3-Benzyl-benzothiophenes

Abstract: This invention relates to the fields of pharmaceutical and organic chemistry and provides novel 3-benzyl-benzothiophenes which are α-substituted with ether, thioether amino, hydrazino, cyano or halo that are useful for the treatment of the various medical indications associated with post-menopausal syndrome, as well as estrogen dependent diseases including cancer of the breast, uterus and cervix. The present invention further relates to intermediate compounds and processes useful for preparing the pharmaceutically active compounds of the present invention, and pharmaceutical compositions.

Description: This invention relates to the fields of pharmaceutical and organic chemistry and provides novel 3-benzylbenzothiophenes which are α-substituted with ether, thioether, amine, hydrazine, cyano, or halo, which are useful for the treatment of the various medical indications associated with post-menopausal syndrome, as well as estrogen dependent diseases including cancer of the breast, uterus and cervix. The present invention further relates to intermediate compounds and processes useful for preparing the pharmaceutically active compounds of the present invention, and pharmaceutical compositions. US 5484798 relates to benzothiophene compounds which are useful for inhibiting uterine fibroid disease, endometriosis and restenosis. "Post-menopausal syndrome" is a term used to describe various pathological conditions which frequently affect women who have entered into or completed the physiological metamorphosis known as menopause. Although numerous pathologies are contemplated by the use of this term, three major effects of post-menopausal syndrome are the source of the greatest longterm medical concern: osteoporosis, cardiovascular effects such as hyperlipidemia, and estrogen-dependent cancer, particularly breast and uterine cancer. Osteoporosis describes a group of diseases which arise from diverse etiologies, but which are characterized by the net loss of bone mass per unit volume. The consequence of this loss of bone mass and resulting bone fracture is the failure of the skeleton to provide adequate structural support for the body. One of the most common types of osteoporosis is that associated with menopause. Most women lose from about 20% to about 60% of the bone mass in the trabecular compartment of the bone within 3 to 6 years after the cessation of mensus. This rapid loss is generally associated with an increase of bone resorption and formation. However, the resorptive cycle is more dominant and the result is a net loss of bone mass. Osteoporosis is a common and serious disease among post-menopausal women. There are an estimated 25 million women in the United States, alone, who are afflicted with this disease. The results of osteoporosis are personally harmful and also account for a large economic loss due its chronicity and the need for extensive and long term support (hospitalization and nursing home care) from the disease sequelae. This is especially true in more elderly patients. Additionally, although osteoporosis is not generally thought of as a life threatening condition, a 20% to 30% mortality rate is related with hip fractures in elderly women. A large percentage of this mortality rate can be directly associated with post-menopausal osteoporosis. The most vulnerable tissue in the bone to the effects of post-menopausal osteoporosis is the trabecular bone. This tissue is often referred to as spongy or cancellous bone and is particularly concentrated near the ends of the bone (near the joints) and in the vertebrae of the spine. The trabecular tissue is characterized by small osteoid structures which interconnect with each other, as well as the more solid and dense cortical tissue which makes up the outer surface and central shaft of the bone. This inter-connected network of trabeculae gives lateral support to the outer cortical structure and is critical to the bio-mechanical strength of the overall structure. In post-menopausal osteoporosis, it is, primarily, the net resorption and loss of the trabeculae which leads to the failure and fracture of bone. In light of the loss of the trabeculae in post-menopausal women, it is not surprising that the most common fractures are those associated with bones which are highly dependent on trabecular support, e.g., the vertebrae, the neck of the weight bearing bones such as the femur and the fore-arm. Indeed, hip fracture, collies fractures, and vertebral crush fractures are hall-marks of post-menopausal osteoporosis. At this time, the only generally accepted method for treatment of post-menopausal osteoporosis is estrogen replacement therapy. Although therapy is generally successful, patient compliance with the therapy is low primarily because estrogen treatment frequently produces undesirable side effects. Throughout premenopausal time, most women have less incidence of cardiovascular disease than age-matched men. Following menopause, however, the rate of cardiovascular disease in women slowly increases to match the rate seen in men. This loss of protection has been linked to the loss of estrogen and, in particular, to the loss of estrogen's ability to regulate the levels of serum lipids. The nature of estrogen's ability to regulate serum lipids is not well understood, but evidence to date indicates that estrogen can upregulate the low density lipid (LDL) receptors in the liver to remove excess cholesterol. Additionally, estrogen appears to have some effect on the biosynthesis of cholesterol, and other beneficial effects on cardiovascular health. It has been reported in the literature that post-menopausal women having estrogen replacement therapy have a return of serum lipid levels to concentrations to those of the pre-menopausal state. Thus, estrogen would appear to be a reasonable treatment for this condition. However, the side-effects of estrogen replacement therapy are not acceptable to many women, thus limiting the use of this therapy. An ideal therapy for this condition would be an agent which would regulate the serum lipid level as does estrogen, but would be devoid of the side-effects and risks associated with estrogen therapy. The third major pathology associated with post-menopausal syndrome is estrogen-dependent breast cancer and, to a lesser extent, estrogen-dependent cancers of other organs, particularly the uterus. Although such neoplasms are not solely limited to a post-menopausal women, they are more prevalent in the older, post-menopausal population. Current chemotherapy of these cancers has relied heavily on the use of anti-estrogen compounds such as, for example, tamoxifen. Although such mixed agonist-antagonists have beneficial effects in the treatment of these cancers, and the estrogenic side-effects are tolerable in acute life-threatening situations, they are not ideal. For example, these agents may have stimulatory effects on certain cancer cell populations in the uterus due to their estrogenic (agonist) properties and they may, therefore, be contraproductive in some cases. A better therapy for the treatment of these cancers would be an agent which is an anti-estrogen compound having negligible or no estrogen agonist properties on reproductive tissues. In response to the clear need for new pharmaceutical agents which are capable of alleviating the symptoms of, inter alia , post-menopausal syndrome, the present invention provides new compounds, pharmaceutical compositions thereof, and methods of using such compounds for the treatment of post-menopausal syndrome and other estrogen-related pathological conditions such as those mentioned below. Uterine fibrosis (uterine fibroid disease) is an old and ever present clinical problem which goes under a variety of names, including uterine fibroid disease, uterine hypertrophy, uterine lieomyomata, myometrial hypertrophy, fibrosis uteri, and fibrotic metritis. Essentially, uterine fibrosis is a condition where there is an inappropriate deposition of fibroid tissue on the wall of the uterus. This condition is a cause of dysmenorrhea and infertility in women. The exact cause of this condition is poorly understood but evidence suggests that it is an inappropriate response of fibroid tissue to estrogen. Such a condition has been produced in rabbits by daily administrations of estrogen for 3 months. In guinea pigs, the condition has been produced by daily administration of estrogen for four months. Further, in rats, estrogen causes similar hypertrophy. The most common treatment of uterine fibrosis involves surgical procedures both costly and sometimes a source of complications such as the formation of abdominal adhesions and infections. In some patients, initial surgery is only a temporary treatment and the fibroids regrow. In those cases a hysterectomy is performed which effectively ends the fibroids but also the reproductive life of the patient. Also, gonadotropin releasing hormone antagonists may be administered, yet their use is tempered by the fact they can lead to osteoporosis. Thus, there exists a need for new methods for treating uterine fibrosis, and the methods of the present invention satisfy that need. Endometriosis is a condition of severe dysmenorrhea, which is accompanied by severe pain, bleeding into the endometrial masses or peritoneal cavity and often leads to infertility. The cause of the symptoms of this condition appear to be ectopic endometrial growths which respond inappropriately to normal hormonal control