BR112019025782B1 - THERAPEUTICLY ACTIVE STEROID DERIVATIVES, THEIR USES AND THEIR METHOD OF PREPARATION, AND PHARMACEUTICAL COMPOSITION - Google Patents

Abstract

The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R1 to R4 are as defined in the claims. The invention further relates to their use as 17β-HSD1 inhibitors and in the treatment or prevention of steroid hormone-dependent diseases or disorders, such as steroid hormone-dependent diseases or disorders that require inhibition of the 17β-HSD1 enzyme and/or that require a reduction in the endogenous concentration of estradiol. The present invention also relates to the preparation of the above-mentioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the above-mentioned compounds or pharmaceutically acceptable salts thereof.

Description

FIELD OF INVENTION

[001] The present invention relates to new C-15 steroid derivatives, their pharmaceutically acceptable salts, and their use in therapy. The invention further relates to pharmaceutical compositions comprising these compounds as active ingredients and to methods for their preparation.

BACKGROUND OF THE INVENTION

[002] 17β-hydroxysteroid dehydrogenases (17β-HSDs), also known as 17-ketosteroid reductases (17-KSR) are NAD (H)- and/or NAPD(H)-dependent alcohol oxidoreductase enzymes, which catalyze the latter and the main step in the formation of all estrogens and androgens. More specifically, 17β-HSDs catalyze the dehydrogenation (oxidation) of 17-hydroxysteroids to the corresponding 17-ketosteroids or the hydrogenation (reduction) of inactive 17-ketosteroids to the corresponding active 17-hydroxysteroids.

[003] Both estrogens and androgens have greater affinity for their receptors in the 17β-hydroxy form, 17β-HSD/KSRs regulate the biological activity of sex hormones. Currently, 15 human members of 17β-HSDs have been described (type 1 - 15). Different types of 17β-HSD/KSRs differ in their substrate and cofactor specificities. The activities of 17KSR convert low-activity precursors into more potent forms, while the activities of 17β-HSD decrease the potency of estrogens and androgens and, consequently, may protect tissues from excessive hormonal action.

[004] Each type of 17β-HSD has a selective substrate affinity and a distinctive, although in some cases overlapping, tissue distribution.

[005] 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is most abundantly expressed in ovarian granulosa cells of developing follicles in human ovaries and placenta, both of which are estrogen biosynthetic tissues. Furthermore, 17β-HSD1 is expressed in estrogen target tissues, including breast, endometrium, and bone. Human 17β-HSD1 is specific for estrogenic substrates and catalyzes the reduction of estrone to estradiol in vivo.

[006] On the other hand, 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) converts estradiol, testosterone and 5a-dihydrotestrosterone into the less active forms estrone, androstenedione and 5a-androstanedione, respectively. Due to its widespread and abundant expression in various estrogen and androgen target tissues, such as the uterus, placenta, liver, and gastrointestinal and urinary tracts, the type 2 enzyme has been suggested to protect tissues against excessive steroid actions.

[007] Estradiol (E2) is about 10 times more potent than estrone (E1) and about 80 times more potent than estratriol (E3) in its estrogenic effect. Unlike some other estrogens, estradiol binds well to the estrogen receptors ERα and ERβ and therefore regulates the expression of a variety of genes.

[008] Although both 17β-HSD1 and 17β-HSD2 are present in healthy premenopausal humans, an increased ratio of 17β-HSD1 to 17β -HSD2 in the tumors of postmenopausal patients with hormone-dependent breast cancer has been demonstrated in several studies. An amplification of the 17β-HSD1 gene and loss of heterozygosity of the 17β -HSD2 allele are potential mechanisms involved in the increase in the estrogen-reducing synthesis pathway in breast tumors. The increased ratio of type 1 enzyme to type 2 enzyme results in an increased level of estradiol which then promotes the proliferation of cancerous tissue through estrogen receptors (ER). Thus, high levels of estrogen support certain types of cancer, such as breast cancer and cancer of the uterine lining, that is, endometrial cancer and uterine cancer.

[009] Likewise, it has been suggested that 17β-HSD2 is downregulated in endometriosis, while both aromatase and 17β-HSD1 are expressed or upregulated compared to normal endometrium. This again results in the presence of a high concentration of estradiol (E2), which drives tissue proliferation. A similar mechanism has been elucidated in uterine leiomyoma (uterine fibroids) and endometrial hyperplasia.

[0010] Reducing the endogenous concentration of estradiol in affected tissues will result in reduced or impaired proliferation of 17β-estradiol cells in said tissues and can, therefore, be used in the prevention and treatment of estradiol-dependent malignant and benign pathologies. Due to the proposed involvement of 17β-estradiol in several malignant and benign pathologies, inhibitors of 17β-hydroxysteroid dehydrogenases, which can be used to impair endogenous production of estradiol from estrone, may have therapeutic value in preventing or treating such diseases. disorders or diseases that are in great demand.

[0011] Some small molecule inhibitors of the 17β-HSD1 enzyme were identified and reviewed in Poirier D. (2003) Curr Med Chem 10: 453-77 and Poirier D. (2010) Expert Opin. The R. Patents 20 (9): 1123-1145. In addition, 17β-hsd small molecules inhibitors were described in WO 2001/42181, WO 2003/022835, WO 2003/033487, WO 2004/046111, WO 2004/060488, WO 2004/110459, WO 2005/032527 and WO 2005/084295.

[0012] WO2004/085457 describes steroid compounds capable of inhibiting 17β-hydroxysteroid dehydrogenase. WO2006/003012 describes 2-substituted D-homo-estrene derivatives suitable for the treatment of estrogen-dependent diseases that can be influenced by the inhibition of 17β-hydroxysteroid dehydrogenase type 1. Likewise, WO2006/003013 discloses 2-substituted estratrienones, useful for preventing and treating estrogen-dependent diseases influenced by inhibition of 17β-hydroxysteroid dehydrogenase type 1.

[0013] 15-Substituted estradiol analogues that act as locally active estrogens are disclosed in WO2004/085345. WO2006/027347 describes 15b-substituted estradiol derivatives having selective estrogenic activity for the treatment or prevention of estrogen receptor-related diseases and physiological conditions. Furthermore, WO2005/047303 describes 3,15-substituted estrone derivatives capable of inhibiting 17β-hydroxysteroid dehydrogenase type 1.

[0014] International application WO2008/034796 refers to estratriene triazoles suitable for use in the treatment and prevention of steroid hormone-dependent diseases or disorders that require the inhibition of a 17β-hydroxysteroid dehydrogenases, such as the 17β-HSD type 1 enzyme , type 2 or type 3. Inhibitors of the 17β-HSD type 3 enzyme have been described in WO99/46279.

[0015] International applications WO2014/207309, WO2014/207310 and WO2014/207311 refer to estrone derivatives C-15 thiazole, estrone derivatives C-17 ketimine C-15 thiazole and estradiol derivatives C-15 thiazole, respectively. as well as its use in therapy.

BRIEF DESCRIPTION OF THE INVENTION

[0016] An object of the present invention is to provide compounds useful in the treatment of disorders and diseases associated with an increased level of estradiol and/or treatable by inhibition of the 17β-HSD1 enzyme. It is a further object of the present invention to provide compounds that have little or no inhibitory effect on the 17β-HSD2 enzyme.

[0017] One of the problems associated with known 17β-HSD1 inhibitors is the disposition, in particular the metabolic stability, of the compounds. Therefore, it is yet another object of the present invention to provide compounds with improved metabolic stability.

[0018] Another problem associated with known 17β-HSD1 inhibitors is the formation of conjugated metabolites and the species selectivity of the compounds. Therefore, it is yet another object of the present invention to provide compounds with improved properties in these parameters.

