-(pentin-1 yl)-propionylamino}phthalide 9a and (-)-5-{2-Hydroxy-3- [1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl] -2-(pentin-1 yl)-propionylamino}phthalide 9b The racemic mixture (120 mg) which was described in example 2 was separated by preparative chiral HPLC (column Chiralpak AD 250x10 mm) into the enantiomers 9a (46 mg) and 9b_(47 mg). 9a: [a]D 20 : + 10.9' (CHCl 3 , 1.01 g/100 ml; ?=589 nM) 9b : [a]D 2 0: - 10.6' (CHC1 3 , 1.08 glOO ml; =589 nM) rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyll-2-(hexin-1 yl)-propionylamino}phthalide 10 F HO H O N 00 CF, Compound 10 was synthesized analogously to Example 9. 'H-NMR (ppm, CDCl 3 , 400 MHz): 0.80-1.06 (7H), 1.30-1.50 (2H), 1.59 (2H), 2.10 (2H), 2.30 (1H), 2.52 (1H), 2.82 (1H), 5.28 (2H), 7.02 (1H), 7.30 (1H), 7.36 (1H), 7.57 (1H), 7.84 (1H), 7.95 (1H), 8.72 (1H).

WO 2006/136462 PCT/EP2006/006532 68 rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-[(4 hydroxy)butin-1-yl]-propionylamino}phthalide 11 OH F HO H |ON O 0 0 CF, Stage A: Reaction of 4-(tert-butyldimethylsilyloxo)but-1-yne (175 mg), nBuLi (0.59 ml, 1.6 M in hexane) 5-{3-[1-(2-Fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2 oxopropionylamino}-phthalide (200 mg) in tetrahydrofuran analogously to the process described under Example 9 yielded 165 mg of product. Stage B: The product obtained under stage A (160 mg) was dissolved in 5 ml of tetrahydrofuran. At 0*C, 270 pl of a 1 molar solution of tetrabutylammonium fluoride in tetrahydrofuran was added and stirred for one hour at 0*C and for another 2 hours at 23*C. Then, the reaction mixture was poured into saturated, aqueous sodium bicarbonate solution. It was extracted several times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution and dried on sodium sulfate. After column chromatography on silica gel, 77 mg of product was obtained. 'H-NMR (ppm, CDCl 3 , 400 MHz): 0.83 (1H), 0.90-1.03 (3H), 2.20-2.40 (3H), 2.50 (1H), 3.39 (1H), 3.68 (2H), 5.25 (2H), 7.01 (1H), 7.32 (2H), 7.57 (1H), 7.82 (1H), 7.93 (1H), 8.91 (1H). Analogously to Example 11, compounds 12 and 13 were produced from 5- {3-[I (2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-oxopropionylamino}phthalide: WO 2006/136462 PCT/EP2006/006532 69 rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyll-2-[(5 hydroxy)pentin-1-yl]-propionylamino}phthalide 12 OH // F HO 0 0 0 CF, 'H-NMR (ppm, CDC1 3 , 400 MHz): 0.83 (1H), 0.90-1.03 (3H), 1.70 (2H), 2.24 (2H), 2.33 (1H), 2.50 (1H), 3.09 (1H), 3.71 (2H), 5.26 (2H), 7.02 (1H), 7.35 (2H), 7.57 (1H), 7.83 (1H), 7.97 (1H), 8.82 (1H). rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-[(3 hydroxy)propin-1-yl]-propionylamino}phthalide 13 OH F HO H 0 0 00 CF, 'H-NMR (ppm, CDC1 3 , 400 MHz): 0.84 (1H), 0.90-1.03 (3H), 2.37 (1H), 2.52 (1H), 3.25 (1H), 4.17 (2H), 5.27 (2H), 7.02 (1H), 7.30-7.40 (2H), 7.58 (1H), 7.83 (1H), 7.91 (1H), 8.77 (1H). (+)-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyll-2-1(3 hydroxy)propin-1-yI]-propionylamino}phthalide 13a and (-)-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl] -2-[(3 hydroxy)propin-1-yI]-propionylamino}phthalide 13b WO 2006/136462 PCT/EP2006/006532 70 The racemic mixture (80 mg) which was described in example 1 was separated by preparative chiral HPLC (column Chiralpak AD 250x10 mm) into the enantiomers 13a (35 mg) and 13b (37 mg). 13a : [a]D20: + 28.3 (CHCl3, 1.01 g/100 ml; X=589 nM) 13b: [a] 20: - 29.3' (CHC1 3 , 1.08 g100 ml; k=589 nM) rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-[(4 hydroxy-3-methyl)butin-1-yl]-propionylamino}phthalide 14 OH I/ F HO H O N 00 0 ' 0 CF, Stage A: Analogously to Example 11, 300 mg of 5-{3-[1-(2-fluoro-5 trifluoromethylphenyl)-cyclopropyl]-2-oxopropionylamino}phthalide and 282 mg of tert-butyl-(1,1-dimethylprop-2-ynyl-oxy)-dimethylsilane are reacted. 15 mg of product A is obtained. Stage B: 70 mg of the compound that is obtained under A was dissolved in 1 ml of dichloromethane. 650 pl of trifluoroacetic acid (20% in dichloromethane) was added at 0*C, and it was stirred for 3.5 hours at 0*C. Then, it was evaporated to the dry state in a vacuum, and the residue was purified by column chromatography on silica gel. 27 mg of product was obtained. 'H-NMR (ppm, CDCl 3 , 400 MHz): 0.82 (lH), 0.90-1.00 (2H), 1.04 (1H), 1.47 (6H), 2.28 (1H), 2.58 (1H), 3.08 (1H), 5.27 (2H), 7.03 (1H), 7.30 (1H), 7.36 (1H), 7.59 (1H), 7.83 (lH), 7.91 (1H), 8.78 (1H).

WO 2006/136462 PCT/EP2006/006532 71 rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-(2-(tert butylcarboxy)ethin-1-yl)-propionylamino}phthalide 15 F HO H N O 7 0- 0 CF, Compound 15 was synthesized analogously to Example 9. 'H-NMR (ppm, CDC1 3 , 400 MHz): 0.87 (1H), 0.93-1.05 (3H), 1.46 (9H), 2.42 (1H), 2.59 (1H), 3.39 (1H), 5.28 (2H), 7.03 (1H), 7.30-7.42 (2H), 7.57 (1H), 7.85 (1H), 7.92 (1H), 8.68 (1H). rac-5-{2-Hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-(2 carboxyethin-1-yl)-propionylamino}phthalide 16 0 OH F HO H ON O 0 CF, 50 mg of the compound that is described under Example 15 was dissolved in 5 ml of dichloromethane. 100 tl of trifluoroacetic acid was added, and it was stirred for 12 more hours at 23'C. Then, it was evaporated to the dry state in a vacuum, and the residue was purified by column chromatography on silica gel. 36 mg of product was obtained. 'H-NMR (ppm, DMSO-D 6 , 300 MHz): 0.48 (1H), 0.78 (1H), 0.86 (1H), 1.09 (1H), 1.73 (1H), 2.89 (1H), 5.27 (2H), 6.62 (1H), 7.13 (1H), 7.31 (1H), 7.41 (1H), 7.53 (1H), 7.62 (1H), 7.68 (1H), 9.85 (1H).

WO 2006/136462 PCT/EP2006/006532 72 Analogously to Example 3, compound 17 was produced from 5-{3-[1-phenyl cyclopropyl]-2-oxopropionylamino}phthalide: rac-5-{2-Hydroxy-3-[1-phenyl-cyclopropyl]-2-(phenyl-ethinyl)propionylamino} phthalide 17 HO H O 0 0 'H-NMR (ppm, CDC1 3 , 400 MHz): 0.78 (1H), 0.90 (1H), 1.10-1.21 (2H), 2.38 (1H), 2.72 (1H), 2.77 (1H), 5.28 (2H), 7.18 (1H), 7.25-7.42 (6H), 7.41-7.52 (4H), 7.82 (1H), 8.06 (1H), 8.79 (1H).

Claims

1. Compounds of general formula I R HB 4a R3 | 0 0 (I), in which R' and R 2 , independently of one another, mean a hydrogen atom, a straight or nonstraight, branched or unbranched Ci-C 5 -alkyl group, also together with the C atom of the chain forming a ring with a total of 3-7 members, R3 means a radical C=C-Ra, whereby Ra means a hydrogen or a Ci-C 8 -alkyl, C 2 -C 8 -alkenyl, C 2 -C 8 -alkinyl, C 3 -Cio-cycloalkyl, or heterocycloalkyl that optionally is substituted in one or more places, in the same way or differently, with K, or an aryl or heteroaryl that optionally is substituted in one or more places, in the same way or differently, with L, b b K is a cyano, halogen, hydroxy, nitro, -C(O)R , CO 2 R , -O-R , -S-R , SO 2 NRCR d, -C(O)-NRCRd, -OC(O)-NRcR', or -C=NOR -NRcRd or a C 3 -Cio-cycloalkyl that optionally is substituted in one or more places, in the same way or differently, with M, heterocycloalkyl, or aryl or heteroaryl that optionally is substituted in one or more places with L, L means Ci-C 8 -alkyl, C 2 -C 8 -alkenyl, C 2 -C8-alkinyl, CI-C 6 - WO 2006/136462 PCT/EP2006/006532 74 perfluoroalkyl, C 1 -C 6 -perfluoroalkoxy, C I-C 6 -alkoxy-Ci C 6 -alkoxy, (CH 2 )p-C 3 -CIo-cycloalkyl, (CH 2 )p heterocycloalkyl, (CH 2 )pCN, (CH 2 )pHal, (CH 2 )pNO 2 , (CH 2 )p-C 6 -Ci 2 -aryl, (CH 2 )p-heteroaryl, -(CH 2 )pPO 3 (R )2, -(CH 2 )pNR'Rd, -(CH 2 )pNReCOR, -(CH 2 )pNReCSRb, -(CH 2 )pNReS(O)Rb, -(CH 2 )pNReS(O) 2 Rb, -(CH 2 )pNR*CONRcRd, -(CH 2 )pNReCOORb, -(CH 2 )pNReC(NI)NRcRd, -(CH 2 )pNReCSNRcR , -(CH 2 )pNReS(O)NRCR', -(CH 2 )pNReS(O) 2 NRcRd, -(CH 2 )pCORb, b -(CH 2 )pCSRb, -(CH 2 )pS(O)R, -(CH2)pS(O)(NH)R b, -(CH2)pS(O)2Rb, -(CH 2 )pS(O) 2 NRcRd, -(CH 2 )pSO 2 OR, -(CH 2 )pCO 2 R , -(CH 2 )pCONRcRd, -(CH 2 )pCSNRcRd, -(CH 2 )pORb, -(CH 2 )pSRb, -(CH 2 )pCRb(OH)-Re, -(CH 2 )p-C=NORb, -O-(CH 2 )n-O-, -O-(CH 2 )n-CH 2 -, -O-CH=CH or -(CH 2 )n+ 2 -, whereby n = 1 or 2, and the terminal oxygen atoms and/or carbon atoms are linked to directly adjacent ring-carbon atoms, M means Ci-C 6 -alkyl or a group -CORb, CO 2 R', -O-R , or cd -NRcR , whereby Rb means a hydrogen or a CI-C 6 -alkyl, C 2 -Cs-alkenyl, C 2 -C 8 -alkinyl, C 3 -Cio-cycloalkyl, C 6 -C 1