and are located in inappropriate tissues. Because of the inappropriate locations for endometrial growth, the tissue seems to initiate local inflammatory-like responses causing macrophage infiltration and a cascade of events leading to initiation of the painful response. The exact etiology of this disease is not well understood and its treatment by hormonal therapy is diverse, poorly defined, and marked by numerous unwanted and perhaps dangerous side effects. One of the treatments for this disease is the use of low dose estrogen to suppress endometrial growth through a negative feedback effect on central gonadotropin release and subsequent ovarian production of estrogen; however, it is sometimes necessary to use continuous estrogen to control the symptoms. This use of estrogen can often lead to undesirable side effects and even the risk of endometrial cancer. Another treatment consists of continuous administration of progestins which induces amenorrhea and by suppressing ovarian estrogen production can cause regressions of the endometrial growths. The use of chronic progestin therapy is often accompanied by the unpleasant CNS side effects of progestins and often leads to infertility due to suppression of ovarian function. A third treatment consists of the administration of weak androgens, which are effective in controlling the endometriosis; however, they induce severe masculinizing effects. Several of these treatments for endometriosis have also been implicated in causing a mild degree of bone loss with continued therapy. Therefore, new methods of treating endometriosis are desirable. Smooth aortal muscle cell proliferation plays an important role in diseases such as atherosclerosis and restenosis. Vascular restenosis after percutaneous transluminal coronary angioplasty (PTCA) has been shown to be a tissue response characterized by an early and late phase. The early phase occurring hours to days after PTCA is due to thrombosis with some vasospasms while the late phase appears to be dominated by excessive proliferation and migration of aortal smooth muscle cells. In this disease, the increased cell motility and colonization by such muscle cells and macrophages contribute significantly to the pathogenesis of the disease. The excessive proliferation and migration of vascular aortal smooth muscle cells may be the primary mechanism to the reocclusion of coronary arteries following PTCA, atherectomy, laser angioplasty and arterial bypass graft surgery. See "Intimal Proliferation of Smooth Muscle Cells as an Explanation for Recurrent Coronary Artery Stenosis after Percutaneous Transluminal Coronary Angioplasty," Austin et al. , Journal of the American College of Cardiology , 8 : 369-375 (Aug. 1985). Vascular restenosis remains a major long term complication following surgical intervention of blocked arteries by percutaneous transluminal coronary angioplasty (PTCA), atherectomy, laser angioplasty and arterial bypass graft surgery. In about 35% of the patients who undergo PTCA, reocclusion occurs within three to six months after the procedure. The current strategies for treating vascular restenosis include mechanical intervention by devices such as stents or pharmacologic therapies including heparin, low molecular weight heparin, coumarin, aspirin, fish oil, calcium antagonist, steroids, and prostacyclin. These strategies have failed to curb the reocclusion rate and have been ineffective for the treatment and prevention of vascular restenosis. See "Prevention of Restenosis after Percutaneous Transluminal Coronary Angioplasty: The Search for a 'Magic Bullet'," Hermans et al ., American Heart Journal, 122 : 171-187 (July 1991). In the pathogenesis of restenosis excessive cell proliferation and migration occurs as a result of growth factors produced by cellular constituents in the blood and the damaged arterial vessel wall which mediate the proliferation of smooth muscle cells in vascular restenosis. Agents that inhibit the proliferation and/or migration of smooth aortal muscle cells are useful in the treatment and prevention of restenosis. The present invention provides for the use of compounds as smooth aortal muscle cell proliferation inhibitors and, thus inhibitors of restenosis. The present invention relates to compounds of formula I wherein R 1 is H, OH, OCO(C 1 -C 6 alkyl), OCO(aryl), OSO 2 (C 4 -C 6 alkyl), OCOO(C 1 -C 6 alkyl), OCOO(aryl), OCONH(C 1 -C 6 alkyl), or OCON(C 1 -C 6 alkyl) 2 ; R 2 is aryl, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or 4-cyclohexanol; R 3 is O(CH 2 ) 2 or O(CH 2 ) 3 ; R 4 and R 5 are optionally CO(CH 2 ) 3 ,CO(CH 2 ) 4 , C 1 -C 6 alkyl, or R 4 and R 5 combine to form, with the nitrogen to which they are attached, piperidine, morpholine, pyrrolidine, 3-methylpyrrolidine, 3,3-dimethylpyrrolidine, 3,4-dimethylpyrrolidine, azepine, or pipecoline; R 6 is O(C 1 -C 6 alkyl), O(aryl), O(C 1 -C 6 alkyl)aryl)), OCH 2 CH 2 cyano, O((C 1 -C 6 alkyl)C 1 -C 6 alcohol) OSO 2 CH 3 , OSO 2 C 6 H 4 CH 3 , SH, S(C 1 -C 6 alkyl), cyano, halo , wherein each of R 7 and R 8 is taken separately and represents H, C 1 -C 6 -alkyl, 2-hydroxyethyl, or 2-fluoroethyl, or both R 7 and R 8 are taken together with the nitrogen and form a ring which is pyrrolidine, piperidine, azepine, or morpholine and which may optionally be substituted by one or two methyl groups, or wherein each of R 10 and R 11 is taken separately and represents H or C 1 -C 2 , or both R 10 and R 11 are taken together with the nitrogen and represent a ring which is a pyrrolidine, piperidine, azepine or morpholine and which may optionally be substituted by one or two methyl groups, and R 12 is hydrogen, methyl, or ethyl; and pharmaceutically acceptable salts thereof. The present invention further relates to pharmaceutical compositions containing compounds of formula I, optionally containing estrogen or progestin, and the use of such compounds, alone, or in combination with estrogen or progestin, for alleviating the symptoms of post-menopausal syndrome, particularly osteoporosis, cardiovascular related pathological conditions, and estrogen-dependent cancer. As used herein, the term "estrogen" includes steroidal compounds having estrogenic activity such as, for example, 17β-estradiol, estrone, conjugated estrogen (Premarin®), equine estrogen, 17β-ethynyl estradiol, and the like. As used herein, the term "progestin" includes compounds having progestational activity such as, for example, progesterone, norethylnodrel, nongestrel, megestrol acetate, norethindrone, and the like. The compounds of the present invention also are useful for inhibiting uterine fibroid disease and endometriosis in women and aortal smooth muscle cell proliferation, particularly restenosis, in humans. One aspect of the present invention includes compounds of formula I wherein R 1 is H, OH, OCO(C 1 -C 6 alkyl), OCO(aryl), OSO 2 (C 4 -C 6 alkyl), OCOO(C 1 -C 6 alkyl) or OCOO(aryl), OCONH(C 1 -C 6 alkyl), or OCON(C 1 -C 6 alkyl) 2 ; R 2 is aryl, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or 4-cyclohexanol; R 3 is O(CH 2 ) 2 or O(CH 2 ) 3 ; R 4 and R 5 are optionally CO(CH 2 ) 3 ,CO(CH 2 ) 4 , C 1 -C 6 alkyl, or R 4 and R 5 combine to form, with the nitrogen to which they are attached, piperidine, morpholine, pyrrolidine, 3-methylpyrrolidine, 3,3-dimethylpyrrolidine, 3,4-dimethylpyrrolidine, azepine, or pipecoline; R 6 is O(C 1 -C 6 alkyl), O(aryl), O(C 1 -C 6 alkyl)aryl)), OCH 2 CH 2 cyano, O((C 1 -C 6 alkyl)C 1 -C 6 alcohol) OSO 2 CH 3 , OSO 2 C 6 H 4 CH 3 , SH, S(C 1 -C 6 alkyl), cyano, halo, wherein each of R 7 and R 8 is taken separately and represents H, C 1 -C 6 -alkyl, 2-hydroxyethyl, or 2-fluoroethyl, or both R 7 and R 8 are taken together with the nitrogen and form a ring which is pyrrolidine, piperidine, azepine, or morpholine and which may optionally be substituted by one or two methyl groups, or wherein each of R 10 and R 11 is taken separately and represents H or C 1 -C 2 , or both R 10 and R 11 are taken together with the nitrogen and represent a ring which is a pyrrolidine, piperidine, azepine or morpholine and which may optionally be substituted by one or two methyl groups, and R 12 is hydrogen, methyl, or ethyl; and pharmaceutically acceptable salts thereof. General terms used in the description of compounds herein described bear their usual meanings. For example, "alkyl" refers to straight or branched aliphatic chains of 1 to 6 carbon atoms including methyl, ethyl, propyl, isopropyl, butyl, n-butyl, pentyl, isopentyl, hexyl, isohexyl, and the like. The term "aryl" refers to phenyl and phenyl substituted once or twice with alkyl, C 1 -C 6 alkoxy, hydroxy, nitro, or halo. "Halo" includes bromo, chloro, iodo and fluoro. The term "(C 1 -C 6 alkyl)aryl" refers to an alkyl chain substituted with aryl. The term "(C 1 -C 6 alkyl)C 1 -C 6 alcohol" refers to an alkyl chain substituted with a C 1 -C 6 alcohol, such as methanol, ethanol, 1-propanol, and 1-butanol. The compounds of the present invention can be made according to established procedures, such as those detailed in U.S. Patent No. 4,133,814 and U.S. Patent No. 4,418,068. Examples of the preparation of analogous compounds are provided in the U.S. Patents discussed above. In the processes for preparing the compounds of the present invention, the starting material is a compound of formula II wherein R is a hydroxy protecting group capable of resisting reduction by a reducing agent; and R 3 , R 4 and R 5 are as defined above; or a salt thereof. Compounds of