[0019] The present invention provides new compounds of Formula (I)

[0020] wherein R1 and R2 are each independently selected from the group consisting of H, and halogen;

[0021] (i) R3 is selected from the group consisting of H, and C1-3-alkyl, and

[0022] R4 is selected from the group consisting of

[0023] C1-3-alkyl,

[0024] unsubstituted 4- to 6-membered saturated heterocycle comprising 1 heteroatom selected from the group consisting of nitrogen, sulfur and oxygen,

[0025] 5-membered partially unsaturated heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituents selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, C(O)N(C1-3-alkyl )2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two independently selected substituent(s)( s) from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy,

[0026] 5-membered unsaturated or aromatic unsubstituted heterocycle comprising 1 nitrogen atom and 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen,

[0027] 5-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, C(O) N(C1-3-alkyl)2, and 6-membered saturated heterocycle containing 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituents (s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, and

[0028] 6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl)2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, or two adjacent substituents can form a saturated 5- or 6-membered fused ring;

[0029] or

[0030] (ii) R3 and R4 form together with the nitrogen atom to which they are bonded to form a group selected from a 5 to 6 membered saturated heterocycle comprising said nitrogen atom and is optionally substituted with a substituent selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, and (CH2)-C1-3-alkoxy; and an unsubstituted bicyclic spirocyclic or fused heterocycle containing said nitrogen atom and optionally 1 or 2 other heteroatom(s) selected from the group consisting of nitrogen, oxygen and sulfur;

[0031] and pharmaceutically acceptable salts thereof.

[0032] The present invention also provides compounds of Formula (II)

[0033] wherein R1, R2, R3 and R4 are as defined for the compounds of Formula (I) the starting materials for providing the compound of Formula (I),

[0034] Compounds of Formula (I) of the present invention may be useful in therapy, especially in the treatment or prevention of diseases or disorders dependent on steroid hormones that require the reduction of the endogenous concentration of estradiol or the inhibition of 17β-hsd enzymes, In Animals, In Particular Mammals And Humans. In particular, the compounds of formula (I) represent inhibitors of the 17β-hsd1 enzyme, having pharmacological properties for the treatment and/or prophylaxis of steroid-dependent diseases and conditions that include, but are not limited to, breast cancer, carcinoma Prostate Cancer, Ovarian Cancer, Uterine Cancer, Endometrial Cancer, Endometrial Hyperplasia, Endometriosis, Uterine Fibroids, Adenomyosis, Polycystic Ovary Syndrome, Dysmenorrhea, Menorrhagia, Metrorrhagia, Contraception, Prostadinia, Benign Prostatic Hyperplasia, Urinary Dysfunction, Lower Urinary Tract Symptoms , Chronic Prostatitis/Chronic Pelvic Pain Syndrome (Cp/Cpps), Systemic Lupus Erythematosus (Sle), Multiple Sclerosis, Obesity, Rheumatoid Arthritis, Chronic Obstructive Pulmonary Disease (Copd), Lung Cancer, Colon Cancer, Tissue Wounds, Wrinkles On The Skin And Cataracts.

[0035] The compounds of Formula (I) of the present invention typically have an inhibitory activity on the 17-β-HSD1 enzyme in the IC50 range of 0.1 nM to 1 μM. An inhibitory activity can be measured as explained in the context of the experimental examples.

[0036] The invention also relates to pharmaceutical compositions comprising an effective amount of one or more compound(s) of Formula (I).

[0037] Furthermore, the invention relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use as a medicine.

[0038] The invention also relates to compounds of Formula (I) and their pharmaceutically acceptable salts for use in the treatment of estradiol-dependent malignant or benign diseases and disorders.

[0039] Finally, the invention provides a method for preparing compounds of Formula (I).

DETAILED DESCRIPTION OF THE INVENTION

[0040] The compounds of the invention contain a steroidal nuclear structure having a defined stereochemistry that is the natural configuration of estrogens.

[0041] The compounds of the invention have a C15 side chain, which, together with the specific substitution pattern of ring A, provides the inventive properties of the compounds of the present invention. Furthermore, the C-17 carbonyl group of the native steroid nucleus can also be masked as a C-17 ketimine to further enhance the metabolic and/or inhibitory properties of the compounds of the present invention.

[0042] The term "halogen" when used here and below by itself or as part of other groups refers to the elements of Group VIIa and includes groups F, Cl, Br and I.

[0043] The term "alkyl" when used herein and hereinafter is a linear, branched or cyclic, especially linear or branched, aliphatic hydrocarbon group having the indicated number of carbon atoms, for example C1-6-alkyl has 1 to 6 atoms of carbon in the alkyl portion and thus, for example, C1-4-alkyl includes methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl and C1-6-alkyl additionally includes pentyl and branched and straight chain hexyl.

[0044] The term "(per)haloalkyl" when used herein and hereinafter refers to any of the above alkyl groups where one or more hydrogen atoms are replaced by halogen(s): in particular I, Br, F or Cl. Examples of haloalkyl groups include without limitation chloromethyl, fluoromethyl and -CH2CF3. The term "perhaloalkyl" is understood to refer to an alkyl group in which all hydrogen atoms are replaced by halogen atoms. Preferred examples include trifluoromethyl (-CF3) and trichloromethyl (-CCl3).

[0045] The term "C1-3-alkoxy" when used herein and hereinafter refers to a -O-(C1-3-alkyl) group where "C1-3-alkyl" has the meaning defined above. Examples of preferred alkoxy groups include, but are not limited to, methoxy, ethoxy, and iso-propyloxy.

[0046] The term "6-membered saturated heterocycle containing 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur", refers to a monocyclic ring, which is saturated and has 4 to 6 ring atoms, and comprises 1 heteroatom selected from N, S and O while the remaining ring atoms are carbon atoms. They may be substituted with one or two substituent(s) as denoted, in particular one, on any suitable ring atom, including N. Preferred substituent groups include, but are not limited to, halogen, in particular fluorine, CN, methoxy, and methyl.

[0047] The term "4 to 6 membered saturated unsubstituted heterocycle containing 1 heteroatom selected from the group consisting of nitrogen, sulfur and oxygen", refers to a monocyclic ring, which is saturated and has 4 to 6 atoms in the ring, and comprises 1 heteroatom selected from N, S and O while the remaining ring atoms are carbon atoms. The ring is not replaced. Representative groups include oxetanyl, pyrrolidinyl, piperidinyl, and tetrahydropyranyl, in particular oxetanyl and tetrahydropyranyl.

[0048] The term "5-membered partially unsaturated heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) selected from the group consisting of nitrogen, sulfur and oxygen" refers to a monocyclic ring that is partially unsaturated with 5 ring atoms comprising at least one double bond between the ring atoms and containing 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) selected from from the group consisting of N, S and O, while the remaining ring atoms are carbon atoms. They may be substituted with one or two substituents as denoted, in particular one, on any suitable ring atom, including N. Preferred substituent groups include, but are not limited to, halogen, in particular fluorine, CN, methoxy, and methyl. Representative groups include dihydrothiazolyl.

[0049] The term "5-membered unsaturated or aromatic heterocycle containing 1 nitrogen atom and 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen" refers to a monocyclic ring with 5 ring atoms that may be aromatic or unsaturated and that contains 1 nitrogen atom and 1 to 2 other heteroatom(s) independently selected from N, S and O , while the remaining ring atoms are carbon atoms. The ring is not replaced. Representative groups include thiadiazolyl.

[0050] The term "5-membered unsaturated or aromatic heterocycle" refers to a monocyclic ring with 5 ring atoms that may be aromatic or unsaturated and comprises 1 nitrogen atom and optionally 1 to 2 other heteroatom(s). ) independently selected from the group consisting of N, and O, while the remaining ring atoms are carbon atoms. They may be substituted with one or two substituents as denoted, in particular one, on any suitable ring atom, including N. Preferred substituent groups include, but are not limited to, halogen, in particular fluorine, CN, methoxy, and methyl. Representative groups include oxazolyl and methyloxazolyl.