2-aryl or Ci C 3 -perfluoroalkyl and WO 2006/136462 PCT/EP2006/006532 75 RC and Rd, independently of one another, mean a hydrogen, CI-C 6 -alkyl, C 2 -Cs-alkenyl, C 2 -Cs-alkinyl, C 3 -Cio cycloalkyl, C 6 -C 12 -aryl, C(O)Rb or a hydroxy group, whereby if RC is a hydroxy group, Rd can be only one hydrogen, a Ci-C 6 -alkyl, C 2 -Cs-alkenyl, C 2 -Cs-alkinyl, C 3 -C 10 cycloalkyl or C 6 -Ci 2 -aryl and vice versa, and Re means a hydrogen, Ci-C 6 -alkyl, C 2 -Cs-alkenyl, C 2 -Cs-alkinyl, C 3 -CIo-cycloalkyl or C 6 -C 12 -aryl, and p can be a number from 0- 6, or R3 is a radical C = C-R9Rh, whereby R9 and Rh, independently of one another, are a hydrogen or a CI-Cs-alkyl, C 2 -Cs-alkenyl or C 2 -Cs-alkinyl that optionally is substituted in one or more places, in the same way or differently, with X, in which X is a cyano, halogen, hydroxy, nitro, -C(O)Rb, CO 2 R , -O-Rb, -C(O)-NRcRd, -NRcRd with the meanings, already further mentioned above, for Rb, Rc and Rd, and R 4 a and R 4 b, independently of one another, mean a hydrogen atom, a C 1 -C 4 -alkyl, a C 2 -C 4 -alkenyl or together with the ring-carbon atom forming a 3- to 6 membered ring, A means a monocyclic or bicyclic, carbocyclic or heterocyclic aromatic ring, which optionally can be substituted in one or more places with C 1 C 8 -alkyl, C 2 -C 8 -alkenyl, C 2 -C 8 -alkinyl, Ci-C 6 -perfluoroalkyl, CI-C 6 - WO 2006/136462 PCT/EP2006/006532 76 perfluoroalkoxy, CI-C 6 -alkoxy-CI-C 6 -alkyl, CI-C 6 -alkoxy-Ci-C 6 -alkoxy, (CH 2 )p-C 3 -C o-cycloalkyl, (CH 2 )p-heterocycloalkyl, (CH 2 )pCN, (CH 2 )pHal, (CH 2 )pNO 2 , (CH 2 )p-C 6 -C 2 -aryl, (CH 2 )p-heteroaryl, -(CH 2 )pPO 3 (R) 2 , -(CH 2 )pNRCRd, -(CH 2 )pNReCORb, -(CH 2 )pNReCSRb, -(CH 2 )pNReS(O)R', -(CH 2 )pNR*S(0) 2 Rb, -(CH 2 )pNReCONRcR', -(CH 2 )pNReCOOR', -(CH 2 )pNReC(NH)NRcRd, -(CH 2 )pNReCSNRRd, -(CH 2 )pNReS(O)NRcRd, -(CH 2 )pNReS(O) 2 NRRd, -(CH 2 )pCORb, -(CH 2 )pCSRb, -(CH 2 )p S(O)Rb, -(CH 2 )pS(O)(NH)Rb, -(CH 2 )pS(O) 2 Rb, -(CH 2 )pS(O) 2 NRcRd, -(CH 2 )pSO 2 ORb, -(CH 2 )pCO 2 Rb, -(CH 2 )pCONR Rd, -(CH 2 )pCSNRcRd, -(CH 2 )pORb, -(CH 2 )pSRb, -(CH 2 )pCRb(OH)-Rd, -(CH 2 )p-C=NORb, -O-(CH 2 )n-O-, -O-(CH 2 )n-CH 2 -, -O-CH=CH- or -(CH 2 )n+ 2 -, whereby n = 1 or 2, and the terminal oxygen atoms and/or carbon atoms are linked to directly adjacent ring-carbon atoms, or bd A means a radical -CO 2 Rb, C(O)NRcRd, CORb, or 5 6 7 A means an alkenyl group -CR = CR R , whereby R , R6 and R are the same or different and, independently of one another, mean hydrogen atoms, halogen atoms, aryl radicals or an unsubstituted or partially or completely fluorinated C,-C 5 -alkyl group, or 5 5 A means an alkinyl group -C=CR , with the meaning cited above for R , and B means a carbonyl group or a CH 2 group as well as their pharmaceutically acceptable salts. 2. Compounds according to claim 1, in which R' and R 2 preferably mean a hydrogen atom, a methyl group or an ethyl group. WO 2006/136462 PCT/EP2006/006532 77

3. Compounds according to claim 1, in which R' and R 2 preferably together with the C atom of the chain form a ring with a total of 3 to 7 links.

4. Compounds according to claims 1 to 3, in which R 3 preferably means alkenyl, alkinyl, arylalkinyl, heteroarylalkinyl, cycloalkylalkinyl, or heterocycloalkylalkinyl.

5. Compounds according to one of the preceding claims, in which R 3 preferably means a vinyl, ethinyl, propinyl, butinyl, pentinyl, hexinyl, heptinyl, octinyl, hydroxypropinyl, hydroxybutinyl, 3-hydroxy-3-methylbutinyl, hydroxypentinyl, carboxypropinyl, t-butylcarboxypropinyl, phenylethinyl, (hydroxyphenyl)ethinyl, (methoxyphenyl)ethinyl, (dimethylaminophenyl)ethinyl, (methylphenyl)ethinyl, (cyanophenyl)ethinyl, (trifluoromethyl)ethinyl, (diphenyl)ethinyl, (nitrophenyl)ethinyl, (tert-butylphenyl)ethinyl, (acetylphenyl)ethinyl, (acetoxyphenyl)ethinyl, (carboxyphenyl)ethinyl or a benzylethinyl group.

6. Compounds according to one of the preceding claims, in which A is preferably an aromatic ring.

7. Compounds according to one of the preceding claims, in which A is preferably a phenyl or naphthyl radical.

8. Compounds according to claim 7, in which A preferably is an unsubstituted phenyl radical or optionally a phenyl radical that is substituted in one or more places.

9. Compounds according to claim 8, whereby the phenyl radical is preferably substituted with one or two halogen atoms or a trifluoromethyl group.

10. Compounds according to claim 9, in which the halogen atoms are preferably chlorine and/or fluorine.

11. Compounds according to claims 1-8, in which A preferably is an -O-(CH2)n 0- or -O-(CH 2 )n-CH 2 -substituted phenyl ring, whereby the respectively directly adjacent ring-carbon atoms are linked. WO 2006/136462 PCT/EP2006/006532 78

12. Compounds according to one of the preceding claims, in which R 4 a and R 4 , independently of one another, in each case are a hydrogen atom.