formula II are known in the art and essentially are prepared via the methods described in U.S. Pat. Nos. 4,133,814; 4,380,635; and 4,418,068, each of which is herein incorporated by reference. Generally, a benzothiophene precursor of formula III is prepared via known procedures. Typically, the two hydroxy groups are protected by known hydroxy protecting groups which are capable of resisting acylation under standard Friedel-Crafts conditions (forming the R protecting groups of formula II compounds) and subsequent reduction by a strong reducing agent. Preferred hydroxy protecting groups are C 1 -C 4 alkyl, and methyl is especially preferred. See, e.g., the above-incorporated United States patents, J. W. Barton, "Protective Groups in Organic Chemistry", J. G. W. McOmie (ed.), Plenum Press, New York, NY, 1973, Chapter 2, and T. W. Green, "Protective Groups in Organic Synthesis", John Wiley and Sons, New York, NY, 1981, Chapter 7. Following preparation of the desired protected formula III precursor, the precursor is acylated, using standard Friedel-Crafts conditions, with a compound of formula IV wherein R 3 , R 4 and R 5 are as defined above; and R* is chloro, bromo, iodo, or an activating ester group. Preparation of formula IV compounds, as well as preferred acylation methods, are disclosed in the above-incorporated United States patents. When R 4 and R 5 each are not combined C 1 -C 4 alkyl, methyl and ethyl are preferred. When R 4 and R 5 are combined, 1-piperidinyl and 1-pyrrolidinyl are preferred. Of these, the piperidino moiety is especially preferred. Following acylation and, thus, preparation of a compound of formula II, compounds with a α-carbinol are prepared by adding a formula II compound or a salt thereof, to an appropriate solvent, and then reacting the formula II compound with a reducing agent such as, for example, lithium aluminum hydride (LAH), under an inert gas such as nitrogen. The amount of reducing agent used in this reaction is an amount sufficient to reduce the carbonyl group of formula II to form a carbinol of formula IIa: wherein R 3 , R 4 and R are as defined above, or a salt thereof. Generally, a liberal excess of the reducing agent per equivalent of the substrate is used. Appropriate solvents include any solvent or mixture of solvents which will remain inert under reducing conditions. Suitable solvents include diethyl ether, dioxane, and tetrahydrofuran (THF). The anydrous form of these solvents is preferred, and anhydrous THF is especially preferred. The temperature employed in this step is that which is sufficient to effect completion of the reduction reaction. Ambient temperature, in the range from about 17° C to about 25° C, generally is adequate. The length of time for this step is that amount necessary for the reaction to occur. Typically, this reaction takes from about 1 to about 20 hours. The optimal time can be determined by monitoring the progress of the reaction via conventional chromatographic techniques. The α-carbinol products from this reaction may be extracted essentially via the method described in preparation 1, infra. The following schemes illustrate the preparation of compounds of formula I. The scheme as set out in Scheme 1 may be used for preparation of the α-ether and α-thioether compounds. In the case of the ether substitutions, the α-carbinol is subjected to an acid, such as trifluoroacetic acid, in an appropriate solvent, such as methylene chloride, at approximately room temperature. Thereafter an alcohol ether precursor (R 6a H) is added, and the hydroxy-protecting groups are removed via known methodology. In the alcohol ether precursor, R 6a is O(C 1 -C 6 alkyl), O(aryl), O(C 1 -C 6 alkyl)aryl), OCH 2 CH 2 cyano, or O((C 1 -C 6 alkyl)C 1 -C 6 alcohol). For the thioether substitution, again the α-carbinol compound is subjected to an acid, such as trifluoroacetic acid, in an organic solvent at room temperature. Thereafter, a thiol thioether precursor (R 6b H) is added, and the hydroxy-protecting groups are removed via known methodology. In the thiol thioether precursor, (R 6b H) is OSO 2 CH 3 , OSO 2 C 6 H 4 CH 3 , SH, or S(C 1 -C 6 alkyl). Scheme 2 above can be used for the preparation of the amino, hydrazino, cyano and halo α-substitutions. In the case of the amino and hydrazino substitution, the α-carbinol is subjected to a dehydrating agent or agents, such as methanesulfonyl chloride and triethylamine, in a solvent, such as methylene chloride, at approximately 0°C. Thereafter, an amino precursor or hydrazino precursor: is added at room temperature. In the case of the cyano, again a dehydrating agent or agents are used as above and a cyano precursor such as potassium cyanide is added as well as a ligand such as a crown ether, particularly 18-crown-6, to aid in solubility. For the halo-α substitution again a dehydrating agent or agents is used and thereafter a halo precursor, such as a halo-containing salt, such as LiF, is added, as well as a solvent such as a crown ether, particularly 12-crown-4, to aid insolubility. Other compounds are prepared by replacing the 4'- and 6-hydroxy groups with a different moiety, such as -O-CO-(C 1 -C 6 alkyl), -O-CO-Ar in which Ar is optionally substituted phenyl, or -O-SO 2 -(C 4 -C 6 alky) via well known procedures. See , e.g., U.S. Pat. No. 4,358,593, supra . For example, when a -O-CO(C 1 -C 6 alkyl) or -O-CO-Ar group is desired, the dihydroxy compound of formula I is reacted with an agent such as acyl chloride, bromide, cyanide, or azide, or with an appropriate anhydride or mixed with anhydride. The reactions are conveniently carried out in a basic solvent such as pyridine, lutidine, quinoline or isoquinoline, or in a tertiary amine solvent such as triethylamine, tributylamine, methylpiperidine, and the like. The reaction also may be carried out in an inert solvent such as ethyl acetate, dimethylformamide, dimethylsulfoxide, dioxane, dimethoxyethane, acetonitrile, acetone, methyl ethyl ketone, and the like, to which at least one equivalent of an acid scavenger, such as a tertiary amine, has been added. If desired, acylation catalysts such as 4-dimethylaminopyridine or 4-pyrrolidinopyridine may be used. See , e.g., Haslam, et al ., Tetrahedron, 36 :2409-2433 (1980). The acylation reactions which provide the aforementioned R 1 and R 2 groups are carried out at moderate temperatures in the range from about -25° C to about 100° C, frequently under an inert atmosphere such as nitrogen gas. However, ambient temperature is usually adequate for the reaction to run. Such acylations of the hydroxy group also may be performed by acid-catalyzed reactions of the appropriate carboxylic acids in inert organic solvents or heat. Acid catalysts such as sulfuric acid, polyphosphoric acid, methanesulfonic acid, and the like are used. The R 1 and R 2 groups also may be provided by forming an active ester of the appropriate acid, such as the esters formed by such known reagents such as dicyclohexylcarbodiimide, acylimidazoles, nitrophenols, pentachlorophenol, N-hydroxysuccinimide, and 1-hydroxybenzotriazole. See , e.g., Bull. Chem. Soc. Japan , 38 :1979 (1965), and Chem. Ber. , 788 and 2024 (1970). Each of the above techniques which provide the R 1 and R 2 groups are carried out in solvents as discussed above. These techniques which do not produce an acid product in the course of the reaction, of course, do not necessitate the use of an acid scavenger in the reaction mixture. When a formula I compound is desired in which R 1 and R 2 is -O-SO 2 -(C 4 -C 6 alkyl), the formula I dihydroxy compound is reacted with, for example, a derivative of the appropriate sulfonic acid such as a sulfonyl chloride, bromide, or sulfonyl ammonium salt, as taught by King and Monoir, J. Am. Chem. Soc. , 97 :2566-2567 (1975). The dihydroxy compound also can be reacted with the appropriate sulfonic anhydride. Such reactions are carried out under conditions such as were explained above in the discussion of reaction with acid halides and the like. Further formula I compounds may then be formed as desired. Specific preparations of compounds of the present invention are described below. Modifications to the above methods may be necessary to accommodate reactive functionalities of particular substituents. Such modifications would be both apparent to, and readily ascertained by, those skilled in the art. Although the free-base form of formula I compounds can be used in the methods of the present invention, it is preferred to prepare and use a pharmaceutically acceptable salt form. Thus, the compounds used in the methods of this invention primarily form pharmaceutically acceptable acid addition salts with a wide variety of organic and inorganic acids, and include the physiologically acceptable salts which are often used in pharmaceutical chemistry. Such salts are also part of this invention. Typical inorganic acids used to form such salts include hydrochloric, hydrobromic, hydroiodic, nitric, sulfuric, phosphoric, hypophosphoric, and the like. Salts derived from organic acids, such as aliphatic mono and dicarboxylic acids, phenyl substituted alkanoic acids, hydroxyalkanoic and hydroxyalkandioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, may also be used. Such pharmaceutically acceptable salts thus include