[0051] The term "6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen and oxygen" refers to a monocyclic ring having 6 ring atoms and which may be aromatic or unsaturated containing 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of N, S, and O, while the remaining ring atoms are carbon atoms. They may be substituted with one or two, preferably one, substituents as denoted, in particular one, on any suitable ring atom, including N. Preferred substituent groups include, however, are not limited to halogen, in particular fluorine, CN, methoxy, and methyl. Advantageously, the substituent is in the para-position of the ring. Representative groups include pyridinyl, fluoropyridinyl, cyanopyridinyl, methylpyridinyl, dimethylpyridinyl, isopropylpyridinyl, hydroxypyridinyl, methoxypyridinyl, morpholinopyridinyl, methylpiperazinylpyridinyl, pyrazinyl, methylpyridazinyl, and methoxypyridazinyl; in particular fluoropyridinyl, methoxypyridinyl, methylpyridazinyl, and methoxypyridazinyl.

[0052] The term "a 5- to 6-membered saturated heterocycle comprising nitrogen atom" refers to a saturated monocyclic ring with 6 ring atoms and contains 1 nitrogen atom while the remaining ring atoms are carbon atoms. It may be substituted by one or two substituents as indicated, in particular one, on any suitable ring atom, including N. Preferred substituent groups include, but are not limited to, halogen, in particular fluorine, CN, methoxy and methyl. Representative groups include pyrrolidinyl and methoxymethylpyrrolidinyl.

[0053] The term "an unsubstituted bicyclic or fused spirocyclic heterocycle, comprising said nitrogen atom and, optionally, 1 or 2 additional heteroatom(s) selected from a group consisting of nitrogen, oxygen and sulfur " refers to a bicyclic ring system in which the rings may be joined as a spirocyclic system or as a fused system, preferably as a spirocyclic system, and contains a nitrogen atom and, optionally, 1 or 2 other heteroatoms selected from N , O and S as indicated while the remaining ring atoms are carbon atoms. The ring system is not replaced. Representative groups include oxaazaespiro[4.5]decanyl.

[0054] The term "a saturated 5- or 6-membered fused ring" refers to a fused ring, which is saturated or partially unsaturated and adds 3 to 4, therefore, additional ring atoms to the original ring into which it is fused and optionally comprises 1 to 2 heteroatoms, each independently selected from N, S and O, while the remaining ring atoms are carbon atoms.

[0055] The term "optionally substituted", when used herein and hereafter in the context of a phenyl group, denotes phenyl that is unsubstituted or independently substituted by one or more, in particular 1, 2 or 3, substituents, attached to any atom available to produce a stable compound, for example, pyridinyl may be substituted once with an indicated substituent attached to any suitable position of the pyridinyl ring. In general, "substituted" refers to a substituent group as defined herein in which one or more bonds to a hydrogen atom contained therein are replaced by a bond to a non-hydrogen atom, unless otherwise indicated. In particular, the substituent groups are each independently selected from the group consisting of halogen, in particular F; C1-4-alkyl, in particular, methyl; OH; C1-4- alkoxy, in particular methoxy; and CN.

[0056] "Optional" or "optionally" indicates that the subsequently described event or circumstance may, but need not, occur, and that the description includes examples in which the event or circumstance occurs and examples in which it does not occur. "Comprises" or "comprising" indicates that the subsequently described set may, but need not, include other elements.

[0057] The expression "pharmaceutically acceptable" represents being useful in the preparation of a pharmaceutical composition that is generally safe, non-toxic and neither biological nor otherwise undesirable, and includes being useful for both veterinary and human pharmaceutical use.

[0058] The term "acid addition salt" includes any non-toxic organic and inorganic acid addition salts that compounds of Formula (I) can form. Illustrative inorganic acids which form suitable salts include, but are not limited to, hydrogen chloride, hydrogen bromide, sulfuric and phosphoric acids. Illustrative organic acids which form suitable salts include, but are not limited to, acetic acid, lactic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid , benzoic acid, phenylacetic acid, cinnamic acid, methanesulfonic acid, salicylic acid and the like. The term "acid addition salt", when used herein, also encompasses solvates that compounds and salts thereof are capable of forming, such as, for example, hydrates, alcoholates and the like. These salts also include salts useful for the chiral resolution of racemates.

[0059] The term "base addition salt" includes any non-toxic base addition salts that the compound of Formula (I) can form. Suitable base salts include, but are not limited to, those derived from inorganic bases, such as aluminum, ammonium, calcium, copper, iron, lithium, magnesium, manganese, potassium, sodium and zinc salts, in particular sodium salts and ammonium. Other examples of organic base addition salt include trialkylamine salts, such as triethylamine and trimethylamine, and choline salts.

[0060] The present invention relates to new compounds of Formula (I)

[0061] wherein R1 and R2 are each independently selected from the group consisting of H, and halogen;

[0062] (i) R3 is selected from the group consisting of H, and C1-3-alkyl; It is

[0063] R4 is selected from the group consisting of

[0064] C1-3-alkyl,

[0065] unsubstituted 4- to 6-membered saturated heterocycle comprising 1 heteroatom selected from the group consisting of nitrogen, sulfur and oxygen,

[0066] 5-membered partially unsaturated heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituents selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, C(O)N(C1-3-alkyl )2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two independently selected substituent(s)( s) from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy,

[0067] 5-membered unsaturated or aromatic unsubstituted heterocycle comprising 1 nitrogen atom and 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen,

[0068] 5-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, C(O) N(C1-3-alkyl)2, and 6-membered saturated heterocycle containing 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituents (s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, and

[0069] 6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl)2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, or two adjacent substituents can form a saturated 5- or 6-membered fused ring;

[0070] or

[0071] (ii) R3 and R4 form together with the nitrogen atom to which they are bonded to form a group selected from a 5 to 6 membered saturated heterocycle comprising said nitrogen atom and is optionally substituted with a substituent selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, and (CH2)-C1-3-alkoxy; and an unsubstituted bicyclic spirocyclic or fused heterocycle containing said nitrogen atom and optionally 1 or 2 other heteroatom(s) selected from the group consisting of nitrogen, oxygen and sulfur;

[0072] and pharmaceutically acceptable salts thereof.

[0073] In the compounds of the present invention, the C-17 carbonyl group of the native estrone nucleus can be masked as a C-17 ketimine to enhance the metabolic and/or inhibitory properties of the compounds of Formula (I) of the present invention.

[0074] The desirably active compounds of the present invention can be easily made from the respective compound bearing the C-17 carbonyl group of the native estrone nucleus. Consequently provided here are compounds of Formula (II)

[0075] wherein R1, R2, R3 and R4 are as defined for the compounds of Formula (I). These compounds are direct starting materials for the preparation of compounds of Formula (I). Consequently, the examples given below of substituents R1 to R4 of compounds of Formula (I) apply to compounds of Formula (II) as well.

[0076] Selection of ring A substituents, which are the substituents R1 and R2, is particularly important to achieve desired properties of the compounds of the present invention.

[0077] In the first example of the present invention, R1 and R2 are each independently selected from the group consisting of H, F and Cl, preferably F and Cl. In the second example of the present invention, one of R1 and R2 is H and the other is F or Cl, preferably F. In a third example of the present invention, both R1 and R are H.

[0078] Thus, in another example of compounds of Formula (I) of the present invention, R1 is as defined above, particularly halogen, preferably F or Cl, more preferably F, and R2 is H. In an alternative example of the present invention, R1 is H and R2 is as defined above, particularly halogen, preferably F or Cl, more preferably F.

[0079] Consequently, the present invention provides compounds of Formula (Ia) wherein R1, R3, and R4 are as defined above.

[0080] Furthermore, the selection of substituents R3 and R4 is particularly important to achieve the desired properties of the compounds of the present invention.