13. Compounds according to claims 1 to 12, namely: No. Racemic or R3 R 3 OH Enantiomer H I 0 1 rac H 0 2 + 3 4 rac 5 + 6 7 rac 8 + 9 10 rac 11 +/ 12 13 rac OH 14 + 15 16 rac OH 17 + 18 19 rac OH WO 2006/136462 PCT/EP2006/006532 79 20 + 21 22 rac 23 + 24 25 rac OH 26 + 27 28 rac 11LOH 29 + 30 31 rac 32 + 33 34 rac 35 + 36 37 rac 38 + 39 40 rac 41 + 42 43 rac WO 2006/136462 PCT/EP2006/006532 80 44 + 45 46 rac 0 47 + 48 49 rac NO2 50 + 51 52 rac 53 + 54 - OH 55 rac 56 + 57 58 rac " N OH 59 + 60 WO 2006/136462 PCT/EP2006/006532 81 No. Racemic or R3 Enantiomer R OH H 61 rac H N 1I 0 62 + 63 64 rac 65 + 66 67 rac 68 + 69 70 rac 71 + 72 73 rac OH 74 + 75 76 rac OH 77 + 78 79 rac " 80 + 81 WO 2006/136462 PCT/EP2006/006532 82 82 rac 83 + 84 85 rac OH 86 + 87 88 rac ILOH 89 + 90 91 rac 92 + 93 94 rac 95 + 96 97 rac CF 98 + 99 100 rac 101 + 102 103 rac 104 + 105 WO 2006/136462 PCT/EP2006/006532 83 106 rac 107 + 108 109 rac NO, 110 + 111 112 rac 113 + 114 115 rac 116 + 117 118 rac " N OH 119 + 120 No. Racemic or R3 Enantiomer R OH H 121 rac H N N 0 I 0 122 + 0 123 124 rac WO 2006/136462 PCT/EP2006/006532 84 125 + 126 127 rac 128 + 129 130 rac 131 + 132 133 rac OH 134 + 135 136 rac OH 137 + 138 139 rac H 140 + 141 142 rac 143 + 144 0 OH 145 rac 146 + WO 2006/136462 PCT/EP2006/006532 85 147 148 rac OH 149 + 150 151 rac 152 + 153 154 rac 155 + 156 157 rac C 158 + 159 160 rac 161 + 162 163 rac 164 + 165 166 rac 167 + 168 169 rac NO2 170 + WO 2006/136462 PCT/EP2006/006532 86 171 172 rac 173 + 174 175 rac 176 + 177 178 rac Om 179 + 180 No. Racemic or R3 Enantiomer R OH H 181 rac H N O 182 + 183 184 rac 185 + 186 187 rac 188 + 189 WO 2006/136462 PCT/EP2006/006532 87 190 rac 191 + 192 193 rac OH 194 + 195 196 rac OH 197 + 198 199 rac OH 200 + 201 202 rae 203 + 204 205 rac OH 206 + 207 208 rac OH 209 + 210 211 rac 212 + 213 WO 2006/136462 PCT/EP2006/006532 88 214 rac 215 + 216 217 rac CF 218 + 219 220 rac 221 + 222 223 rac 224 + 225 226 rac 227 + 228 229 rac -NO 230 + 231 232 rac 233 + 234 235 rac OH 236 + 237 WO 2006/136462 PCT/EP2006/006532 89 238 rac 239 + 240 No. Racemic or R3 R 3 Enantiomer H H 241 rac H 242 + 0 243 244 rac 245 + 246 247 rac 248 + 249 250 rac 251 + 252 253 rac OH 254 + 255 256 rac OH WO 2006/136462 PCT/EP2006/006532 90 257 + 258 259 rac OH 260 + 261 262 rac 263 + 264 265 rac OH 266 + 267 268 rac OH 269 + 270 271 rac 272 + 273 274 rac 275 + 276 277 rac 278 + 279 280 rac WO 2006/136462 PCT/EP2006/006532 91 281 + 282 283 rac 284 + 285 286 rac 287 + 288 289 rac . NO2 290 + 291 292 rac 0 293 + 294 295 rac o 296 + 297 298 rac 299 + 300 WO 2006/136462 PCT/EP2006/006532 92 No. Racemic or R3 Enantiomer R OH H 301 rac H 302 + 0 303 304 rac 305 + 306 307 rac 308 + 309 310 rac 311 + 312 313 rac OH 314 + 315 316 rac OH 317 + 318 319 rac OH 320 + 321 322 rac WO 2006/136462 PCT/EP2006/006532 93 323 + 324 325 rac t OH 326 + 327 328 rac o~YOH 329 + 330 331 rac 332 + 333 334 rac 335 + 336 _ CF, 337 rac 338 + 339 340 rac 341 + 342 343 rac 344 + WO 2006/136462 PCT/EP2006/006532 94 345 346 rac 347 + 348 349 rac NO, 350 + 351 352 rac 353 + 354 355 rac Om 356 + 357 358 rac 359 + 360 No. Racemic or R3 Enantiomer R OH H 361 rac H N,| 0 00 362 + 0 363 WO 2006/136462 PCT/EP2006/006532 95 364 rac 365 + 366 367 rac 368 + 369 370 rac 371 + 372 373 rac OH 374 + 375 376 rac OH 377 + 378 OH 379 rac 380 + 381 382 rac 383 + 384 385 rac OH WO 2006/136462 PCT/EP2006/006532 96 386 + 387 388 rac OH 389 + 390 391 rac 392 + 393 394 rac 395 + 396 397 rac CF, 398 + 399 400 rac 401 + 402 403 rac 404 + 405 406 rac 0 407 + 408 409 rac NO, WO 2006/136462 PCT/EP2006/006532 97 410 + 411 412 rac 413 + 414 415 rac OH 416 + 417 418 rac H OH 419 + 420 No. Racemic or R3 Enantiomer R OH CI H 421 rac H N O 422 + 0 423 424 rac 425 + 426 427 rac 428 + 429 WO 2006/136462 PCT/EP2006/006532 98 430 rac 431 + 432 433 rac OH 434 + 435 436 rac OH 437 + 438 439 rac OH 440 + 441 442 rac 443 + 444 445 rac OH 446 + 447 448 rac I OH 449 + 450 451 rac 452 + 453 WO 2006/136462 PCT/EP2006/006532 99 454 rac 455 + 456 457 rac CF3 458 + 459 460 rac 461 + 462 463 rac 0 464 + 465 466 rac 467 + 468 469 rac NO, 470 + 471 472 rac 473 + 474 475 rac OH 476 + 477 WO 2006/136462 PCT/EP2006/006532 100 0 478 rac 479 + 480 No. Racemic or R3 Enantiomer R OH N 0 H 481 rac N Br 482 + 483 484 rac 485 + 486 487 rac 488 + 489 490 rac 491 + 492 493 rac OH 494 + WO 2006/136462 PCT/EP2006/006532 101 495 496 rac OH 497 + 498 499 rac OH 500 + 501 502 rac 503 + 504 505 rac OH 506 + 507 508 rac OH 509 + 510 511 rac 512 + 513 214 rac 515 + 516 517 rac 518 + WO 2006/136462 PCT/EP2006/006532 102 519 520 rac 521 + 522 523 rac 524 + 525 526 rac 227 + 528 529 rac NO, 530 + 531 532 rac 0 533 + 534 535 rac OH 536 + 537 538 rac OH N 539 + 540 WO 2006/136462 PCT/EP2006/006532 103 No. Racemic or R3 R 3 OH Enantiomer H 541 rac H O O 0 542 + 0 543 544 rac 545 + 546 547 rac 548 + 549 550 rac 551 + 552 553 rac OH 554 + 555 556 rac OH 557 + 558 559 rac OH 560 + 561 562 rae WO 2006/136462 PCT/EP2006/006532 104 563 + 564 565 rac OH 566 + 567 568 rac IXOH 569 + 570 571 rac 572 + 573 574 rac 575 + 576 577 rac 578 + 579 580 rac N 581 + 582 583 rac 584 + 585 586 rac WO 2006/136462 PCT/EP2006/006532 105 587 + 588 589 rac NO 590 + 591 592 rac 593 + 594 595 rac OH 596 + 597 598 rac 599 + 600 No. Racemic or R3 Enantiomer OH H 601 rac N O 602 + CF 3 O 603 604 rac 605 + WO 2006/136462 PCT/EP2006/006532 106 606 607 rac 608 + 609 610 rac 611 + 612 613 rac OH 614 + 615 616 rac OH 617 + 618 OH 619 rac 620 + 621 622 rac 623 + 624 625 rac OH 626 + 627 WO 2006/136462 PCT/EP2006/006532 107 628 rac 629 + 630 631 rac 632 + 633 634 rac 635 + 636 637 rac CF. 638 + 639 640 rac 641 + 642 643 rac 644 + 645 646 rac O 647 + 648 649 rac 650 + 651 WO 2006/136462 PCT/EP2006/006532 108 652 rac 653 + 654 655 rac 656 + 657 658 rac H 659 + 660 R 3 OH No. Racemic or R3 0 H Enantiomer 0 o F 0 661 rac H 662 + 663 664 rac 665 + 666 667 rac 668 + 669 670 rac WO 2006/136462 PCT/EP2006/006532 109 671 + 672 673 rac OH 674 + 675 676 rac OH 677 + 678 679 rac OH 680 + 681 682 rac 683 + 684 685 rac OH 686 + 687 688 rac OH 689 + 690 691 rac 692 + 693 694 rac WO 2006/136462 PCT/EP2006/006532 110 695 + 696 697 rac 698 + 699 700 rac 701 + 702 703 rac 704 + 705 706 rac 707 + 708 709 rac 710 + 711 712 rac 713 + 714 OH 715 rac 716 + WO 2006/136462 PCT/EP2006/006532 111 717 718 rac OH 719 + 720 No. Racemic or R3 Enantiomer R OH H 721 rac H 0 NO 0 0 722 + 0 723 724 rac 725 + 726 727 rac 728 + 729 730 rac 731 + 732 733 rac OH 734 + 735 WO 2006/136462 PCT/EP2006/006532 112 736 rac OH 737 + 738 739 rac OH 740 + 741 742 rac 743 + 744 745 rac OH 746 + 747 748 rac OH 749 + 750 751 rac 752 + 753 754 rac 755 + 756 757 rac CF, 758 + 759 WO 2006/136462 PCT/EP2006/006532 113 N 760 rac 761 + 762 763 rac 764 + 765 766 rac 767 + 768 769 rac NO 770 + 771 772 rac 773 + 774 775 rac 776 + 777 778 rac OH 779 + 780 WO 2006/136462 PCT/EP2006/006532 114 R OH No. Racemic or R3 H Enantiomer F N CFk O 781 rac H 782 + 783 784 rac 785 + 786 787 rac 788 + 789 790 rac 791 + 792 793 rac OH 794 + 795 796 rac OH 797 + 798 799 rac O" 800 + 801 WO 2006/136462 PCT/EP2006/006532 115 802 rac ' 803 + 804 805 rac OH 806 + 807 808 rac OH 809 + 810 811 rac 812 + 813 814 rac 815 + 816 817 rac 818 + 819 820 rac 821 + 822 823 rac 824 + 825 WO 2006/136462 PCT/EP2006/006532 116 826 rac 827 + 828 829 rac - NO, 830 + 831 832 rac 833 + 834 835 rac oH 836 + 837 838 rac 839 + 840 No. Racemic or R3 R 3 Enantiomer 0 OH H 841 raC H O 842 + CF 3 O 843 844 rac WO 2006/136462 PCT/EP2006/006532 