acetate, phenylacetate, trifluoroacetate, acrylate, ascorbate, benzoate, chlorobenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, methylbenzoate, o-acetoxybenzoate, naphthalene-2-benzoate, bromide, isobutyrate, phenylbutyrate, β-hydroxybutyrate, butyne-1,4-dioate, hexyne-1,4-dioate, caprate, caprylate, chloride, cinnamate, citrate, formate, fumarate, glycollate, heptanoate, hippurate, lactate, malate, maleate, hydroxymaleate, malonate, mandelate, mesylate, nicotinate, isonicotinate, nitrate, oxalate, phthalate, terephthalate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, propiolate, propionate, phenylpropionate, salicylate, sebacate, succinate, suberate, sulfate, bisulfate, pyrosulfate, sulfite, bisulfite, sulfonate, benzenesulfonate, p-bromophenylsulfonate, chlorobenzenesulfonate, ethanesulfonate, 2-hydroxyethanesulfonate, methanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, p-toluenesulfonate, xylenesulfonate, tartarate, and the like. A preferred salt is the hydrochloride salt. The pharmaceutically acceptable acid addition salts are typically formed by reacting a compound of formula I with an equimolar or excess amount of acid. The reactants are generally combined in a mutual solvent such as diethyl ether or ethyl acetate. The salt normally precipitates out of solution within about one hour to 10 days and can be isolated by filtration or the solvent can be stripped off by conventional means. The pharmaceutically acceptable salts generally have enhanced solubility characteristics compared to the compound from which they are derived, and thus are often more amenable to formulation as liquids or emulsions. The following examples are presented to further illustrate the preparation of compounds of the present invention. It is not intended that the invention be limited in scope by reason of any of the following examples. NMR data for the following Examples were generated on a GE 300 MHz NMR instrument, and anhydrous d-6 DMSO was used as the solvent unless otherwise indicated. Preparation 1 To a slurry of lithium aluminum hydride (4.11 g, 106.8 mmol) in tetrahydrofuran (700 ml) at 0°C is added dropwise a solution of the ketone (1' position) (30.0 g, 42.7 mmol) in tetrahydrofuran (500 ml). The mixture is stirred 1 hour at 0°C then is quenched dropwise with water (4.1 ml), 15% (w/w) NaOH (16.4 ml), and water (4.1 ml). This slurry is filtered through celite and evaporated to dryness (silica gel, MeOH/CHCl 3 gradient) to give the desired product as a white foam (23.3 g, 77%). 1 H-NMR (CDCl 3 ) consistent with structure; FD (MS) 703 (M-); elemental analysis for C 40 H 57 NO 4 SSi 2 cal'c/found C 68.23/68.50, H 8.16/8.29, N 1.99/2.15. Example 1 To a solution of the compound of preparation 1 (0.7 g, 0.98 mmol) in CH 2 Cl 2 (25 ml) at room temperature is added trifluoroacetic acid (0.12 ml, 1.47 mmol). To this stirring solution, MeOH (0.06 ml, 1.47 mmol) is added. The resulting solution is stirred overnight and is then washed twice with NaHCO 3 , twice with brine, dried (Na 2 SO 4 ), filtered and evaporated to dryness. The resulting white solid is dissolved in CH 2 Cl 2 (125 ml) at 0°C and Bu 4 NF (1.9 ml of a 1.0 M solution in tetrahydrofuran, 1.9 mmol) is added. Immediately thereafter, isopropanol (40 ml) and CHCl 3 (125 ml) are added. The organics are washed twice with NaHCO 3 , twice with brine, dried (Na 2 SO 4 ), filtered and evaporated to dryness. The resulting yellow foam is purified by radial chromatography (MeOH/CHCl 3 gradient) to yield the desired product as a brown solid (0.31 g, 65%). 1 H-NMR is consistent with structure; FD (MS) 490 (M+); elemental analysis for C 29 H 31 NO 4 S calc'd/found C 71.14/71.21, H 6.38/6.43, N 2.86/3.12. Example 2 The process from Example 1 is employed using the compound from preparation 1 (1.5 g, 2.1 mmol), trifluoroacetic acid (0.26 ml, 3.15 mmol), EtOH (0.19 ml, 2.13 mmol), CH 2 Cl 2 (40 ml), Bu 4 NF (3.6 ml of a 1.0 M solution in tetrahydrofuran, 3.6 mmol), and tetrahydrofuran (50 ml). The mixture is washed four times with brine (300 ml portions). Purified by radial chromatography (MeOH/CHCl 3 /hexanes gradient); recovered: 0.66 g (73%). 1 H-NMR consistent with structure; FD (MS) 504 (M+); elemental analysis for C 30 H 33 NO 4 S calc'd/found C 71.54/71.84, H 6.60/6.48, N 2.78/2.93. Example 3 The process from Example 1 is employed using the compound from preparation 1 (1.0 g, 0.98 mmol), trifluoroacetic acid (0.12 ml, 1.5 mmol), n-PrOH (0.055 ml, 1.5 mmol), CH 2 Cl 2 (60 ml), Bu 4 NF (2.4 ml of a 1.0 M solution in tetrahydrofuran, 2.4 mmol), and CH 2 Cl 2 (20 ml). The mixture is purified by radial chromatography (MeOH/CHCl 3 /hexanes gradient); recovered: 0.3 g (48%). 1 H-NMR consistent with structure; high res mass spec, calc'd for C 31 H 36 NO 4 S = 518.2365, found = 518.2365. Example 4 The process from Example 1 is employed using the compound from preparation 1 (1.5 g, 2.1 mmol), trifluoroacetic acid (0.24 ml, 3.0 mmol), i-PrOH (0.24 ml, 3.0 mmol), CH 2 Cl 2 (40 ml), Bu 4 NF (3.8 ml of a 1.0 M solution in tetrahydrofuran, 3.8 mmol), and tetrahydrofuran (40 ml). The mixture is purified by radial chromatography (MeOH/CHCl 3 /hexanes gradient); recovered: 0.620 mg (63%). 1 H-NMR consistent with structure; high res mass spec, calc'd for C 31 H 36 NO 4 S = 518.2365, found = 518.2392. Example 5 The process from Example 1 is employed using the compound from preparation 1 (1.5 g, 2.1 mmol), trifluoroacetic acid (0.24 ml, 3.0 mmol), n-BuOH (0.29 ml, 3.0 mmol), CH 2 Cl 2 (40 ml), Bu 4 NF (3.8 ml of a 1.0 M solution in tetrahydrofuran, 3.8 mmol), and tetrahydrofuran (40 ml). The mixture is purified by radial chromatography (MeOH/CHCl 3 /hexanes gradient), then dissolved in distilled tetrahydrofuran (50 ml) and washed exhaustively with brine and dried (Na 2 SO 4 ), filtered and evaporated to give 0.6 g (60%) of a brown foam. 1 H-NMR consistent with structure; FD (MS) 532 (M+); elemental analysis for C 32 H 37 NO 4 S calc'd/found C 72.29/72.32, H 7.01/7.24, N 2.63/2.53. Example 6 The process of Example 1 is employed using the compound from preparation 1 (1.5 g, 2.1 mmol), trifluoroacetic acid (0.24 ml, 3.0 mmol), BzOH (0.32 ml, 3.0 mmol), CH 2 Cl 2 (40 ml), Bu 4 NF (4.0 ml of a 1.0 M solution in tetrahydrofuran, 4.0 mmol), and tetrahydrofuran (40 ml). The mixture was purified by radial chromatography (MeOH/CHCl 3 /hexanes), then dissolved in distilled tetrahydrofuran (50 ml) and washed exhaustively with brine and dried (Na 2 SO 4 ), filtered and evaporated to give 0.6 g (53%) of a brown foam. 1 H-NMR is consistent with structure; FD (MS) 566 (M+); elemental analysis for C 35 H 35 NO 4 S calc'd/found C 74.13/74.11, H 6.24/6.41, N 2.48/2.58. Example 7 The process of Example 1 is employed using the compound from preparation 1 (1.5 g, 2.1 mmol), trifluoroacetic acid (0.24 ml, 3.0 mmol), 3-hydroxypropionitrile (0.22 ml, 3.0 mmol), CH 2 Cl 2 (40 ml), Bu 4 NF (3.6 ml of a 1.0 M solution in tetrahydrofuran, 3.6 mmol), and tetrahydrofuran (40 ml). The mixture was purified by radial chromatography (MeOH/CHCl 3 /hexanes), then dissolved in distilled tetrahydrofuran (50 ml) and washed exhaustively with brine and dried (Na 2 SO 4 ), filtered and evaporated to give 0.72 g (76%) of a brown foam. 1 H-NMR is consistent with structure; FD (MS) 529 (M+); elemental analysis for C 31 H 32 N 2 O 4 S calc'd/found C 70.43/70.34, H 6.10/6.36, N 5.30/5.05. Example 8 The process of Example 1 is employed using the compound from preparation 1 (1.5 g, 2.1 mmol), trifluoroacetic acid (0.24 ml, 3.0 mmol), ethylene glycol (0.18 ml, 3.0 mmol), CH 2 Cl 2 (100 ml), Bu 4 NF (4.0 ml of a 1.0 M solution in tetrahydrofuran, 4.0 mmol), and tetrahydrofuran (100 ml). The mixture was purified by radial chromatography (MeOH/CHCl 3 /hexanes), then dissolved in distilled tetrahydrofuran (50 ml) and washed exhaustively with brine and dried (Na 2 SO 4 ), filtered and evaporated to give 0.6 g (58%) of a brown foam. 1 H-NMR is consistent with structure; high res mass spec, calc'd for C 30 H 34 NO 5 S = 502.2158, found = 520.2144. Example 9 The process of Example 1 is employed using the compound from preparation 1 (1.5 g, 2.1 mmol), trifluoroacetic acid (0.24 ml, 3.0 mmol), CH 2 Cl 2 (40 ml), MeSH (gas bubbled in for 10 minutes), Bu 4 NF (4.2 ml of a 1.0 M solution in tetrahydrofuran, 4.2 mmol), and tetrahydrofuran (50 ml). The mixture was purified by radial chromatography (MeOH/CHCl 3 /hexanes), then dissolved in distilled tetrahydrofuran (50 ml) and washed exhaustively with brine and dried (Na 2 SO 4 ), filtered and evaporated to give 0.6 g (57%) of a brown foam. 1 H-NMR is consistent with structure; high res mass spec, calc'd for C 29 H 32 NO 3 S 2 = 506.1824, found = 506.1842. Example 10 The process of Example 1 is employed using the compound from preparation 1 (1.5 g, 2.1 mmol), trifluoroacetic acid (0.24 ml, 3.0 mmol), CH 2 Cl 2 (50 ml), EtSH (gas bubbled in for 10 min), Bu 4 NF (3.6 ml of a 1.0 M solution in tetrahydrofuran, 3.6 mmol), and tetrahydrofuran (50 ml). The mixture was purified by radial chromatography (MeOH/CHCl 3 /hexanes), then dissolved in distilled tetrahydrofuran (50 ml) and washed exhaustively with brine and dried (Na 2 SO 4 ), filtered and evaporated to give 0.45 g (48%) of a yellow foam. 1 H-NMR is consistent with structure; high res mass spec, calc'd for C 30 H 34 NO 3 S 2 = 520.1980, found = 520.2012. Example 11 To a solution of the compound from preparation 1 (2.0 g, 2.8 mmol) in CH 2 Cl 2 (100 ml) at 0°C is added Et 3 N (1.6 ml, 11.4 mmol) and mesyl chloride (0.26 ml, 1.23 mmol). This solution is stirred at 0°C for 15 minutes then Me 2 HN gas is bubbled in for 10 minutes and the reaction mixture is stirred overnight. The reaction mixture is washed twice with NaHCO 3 , twice with brine, dried (Na 2 SO 4 ), filtered, and evaporated to dryness. The resulting brown oil is dissolved in tetrahydrofuran (40 ml) and Bu 4 NF (5.8 ml of a 1.0 M solution in tetrahydrofuran, 5.8 mmol) is added at 0°C. The organic solution is washed twice with brine, dried (Na 2 SO 4 ), filtered, and evaporated to dryness. The resulting yellow oil is purified by radial chromatography (MeOH/CHCl 3 /hexanes gradient) and evaporated to a brown foam. This foam is dissolved in tetrahydrofuran (50 ml), washed twice with brine, dried (Na 2 SO 4 ), filtered, and evaporated to give the desired product as a brown foam (0.83 g, 57%). 