[0081] In one aspect of the present invention, R3 is H or methyl, in particular H, and R4 is selected from the group consisting of

[0082] 5-membered unsaturated or aromatic unsubstituted heterocycle comprising 1 nitrogen atom and 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen,

[0083] 5-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, C(O) N(C1-3-alkyl)2, and 6-membered saturated heterocycle containing 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituents (s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, and

[0084] 6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl)2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, or two Adjacent substituents can form a saturated 5- or 6-membered fused ring.

[0085] In another aspect of the present invention, R3 is H or methyl, in particular H, and R4 is selected from the group consisting of oxetanyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, dihydrothiazolyl, thiadiazolyl, oxazolyl, methyloxazolyl, pyridinyl, fluoropyridinyl, cyanopyridinyl, methylpyridinyl, dimethylpyridinyl, isopropylpyridinyl, hydroxypyridinyl, methoxypyridinyl, morpholinopyridinyl, methylpiperazinylpyridinyl, pyrazinyl, methylpyridazinyl, and methoxypyridazinyl; in particular from the group consisting of oxetanyl and tetrahydropyranyl, dihydrothiazolyl, thiadiazolyl, oxazolyl, methyloxazolyl, fluoropyridinyl, methoxypyridinyl, methylpyridazinyl, and methoxypyridazinyl.

[0086] In an alternative aspect of the present invention, R3 and R4 form together with the nitrogen to which they are attached, a ring selected from the group consisting of pyrrolidinyl, and methoxymethylpyrrolidinyl, and oxaazaespiro[4.5]decanyl.

[0087] In a particular aspect of the compounds of Formula (Ia),

[0088] R1 is halogen, preferably F;

[0089] R3 is H, and

[0090] R4 is selected from the group consisting of

[0091] 5-membered unsaturated or aromatic unsubstituted heterocycle comprising 1 nitrogen atom and 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen,

[0092] 5-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, C(O) N(C1-3-alkyl)2, and 6-membered saturated heterocycle containing 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituents (s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, and

[0093] 6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl)2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, or two adjacent substituents can form a saturated 5- or 6-membered fused ring; and pharmaceutically acceptable salts thereof.

[0094] The present invention therefore provides compounds of Formula (I) in which R2 and R3 are H, and the compounds have Formula (Ib) wherein R1 and R4 are as defined above.

[0095] In the examples of compounds of Formula (I), (Ia) and (Ib) R4 is a 6-membered aromatic heterocycle of Formula (A) on what

[0096] X is CR9 or N;

[0097] one of R6, R7, R8 is H, and the others are independently selected from the group consisting of H, halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1 -3-alkoxy, and morpholine ring; It is

[0098] R9 is H or C1-3-alkyl.

[0099] In a particularly advantageous aspect of the present invention, R4 is a 6-membered aromatic heterocycle of Formula (A), wherein R6 and R7 are both H and has Formula (B) on what

[00100] X is CH or N, preferably CH; It is

[00101] R8 is selected from the group consisting of H, halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, and morpholine ring.

[00102] In one aspect, R8 is selected from the group consisting of halogen, preferably F, methyl, methoxy. More preferably, R8 is F.

[00103] In other examples of compounds of Formula (I), (Ia) and (Ib) R4 is a 6-membered aromatic heterocycle of Formula (B), wherein R6 and R8 are both H and has Formula (C)

[00104] where

[00105] X is CH or N, preferably CH; It is

[00106] R7 is selected from the group consisting of H, halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, and morpholine ring.

[00107] In one aspect, R7 is selected from the group consisting of halogen, preferably F, OH, methyl, methoxy. More preferably, R7 is methoxy and methyl.

[00108] In another aspect of the present invention, the compounds of Formula (I) are those presented in Table 1.

[00109] In a typical example of the present invention, compounds of Formula (I) are selected from the group consisting of:

[00110] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide;

[00111] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide;

[00112] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide;

[00113] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide;

[00114] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(oxetan-3-yl)propanamide;

[00115] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-methyl-(oxetan-3-yl)propanamide;

[00116] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-1-(pyrrolidin-1-yl)propan-1-one;

[00117] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide;

[00118] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(1,3,4-thiadiazol-2-yl)propanamide;

[00119] 3-((13S,15R,E)-4-fluoro-17-(hydroxyamino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide;

[00120] N-(4,5-dihydrothiazol-2-yl)-3-((13S,15R,E)-4-fluoro-17-(hydroxyamino)-13-methyl-7,8,9, 11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00121] N,N-diethyl-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15, 16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00122] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide;

[00123] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide;

[00124] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide;

[00125] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide;

[00126] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide;

[00127] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-methyl-N-(oxetan-3-yl)propanamide;

[00128] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(1,3,4-thiadiazol-2-yl)propanamide;

[00129] N,N-diethyl-3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15, 16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00130] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide;

[00131] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide;

[00132] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4,5-dihydrothiazol-2-yl)propanamide;

[00133] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-1-(8-oxa-2-azaspiro[4.5]decan-2-yl)propan-1-one;

[00134] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide;

[00135] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N,N-diethylpropanamide;

[00136] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide;

[00137] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide;

[00138] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide;

[00139] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3-methylpyridin-2-yl)propanamide;

[00140] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00141] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methyloxazol-2-yl)propanamide;

[00142] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide;

[00143] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide;

[00144] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide;

[00145] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-cyanopyridin-2-yl)propanamide;

[00146] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide;

[00147] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide;

[00148] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide;

[00149] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)propanamide;

[00150] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide;

[00151] 3-((13S,15R,E)-17-(hydroxyamino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide;

[00152] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide;

[00153] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide;

[00154] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide;

[00155] 6-(3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide;

[00156] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide;

[00157] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide;

[00158] N-(5-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14, 15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00159] N-(5-cyanopyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14, 15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00160] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(3-hydroxypyridin-2-yl)propanamide;

[00161] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide;

[00162] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide;

[00163] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-methyloxazol-2-yl)propanamide;

[00164] 3-((13S,15R,E)-17-(hydroxyamino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide;

[00165] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide;

[00166] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide;

[00167] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide;

[00168] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-methylpropanamide;

[00169] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N,N-dimethylpropanamide;

[00170] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(tetrahydro-2H-pyran-4-yl)propanamide;

[00171] N-Cyclohexyl-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15, 16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00172] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide;

[00173] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-1-(8-oxa-2-azaspiro[4.5]decan-2-yl)propan-1-one;

[00174] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide;

[00175] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide;

[00176] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide;

[00177] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-1-morpholinopropan-1-one;

[00178] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide;

[00179] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide;

[00180] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00181] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide;

[00182] N-(3,5-difluoropyridin-2-yl)-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11, 12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00183] N-(5-cyanopyridin-2-yl)-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12, 13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00184] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00185] N-(3,5-difluoropyridin-2-yl)-3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11, 12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00186] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide;

[00187] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide;

[00188] N-(4-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14, 15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00189] N-(3-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14, 15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00190] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00191] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3,5-difluoropyridin-2-yl)propanamide;

[00192] N-(3,5-difluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)- 13-methyl-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00193] N-(6-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14, 15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00194] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide;

[00195] 6-(3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide;

[00196] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide;

[00197] 6-(3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide;

[00198] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide;

[00199] and pharmaceutically acceptable salts thereof.

[00200] In a preferred aspect of the present invention, the compounds of Formula (I) are selected from the group consisting of:

[00201] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide;

[00202] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide;

[00203] and pharmaceutically acceptable salts thereof.