117 845 + 846 847 rac 848 + 849 850 rac 851 + 852 OH 853 rac 854 + 855 856 rac OH 857 + 858 859 rac OH 860 + 861 862 rac 863 + 864 865 rac OH 866 + 867 WO 2006/136462 PCT/EP2006/006532 118 868 rac OH 869 + 870 871 rac 872 + 873 874 rac 875 + 876 877 rac 878 + 879 880 rac 881 + 882 883 rac 884 + 885 886 rac 887 + 888 889 rac NO, 890 + 891 WO 2006/136462 PCT/EP2006/006532 119 892 rac 893 + 894 895 rac 896 + 897 898 rac 0 899 + 900 No. Racemic or R3 Enantiomer Ra OH F H 901 rac N O 00 902 + CF 3 0 903 904 rac 905 + 906 907 rac 908 + 909 910 rac WO 2006/136462 PCT/EP2006/006532 120 911 + 912 913 rac OH 914 + 915 916 rac OH 917 + 918 919 rac OH 920 + 921 922 rac 923 + 924 925 rac OH 926 + 927 928 rac OH 929 + 930 931 rac 932 + 933 934 rac WO 2006/136462 PCT/EP2006/006532 121 935 + 936 937 rac 938 + "' 939 940 rac 941 + 942 943 rac 944 + 945 946 rac 947 + 948 949 rac .. NO, 950 + 951 952 rac 953 + 954 955 rac 956 + 957 958 rac OH OH WO 2006/136462 PCT/EP2006/006532 122 959 + 960 No. Racemic or R3 Enantiomer R OH H 961 rac H N O FO 962 + 0 963 964 rac 965 + 966 967 rac 968 + 969 970 rac 971 + 972 973 rac OH 974 + 975 976 rac OH 977 + WO 2006/136462 PCT/EP2006/006532 123 978 979 rac OH 980 + 981 982 rac 983 + 984 985 rac OH 986 + 987 988 rac OH 989 + 990 991 rac 992 + 993 994 rac 995 + 996 CF, 997 rac 998 + 999 WO 2006/136462 PCT/EP2006/006532 124 1000 rac 1001 + 1002 1003 rac 1004 + 1005 1006 rac 1007 + 1008 1009 rac NOr 1010 + 1011 1012 rac 1013 + 1014 1015 rac 1016 + 1017 1018 rac 0 1019 + 1020 WO 2006/136462 PCT/EP2006/006532 125 No. Racemic or R3 Enantiomer R OH NO 0_ H 1021 rac H N O / - 0 1022 + F 0 1023 1024 rac 1025 + 1026 1027 rac 1028 + 1029 1030 rac 1031 + 1032 1033 rac OH 1034 + 1035 1036 rac OH 1037 + 1038 1039 rac OH 1040 + 1041 WO 2006/136462 PCT/EP2006/006532 126 1042 rac 1043 + 1044 1045 rac 0 OH 1046 + 1047 1048 rac OH 1049 + 1050 1051 rac 1052 + 1053 1054 rac 1055 + 1056 1057 rac CF, 1058 + 1059 1060 rac 1061 + 1062 1063 rac 1064 + WO 2006/136462 PCT/EP2006/006532 127 1065 1066 rac 1067 + 1068 1069 rac NO, 1070 + 1071 1072 rac 1073 + 1074 1075 rac OH 1076 + 1077 1078 rac 0 Nm 1079 + 1080 R 3 OH No. Racemic or R3 0 H Nz Enantiomer o N 0 I 0 1081 rac H 1082 + 1083 WO 2006/136462 PCT/EP2006/006532 128 1084 rac 1085 + 1086 1087 rac 1088 + 1089 1090 rac 1091 + 1092 1093 rac OH 1094 + 1095 1096 rac OH 1097 + 1098 1099 rac OH 1100 + 1101 1102 rac 1103 + 1104 1105 rac OH 1106 + 1107 WO 2006/136462 PCT/EP2006/006532 129 1108 rac OH 1109 + 1110 1111 rac 1112 + 1113 1114 rac 1115 + 1116 1117 rac CF, 1118 + 1119 1120 rac 1121 + 1122 1123 rac 1124 + 1125 1126 rac 1127 + 1128 1129 rac NO, 1130 + 1131 WO 2006/136462 PCT/EP2006/006532 130 1132 rac 1133 + 1134 1135 rac 1136 + 1137 1138 rac 1139 + 1140 No. Racemic or R3 R O Enantiomer 0 H H 1141 rac H O O 1142 + 0 1143 1144 rac 1145 + 1146 1147 rac 1148 + 1149 1150 rac 1151 + WO 2006/136462 PCT/EP2006/006532 131 1152 1153 rac OH 1154 + 1155 1156 rac OH 1157 + 1158 1159 rac OH 1160 + 1161 1162 rac 1163 + 1164 1165 rac OH 1166 + 1167 1168 rac IXOH 1169 + 1170 1171 rac 1172 + 1173 1174 rac 1175 + -- WO 2006/136462 PCT/EP2006/006532 132 1176 1177 rac 1178 + 1179 1180 rac 1181 + 1182 1183 rac 1184 + 1185 1186 rac 1187 + 1188 1189 rac NO2 1190 + 1191 1192 rac 1193 + 1194 1195 rac OK 1196 + 1197 1198 rac 1199 + WO 2006/136462 PCT/EP2006/006532 133 1200 No. Racemic or R3 Enantiomer R OH H 1201 rac 0 1202 + 1203 1204 rac 1205 + 1206 1207 rac 1208 + 1209 1210 rac 1211 + 1212 1213 rac OH 1214 + 1215 1216 rac O 1217 + 1218 WO 2006/136462 PCT/EP2006/006532 134 1219 rac CH 1220 + 1221 1222 rac 1223 + 1224 1225 rac OH 1226 + 1227 1228 rac OH 1229 + 1230 1231 rac 1232 + 1233 1234 rac 1235 + 1236 .. CF, 1237 rac 1238 + 1239 1240 rac WO 2006/136462 PCT/EP2006/006532 135 1241 + 1242 1243 rac 1244 + 1245 1246 rac 1247 + 1248 1249 rac * 1250 1251 1252 rac 1253 + 1254 1255 rac OH 1256 + 1257 1258 rac " N ON 1259 + 1260 WO 2006/136462 PCT/EP2006/006532 136 No. Racemic or R3 Enantiomer R OH 0 H 1261 rac H N 0 0 0 1262 + F 0 1263 1264 rac 1265 + 1266 1267 rac 1268 + 1269 1270 rac 1271 + 1272 1273 rac OH 1274 + 1275 1276 rac OH 1277 + 1278 1279 rac OH 1280 + 1281 WO 2006/136462 PCT/EP2006/006532 137 1282 rac 1283 + 1284 1285 rac OH 1286 + 1287 1288 rac 1289 + O 1290 1291 rac 1292 + 1293 1294 rac 1295 + 1296 1297 rac 1298 + 1299 1300 rac 1301 + 1302 1303 rac WO 2006/136462 PCT/EP2006/006532 138 1304 + 1305 1306 rac 1307 + 1308 1309 rac NO, 1310 + 1311 1312 rac 1313 + 1314 1315 rac 1316 + 1317 1318 rac OH 1319 + 1320 No. Racemic or R3 Enantiomer R OH Cl H 1321 rac H N O 0 1322 + F 0 WO 2006/136462 PCT/EP2006/006532 139 1323 1324 rac 1325 + 1326 1327 rac 1328 + 1329 1330 rac 1331 + 1332 1333 rac OH 1334 + 1335 1336 rac 1337 + 1338 1339 rac 1340 + 1341 1342 rac 1343 + 1344 WO 2006/136462 PCT/EP2006/006532 140 1345 rac OH 1346 + 1347 1348 rac oOH 1349 + 1350 1351 rac 1352 + 1353 1354 rac 1355 + 1356 1357 rac 1358 + 1359 1360 rac 1361 + 1362 1363 rac 1364 + 1365 1366 rac 1367 + 1368 WO 2006/136462 PCT/EP2006/006532 141 1369 rac - NO, 1370 + 1371 1372 rac 0 1373 + 1374 1375 rac OH 1376 + 1377 0 OH 1378 rac 1379 + 1380 No. Racemic or R3 Ra3 OH Enantiomer N 1381 rac H O 0 1382 + 1383 1384 rac 1385 + WO 2006/136462 PCT/EP2006/006532 142 1386 1387 rac 1388 + 1389 1390 rac 1391 + 1392 1393 rac OH 1394 + 1395 1396 rac 1397 + 1398 1399 rac OH 1400 + 1401 1402 rac 1403 + 1404 1405 rac OH 1406 + 1407 1408 rac 1409 + WO 2006/136462 PCT/EP2006/006532 143 1410 1411 rac 1412 + 1413 1414 rac 1415 + - 1416 1417 rac CF 1418 + 1419 o 1420 rac 1421 + 1422 1423 rac 1424 + 1425 1426 rac 1427 + 1428 1429 rac NO, 1430 + 1431 WO 2006/136462 PCT/EP2006/006532 144 1432 rac 1433 + 1434 1435 rac OH 1436 + 1437 1438 rac 1439 + 1440 No. Racemic or R3 Ra3 OH Enantiomer H N 1441 rac H 0 1442 + 1443 1444 rac 1445 + 1446 1447 rac 1448 + 1449 1450 rac WO 2006/136462 PCT/EP2006/006532 145 1451 + 1452 1453 rac OH 1454 + 1455 1456 rac OH 1457 + 1458 1459 rac OH 1460 + 1461 1462 rac 1463 + 1464 0 1465 rac 1466 + 1467 1468 rac OH 1469 + 1470 1471 rac 1472 + 1473 WO 2006/136462 PCT/EP2006/006532 146 1474 rac 1475 + 1476 1477 rac CF 1478 + 1479 1480 rac N 1481 + 1482 1483 rac 1484 + 1485 1486 rac 1487 + 1488 1489 rac 1490 + 1491 1492 rac 1493 + 1494 1495 rac 1496 + 1497 WO 2006/136462 PCT/EP2006/006532 147 1498 rac OH 1499 + 1500 No. Racemic or R3 Enantiomer OH /0 H 1501 rac H O O N0O 1502 + 0 1503 1504 rac 1505 + 1506 1507 rac 1508 + 1509 1510 rac 1511 + 1512 1513 rac OH 1514 + WO 2006/136462 PCT/EP2006/006532 148 1515 1516 rac OH 1517 + 1518 1519 rac OH 1520 + 1521 1522 rac 1523 + 1524 1525 rac OH 1526 + 1527 1528 rac OH 1529 + 1530 1531 rac 1532 + 1533 1534 rac 1535 + 1536 1537 rac 1 3CF, 1538 + N WO 2006/136462 PCT/EP2006/006532 149 1539 1540 rac 1541 + 1542 1543 rac 1544 + 1545 1546 rac 1547 + 1548 1549 rac NO, 1550 + 1551 1552 rac 1553 + 1554 1555 rac 1556 + 1557 1558 rac OH 1559 + 1560 WO 2006/136462 PCT/EP2006/006532 150 No. Racemic or R3 Enantiomer R OH H 1561 rac H N I 0 0 1562 + 0 1563 1564 rac 1565 + 1566 1567 rac 1568 + 1569 1570 rac 1571 + 1572 1573 rac OH 1574 + 1575 1576 rac OH 1577 + 1578 1579 rac OH 1580 + 1581 1582 rac WO 2006/136462 PCT/EP2006/006532 151 1583 + 1584 1585 rac OH 1586 + 1587 1588 rac 11LOH 1589 + 1590 1591 rac 1592 + 1593 1594 rac 1595 + 1596 1597 rac 1598 + 1599 1600 rac 1601 + 1602 1603 rac 1604 + 1605 1606 rac WO 2006/136462 PCT/EP2006/006532 152 1607 + 1608 _ NO2 1609 rac 1610 + 1611 1612 rac 1613 + 1614 1615 rac OH 1616 + 1617 1618 rac 0 1619 + 1620