1 H-NMR is consistent with structure; high res mass spec, calc'd for C 30 H 35 N 2 O 3 S = 503.2368, found = 503.2331. Example 12 The process of Example 11 is employed using the compound from preparation 1 (2.0 g, 2.8 mmol), Et 3 N (1.6 ml, 11.2 mmol), mesyl chloride (0.26 ml, 3.4 mmol), MeH 2 N (gas bubbled in for 10 minutes, CH 2 Cl 2 (100 ml), Bu 4 NF (5.2 ml of a 1.0 M solution in tetrahydrofuran, 5.2 mmol), and tetrahydrofuran (50 ml). The mixture is purified by radial chromatography (MeOH/CHCl 3 /hexanes gradient); recovered 0.8 g (63%). 1 H-NMR consistent with structure; FD (MS) 489 (M+). Example 13 The process of Example 11 is employed using the compound from preparation 1 (0.5 g, 0.7 mmol), Et 3 N (0.5 ml, 3.5 mmol), mesyl chloride (0.07 ml, 0.8 mmol), and tetrahydrofuran (25 ml). To this solution at 0°C is added a slurry of KCN (0.46 g, 7.0 mmol) and 18-crown-6 (0.93 g, 2.5 mmol) in tetrahydrofuran (75 ml). The resulting slurry is refluxed 20 hours, washed twice with brine, dried (Na 2 SO 4 ), filtered, and evaporated to dryness. The resulting mixture is purified by radial chromatography (MeOH/CHCl 3 /hexanes gradient); recovered 0.17g (34%) as a yellow foam. 'H-NMR consistent with structure; FD (MS) 484 (M+); elemental analysis for C 41 H 56 N 2 O 3 SSi 2 calc'd/found C 71.87/71.45, H 5.82/6.43, N 5.78/4.41. Example 14 The process of Example 11 is employed using the compound from preparation 1 (2.0 g, 3.0 mmol), Et 3 N (1.7 ml, 12.0 mmol), mesyl chloride (0.3 ml, 3.6 mmol), anhydrous ammonia (bubbled in over 10 minutes), CH 2 Cl 2 (100 ml), HF/NaF (12.0 ml of a pH=5 buffer made from NaF (7.0 g), HF (12.0 ml 48% (aq) and water (50 ml)), tetrahydrofuran (50 ml). Purified by radial chromatography (MeOH/CHCl 3 /NH 3 ) gradient); recovered as a white solid 1.1 g (78%). 1 H-NMR consistent with structure; High res mass spec: calc. for C 28 H 31 N 2 O 3 S 475.2055; found: 475.2052. IR (KBr) 2936.03, 1609.80, 1544.21, 1508.53, 1468.98, 1369.63, 1242.32, 1169.98, 1129.47, 1034.94, 944.38, 906.66, 833.35, 753.30, 666.49, 638.52, 587.40, 538.21, 435.00 cm -1 . Example 15 The process of Example 11 is employed using the compound from preparation 1 (2.0 g, 3.0 mmol), Et 3 N (1.7 ml, 12.0 mmol), mesyl chloride (0.3 ml, 3.6 mmol), diethylamine (1.7 ml, 12.0 mmol), CH 2 Cl 2 (100 ml), HF/NaF (12.0 ml of a pH=5 buffer made from NaF (7.0 g), HF (12.0 ml 48% (aq) and water (50 ml)), tetrahydrofuran (50 ml). Purified by radial chromatography (MeOH/CHCl 3 /NH 3 ) gradient); HCl gas (bubbled in for 10 minutes, filtered); recovered as a white solid 1.2 g (76%). 1 H-NMR consistent with structure; High res mass spec: calc. for C 37 H 39 N 2 O 3 S 531.2681; found: 531.2669. IR (KBr) 3211.89, 2947.61, 2660.18, 1609.80, 1540.36, 1515.28, 1470.91, 1425.58, 1348.41, 1248.10, 1186.37, 1170.94, 1082.20, 1037.84, 1012.76, 910.52, 843.00, 796.70, 751.37, 538.21 cm -1 . Example 16 To a solution of the compound of preparation 1 (2.0 g, 3.0 mmol) in CH 2 Cl 2 (100 ml) at 0°C is added Et 3 N (1.7 ml, 12.0 mmol) and mesyl chloride (0.30 ml, 3.6 mmol). This solution is stirred at 0°C for 15 minutes then pyrollidine (1.25 ml, 15.0 mmol) is added and the reaction mixture is stirred overnight. The reaction mixture is washed twice with NaHCO 3 , twice with brine, dried (Na 2 SO 4 ), filtered, and evaporated to dryness. The resulting brown oil is dissolved in tetrahydrofuran (100 ml) and HF/NaF (12.0 ml of a pH=5 buffer made from 7.0 g NaF, 0.21 ml 48% HF (aq) and 50 ml water) is added at ambient temperature. This mixture is stirred overnight at reflux. The organic solution is washed twice with brine, dried (Na 2 SO 4 ), filtered, and evaporated to dryness. The resulting yellow foam is purified by radial chromatography (MeOH/CHCl 3 gradient) and evaporated to dryness. The resulting yellow foam was dissolved in EtOAc (125 ml) and HCl gas was bubbled in for 10 min. The resulting white precipitate was filtered to give the desired product (0.83 g, 57%). 1 H-NMR is consistent with structure; FD (MS) 530 (M+); IR (KBr) 3149.19, 2947.61, 2649.57, 1609.80, 1541.32, 1515.28, 1470.91, 1424.81, 1248.10, 1184.44, 1085.10, 1038.80, 1013.72, 909.55, 838.18, 746.55, 600.90, 527.60, 434.04 cm -1 . Example 17 The process of Example 16 was employed using the compound of preparation 1 (2.0 g, 3.0 mmol), Et 3 N (1.7 ml, 12.0 mmol), mesyl chloride (0.3 ml, 3.6 mmol), hexamethyleneimine (1.7 ml, 15.0 mmol), CH 2 Cl 2 (100 ml), HF/NaF (12.0 ml of a pH=5 buffer made from NaF (7.0 g), HF (12.0 ml 48% (aq)) and water (50 ml)). Purified by radial chromatography (MeOH/CHCl 3 /NH 3 gradient); recovered as a white foam 0.9 g (54%). 1 H-NMR consistent with structure; FD (MS) 557 (M+); IR (KBr) 3376.82, 2925.42, 2854.05, 1608.84, 1543.25, 1507.56, 1466.09, 1353.24, 1236.53, 1168.05, 1127.54, 1085.10, 1033.98, 992.50, 905.69, 834.32, 752.33, 690.60, 666.49, 531.46 cm -1 Example 18 The process of Example 16 was employed using the compound of preparation 1 (2.0 g, 3.0 mmol), Et 3 N (1.7 ml, 12.0 mmol), mesyl chloride (0.3 ml, 3.6 mmol), 2-ethanolamine (0.9 ml, 15.0 mmol), CH 2 Cl 2 (100 ml), HF/NaF (12.0 ml of a pH=5 buffer made from NaF (7.0 g), HF (12.0 ml 48% (aq)) and water (50 ml)), tetrahydrofuran (50 ml). Purified by radial chromatography (MeOH/CHCl 3 gradient); recovered as a white foam 0.31 g (20%). 1 H-NMR consistent with structure; FD (MS) 519 (M+). Example 19 The process of Example 16 was employed using the compound of preparation 1 (2.0 g, 3.0 mmol), Et 3 N (1.7 ml, 12.0 mmol), mesyl chloride (0.3 ml, 3.6 mmol), 2-fluoroethylamine hydrochloride (1.2 g, 12.0 mmol), CH 2 Cl 2 (100 ml), HF/NaF (12.0 ml of a pH=5 buffer made from NaF (7.0 g), HF (12.0 ml, 48% (aq)) and water (50 ml)), tetrahydrofuran (150 ml). Purified by radial chromatography (MeOH/CHCl 3 /NH 3 gradient); recovered as a yellow foam 1.2 g (82%). 1 H-NMR consistent with structure; FD (MS) 520 (M + ). Example 20 The process of Example 16 was employed using the compound of preparation 1 (2.0 g, 3.0 mmol), Et 3 N (1.7 ml, 12.0 mmol), mesyl chloride (0.3 ml, 3.6 mmol), N-aminopiperidine (1.6 ml, 15.0 mmol), CH 2 Cl 2 (100 ml), HF/NaF (12.0 ml of a pH=5 buffer made from NaF (7.0 g), HF (12.0 ml 48% (aq)) and water (50 ml)), tetrahydrofuran (50 ml). Purified by radial chromatography (MeOH/CHCl 3 /NH 3 gradient); recovered as a yellow foam 1.3 g (78%). 1 H-NMR consistent with structure; FD (MS) 558 (M+); IR (KBr) 3064.31, 2937.00, 2855.98, 2790.39, 1609.80, 1545.18, 1508.53, 1468.98, 1442.94, 1353.24, 1241.35, 1170.94, 1131.39, 1094.74, 1035.91, 906.66, 834.32, 756.19, 666.49, 534.35 cm -1 Test Procedure General Preparation Procedure In the examples illustrating the methods, a post-menopausal model was used in which effects of different treatments upon circulating lipids were determined. Seventy-five day old female Sprague Dawley rats (weight range of 200 to 225g) are obtained from Charles River Laboratories (Portage, MI). The animals are either bilaterally ovariectomized (OVX) or exposed to a Sham surgical procedure at Charles River Laboratories, and then shipped after one week. Upon arrival, they are housed in metal hanging cages in groups of 3 or 4 per cage and had ad libitum access to food (calcium content approximately 0.5%) and water for one week. Room temperature is maintained at 22.2° ± 1.7° C with a minimum relative humidity of 40%. The photoperiod in the room was 12 hours light and 12 hours dark. Dosing Regimen Tissue Collection. After a one week acclimation period (therefore, two weeks post-OVX) daily dosing with test compound is initiated. 