[00204] In a particular advantageous aspect of the present invention the compounds of Formula (II) are selected from the group consisting of:

[00205] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide;

[00206] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide;

[00207] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide;

[00208] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide;

[00209] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(oxetan-3-yl)propanamide

[00210] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-methyl-(oxetan-3-yl)propanamide;

[00211] (13S,15R)-4-fluoro-13-methyl-15-(3-oxo-3-(pyrrolidin-1-yl)propyl)-6,7,8,9,11,12,13, 14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one

[00212] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide;

[00213] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(1,3,4-thiadiazol-2-yl)propanamide;

[00214] N-(4,5-dihydrothiazol-2-yl)-3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12, 13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00215] N,N-diethyl-3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17- decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00216] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide;

[00217] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide;

[00218] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide;

[00219] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-methylpropanamide;

[00220] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N,N-dimethylpropanamide;

[00221] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(tetrahydro-2H-pyran-4-yl)propanamide;

[00222] N-cyclohexyl-3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17- decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00223] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide;

[00224] (13S,15R)-4-fluoro-13-methyl-15-(3-oxo-3-(8-oxa-2-azaspiro[4.5]decan-2-yl)propyl)-6,7, 8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one;

[00225] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide;

[00226] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide;

[00227] 3-((13S,15R)-3-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide;

[00228] (13S,15R)-4-fluoro-13-methyl-15-(3-morpholino-3-oxopropyl)- 6,7,8,9,11,12,13,14,15,16-deca -hydro-17H-cyclopenta[a]phenanthren-17-one;

[00229] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide;

[00230] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide;

[00231] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00232] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide;

[00233] N-(3,5-difluoropyridin-2-yl)-3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00234] N-(5-cyanopyridin-2-yl)-3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14, 15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00235] 3-((13S,15R)-3-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00236] N-(3,5-difluoropyridin-2-yl)-3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00237] 3-((13S,15R)-3-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide;

[00238] 3-((13S,15R)-3-chloro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide;

[00239] N-(4-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16, 17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00240] N-(3-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16, 17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00241] 3-((13S,15R)-3-chloro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00242] 3-((13S,15R)-3-chloro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(3,5-difluoropyridin-2-yl)propanamide;

[00243] N-(3,5-difluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15, 16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00244] N-(6-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16, 17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00245] 3-((13S,15R)-3-chloro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide;

[00246] 6-(3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide;

[00247] 3-((13S,15R)-3-chloro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide;

[00248] 6-(3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide;

[00249] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide;

[00250] and pharmaceutically acceptable salts thereof.

[00251] The invention also relates to a method for preparing a compound of the present invention, which comprises the steps of:

[00252] react a compound of Formula (III)

[00253] wherein R1 and R2 are each independently selected from the group consisting of H, and halogen;

[00254] with the compound of Formula (IV)

[00255] NR3R4 (IV)

[00256] wherein R3 and R4 are as defined for the compound of Formula (I),

[00257] in the presence of amide bond-forming reagents, in particular T3P and a base, preferably pyridine,

[00258] to obtain a compound of Formula (II), and react the obtained compound with

[00259] NH2-OH (V)

[00260] or hydrogen halide thereof,

[00261] in the presence of a base, preferably pyridine,

[00262] to obtain a compound of Formula (I);

[00263] and optionally converting the compound of Formula (I) to a pharmaceutically acceptable salt thereof.

LISTED FORMS OF REALIZATION

[00264] 1. A compound of Formula (I)

[00265] wherein R1 and R2 are each independently selected from the group consisting of H and halogen;

[00266] (i) R3 is selected from the group consisting of H and C1-3-alkyl; It is

[00267] R4 is selected from the group consisting of

[00268] C1-3-alkyl,

[00269] unsubstituted 4- to 6-membered saturated heterocycle comprising 1 heteroatom selected from the group consisting of nitrogen, sulfur and oxygen,

[00270] 5-membered partially unsaturated heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituents selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, C(O)N(C1-3-alkyl )2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two independently selected substituent(s)( s) from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy,

[00271] 5-membered unsaturated or aromatic unsubstituted heterocycle comprising 1 nitrogen atom and 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen,

[00272] 5-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, C(O) N(C1-3-alkyl)2, and saturated 6-membered heterocycle containing 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituents (s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, and

[00273] 6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl)2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, or two adjacent substituents can form a saturated 5- or 6-membered fused ring;

[00274] or

[00275] R3 and R4 form together with the nitrogen atom, they are linked to form a group selected from a saturated 5 to 6 member heterocycle comprising said nitrogen atom and is optionally substituted with a substituent selected from from the group consisting of halogen, CN, methyl, C1-3-(per)haloalkyl, OH, and methoxy; and an unsubstituted bicyclic spirocyclic or fused heterocycle containing said nitrogen atom and optionally 1 or 2 other heteroatom(s) selected from the group consisting of nitrogen, oxygen and sulfur;

[00276] or a pharmaceutically acceptable salt thereof.

[00277] 2. A compound as recited in embodiment 1, having Formula (Ia) wherein R1, R2, R3, and R4 are as defined in embodiment 1.

[00278] 3. A compound as recited in embodiment 2, wherein R1 is selected from the group consisting of H, F and Cl, preferably F and Cl.

[00279] 4. A compound as recited in any one of embodiments 1 to 3, wherein R3 is H or methyl.

[00280] 5. A compound as recited in embodiment 4, wherein R3 is H.

[00281] 6. A compound as recited in any one of embodiments 1 to 5, wherein R4 is selected from the group consisting of

[00282] 5-membered unsaturated or aromatic unsubstituted heterocycle comprising 1 nitrogen atom and 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen,

[00283] 5-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, C(O) N(C1-3-alkyl)2, and saturated 6-membered heterocycle containing 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituents (s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, and

[00284] 6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl)2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, or two Adjacent substituents can form a saturated 5- or 6-membered fused ring.

[00285] 7. A compound as recited in any one of embodiments 1 to 5, wherein R4 is selected from the group consisting of oxetanyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, dihydrothiazolyl, thiadiazolyl, oxazolyl, methyloxazolyl, pyridinyl, fluoropyridinyl, cyanopyridinyl, methylpyridinyl, dimethylpyridinyl, isopropylpyridinyl, hydroxypyridinyl, methoxypyridinyl, morpholinopyridinyl, methylpiperazinylpyridinyl, pyrazinyl, methylpyridazinyl, and methoxypyridazinyl; in particular from the group consisting of oxetanyl and tetrahydropyranyl, dihydrothiazolyl, thiadiazolyl, oxazolyl, methyloxazolyl, fluoropyridinyl, methoxypyridinyl, methylpyridazinyl and methoxypyridazinyl.

[00286] 8. A compound as recited in any one of embodiments 1 to 4, in which R3 and R4 form together with nitrogen, they are attached to a ring selected from the group consisting of pyrrolidinyl, methoxymethylpyrrolidinyl, and oxaazaespiro[4.5]decanyl.

[00287] 9. A compound as recited in embodiment 3, wherein the compound has Formula (Ib) wherein R1 and R4 are as defined in embodiment 1.

[00288] 10. A compound as recited in embodiment 9, wherein R4 is a 6-membered aromatic heterocycle of Formula (A) on what

[00289] X is CR9 or N;

[00290] one of R6, R7, R8 is H, and the others are independently selected from the group consisting of H, halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1 -3-alkoxy, and morpholine ring; It is

[00291] R9 is H or C1-3-alkyl.