14. Pharmaceutical composition that contains at least one compound of general formula I according to one of claims 1 to 13 and optionally at least one additional active ingredient together with pharmaceutically compatible adjuvants and/or vehicles.

15. Pharmaceutical composition according to claim 14, wherein the additional active ingredient is a SERM (selective estrogen receptor modulator), an aromatase inhibitor, an antiestrogen, or a prostaglandin.

16. Pharmaceutical composition according to claim 14, whereby the active WO 2006/136462 PCT/EP2006/006532 153 ingredients can be tamoxifen, 5-(4-{5-[(RS)-(4,4,5,5,5-pentafluoropentyl)sulfinyl] pentyloxy}phenyl)-6-phenyl-8,9-dihydro-7H-benzocyclohepten-2-ol, ICI 182 780 (7alpha-[9-(4,4,5,5-pentafluoropentylsulfinyl)nonyl]estra-1,3,5(10)-triene-3,17-beta diol), 11 beta-fluoro-7alpha-[5-(methyl{3-[(4,4,5,5,5-pentafluoropentyl)sulfanyl] propyl}amino)pentyl]estra-1,3,5(10)-triene-3,17beta-diol, 11 beta-fluoro-7alpha-{5 [methyl(7,7,8,8,9,9,10,10,10-nonafluorodecyl)amino]pentyl}estra-1,3,5(10)-triene 3,17beta-diol, 11 beta-fluoro- 1 7alpha-methyl-7alpha- {5- [methyl(8,8,9,9,9-pentafluoro nonyl)amino]pentyl}estra-1,3,5(10)-triene-3,17beta-diol, clomifene, raloxifene, fadrozole, formestane, letrozole, anastrozole or atamestane.

17. Use of compounds according to one of claims 1 to 13 for the production of a pharmaceutical agent.

18. Use of compounds according to claim 17 for the production of a pharmaceutical agent for therapy and prophylaxis of gynecological diseases such as endometriosis, leiomyomas of the uterus, dysfunctional bleeding and dysmenorrhea.

19. Use of compounds according to claim 17 for the production of a pharmaceutical agent for therapy and prophylaxis of hormone-dependent tumors.

20. Use of compounds according to claim 17 for the production of a pharmaceutical agent for therapy and prophylaxis of breast cancer.

21. Use of compounds according to claim 17 for the production of a pharmaceutical agent for therapy and prophylaxis of endometrial carcinoma.

22. Use of compounds according to claim 17 for the production of a pharmaceutical agent for therapy and prophylaxis of ovarian cancer.

23. Use of compounds according to claim 17 for the production of a pharmaceutical agent for therapy and prophylaxis of prostate cancer. WO 2006/136462 PCT/EP2006/006532 154

24. Use of compounds according to claim 17 for the production of a pharmaceutical agent for female hormone replacement therapy.