17α-ethynyl estradiol or the test compound is given orally, unless otherwise stated, as a suspension in 1% carboxymethylcellulose or dissolved in 20% cyclodextrin. Animals are dosed daily for 4 days. Following the dosing regimen, animals are weighed and anesthetized with a ketamine: Xylazine (2:1, V:V) mixture and a blood sample is collected by cardiac puncture. The animals are then sacrificed by asphyxiation with CO 2 , the uterus is removed through a midline incision, and a wet uterine weight is determined. Cholesterol Analysis. Blood samples are allowed to clot at room temperature for 2 hours, and serum is obtained following centrifugation for 10 minutes at 3000 rpm. Serum cholesterol is determined using a Boehringer Mannheim Diagnostics high performance cholesterol assay. Briefly the cholesterol is oxidized to cholest-4-en-3-one and hydrogen peroxide. The hydrogen peroxide is then reacted with phenol and 4-aminophenazone in the presence of peroxidase to produce a p-quinone imine dye, which is read spectrophotemetrically at 500 nm. Cholesterol concentration is then calculated against a standard curve. The entire assay is automated using a Biomek Automated Workstation. Uterine Eosinophil Peroxidase (EPO) Assay . Uteri are kept at 4° C until time of enzymatic analysis. The uteri are then homogenized in 50 volumes of 50 mM Tris buffer (pH - 8.0) containing 0.005% Triton X-100. Upon addition of 0.01% hydrogen peroxide and 10 mM O-phenylenediamine (final concentrations) in Tris buffer, increase in absorbance is monitored for one minute at 450 nm. The presence of eosonophils in the uterus is an indication of estrogenic activity of a compound. The maximal velocity of a 15 second interval is determined over the initial, linear portion of the reaction curve. Source of Compound : 17α-ethynyl estradiol is obtained from Sigma Chemical Co., St. Louis, MO. Influence of Formula I Compounds on Serum Cholesterol Data presented in Table 1 below show results when rats were treated with certain compounds of the present invention. The compounds of the present invention generally reduce serum cholesterol compared to the ovariectomized control animals. The data presented in the Tables 1 below reflects the response per treatment. Compound Serum Cholesterol ED 50 (mg/kg) Example 1 3.5 Example 2 10 Example 3 10 Example 4 4.1 Example 5 2.5 Example 6 10 Example 7 2.4 Example 8 2.9 Example 9 5.1 Example 10 1.7 Example 11 0.1 Example 12 0.8 Example 13 0.8 Example 14 5.7 Example 15 3.8 Example 16 10.0 Example 17 10.0 Example 18 N.A. at 10.0; not tested at higher dose Example 20 10.0 No deleterious toxicological effects (survival) were observed with any treatment. Osteoporosis Test Procedure Following the General Preparation Procedure, infra, the rats are treated daily for 35 days (6 rats per treatment group) and sacrificed by carbon dioxide asphyxiation on the 36th day. The 35 day time period is sufficient to allow maximal reduction in bone density, measured as described herein. At the time of sacrifice, the uteri is removed, dissected free of extraneous tissue, and the fluid contents is expelled before determination of wet weight in order to confirm estrogen deficiency associated with complete ovariectomy. Uterine weight is routinely reduced about 75% in response to ovariectomy. The uteri are then placed in 10% neutral buffered formalin to allow for subsequent histological analysis. The right femurs are excised and digitilized x-rays generated and analyzed by an image analysis program (NIH image) at the distal metaphysis. The proximal aspect of the tibiae from these animals are also scanned by quantitative computed tomography. In accordance with the above procedures, compounds of the present invention are orally administered to test animals. A positive impact in the above assay is indicated by an inhibition in bone loss provided by the compounds of formula 1. MCF-7 Proliferation Assay MCF-7 breast adenocarcinoma cells (ATCC HTB 22) were maintained in MEM (minimal essential medium, phenol red-free, Sigma, St. Louis, MO) supplimented with 10% fetal bovine serum (FBS) (V/V), L-glutamine (2 mM), sodium pyruvate (1 mM), HEPES {[N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid]10 mM), non-essential amino acids and bovine insulin (1 ug/mL) (maintenance medium). Ten days prior to assay, MCF-7 cells were switched to maintenance medium supplemented with 10% dextran coated charcoal stripped fetal bovine serum (DCC-FBS) assay medium) in place of 10% FBS to deplete internal stores of steroids. MCF-7 cells were removed from maintenance flasks using cell dissociation medium (Ca++/Mg++ free HBSS (phenol red-free) supplemented with 10 mM HEPES and 2 mM EDTA). Cells were washed twice with assay medium and adjusted to 80,000 cells/mL. Approximately 100 µL (8,000 cells) were added to flat-bottom microculture wells (Costar 3596) and incubated at 37° C in a 5% CO 2 humidified incubator for 48 hours to allow for cell adherence and equilibration after transfer. Serial dilutions of drugs or DMSO as a diluent control were prepared in assay medium and 50 µL transferred to triplicate microcultures followed by 50 µL assay medium for a final volume of 200 µL. After an additional 48 hours at 37° C in a 5% CO 2 humidified incubator, microcultures were pulsed with tritiated thymidine (1 uCi/well) for 4 hours. Cultures were terminated by freezing at -70° C for 24 hours followed by thawing and harvesting of microcultures using a Skatron Semiautomatic Cell Harvester. Samples were counted by liquid scintillation using a Wallac BetaPlace β counter. Results in Table 2 below show the ED 50 for certain compounds of the present invention. Compound (Example Reference) ED 50 nM 1 0.8 2 3 3 2 4 10.0 5 1.5 6 0.5 7 7 8 20.0 9 3 10 1.2 11 20.0 12 4.0 13 0.8 14 6.0 15 7.0 16 15.0 17 30.0 18 90.0 20 7.0 DMBA-Induced Mammary Tumor Inhibition Estrogen-dependent mammary tumors are produced in female Sprague-Dawley rats which are purchased from Harlan Industries, Indianapolis, Indiana. At about 55 days of age, the rats receive a single oral feeding of 20 mg of 7,12-dimethylbenz[a]anthracene (DMBA). About 6 weeks after DMBA administration, the mammary glands are palpated at weekly intervals for the appearance of tumors. Whenever one or more tumors appear, the longest and shortest diameters of each tumor are measured with a metric caliper, the measurements are recorded, and that animal is selected for experimentation. An attempt is made to uniformly distribute the various sizes of tumors in the treated and control groups such that average-sized tumors are equivalently distributed between test groups. Control groups and test groups for each experiment contain 5 to 9 animals. Compounds of Formula I are administered either through intraperitoneal injections in 2% acacia, or orally. Orally administered compounds are either dissolved or suspended in 0.2 mL corn oil. Each treatment, including acacia and corn oil control treatments, is administered once daily to each test animal. Following the initial tumor measurement and selection of test animals, tumors are measured each week by the above-mentioned method. The treatment and measurements of animals continue for 3 to 5 weeks at which time the final areas of the tumors are determined. For each compound and control treatment, the change in the mean tumor area is determined. Uterine Fibrosis Test Procedures Test 1 Between 3 and 20 women having uterine fibrosis are administered a compound of the present invention. The amount of compound administered is from 0.1 to 1000 mg/day, and the period of administration is 3 months. The women are observed during the period of administration, and up to 3 months after discontinuance of administration, for effects on uterine fibrosis. Test 2 The same procedure is used as in Test 1, except the period of administration is 6 months. Test 3 The same procedure is used as in Test 1, except the period of administration is 1 year. Test 4 A. Induction of fibroid tumors in guinea pig. Prolonged estrogen stimulation is used to induce leiomyomata in sexually mature female guinea pigs. Animals are dosed with estradiol 3-5 times per week by injection for 2-4 months or until tumors arise. Treatments consisting of a compound of the invention or vehicle is administered daily for 3-16 weeks and then animals are sacrificed and the uteri harvested and analyzed for tumor regression. B. Implantation of human uterine fibroid tissue in nude mice. Tissue from human leiomyomas are implanted into the peritoneal cavity and or uterine myometrium of sexually mature, castrated, female, nude mice. Exogenous estrogen are supplied to induce growth of the explanted tissue. In some cases, the harvested tumor cells are cultured in vitro prior to implantation. Treatment consisting of a compound of the present invention or vehicle is supplied by gastric lavage on a daily basis for 3-16 weeks and implants are removed and measured for growth or regression. At the time of sacrifice, the uteri is harvested to assess the status of the organ. Test 5 A. Tissue from human uterine fibroid tumors is harvested and maintained, in vitro , as primary nontransformed cultures. Surgical specimens are pushed through a sterile mesh or sieve, or alternately teased apart from surrounding tissue to produce a single cell suspension. Cells are maintained in media containing 10% serum and antibiotic. Rates of growth in the presence and absence of estrogen are determined. Cells are assayed for their ability to produce complement component C3 and their response to growth factors and growth hormone. In vitro cultures are assessed for their proliferative response following treatment with progestins, GnRH, a compound of the present invention and vehicle. Levels of steroid hormone receptors are assessed weekly to determine whether important cell characteristics are maintained in vitro. Tissue from 5-25 patients are utilized. Activity in at least one of the above tests indicates the compounds of the present invention are of potential in the treatment of uterine fibrosis. Endometriosis Test Procedure In Tests 1 and 2, effects of 14-day and 21-day administration of compounds of the present invention on the growth of explanted endometrial tissue can be examined. Test 1 Twelve to thirty adult CD strain female rats are used as test animals. They are divided into three groups of equal numbers. The estrous cycle of all animals is monitored. On the day of proestrus, surgery is performed on each female. Females in each group have the left uterine horn removed, sectioned into small squares, and the squares are loosely sutured at various sites adjacent to the mesenteric blood flow. In addition, females in Group 2 have the ovaries removed. On the day following surgery, animals in Groups 1 and 2 receive intraperitoneal injections