[00292] 11. The Compound as recited in embodiment 1 selected from the group consisting of:

[00293] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide;

[00294] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide;

[00295] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide;

[00296] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide;

[00297] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(oxetan-3-yl)propanamide;

[00298] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-methyl-(oxetan-3-yl)propanamide;

[00299] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-1-(pyrrolidin-1-yl)propan-1-one;

[00300] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide;

[00301] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(1,3,4-thiadiazol-2-yl)propanamide;

[00302] 3-((13S,15R,E)-4-fluoro-17-(hydroxyamino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide;

[00303] N-(4,5-dihydrothiazol-2-yl)-3-((13S,15R,E)-4-fluoro-17-(hydroxylamino)-13-methyl-7,8,9, 11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00304] N,N-diethyl-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15, 16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00305] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide;

[00306] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide;

[00307] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide;

[00308] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide;

[00309] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide;

[00310] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-methyl-N-(oxetan-3-yl)propanamide;

[00311] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(1,3,4-thiadiazol-2-yl)propanamide;

[00312] N,N-diethyl-3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15, 16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00313] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide;

[00314] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide;

[00315] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4,5-dihydrothiazol-2-yl)propanamide;

[00316] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-1-(8-oxa-2-azaspiro[4.5]decan-2-yl)propan-1-one;

[00317] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide;

[00318] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N,N-diethylpropanamide;

[00319] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide;

[00320] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide;

[00321] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide;

[00322] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3-methylpyridin-2-yl)propanamide;

[00323] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00324] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methyloxazol-2-yl)propanamide;

[00325] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide;

[00326] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide;

[00327] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide;

[00328] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-cyanopyridin-2-yl)propanamide;

[00329] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide;

[00330] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide;

[00331] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide;

[00332] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)propanamide;

[00333] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide;

[00334] 3-((13S,15R,E)-17-(hydroxyamino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide;

[00335] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide;

[00336] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide;

[00337] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide;

[00338] 6-(3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide;

[00339] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide;

[00340] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide;

[00341] N-(5-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14, 15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00342] N-(5-cyanopyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14, 15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00343] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(3-hydroxypyridin-2-yl)propanamide;

[00344] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide;

[00345] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide;

[00346] 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-methyloxazol-2-yl)propanamide;

[00347] 3-((13S,15R,E)-17-(hydroxyamino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide;

[00348] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide;

[00349] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide;

[00350] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide;

[00351] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-methylpropanamide;

[00352] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N,N-dimethylpropanamide;

[00353] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(tetrahydro-2H-pyran-4-yl)propanamide;

[00354] N-Cyclohexyl-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15, 16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00355] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide;

[00356] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-1-(8-oxa-2-azaspiro[4.5]decan-2-yl)propan-1-one;

[00357] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide;

[00358] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide;

[00359] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide;

[00360] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-1-morpholinopropan-1-one;

[00361] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide;

[00362] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide;

[00363] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00364] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide;

[00365] N-(3,5-difluoropyridin-2-yl)-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11, 12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00366] N-(5-cyanopyridin-2-yl)-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12, 13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00367] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00368] N-(3,5-difluoropyridin-2-yl)-3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11, 12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00369] 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide;

[00370] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide;

[00371] N-(4-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14, 15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00372] N-(3-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14, 15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00373] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00374] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3,5-difluoropyridin-2-yl)propanamide;

[00375] N-(3,5-difluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)- 13-methyl-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00376] N-(6-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14, 15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00377] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide;

[00378] 6-(3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide;

[00379] 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide;

[00380] 6-(3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide;

[00381] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide;

[00382] or a pharmaceutically acceptable salt thereof.

[00383] 12. The Compound as recited in embodiment 11 selected from the group consisting of:

[00384] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide;

[00385] 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide;

[00386] or a pharmaceutically acceptable salt thereof.

[00387] 13. A compound of Formula (II) wherein R1, R2, R3, and R4 are as defined in embodiment 1.

[00388] 14. A compound as recited in embodiment 13, wherein R1 and R2 are each independently selected from the group consisting of H and halogen, preferably F and Cl.

[00389] 15. A compound as recited in any of embodiments 13 to 14, wherein R3 is H or methyl.

[00390] 16. A compound as recited in any one of embodiments 13 to 15, wherein R4 is selected from the group consisting of

[00391] 5-membered unsaturated or aromatic unsubstituted heterocycle comprising 1 nitrogen atom and 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen,

[00392] 5-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3-alkoxy, C(O) N(C1-3-alkyl)2, and saturated 6-membered heterocycle containing 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituents (s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, and

[00393] 6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl)2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, or two Adjacent substituents can form a saturated 5- or 6-membered fused ring.

[00394] 17. A compound as recited in any one of embodiments 13 to 16, wherein R4 is selected from the group consisting of oxetanyl, pyrrolidinyl, piperidinyl, tetrahydropyranyl, dihydrothiazolyl, thiadiazolyl, oxazolyl, methyloxazolyl, pyridinyl, fluoropyridinyl, cyanopyridinyl, methylpyridinyl, dimethylpyridinyl, isopropylpyridinyl, hydroxypyridinyl, methoxypyridinyl, morpholinopyridinyl, methylpiperazinylpyridinyl, pyrazinyl, methylpyridazinyl, and methoxypyridazinyl; in particular from the group consisting of oxetanyl and tetrahydropyranyl, dihydrothiazolyl, thiadiazolyl, oxazolyl, methyloxazolyl, fluoropyridinyl, methoxypyridinyl, methylpyridazinyl, and methoxypyridazinyl.

[00395] 18. A compound as recited in embodiment 13 or 14, in which R3 and R4 form together with nitrogen, they are attached to a ring selected from the group consisting of pyrrolidinyl, methoxymethylpyrrolidinyl, and oxaazaespiro[4.5 ]decanyl.

[00396] 19. The Compound as recited in embodiment 13 selected from the group consisting of:

[00397] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide;

[00398] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide;

[00399] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide;

[00400] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide;

[00401] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(oxetan-3-yl)propanamide

[00402] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-methyl-(oxetan-3-yl)propanamide;

[00403] (13S,15R)-4-fluoro-13-methyl-15-(3-oxo-3-(pyrrolidin-1-yl)propyl)-6,7,8,9,11,12,13, 14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one

[00404] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide;

[00405] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(1,3,4-thiadiazol-2-yl)propanamide;

[00406] N-(4,5-dihydrothiazol-2-yl)-3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12, 13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00407] N,N-diethyl-3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17- decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00408] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide;

[00409] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide;

[00410] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide;

[00411] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-methylpropanamide;

[00412] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N,N-dimethylpropanamide;

[00413] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(tetrahydro-2H-pyran-4-yl)propanamide;

[00414] N-cyclohexyl-3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17- decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00415] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide;

[00416] (13S,15R)-4-fluoro-13-methyl-15-(3-oxo-3-(8-oxa-2-azaspiro[4.5]decan-2-yl)propyl)-6,7, 8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one;

[00417] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide;

[00418] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide;

[00419] 3-((13S,15R)-3-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide;

[00420] (13S,15R)-4-fluoro-13-methyl-15-(3-morpholino-3-oxopropyl)- 6,7,8,9,11,12,13,14,15,16-deca -hydro-17H-cyclopenta[a]phenanthren-17-one;

[00421] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide;

[00422] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide;

[00423] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00424] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide;

[00425] N-(3,5-difluoropyridin-2-yl)-3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00426] N-(5-cyanopyridin-2-yl)-3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14, 15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00427] 3-((13S,15R)-3-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00428] N-(3,5-difluoropyridin-2-yl)-3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00429] 3-((13S,15R)-3-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide;

[00430] 3-((13S,15R)-3-chloro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide;

[00431] N-(4-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16, 17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00432] N-(3-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16, 17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00433] 3-((13S,15R)-3-chloro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide;

[00434] 3-((13S,15R)-3-chloro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(3,5-difluoropyridin-2-yl)propanamide;

[00435] N-(3,5-difluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15, 16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00436] N-(6-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16, 17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide;

[00437] 3-((13S,15R)-3-chloro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide;

[00438] 6-(3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide;

[00439] 3-((13S,15R)-3-chloro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide;

[00440] 6-(3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide, and

[00441] 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide.

[00442] 20. A compound as recited in any one of embodiments 1 to 12, for use as a medicine.