25. Use of compounds according to claim 17 for female birth control.

26. Process for the selective addition of lithium alkinyl compounds and magnesium haloalkinyl compounds to ketoamide. WO 2006/136462 PCT/EP2006/006532 155 AMENDED CLAIMS received by the International Bureau on 04 October 2006 (04.10.2006) +STATEMENT Claims 1. Compounds of general formula I R 2 HBH R4a 4b A ~OR H 4b 0 (I), in which Ri and R 2 , independently of one another, mean a hydrogen atom, a straight or nonstraight, branched or unbranched C1-C 5 -alkyl group, also together with the C atom of the chain forming a ring with a total of 3-7 members, R3 means a radical C=C-Ra, whereby Ra means a hydrogen or a C1-C 8 -alkyl, C 2 -Cs-alkenyl, C 2 -C 8 -alkinyl, C 3 -Cio-cycloalkyl, or heterocycloalkyl that optionally is substituted in one or more places, in the same way or differently, with K, or an aryl or heteroaryl that optionally is substituted in one or more places, in the same way or differently, with L, K is a cyano, halogen, hydroxy, nitro, -C(O)R, CO 2 Rb, -O-R , -S-R , SO 2 NRCRd, -C(O)-NRRd, -OC(O)-NR R, or -C=NOR -NR Rd or a C 3 -Cio-cycloalkyl that optionally is substituted in one or more places, in the same way or differently, with M, heterocycloalkyl, or aryl or heteroaryl that optionally is substituted in one or more places with L, L means C 1 -Cs-alkyl, C2-Cs-alkenyl, C 2 -C 8 -alkinyl, C 1 -C 6 - WO 2006/136462 PCT/EP2006/006532 156 perfluoroalkyl, C 1 -C 6 -perfluoroalkoxy, C 1 -C 6 -alkoxy-CI-C 6 alkoxy, (CH 2 )p-C 3 -Cio-cycloalkyl, (CH 2 )p-heterocycloalkyl, (CH 2 )pCN, (CH 2 )pHal, (CH 2 )pNO 2 , (CH 2 )p-C 6 -CI 2 -aryl, (CH 2 )p heteroaryl, -(CH 2 )pPO 3 (Re) 2 , -(CH 2 )pNR R , -(CH 2 )pNR*CORb, -(CH 2 )pNR CSRe, -(CH 2 )pNReS(O)R, -(CH 2 )pNReS(O) 2 Rb, -(CH 2 )pNReCONRcRd, -(CH 2 )pNReCOORe, -(CH2)pNRC(NH)NRRd, -(CH 2 )pNReCSNRrRd, -(CH 2 )pNReS(O)NRcRd, -(CH 2 )pNReS(O) 2 NR"Rd, -(CH 2 )pCORe, -(CH 2 )pCSRe, -(CH 2 )pS(O)Re, -(CH 2 ),S(O)(NH)Re, -(CH 2 )pS(O) 2 Rb, -(CH 2 )pS(O) 2 NR Rd, -(CH 2 )pSO 2 OR, -(CH 2 )pCO 2 Re, -(CH 2 )pCONRcRd, -(CH 2 )pCSNR4Rd, -(CH 2 )pORe, -(CH 2 )pSRe, -(CH 2 )pCRb(OH)-R*, -(CH 2 )p-C=NOR', -O-(CH2)n-O-, -O-(CH2)n-CH2-, -O-CH=CH or -(CH 2 )n+ 2 -, whereby n = 1 or 2, and the terminal oxygen atoms and/or carbon atoms are linked to directly adjacent ring carbon atoms, M means C1-C 6 -alkyl or a group -CORb, CO 2 Rb, -O-Rb, or -NRcRd, whereby Re means a hydrogen or a CI-C-alkyl, C 2 -Cs-alkenyl, C 2 -C 8 -alkinyl, C 3 -Cio-cycloalkyl, C 6 -C 12 -aryl or CI-C 3 perfluoroalkyl and Rc and Rd, independently of one another, mean a hydrogen, WO 2006/136462 PCT/EP2006/006532 157 C1-C-alkyl, C 2 -Cs-alkenyl, C 2 -Cs-alkinyl, C 3 -CIO cycloalkyl, C 6 -C 1 2 -aryl, C(O)R or a hydroxy group, whereby if R is a hydroxy group, Rd can be only one hydrogen, a CI-C-alkyl, C 2 -C 8 -alkenyl, C 2 -C 8 -alkinyl, C 3 -C 10 cycloalkyl or C 6 -C 1 2 -aryl and vice versa, and Re means a hydrogen, C 1 -C-alkyl, C 2 -C 8 -alkenyl, C 2 -C 8 -alkinyl, C 3 -Cio-cycloalkyl or C-C 1 2 -aryl, and p can be a number from 0- 6, or R 3 is a radical C = C-RgRh, whereby R9 and Rh, independently of one another, are a hydrogen or a C 1 -Cs-alkyl, C 2 -C 8 -alkenyl or C 2 -C 8 -alkinyl that optionally is substituted in one or more places, in the same way or differently, with X, in which X is a cyano, halogen, hydroxy, nitro, -C(O)Rb, CO 2 Re, -- O-R, -C(O)-NR*Rd, -NR R with the meanings, already further mentioned above, for Rb, R* and Rd, and Ra and R 4 b, independently of one another, mean a hydrogen atom, a C 1 -C 4 -alkyl, a C 2 -C 4 -alkenyl or together with the ring-carbon atom forming a 3- to 6 membered ring, A means a monocyclic or bicyclic, carbocyclic or heterocyclic aromatic ring, which optionally can be substituted in one or more places with C 1 -C 8 alkyl, C 2 -C 8 -alkenyl, C 2 -Cs-alkinyl, C 1 -C 6 -perfluoroalkyl, C 1 -C 6 perfluoroalkoxy, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C1-C6-alkoxy, (CH 2 )p-C 3 -Cio-cycloalkyl, (CH 2 )p-heterocycloalkyl, (CH 2 )pCN, (CH 2 )pHal, (CH 2 )pNO 2 , (CH 2 )p-C 6 -C 12 -aryl, (CH 2 )p-heteroaryl, WO 2006/136462 PCT/EP2006/006532 158 -(CH 2 )pPO 3 (R) 2 , -(CH 2 )pNR R', -(CH 2 )pNReCOR , -(CH 2 )pNReCSR , -(CH 2 )pNR*S(O)R , -(CH 2 )pNReS(O) 2 R , -(CH 2 )pNR*CONR R, -(CH 2 )pNReCOORe, -(CH 2 )pNReC(NH)NRRd, -(CH 2 )pNReCSNR*Rd -(CH 2 )pNR*S(O)NR Rd , -(CH 2 )pNR*S(0) 2 NRcRd, -(CH 2 )pCOR , -(CH 2 )pCSRb, -(CH 2 )p S(O)R, -(CH 2 )pS(O)(NH)R, -(CH 2 )pS(O) 2 Rb, -(CH 2 )pS(O) 2 NR*Rd, -(CH 2 )pSO 2 0R", -(CH 2 )pCO 2 Rb, -(CH 2 )pCONRRd, -(CH 2 )pCSNRcRd, -(CF1 2 )pORb, -(CH 2 )pSRe, -(CH 2 )pCRb(OH)-Rd, -(CH 2 )p-C=NORe, -O-(CH 2 )n-O-, -O-(CH 2 )n-CH 2 -, -O-CH=CH- or -(CH 2 )n 1 + 2 -, whereby n = 1 or 2, and the terminal oxygen atoms and/or carbon atoms are linked to directly adjacent ring-carbon atoms, or A means a radical -CO 2 Re, C(O)NRRd, CORb, or A means an alkenyl group -CR = CR R , whereby 5 6 7 R , R and R are the same or different and, independently of one another, mean hydrogen atoms, halogen atoms, aryl radicals or an unsubstituted or partially or completely fluorinated C 1 -C 5 -alkyl group, or A means an alkinyl group -C=CRs, with the meaning cited above for R5, and B means a carbonyl group or a CH 2 group as well as their pharmaceutically acceptable salts. 2. Compounds according to claim 1, in which R 1 and R 2 mean a hydrogen atom, a methyl group or an ethyl group. 3. Compounds according to claim 1, in which R' and R2 together with the C atom of the chain form a ring with a total of 3 to 7 links. 4. Compounds according to claims 1 to 3, in which R3 means alkenyl, alkinyl, arylalkinyl, heteroarylalkinyl, cycloalkylalkinyl, or heterocycloalkylalkinyl. WO 2006/136462 PCT/EP2006/006532 159 5. Compounds according to one of the preceding claims, in which R3 means a vinyl, ethinyl, propinyl, butinyl, pentinyl, hexinyl, heptinyl, octinyl, hydroxypropinyl, hydroxybutinyl, 3 -hydroxy-3 -methylbutinyl, hydroxypentinyl, carboxypropinyl, t butylcarboxypropinyl, phenylethinyl, (hydroxyphenyl)ethinyl, (methoxyphenyl)ethinyl, (dimethylaminophenyl)ethinyl, (methylphenyl)ethinyl, (cyanophenyl)ethinyl, (trifluoromethyl)ethinyl, (diphenyl)ethinyl, (nitrophenyl)ethinyl, (tert-butylphenyl)ethinyl, (acetylphenyl)ethinyl, (acetoxyphenyl)ethinyl, (carboxyphenyl)ethinyl or a benzylethinyl group. 6. Compounds according to one of the preceding claims, in which A is an aromatic ring. 7. Compounds according to one of the preceding claims, in which A is preferably a phenyl or naphthyl radical. 8. Compounds according to claim 7, in which A is an unsubstituted phenyl radical or optionally a phenyl radical that is substituted in one or more places. 9. Compounds according to claim 8, whereby the phenyl radical is substituted with one or two halogen atoms or a trifluoromethyl group. 10. Compounds according to claim 9, in which the halogen atoms are chlorine and/or fluorine. 11. Compounds according to claims 1-8, in which A is an -O-(CH 2 )n-O- or -0 (CH 2 )n-CH 2 -substituted phenyl ring, whereby the respectively directly adjacent ring-carbon atoms are linked. 