of water for 14 days whereas animals in Group 3 receive intraperitoneal injections of 1.0 mg of a compound of the present invention per kilogram of body weight for the same duration. Following 14 days of treatment, each female is sacrificed and the endometrial explants, adrenals, remaining uterus, and ovaries, where applicable, are removed and prepared for histological examination. The ovaries and adrenals are weighed. Test 2 Twelve to thirty adult CD strain female rats are used as test animals. They are divided into two equal groups. The estrous cycle of all animals is monitored. On the day of proestrus, surgery is performed on each female. Females in each group have the left uterine horn removed, sectioned into small squares, and the squares are loosely sutured at various sites adjacent to the mesenteric blood flow. Approximately 50 days following surgery, animals assigned to Group 1 receive intraperitoneal injections of water for 21 days whereas animals in Group 2 receive intraperitoneal injections of 1.0 mg of a compound of the present invention per kilogram of body weight for the same duration. Following 21 days of treatment, each female is sacrificed and the endometrial explants and adrenals are removed and weighed. The explants are measured as an indication of growth. Estrous cycles are monitored. Test 3 A. Surgical induction of endometriosis Autographs of endometrial tissue are used to induce endometriosis in rats and/or rabbits. Female animals at reproductive maturity undergo bilateral oophorectomy, and estrogen is supplied exogenously thus providing a specific and constant level of hormone. Autologous endometrial tissue is implanted in the peritoneum of 5-150 animals and estrogen supplied to induce growth of the explanted tissue. Treatment consisting of a compound of the present invention is supplied by gastric lavage on a daily basis for 3-16 weeks, and implants are removed and measured for growth or regression. At the time of sacrifice, the intact horn of the uterus is harvested to assess status of endometrium. B. Implantation of human endometrial tissue in nude mice. Tissue from human endometrial lesions is implanted into the peritoneum of sexually mature, castrated, female, nude mice. Exogenous estrogen is supplied to induce growth of the explanted tissue. In some cases, the harvested endometrial cells are cultured in vitro prior to implantation. Treatment consisting of a compound of the present invention supplied by gastric lavage on a daily basis for 3-16 weeks, and implants are removed and measured for growth or regression. At the time of sacrifice, the uteri is harvested to assess the status of the intact endometrium. Test 4 A. Tissue from human endometrial lesions is harvested and maintained in vitro as primary nontransformed cultures. Surgical specimens are pushed through a sterile mesh or sieve, or alternately teased apart from surrounding tissue to produce a single cell suspension. Cells are maintained in media containing 10% serum and antibiotic. Rates of growth in the presence and absence of estrogen are determined. Cells are assayed for their ability to produce complement component C3 and their response to growth factors and growth hormone. In vitro cultures are assessed for their proliferative response following treatment with progestins, GnRH, a compound of the invention, and vehicle. Levels of steroid hormone receptors are assessed weekly to determine whether important cell characteristics are maintained in vitro. Tissue from 5-25 patients is utilized. Activity in any of the above assays indicates that the compounds of the present invention are useful in the treatment of endometriosis. Inhibition of Aortal Smooth Cell Proliferation/Restenosis Test Procedure Compounds of the present invention have capacity to inhibit aortal smooth cell proliferation. This can be demonstrated by using cultured smooth cells derived from rabbit aorta, proliferation being determined by the measurement of DNA synthesis. Cells are obtained by explant method as described in Ross, J. of Cell Bio. 50 : 172 (1971). Cells are plated in 96 well microtiter plates for five days. The cultures become confluent and growth arrested. The cells are then transferred to Dulbecco's Modified Eagle's Medium (DMEM) containing 0.5 - 2% platelet poor plasma, 2 mM L-glutamine, 100 U/ml penicillin, 100 mg ml streptomycin, 1 mC/ml 3 H-thymidine, 20 ng/ml platelet-derived growth factor, and varying concentrations of the present compounds. Stock solution of the compounds is prepared in dimethyl sulphoxide and then diluted to appropriate concentration (0.01 - 30 mM) in the above assay medium. Cells are then incubated at 37° C. for 24 hours under 5% CO 2 /95% air. At the end of 24 hours, the cells are fixed in methanol. 3 H thymidine incorporation in DNA is then determined by scintillation counting as described in Bonin, et al ., Exp. Cell Res. 181 : 475-482 (1989). Inhibition of aortal smooth muscle cell proliferation by the compounds of the present invention are further demonstrated by determining their effects on exponentially growing cells. Smooth muscle cells from rabbit aortae are seeded in 12 well tissue culture plates in DMEM containing 10% fetal bovine serum, 2 mM L-glutamine, 100 U/ml penicillin, and 100 mg/ml streptomycin. After 24 hours, the cells are attached and the medium is replaced with DMEM containing 10% serum, 2 mM L-glutamine, 100 U/ml penicillin, 100 mg/ml streptomycin, and desired concentrations of the compounds. Cells are allowed to grow for four days. Cells are treated with trypsin and the number of cells in each culture is determined by counting using a ZM-Coulter counter. Activity in the above tests indicates that the compounds of the present invention are of potential in the treatment of restenosis. The present invention also provides a method of alleviating post-menopausal syndrome in women which comprises the aforementioned method using compounds of Formula I and further comprises administering to a woman an effective amount of estrogen or progestin. These treatments are particularly useful for treating osteoporosis and lowering serum cholesterol because the patient will receive the benefits of each pharmaceutical agent while the compounds of the present invention would inhibit undesirable side-effects of estrogen and progestin. Activity of these combination treatments in any of the post-menopausal tests, infra , indicates that the combination treatments are useful for alleviating the symptoms of post-menopausal symptoms in women. Various forms of estrogen and progestin are commercially available. Estrogen-based agents include, for example, ethynyl estrogen (0.01 - 0.03 mg/day), mestranol (0.05 - 0.15 mg/day), and conjugated estrogenic hormones such as Premarin® (Wyeth-Ayerst; 0.3 - 2.5 mg/day). Progestin-based agents include, for example, medroxyprogesterone such as Provera® (Upjohn; 2.5 -10 mg/day), norethylnodrel (1.0 - 10.0 mg/day), and nonethindrone (0.5 - 2.0 mg/day). A preferred estrogen-based compound is Premarin, and norethylnodrel and norethindrone are preferred progestin-based agents. The method of administration of each estrogen- and progestin-based agent is consistent with that which is known in the art. For the majority of the methods of the present invention, compounds of Formula I are administered continuously, from 1 to 3 times daily. However, cyclical therapy may especially be useful in the treatment of endometriosis or may be used acutely during painful attacks of the disease. In the case of restenosis, therapy may be limited to short (1-6 months) intervals following medical procedures such as angioplasty. As used herein, the term "effective amount" means an amount of compound of the present invention which is capable of alleviating the symptoms of the various pathological conditions herein described. The specific dose of a compound administered according to this invention will, of course, be determined by the particular circumstances surrounding the case including, for example, the compound administered, the route of administration, the state of being of the patient, and the pathological condition being treated. A typical daily dose will contain a nontoxic dosage level of from about 5 mg to about 600 mg/day of a compound of the present invention. Preferred daily doses generally will be from about 15 mg to about 80 mg/day. The compounds of this invention can be administered by a variety of routes including oral, rectal, transdermal, subucutaneus, intravenous, intramuscular, and intranasal. These compounds preferably are formulated prior to administration, the selection of which will be decided by the attending physician. Thus, another aspect of the present invention is a pharmaceutical composition comprising an effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, optionally containing an effective amount of estrogen or progestin, and a pharmaceutically acceptable carrier, diluent, or excipient. The total active ingredients in such formulations comprises from 0.1% to 99.9% by weight of the formulation. By "pharmaceutically acceptable" it is meant the carrier, diluent, excipients and salt must be compatible with the other ingredients of the formulation, and not deleterious to the recipient thereof. Pharmaceutical formulations of the present invention can be prepared by procedures known in the art using well known and readily available ingredients. For example, the compounds of formula I, with or without an estrogen or progestin compound, can