[00443] 21. A compound as recited in any one of embodiments 1 to 12, for use in treating or preventing a disease selected from a group consisting of breast cancer, prostate carcinoma, ovarian cancer, uterine cancer , endometrial cancer, endometrial hyperplasia, endometriosis, uterine fibroids, adenomyosis, polycystic ovary syndrome, dysmenorrhea, menorrhagia, metrorrhagia, contraception, prostadynia, benign prostatic hyperplasia, urinary dysfunction, lower urinary tract symptoms, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), systemic lupus erythematosus (SLE), multiple sclerosis, obesity, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), lung cancer, colon cancer, tissue wounds, skin wrinkles and cataracts.

[00444] 22. A compound as recited in any one of embodiments 1 to 12, for use in treating a disease selected from a group consisting of breast cancer, prostate carcinoma, ovarian cancer, uterine cancer, cancer endometrial, endometrial hyperplasia, endometriosis, uterine fibroids, adenomyosis, polycystic ovary syndrome, dysmenorrhea, menorrhagia, metrorrhagia, contraception, prostadynia, benign prostatic hyperplasia, urinary dysfunction, lower urinary tract symptoms, chronic prostatitis/chronic pelvic pain syndrome (CP /CPPS), systemic lupus erythematosus (SLE), multiple sclerosis, obesity, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), lung cancer, colon cancer, tissue wounds, skin wrinkles and cataracts.

[00445] 23. A pharmaceutical composition comprising an effective amount of one or more compounds, as recited in any one of embodiments 1 to 12, together with one or more pharmaceutically acceptable excipient(s).

[00446] 24. Pharmaceutical composition, as recited in embodiment 23, comprising one or more compounds, as recited in any one of embodiments 1 to 12, in combination with one or more other active ingredients.

[00447] 25. A method for preparing a compound of Formula (I) as defined in any one of embodiments 1 to 12,

[00448] comprising the steps of:

[00449] react a compound of Formula (III)

[00450] wherein R1 and R2 are each independently selected from the group consisting of H and halogen;

[00451] with the compound of Formula (IV)

[00452] NR3R4 (IV)

[00453] wherein R3 and R4 are as defined for the compound of Formula (I),

[00454] in the presence of amide bond-forming reagents, in particular T3P and a base, preferably pyridine,

[00455] to obtain a compound of Formula (II), and react the obtained compound with

[00456] NH2-OH (V)

[00457] or hydrogen halide thereof,

[00458] in the presence of a base, preferably pyridine,

[00459] to obtain a compound of Formula (I); and optionally converting the compound of Formula (I) into a pharmaceutically acceptable salt thereof.

[00460] 26. Method for treating or preventing a disease selected from a group consisting of breast cancer, prostate carcinoma, ovarian cancer, uterine cancer, endometrial cancer, endometrial hyperplasia, endometriosis, uterine fibroids, adenomyosis, polycystic ovarian syndrome , dysmenorrhea, menorrhagia, metrorrhagia, contraception, prostadynia, benign prostatic hyperplasia, urinary dysfunction, lower urinary tract symptoms, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), systemic lupus erythematosus (SLE), multiple sclerosis, obesity, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), lung cancer, colon cancer, tissue wounds, skin wrinkles and cataracts in a patient in need thereof, comprising administering the compound as recited in any one of embodiments 1 to 12 to the patient.

[00461] 27. A method for treating a disease selected from a group consisting of breast cancer, prostate carcinoma, ovarian cancer, uterine cancer, endometrial cancer, endometrial hyperplasia, endometriosis, uterine fibroids, adenomyosis, polycystic ovary syndrome , dysmenorrhea, menorrhagia, metrorrhagia, contraception, prostadynia, benign prostatic hyperplasia, urinary dysfunction, lower urinary tract symptoms, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), systemic lupus erythematosus (SLE), multiple sclerosis, obesity, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), lung cancer, colon cancer, tissue wounds, skin wrinkles and cataracts in a patient in need thereof, comprising administering the compound as recited in any of the embodiments 1 to 12 to the patient.

EXAMPLES OF THE INVENTION

[00462] Representative examples of compounds of Formula (I) and (II) are shown in Table 1. Table 1

[00463] Compounds of this invention are also useful in the form of acid or base addition salts, hydrates, or solvates thereof.

GENERAL PREPARATION METHODS

[00464] The compounds of the present invention can be prepared by methods known in the art.

[00465] The following examples illustrate the preparation of Compounds of Formula (I).

Preparation of precursors and synthetic starting materials Preparation of starting material Acid IX

[00466] Compound SM-IX was synthesized from Estrone (Scheme 1.). Methods of Horwitz et al (J. Med. Chem., 1986, 29(5), 692-698) produced amine SM-III, which was fluorinated using conditions of Labrie et al. WO 2008124922. SM-IV fluoride was converted to SM-VI enone by the silylation/oxidation method of Kobaiashi et al (Tetrahedron, 71(35), 5918-5924; 2015). The allylation, hydroboration and oxidation of SM-VI to SM-IX was carried out as in patents WO2005/047303 and WO2006/125800. Figure Caption: Estrone Compound SM-IV:

[00467] The solution of Compound SM-III (11.00 g, 40.8 mmol, 100 mol %) in dichloromethane (430 mL) was added to liquid boron trifluoride diethyl etherate (7.9 mL, 64 .20 mmol, 157 mol %) while stirring at -15 °C under nitrogen (addition time approx. 10-15 mins). The reaction mixture was stirred for 15 min. at -15 °C before the solution of tert-butyl nitrite (5.9 mL, 49.80 mmol, 122 mol %) in dichloromethane (50 mL) is added thereto dropwise over a period of 10 min. The reaction mixture was stirred for another 15 min. at -15°C, and then at 0-5°C for 30 min.

[00468] The solution was added to n-pentane (2.25 L) in order to produce a beige precipitate. The liquors were decanted, and the residue was washed with more n-pentane (400 mL). The beige solid (12.00 g) was dried in vacuum at room temperature overnight.

[00469] The crude material was purified by flash column chromatography using n-hexanes and ethyl acetate (10-30%) as a solvent system. The desired product was isolated as a cream solid. The yield of Compound SM-IV was 70% (7.82 g).

[00470] H NMR (400 MHz, CDCl3) δ ppm 0.91 (s, 3 H, -CH3), 1.34 1.70 (m, 6 H), 1.93-1.99 (m, 1 H), 2.04-2.21 (m, 3 H), 2.27-2.46 (m, 2 H), 2.48-2.56 (m, 1 H), 2.66-2 .77 (m, 1 H), 2.95-3.03 (m, 1 H), 6.84-6.90 (m, 1 H, -Ar H), 7.06-7.16 (m , 2H, 2x-ArH). SM-V compound:

[00471] tert-Butyldimethylsilyl triflate (7.1 mL, 31.10 mmol, 110 mol %) was added dropwise over a 20 min period to a stirred solution of Compound SM-IV (7.70 g, 28.27 mmol, 100 mol %) and triethylamine (6.0 mL, 42.72 mmol, 151 mol %) in dichloromethane (75 mL) at room temperature under nitrogen. The reaction mixture was stirred at room temperature for 2 h.

[00472] The reaction mixture was diluted with dichloromethane (95 mL) and washed with saturated aqueous sodium bicarbonate solution (2x70 mL) and brine (70 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the desired Example as a cream solid. The yield of Compound SM-V was quantitative (11.42 g). This Example was used in the next reaction without further purification.

[00473] 1H NMR (400 MHz, CDCl3) δ ppm 0.14-0.19 (m, 6H, 2x-CH3), 0.86 (s, 3 H, -CH3), 0.94 (s, 9H , 3 x -CH3), 1.21-1.62 (m, 5 H), 1.78-2.06 (m, 3 H), 2.08-2.16 (m, 1 H), 2 .25-2.38 (m, 2 H), 2.64-2.88 (m, 1 H), 2.90-2.99 (m, 1 H), 4.48 (dd, 1 H, J = 3.1, 1.5 Hz), 6.82-6.88 (m, 1H, -ArH), 7.05-7.13 (m, 2H, 2x-ArH). SM-VI compound:

[00474] The mixture of Compound SM-V (11.42 g, 28.27 mmol, 100 mol %) and palladium acetate (0.63 g, 2.83 mmol, 10 mol %) in dimethyl sulfoxide (75 mL) and dichloromethane (50 mL) was stirred at 35 °C under an oxygen atmosphere (balloon) for 16 h. After this time, the starting material was still present by tlc. Then, more palladium acetate (126 mg, 0.56 mmol, 2 mol %) was added to the mixture and stirred for another 7 h at 35 °C. After this time, TLC showed that the reaction was complete.