12. Compounds according to one of the preceding claims, in which R 4 a and R 4 b, independently of one another, in each case are a hydrogen atom. 13. Compounds according to claims 1 to 12, namely: WO 2006/136462 PCT/EP2006/006532 160 No. Racemic or R3 OH Enantiomer H 1 rac o N 2 + 3 4 rac 5 + 6 7 rac 8 + 9 10 rac 11 + 12 13 rac OH 14 + 15 16 rac 17 + 18 19 rac OH 20 + 21 22 rac 23 + WO 2006/136462 PCT/EP2006/006532 161 24 25 rac C-H 26 + 27 28 rac 29 + 30 31 rac 32 + 33 34 rac 35 + 36 37 rac CF3 38 + 39 40 rac 41 + 42 43 rac 44 + 45 46 rac 47 + 48 WO 2006/136462 PCT/EP2006/006532 162 49 rac 50 + 51 52 rac 0 53 + 54 OH 55 rac 56 + 57 58 rac OH 59 + 60 WO 2006/136462 PCT/EP2006/006532 163 No. Racemic or R3 Enantiomer R OH H 61 rac H 62 + 63 64 rac 65 + 66 67 rac 68 + 69 70 rac 71 + 72 73 rac OH 74 + 75 76 rac o 77 + 78 79 rac OH 80 + 81 82 rac WO 2006/136462 PCT/EP2006/006532 164 83 + 84 85 rac 86 + 87 88 rac XOH 89 + 90 91 rac 92 + 93 94 rac 95 + 96 97 rac CF 98 + 99 100 rac 101 + 102 103 rac 104 + 105 106 rac 107 + WO 2006/136462 PCT/EP2006/006532 165 108 109 rac 110 + 111 112 rac 113 + 114 115 rac OH 116 + 117 118 rac 119 + 120 No. Racemic or R3 Enantiomer R OH H 121 rac N 122 + 0 123 124 rac 125 + 126 127 rac WO 2006/136462 PCT/EP2006/006532 166 128 + 129 130 rac 131 + " 132 133 rac OH 134 + 135 136 rac 137 + 138 139 rac 140 + 141 142 rac 143 + 144 145 rac 146 + 147 148 rac OH 149 + 150 - WO 2006/136462 PCT/EP2006/006532 167 151 rac 152 + 153 154 rac 155 + 156 157 rac 158 + 159 160 rac 161 + NN 162 163 rac 164 + 165 166 rac 167 + 168 169 rac NO2 170 + 171 172 rac 173 + 174 175 rac OH WO 2006/136462 PCT/EP2006/006532 168 176 + 177 178 rac OH 179 + 180 No. Racemic or R3 Enantiomer R OH H 181 rac N 182 + 183 184 rac 185 + 186 187 rac 188 + 189 190 rac 191 + 192 193 rac OH 194 + 195 - WO 2006/136462 PCT/EP2006/006532 169 196 rac OH 197 + 198 199 rac oH 200 + 201 202 rac 203 + 204 205 rac OH 206 + 207 208 rac OH 209 + 210 211 rac 212 + 213 214 rac 215 + 216 217 rac 218 + 219 220 rac . N... WO 2006/136462 PCT/EP2006/006532 170 221 + 222 223 rac 224 + 225 226 rac 227 + 228 229 rac NO, 230 + 231 232 rac 233 + 234 235 rac H 236 + 237 238 rac 0 N i 239 + 240 No. Racemic or R3 Ra Enantiomner OH H 0 WO 2006/136462 PCT/EP2006/006532 171 241 rac 242 + 243 244 rac 245 + 246 247 rac 248 + 249 250 rae 251 + 252 253 rac OH 254 + 255 256 rac aH 257 + 258 259 rac OH 260 + 261 262 rac 263 + 264 265 rac o-H WO 2006/136462 PCT/EP2006/006532 172 266 + 267 268 rac XOH_ 269 + 270 271 rac 272 + 273 274 rac 275 + 276 277 rac CF. 278 + 279 280 rac 281 + 282 283 rac 284 + 285 286 rac O 287 + 288 289 rac NO2 290 + WO 2006/136462 PCT/EP2006/006532 173 291 292 rac 293 + 294 295 rac 296 + 297 298 rac OH 299 + 300 No. Racemic or R3 Enantiomer R OH H 301 rac H O o _____________Cie 0 302 + 0 303 304 rac 305 + 306 307 rac 308 + 309 WO 2006/136462 PCT/EP2006/006532 174 310 rac 311 + 312 313 rac OH 314 + 315 316 rac OH 317 + 318 319 rac OH 320 + 321 322 rac 323 + 324 325 rac oH 326 + 327 328 rac XH 329 + 330 331 rac 332 + 333 334 rac WO 2006/136462 PCT/EP2006/006532 175 335 + 336 -CF, 337 rac 338 + 339 340 rac N 341 + 342 343 rac 344 + 345 346 rac 347 + 348 349 rac NOz 350 + 351 352 rac 353 + 354 355 rac oH 356 + 357 WO 2006/136462 PCT/EP2006/006532 176 358 rac OH 359 + 360 No. Racemic or R3 Enantiomer OH H 361 rac N:| ::o 0 362 + 0 363 364 rac 365 + 366 367 rac 368 + 369 370 rac 371 + 372 373 rac OH 374 + 375 376 rac OH 377 + WO 2006/136462 PCT/EP2006/006532 177 378 OH 379 rac 380 + 381 382 rac 383 + 384 385 rac 386 + 387 388 rac OH 389 + 390 391 rac 392 + 393 394 rac 395 + 396 397 rac CF, 398 + 399 400 rac _____ _____ ____N WO 2006/136462 PCT/EP2006/006532 178 401 + 402 403 rac 404 + 405 406 rac 407 + 408 409 rac NO 410 + 411 412 rac 413 + 414 415 rac o 416 + 417 418 rac o OH 419 + 420 No. Racemic or R3 Enantiomer R OH Cl 421 rac N AO 0 0 WO 2006/136462 PCT/EP2006/006532 179 422 + 423 424 rac 425 + 426 427 rac 428 + "A 429 430 rac 431 + 432 433 rac OH 434 + 435 436 rac OH 437 + 438 439 rac OH 440 + 441 442 rac 443 + 444 445 rac OH 446 + WO 2006/136462 PCT/EP2006/006532 180 447 448 rac ILOH 449 + 450 451 rac 452 + 453 454 rac 455 + 456 457 rac OF N.a 458 + 459 460 rac 461 + 462 463 rac 0 464 + 465 466 rac 467 + 468 469 rac NO, 470 + 471 - WO 2006/136462 PCT/EP2006/006532 181 472 rac 473 + 474 475 rac 476 + 477 478 rac 479 + 480 No. Racemic or R3 Enantiomer OH 0 H 481 rac H Br 482 + 483 484 rac 485 + 486 487 rac 488 + 489 WO 2006/136462 PCT/EP2006/006532 182 490 rac 491 + 492 493 rac OH 494 + 495 496 rac OH 497 + 498 499 rac OH 500 + 501 502 rac 503 + 504 505 rac 506 + 507 508 rac OH 509 + 510 511 rac 512 + 513 214 rac WO 2006/136462 PCT/EP2006/006532 183 515 + 516 517 rac F, 518 + 519 520 rac 521 + 522 523 rac 524 + 525 526 rac 227 + 528 529 rac NO2 530 + 531 532 rac 533 + 534 535 rac 536 + 537 538 rac 0 539 + WO 2006/136462 PCT/EP2006/006532 184 540 No. Racemic or R3 Ra - OH Enantiomer H 541 rac N Njo 542 + 543 544 rac 545 + 546 547 rac 548 + 549 550 rac 551 + / 552 553 rac OH 554 + 555 556 rac oH 557 + 558 559 rac OH WO 2006/136462 PCT/EP2006/006532 185 560 + 561 562 rac 563 + 564 565 rac 566 + 567 568 rac OH 569 + 570 571 rac 572 + 573 574 rac 575 + 576 577 rac F 578 + 579 580 rac N 581 + 582 583 rac 584 + WO 2006/136462 PCT/EP2006/006532 186 585 586 rac 587 + 588 589 rac NO2 590 + 591 592 rac 593 + 594 595 rac 596 + 597 598 rac 0 599 + 600 No. Racemic or R3 Enantiomer OH H 601 rac H N o 0 602 + cF 3 603 604 rac WO 2006/136462 PCT/EP2006/006532 187 605 + 606 607 rac 608 + 609 610 rac 611 + 612 613 rac OH 614 + 615 616 rac OH 617 + 618 OH 619 rac 620 + 621 622 rac 623 + 624 625 rac o-H 626 + 627 WO 2006/136462 PCT/EP2006/006532 188 628 rac OH 629 + 630 631 rac 632 + 633 634 rac 635 + 636 637 rac 638 + 639 640 rac 641 + 642 643 rac 644 + 645 646 rac 647 + 648 649 rac 650 + 651 652 rac WO 2006/136462 PCT/EP2006/006532 189 653 + 654 655 rac -OH 656 + 657 658 rac 659 + 660 R OH No. Racemic or R3 0 H Enantiomer 0 F 0 661 rac H 662 + 663 664 rac 665 + 666 667 rac 668 + 669 670 rac 671 + 672 WO 2006/136462 PCT/EP2006/006532 190 673 rac OH 674 + 675 676 rac 677 + 678 679 rac oH 680 + 681 682 rac 683 + 684 685 rac 686 + 687 688 rac OH 689 + 690 691 rac 692 + 693 694 rac 695 + 696 697 rac CF, WO 2006/136462 PCT/EP2006/006532 191 698 + 699 700 rac 701 + 702 703 rac 704 + 705 706 rac 707 + 708 709 rac 710 + 711 712 rac 0 713 + 714 OH 715 rac 716 + 717 718 rac OH 719 + 720 WO 2006/136462 PCT/EP2006/006532 192 No. Racemic or R3 Enantiomer R OH H 721 rac H O0N 722 + 723 724 rac 725 + 726 727 rac 728 + 729 730 rac 731 + 732 733 rac 734 + -/ 735 736 rac OH 737 + 738 739 rac OH 740 + 741 - WO 2006/136462 PCT/EP2006/006532 193 742 rac 743 + 744 745 rac OH 746 + 747 748 rac 749 + 750 751 rac 752 + 753 754 rac 755 + 756 757 rac CF, 758 + 759 N 760 rac 761 + 762 763 rac 764 + WO 2006/136462 PCT/EP2006/006532 194 765 766 rac 767 + 768 769 rac N, 770 + 771 772 rac 773 + 774 775 rac OH 776 + 777 778 rac H 779 + 780 R3 OH No. Racemic or R3 H Enantiomer F ONO CFa 0 781 rac H 782 + 783 784 rac WO 2006/136462 PCT/EP2006/006532 195 785 + 786 787 rac 788 + 789 790 rac 791 + 792 793 rac OH 794 + 795 796 rac OH 797 + 798 799 rac OH 800 + 801 802 rac 803 + 804 805 rac OH 806 + 807 808 rac OH 809 + WO 2006/136462 PCT/EP2006/006532 196 810 811 rac 812 + 813 814 rac 815 + 816 817 rac CFa 818 + 819 820 rac 821 + 822 823 rac 824 + 825 826 rac 827 + 828 829 rac 830 + 831 832 rac 833 + 834 - WO 2006/136462 PCT/EP2006/006532 197 835 rac - 0 836 + 837 838 rac OH 839 + 840 No. Racemic or R3 R 3 Enantiomer 0,, OH H 841 rac H ON O 842 + CF 3 0 843 844 rac 845 + 846 847 rac 848 + 849 850 rac 851 + 852 OH 853 rac WO 2006/136462 PCT/EP2006/006532 198 854 + 855 856 rac H 857 + 858 859 rac 860 + 861 862 rac 863 + 864 865 rac 0 866 + 867 868 rac H 869 + 870 871 rac 872 + 873 874 rac 875 + 876 877 rac CF. 878 + WO 2006/136462 PCT/EP2006/006532 199 879 880 rac 881 + 882 883 rac 0 884 + 885 886 rac 887 + 888 889 rac NO 890 + 891 892 rac c 893 + 894 895 rac 896 + 897 898 rac 899 + 900 WO 2006/136462 PCT/EP2006/006532 200 No. Racemic or R3 Enantiomer R OH F H 901 rac H 902 + CF 3 0 903 904 rac 905 + 906 907 rac 908 + 909 910 rac 911 + 912 913 rac OH 914 + 915 916 rac 917 + 918 919 rac OH 920 + 921 922 rac 923 + WO 2006/136462 PCT/EP2006/006532 201 924 925 rac OH 926 + 927 928 rac 929 + 930 931 rac 932 + 933 934 rac 935 + 936 937 rac CF, 938 + 939 940 rac 941 + 942 943 rac 944 + 945 946 rac 947 +