be formulated with common excipients, diluents, or carriers, and formed into tablets, capsules, suspensions, powders, and the like. Examples of excipients, diluents, and carriers that are suitable for such formulations include the following: fillers and extenders such as starch, sugars, mannitol, and silicic derivatives; binding agents such as carboxymethyl cellulose and other cellulose derivatives, alginates, gelatin, and polyvinylpyrrolidone; moisturizing agents such as glycerol; disintegrating agents such as calcium carbonate and sodium bicarbonate; agents for retarding dissolution such as paraffin; resorption accelerators such as quaternary ammonium compounds; surface active agents such as cetyl alcohol, glycerol monostearate; adsorptive carriers such as kaolin and bentonite; and lubricants such as talc, calcium and magnesium stearate, and solid polyethyl glycols. The compounds also can be formulated as elixirs or solutions for convenient oral administration or as solutions appropriate for parenteral administration, for example, by intramuscular, subcutaneous or intravenous routes. Additionally, the compounds are well suited to formulation as sustained release dosage forms and the like. The formulations can be so constituted that they release the active ingredient only or preferably in a particular physiological location, possibly over a period of time. The coatings, envelopes, and protective matrices may be made, for example, from polymeric substances or waxes. Compounds of formula I, alone or in combination with a pharmaceutical agent of the present invention, generally will be administered in a convenient formulation. The following formulation examples illustrate the present invention. Formulations In the formulations which follow, "active ingredient" means a compound of formula I, or a salt or solvate thereof. Formulation 1 : Gelatin Capsules Hard gelatin capsules are prepared using the following: Ingredient Quantity (mg/capsule) Active ingredient 0.1 - 1000 Starch, NF 0 - 650 Starch flowable powder 0 - 650 Silicone fluid 350 centistokes 0 - 15 The formulation above may be changed in compliance with the reasonable variations provided. A tablet formulation is prepared using the ingredients below: Formulation 2 : Tablets Ingredient Quantity (mg/tablet) Active ingredient 2.5 - 1000 Cellulose, microcrystalline 200 - 650 Silicon dioxide, fumed 10 - 650 Stearate acid 5 - 15 The components are blended and compressed to form tablets. Alternatively, tablets each containing 2.5 - 1000 mg of active ingredient are made up as follows: Formulation 3 : Tablets Ingredient Quantity (mg/tablet) Active ingredient 25 - 1000 Starch 45 Cellulose, microcrystalline 35 Polyvinylpyrrolidone (as 10% solution in water) 4 Sodium carboxymethyl cellulose 4.5 Magnesium stearate 0.5 Talc 1 The active ingredient, starch, and cellulose are passed through a 3.5x10 -4 m aperture (No. 45 mesh U.S.) sieve and mixed thoroughly. The solution of polyvinylpyrrolidone is mixed with the resultant powders which are then passed through a 1.425x10 -3 m aperture (No. 14 mesh U.S.) sieve. The granules so produced are dried at 50°-60°C and passed through a 1x10 -3 m aperture (No. 18 mesh U.S.) sieve. The sodium carboxymethyl starch, magnesium stearate, and talc, previously passed through a 2.5x 10 -4 m aperture (No. 60 U.S.) sieve, are then added to the granules which, after mixing, are compressed on a tablet machine to yield tablets. Suspensions each containing 0.1 - 1000 mg of medicament per 5 ml dose are made as follows: Formulation 4 : Suspensions Ingredient Quantity (mg/5 ml) Active ingredient 0.1 - 1000 mg Sodium carboxymethyl cellulose 50 mg Syrup 1.25 mg Benzoic acid solution 0.10 mL Flavor q.v. Color q.v. Purified water to 5 mL The medicament is passed through a 3.5x10 -4 m aperture (No. 45 mesh U.S.) sieve and mixed with the sodium carboxymethyl cellulose and syrup to form a smooth paste. The benzoic acid solution, flavor, and color are diluted with some of the water and added, with stirring. Sufficient water is then added to produce the required volume. Sufficient water is then added to produce the required volume. An aerosol solution is prepared containing the following ingredients: Formulation 5 : Aerosol Ingredient Quantity (% by weight) Active ingredient 0.25 Ethanol 25.75 Propellant 22 (Chlorodifluoromethane) 70.00 The active ingredient is mixed with ethanol and the mixture added to a portion of the propellant 22, cooled to 30° C, and transferred to a filling device. The required amount is then fed to a stainless steel container and diluted with the remaining propellant. The valve units are then fitted to the container. Suppositories are prepared as follows: Formulation 6 : Suppositories Ingredient Quantity (mg/suppository) Active ingredient 250 Saturated fatty acid glycerides 2,000 The active ingredient is passed through a 2.5x10 -4 m aperture (No. 60 mesh U.S.) sieve and suspended in the saturated fatty acid glycerides previously melted using the minimal necessary heat. The mixture is then poured into a suppository mold of nominal 2 g capacity and allowed to cool. An intravenous formulation is prepared as follows: Formulation 7 : Intravenous Solution Ingredient Quantity Active ingredient 50 mg Isotonic saline 1,000 mL The solution of the above ingredients is intravenously administered to a patient at a rate of about 1 mL per minute. Formulation 8 : Combination Capsule I Ingredient Quantity (mg/capsule) Active ingredient 50 Premarin 1 Avicel pH 101 50 Starch 1500 117.50 Silicon Oil 2 Tween 80 0.50 Cab-O-Sil 0.25 Formulation 9 : Combination Capsule II Ingredient Quantity (mg/capsule) Active ingredient 50 Norethylnodrel 5 Avicel pH 101 82.50 Starch 1500 90 Silicon Oil 2 Tween 80 0.50 Formulation 10 : Combination Tablet Ingredient Quantity (mg/capsule) Active ingredient 50 Premarin 1 Corn Starch NF 50 Povidone, K29-32 6 Avicel pH 101 41.50 Avicel pH 102 136.50 Crospovidone XL10 2.50 Magnesium Stearate 0.50 Cab-O-Sil 0.50

Claims: A compound of the formula I wherein R 1 is H, OH, halo, OCO(C 1 -C 6 alkyl), OCO(aryl), OSO 2 (C 4 -C 6 alkyl), OCOO(C 1 -C 6 alkyl), OCOO(aryl), OCONH(C 1 -C 6 alkyl), or OCON(C 1 -C 6 alkyl) 2 ; R 2 is aryl, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or 4-cyclohexanol; R 3 is O(CH 2 ) 2 or O(CH 2 ) 3 ; R 4 and R 5 are optionally CO(CH 2 ) 2 CH 3 ,CO(CH 2 ) 3 CH 3 , C 1 -C 6 alkyl, or R 4 and R 5 combine to form, with the nitrogen to which they are attached, piperidine, morpholine, pyrrolidine, 3-methylpyrrolidine, 3,3-dimethylpyrrolidine, 3,4-dimethylpyrrolidine, azepine, or pipecoline; R 6 is O(C 1 -C 6 alkyl), O(aryl), O(C 1 -C 6 alkyl)aryl)), OCH 2 CH 2 cyano, O((C 1 -C 6 alkyl)C 1 -C 6 alcohol), OSO 2 CH 3 , OSO 2 C 6 H 4 CH 3 , SH, S(C 1 -C 6 alkyl), cyano, halo, wherein each of R 7 and R 8 is taken separately and represents H, C 1 -C 6 -alkyl, 2-hydroxyethyl, or 2-fluoroethyl, or both R 7 and R 8 are taken together with the nitrogen and form a ring which is pyrrolidine, piperidine, azepine, or morpholine and which may optionally be substituted by one or two methyl groups, or wherein each of R 10 and R 11 is taken separately and represents H or C 1 -C 2 , or both R 10 and R 11 are taken together with the nitrogen and represent a ring which is a pyrrolidine, piperidine, azepine or morpholine and which may optionally be substituted by one or two methyl groups, and R 12 is hydrogen, methyl, or ethyl; and pharmaceutically acceptable salts thereof. A compound according to Claim 1 wherein R 6 is -OCH 3 , -OCH 2 CH 3 , -O(CH 2 ) 2 CH 3 , -O(CH 2 ) 3 CH 3 , -O-CH 2 -phenyl, -O(CH 2 ) 2 OH,-SCH 3 , -SCH 2 CH 3 , -N(CH 3 ) 2 , -NHCH 3 , or cyano. The compound of Claim 2 which is 3-(α-(dimethylamino)-4-(2-piperidinoethoxy)benzyl)-6-hydroxy-2-(4-hydroxyphenyl)-benzo(b)thiophene or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprising a compound according to Claim 1, and, optionally, an effective amount of estrogen or progestin, in combination with a pharmaceutically acceptable carrier, diluent or excipient. An article of manufacture comprising packaging material and a pharmaceutical agent contained within said packaging material, wherein said pharmaceutical agent is effective for treatment of a malady selected from 1) a various medical indication associated with postmenopausal syndrome, and 2) estrogen dependent diseases, and wherein said packaging material comprises a label which indicates that said pharmaceutical agent can be used for treating one of said maladies, and wherein said pharmaceutical agent is selected from the group consisting of a compound of formula (I) of claim 1. A compound of the formula I as claimed in any of claims 1 to 3 for use in alleviating the symptoms of post-menopausal syndrome. A compound of the formula I as claimed in any of claims 1 to 3 for use in the post-menopausal syndrome pathological condition of osteoporosis. A compound of the formula I as claimed in any of claims 1 to 3 for use in the post-menopausal syndrome pathological condition related to a cardiovascular disease. A compound of the formula I as claimed in any of claims 1 to 3 for use in inhibiting uterine fibroid disease. A compound of the formula I as claimed in any of claims 1 to 3 for use in inhibiting aortal smooth muscle cell proliferation

Inventors: MUEHL BRIAN STEPHEN, MUEHL, BRIAN STEPHEN
Applicants: LILLY CO ELI, ELI LILLY AND COMPANY
Application year: 1996
Main classification: C07D333
IPC codes: A61K31, C07D333, A61P43, A61P13, C07D409, A61P35, A61P15