948- WO 2006/136462 PCT/EP2006/006532 202 949 rac 950 + 951 952 rac 953 + 954 955 rac 956 + 957 958 rac 0 959 + 960 No. Racemic or R3 Enantiomer OH H 961 rac N,:. O F / 962 + 963 964 rac 965 + 966 967 rac 968 + WO 2006/136462 PCT/EP2006/006532 203 969 970 rac 971 + 972 973 rac OH 974 + 975 976 rac OH 977 + 978 979 rac OH 980 + 981 982 rac 983 + 984 985 rac OH 986 + 987 988 rac OH 989 + 990 991 rac 992 + 993 WO 2006/136462 PCT/EP2006/006532 204 994 rac 995 + 996 CF, 997 rac 998 + 999 1000 rac

1001. + 1002 1003 rac 1004 + 1005 1006 rac 1007 + 1008 1009 rac 1010 + 1011 1012 rac 1013 + 1014 1015 rac OH 1016 + WO 2006/136462 PCT/EP2006/006532 205 1017 1018 rac 1019 + 1020 No. Racemic or R3 Enantiomer R OH 0_ H 1021 rac H 1022 + F O 1023 1024 rac 1025 + 1026 1027 rac 1028 + 1029 1030 rac 1031 + 1032 1033 rac OH 1034 + 1035 1036 rac OH WO 2006/136462 PCT/EP2006/006532 206 1037 + 1038 1039 rac OH 1040 + 1041 0 1042 rac 1043 + 1044 1045 rac 0 1046 + 1047 1048 rac OH 1049 + 1050 1051 rac 1052 + 1053 1054 rac 1055 + 1056 1057 rac CF, 1058 + 1059 - WO 2006/136462 PCT/EP2006/006532 207 1060 rac 1061 + 1062 1063 rac 1064 + 1065 1066 rac 1067 + 1068 1069 rac NO, 1070 + 1071 1072 rac 1073 + 1074 1075 rac 1076 + 1077 1078 rae 1079 + 1080 R OH No. Racemic or R3 0 H ONO I 0 1 0 WO 2006/136462 PCT/EP2006/006532 208 Enantiomer 1081 rac H 1082 + 1083 1084 rac 1085 + 1086 1087 rac 1088 + 1089 1090 rac 1091 + 1092 1093 rac H 1094 + 1095 1096 rac 1097 + 1098 1099 rac O 1100 + 1101 1102 rac 1103 + 1104 - WO 2006/136462 PCT/EP2006/006532 209 1105 rac OH 1106 + 1107 1108 rac ILOH 1109 + 1110 1111 rac 1112 + 1113 1114 rac 1115 + 1116 1117 rac CF, 1118 + 1119 1120 rac 1121 + 1122 1123 rac 1124 + 1125 1126 rac O 1127 + 1128 1129 rac NO2 WO 2006/136462 PCT/EP2006/006532 210 1130 + 1131 1132 rac 1133 + 1134 1135 rac 1136 + 1137 1138 rac 1139 + 1140 No. Racemic or R3 R OH Enantiomer H 1141 rac N, O, 1142 + 0 1143 1144 rac 1145 + 1146 1147 rac 1148 + 1149 1150 rac WO 2006/136462 PCT/EP2006/006532 211 1151 + 1152 1153 rac OH 1154 + 1155 1156 rac OH 1157 + 1158 1159 rac OH 1160 + 1161 1162 rac 1163 + 1164 1165 rac OH 1166 + 1167 1168 rac OH 1169 + 1170 1171 rac 1172 + 1173 1174 rac 1175 + WO 2006/136462 PCT/EP2006/006532 212 1176 1177 rac CF, 1178 + 1179 1180 rac 1181 + 1182 1183 rac 1184 + 1185 1186 rac 1187 + 1188 1189 rac 1190 + 1191 1192 rac 0 1193 + 1194 1195 rac OH 1196 + 1197 1198 rac 0 N OH 1199 + 1200 - WO 2006/136462 PCT/EP2006/006532 213 No. Racemic or R3 Enantiomer R OH O H 1201 rac H No cl0 1202 +0 1203 1204 rac 1205 + 1206 1207 rac 1208 + 1209 1210 rac 1211 + 1212 1213 rac OH 1214 + 1215 1216 rac oH 1217 + 1218 1219 rac OH 1220 + 1221 WO 2006/136462 PCT/EP2006/006532 214 1222 rac 1223 + 1224 1225 rac OH_ 1226 + 1227 1228 rac OH 1229 + 1230 1231 rac 1232 + 1233 1234 rac 1235 + 1236 CFa 1237 rac 1238 + 1239 1240 rac 1241 + 1242 1243 rac 1244 + WO 2006/136462 PCT/EP2006/006532 215 1245 1246 rac 1247 + 1248 1249 rac N, 1250 + 1251 1252 rac 1253 + 1254 1255 rac OH 1256 + 1257 1258 rac H 1259 + 1260 WO 2006/136462 PCT/EP2006/006532 216 No. Racemic or R3 Enantiomer R OH *'0 H 1261 rac H 1262 + F 0 1263 1264 rac 1265 + 1266 1267 rac 1268 + 1269 1270 rac 1271 + 1272 1273 rac 0H 1274 + 1275 1276 rac oH 1277 + 1278 1279 rac OH 1280 + 1281 - WO 2006/136462 PCT/EP2006/006532 217 0 1282 rac 1283 + 1284 1285 rac ;-AOH_ 1286 + 1287 1288 rac OH 1289 + 1290 1291 rac 1292 + 1293 1294 rac 1295 + 1296 1297 rac CF, 1298 + 1299 1300 rac 1301 + 1302 1303 rac 1304 + 1305 WO 2006/136462 PCT/EP2006/006532 218 1306 rac 1307 + 1308 1309 rac 1310 + 1311 1312 rac 0 1313 + 1314 1315 rac OH 1316 + 1317 1318 rac OH 1319 + 1320 No. Racemic or R3 Enantiomer OH Cl H 1321 rac H N O 1322 + F 0 1323 1324 rac 1325 + WO 2006/136462 PCT/EP2006/006532 219 1326 1327 rac 1328 + 1329 1330 rac 1331 + 1332 1333 rac OH 1334 + 1335 1336 rac OH 1337 + 1338 1339 rac 1340 + 1341 1342 rac 1343 + 1344 1345 rac OH 1346 + 1347 1348 rac OH WO 2006/136462 PCT/EP2006/006532 220 1349 + 1350 1351 rac 1352 + 1353 1354 rac 1355 + 1356 1357 rac 1358 + 1359 1360 rac 1361 + 1362 1363 rac 1364 + 1365 1366 rac 1367 + 1368 1369 rac NO2 1370 + 1371 1372 rac 1373 + WO 2006/136462 PCT/EP2006/006532 221 1374 1375 rac OH 1376 + 1377 N'OH 1378 rac 1379 + 1380 No. Racemic or R3 Ra OH Enantiomer H 1381 rac H 0 0 0 1382 + 1383 1384 rac 1385 + 1386 1387 rac 1388 + 1389 1390 rac 1391 + WO 2006/136462 PCT/EP2006/006532 222 1392 1393 rac OH 1394 + 1395 1396 rac OH 1397 + 1398 1399 rac OH 1400 + 1401 1402 rac 1403 + 1404 1405 rac 0 OH 1406 + 1407 1408 rac OH 1409 + 1410 1411 rac 1412 + 1413 1414 rac 1415 + 1416 - WO 2006/136462 PCT/EP2006/006532 223 1417 rac 1418 + 1419 1420 rac 1421 + 1422 1423 rac 1424 + 1425 1426 rac 1427 + 1428 1429 rac NO 1430 + 1431 1432 rac 1433 + 1434 1435 rac o 1436 + 1437 1438 rac 1439 + WO 2006/136462 PCT/EP2006/006532 224 1440 No. Racemic or R3 OH Enantiomer H N N N 1441 rac 0 1 N 00 1442 + 1443 1444 rac 1445 + 1446 1447 rac 1448 + 1449 1450 rac 1451 + 1452 1453 rac OH 1454 + 1455 1456 rac oH 1457 + 1458 1459 rac O[ WO 2006/136462 PCT/EP2006/006532 225 1460 + 1461 1462 rac 1463 + 1464 1465 rac 1466 + 1467 1468 rac ILOH 1469 + 1470 1471 rac 1472 + 1473 1474 rac 1475 + 1476 1477 rac CF, 1478 + 1479 1480 rac 1481 + 1482 1483 rac WO 2006/136462 PCT/EP2006/006532 226 1484 + 1485 1486 rac 1487 + 1488 1489 rac NO2 1490 + 1491 1492 rac 1493 + 1494 1495 rac 1496 + 1497 1498 rac OH 1499 + 1500 No. Racernic or R3 Enantiomer R OH 0H 1501 rac H o 0 1502 + 0 1503 - WO 2006/136462 PCT/EP2006/006532 227 1504 rac 1505 + 1506 1507 rac 1508 + 1509 1510 rac 1511 + 1512 1513 rac OH 1514 + 1515 1516 rac OH 1517 + 1518 1519 rac OH 1520 + 1521 1522 rac 1523 + 1524 1525 rac 1526 + WO 2006/136462 PCT/EP2006/006532 228 1527 1528 rac '>LH 1529 + 1530 1531 rac 1532 + 1533 1534 rac 1535 + 1536 1537 rac F, 1538 + 1539 1540 rac 1541 + 1542 1543 rac 1544 + 1545 1546 rac 1547 + 1548 1549 rac NO2 1550 + 1551 - WO 2006/136462 PCT/EP2006/006532 229 1552 rac 1553 + 1554 1555 rac ox 1556 + 1557 1558 rac OH 1559 + 1560 No. Racemic or R3 Enantiomer R OH "'0 H 1561 rac N 1562 + 0 1563 1564 rac 1565 + 1566 1567 rac 1568 + 1569 1570 rac 1571 + WO 2006/136462 PCT/EP2006/006532 230 1572 1573 rac OH 1574 + 1575 1576 rac /o 1577 + 1578 1579 rac OH 1580 + 1581 1582 rac 1583 + 1584 1585 rac 0 1586 + 1587 1588 rac XOH 1589 + 1590 1591 rac 1592 + 1593 1594 rac 1595 + 1596 - WO 2006/136462 PCT/EP2006/006532 231 1597 rac CF, 1598 + 1599 1600 rac 1601 + 1602 1603 rac 1604 + 1605 1606 rac 1607 + 1608 1609 rac 1610 + 1611 1612 rac 1613 + 1614 1615 rac 1616 + 1617 1618 rac 1619 + WO 2006/136462 PCT/EP2006/006532 232 1620 14. Pharmaceutical composition that contains at least one compound of general formula I according to one of claims 1 to 13 and optionally at least one additional active ingredient together with pharmaceutically compatible adjuvants and/or vehicles. 15. Pharmaceutical composition according to claim 14, wherein the additional active ingredient is a SERM (selective estrogen receptor modulator), an aromatase inhibitor, an antiestrogen, or a prostaglandin. 16. Pharmaceutical composition according to claim 14, whereby the active ingredients can be tamoxifen, 5-(4- {5-[(RS)-(4,4,5,5,5-pentafluoropentyl)sulfinyl] pentyloxy}phenyl)-6-phenyl-8,9-dihydro-7H-benzocyclohepten-2-ol, ICI 182 780 (7alpha-[9 (4,4,5,5-pentafluoropentylsulfinyl)nonyl]estra-1,3,5(10)-triene-3,17-beta-diol), 1lbeta-fluoro 7alpha-[5-(methyl {3-[(4,4,5,5,5-pentafluoropentyl)sulfanyl]propyl}amino)pentyl]estra 1,3,5(10)-triene-3,17beta-diol, llbeta-fluoro-7alpha-{5-[methyl(7,7,8,8,9,9,10,10,10 nonafluorodecyl)amino]pentyl}estra-1,3,5(10)-triene-3,17beta-diol, 1 Ibeta-fluoro- 1 7alpha methyl-7alpha- {5-[methyl(8,8,9,9,9-pentafluorononyl)amino]pentyl} estra- 1,3,5(1 0)-triene 3,17beta-diol, clomifene, raloxifene, fadrozole, formestane, letrozole, anastrozole or atamestane. 17. Compounds according to one of claims 1 to 13 for the manufacture of a medicament. 18. Use of compounds according to claim 1-13 for the manufacture of a medicament for therapy and prophylaxis of gynecological diseases such as endometriosis, leiomyomas of the uterus, dysfunctional bleeding and dysmenorrhea. 19. Use of compounds according to claim 1-13 for the production of a pharmaceutical agent for therapy and prophylaxis of hormone-dependent tumors. WO 2006/136462 PCT/EP2006/006532 233 20. Use of compounds according to claim 1-13 for the production of a pharmaceutical agent for therapy and prophylaxis of breast cancer. 21. Use of compounds according to claim 1-13 for the production of a pharmaceutical agent for therapy and prophylaxis of endometrial carcinoma. 22. Use of compounds according to claim 1-13 for the production of a pharmaceutical agent for therapy and prophylaxis of ovarian cancer. 23. Use of compounds according to claim 1-13 for the production of a pharmaceutical agent for therapy and prophylaxis of prostate cancer. 24. Use of compounds according to claim 1-13 for the production of a pharmaceutical agent for female hormone replacement therapy. 25. Use of compounds according to claim 1-13 for female birth control. WO 2006/136462 PCT/EP2006/006532 234 Statement under Article 19(1) PCT Under Article 19 of the PCT hereby applicant submits the replacement of claims as follows: Claims 1 as well as claims 12 - 16 have not been changed, claims 2 - 11 have been changed according to the Written Opinion of the International Searching Authority, Form PCT/ISA/237, sheet 3, in order to delete the wording "preferably", claim 17 has been rephrased so as to clarify that the claim is directed to the first medical use, claims 18 - 25 have been amended in order to specify the relation to claims 1 - 13 and WO 2006/136462 PCT/EP2006/006532 235 claim 26 has been deleted. We warrant that, to the best of our knowledge, no inadmissible new subject matter has been introduced into the application by the amendments performed. Dr. Ina Scherlitz-Hmann Astrid Hinze SCHERING AKTIENGESELLSCHAFT Corporate Patents