[00475] The reaction mixture was cooled to room temperature and was poured into a saturated aqueous sodium bicarbonate solution (300 mL). The mixture was extracted with ethyl acetate (400 ml). The organic layer was washed with water (300 ml) and brine (200 ml) and dried over sodium sulfate, filtered and concentrated under reduced pressure to provide an orange/brown solid.

[00476] The crude material was purified by flash column chromatography using n-hexanes and ethyl acetate (0-30%) as a solvent system. The desired product was isolated as a pink/white solid and dried in a vacuum oven. The yield of Compound SM-VI was 72% (5.50 g).

[00477] 1H NMR (400 MHz, CDCl3) δ ppm 1.11 (s, 3 H, -CH3), 1.46 1.58 (m, 1 H), 1.66-1.88 (m, 3 H), 1.97-2.07 (m, 1 H), 2.23-2.31 (m, 1 H), 2.35-2.54 (m, 3 H), 2.72-2 .84 (m, 1 H), 3.03 (dd, 1 H, J = 17.9, 6.4 Hz), 6.11 (dd, 1 H, J = 6.0, 3.2 Hz) , 6.83-6.92 (m, 1H, -Ar H), 7.05-7.18 (m, 2H, 2x-Ar H), 7.63-7.66 (m, 1H) .

[00478] MS m/z (ES+): 271 (M + H). SM-VII compound:

[00479] A dry three-neck flask was charged under nitrogen atmosphere with copper iodide (7.90 g, 41.48 mmol, 350 mol %), lithium chloride (1.76 g, 41.48 mmol , 350 mol%) and anhydrous tetrahydrofuran (60 mL). The mixture was stirred for 20 min. at room temperature and was cooled to -70 °C. Allyl magnesium bromide (41.5 mL, 41.48 mmol, 350 mol %) was then added dropwise, keeping the temperature below -70 °C. Chlorotrimethylsilane (5.3 mL, 41.48 mmol, 350 mol %) was added dropwise to the reaction mixture, maintaining the temperature at -70 °C, followed by the addition of a solution of Compound SM-VI (3, 20 g, 11.85 mmol, 350 mol %) in anhydrous tetrahydrofuran (60 mL), which was added dropwise keeping the temperature below -65 °C. The reaction mixture was allowed to slowly warm to room temperature while stirring overnight.

[00480] The mixture was poured into a saturated aqueous solution of ammonium chloride (75 mL) and extracted with ethyl acetate (3 x 70 mL). The combined extracts were washed with 1M HCl (2 x 50 mL), water (2 x 50 mL) and dilute aqueous ammonia solution (5 x 25 mL) (until the solution became colorless). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash column chromatography using n-hexanes and ethyl acetate (10%) as the solvent system. The yield of Compound SM-VII was 77% (2.85 g).

[00481] 1H NMR (400 MHz, CDCl3) δ ppm 1.05 (s, 3 H, -CH3), 1.40 1.57 (m, 3 H), 1.71-1.82 (m, 2 H), 1.89-1.96 (m, 1 H), 2.04-2.20 (m, 2 H), 2.31-2.50 (m, 6 H), 2.72-2 .84 (m, 1 H), 2.94-3.03 (m, 1 H), 5.02-5.08 (m, 2 H, CH=CH2), 5.69-5.81 (m , 1 H, CH=CH2), 6.88 (t, 1 H, ArH, J = 8.7Hz), 7.05-7.16 (m, 2 H, 2 x ArH). SM-VIII Compound:

[00482] A dry, nitrogen-stimulated flask was charged with Compound SM-VII (2.85 g, 9.13 mmol, 100 mol%) and anhydrous tetrahydrofuran (70 mL). A 1 M solution of borane-THF complex (18.3 mL, 18.30 mmol, 200 mol %) was added dropwise to the previous solution. The resulting reaction mixture was heated until gently fluxed and stirred for 1 h. After this time, the reaction mixture was cooled in an ice bath to -5 °C and a 3 M aqueous solution of sodium hydroxide (28 mL) was added to it very carefully. After the addition was complete and the effervescence ceased, 30% hydrogen peroxide (28 mL) was added, and the mixture was gently refluxed for 2 h.

[00483] The reaction mixture was cooled to room temperature and extracted with ethyl acetate (3 x 70 mL). The combined extracts were washed with water (2 x 50 mL) and brine (50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the desired Example. The yield of Compound SM-VIII was quantitative (3.09 g).

[00484] 1H NMR (400 MHz, CDCl3) δ ppm 0.82 (s, 3 H, -CH3), 1.13 1.64 (m, 9 H), 1.81-1.88 (m, 1 H), 1.91-2.06 (m, 2 H), 2.16-2.27 (m, 2 H), 2.30-2.39 (m, 1 H), 2.63-2 .74 (m, 1 H), 2.81-2.89 (m, 1 H), 3.54-3.69 (m, 3 H), 6.76-6.82 (m, 1 H, -Ar H), 6.98-7.08 (m, 2 H, 2 x -ArH).

[00485] SM-IX acid: acid [3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16, 17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanoic acid]

[00486] Periodic acid (5.15 g, 22.60 mmol, 500 mol %) and chromium trioxide (23 mg, 0.23 mmol, 5.0 mol %) were dissolved in a mixture of acetonitrile (36 mL) and water (12 mL). The solution was cooled to 0 °C in an ice/salt bath. A suspension of Compound SM-VIII (1.5 g, 4.52 mmol, 100 mol %) in acetonitrile (30 mL) was added to the above solution over a period of 40 min. while maintaining the temperature at or below 0°C. The reaction mixture was stirred for 1 h at 0 °C, then the mixture was slowly warmed to room temperature and stirred for an additional 3.5 h.

[00487] The reaction mixture was poured into aqueous sodium dibasic phosphate (~5 g in 100 mL) and extracted with ethyl acetate (3 x 60 mL). The organic extracts were combined and washed with a 5% aqueous solution of sodium bisulfite (2 x 40 mL), water (50 mL) and brine (50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure.

[00488] The crude material was purified by flash column chromatography using n-hexanes, ethyl acetate (10-30%) and acetic acid (1%) as a solvent system to provide a white solid. The solid was dissolved in toluene (50 mL) and stirred for 15 min. The solvent was removed in vacuo, and the solid was dried in vacuo at 50°C to provide the desired product as a white solid. The crude yield of acidic Compound SM-IX was 71% (1.11 g).

[00489] 1H NMR (400 MHz, CDCl3) δ ppm 0.99 (s, 3 H, -CH3), 1.31 1.53 (m, 3 H), 1.55-1.78 (m, 3 H), 1.83-2.00 (m, 2 H), 2.09-2.17 (m, 1 H), 2.23-2.47 (m, 7 H), 2.68-2 .80 (m, 1 H), 2.88-2.97 (m, 1 H), 6.81 (t, 1 H, -ArH, J = 8.6 Hz), 6.98-7.10 (m, 2 H, 2 x -ArH).

[00490] MS m/z (ES-): 343 (M - H).

Preparation of starting material SM-XV Acid

[00491] C-3 Fluoro SM-XV was synthesized from Estrone (Scheme 2.) using Compound SM-X, which can be synthesized as described in Messinger et al. Mol Cell Endocrinol. 2009 (301) 216-224. The detailed synthesis of compound SM-X acid was methylated by heating in methanol in the presence of sulfuric acid followed by triflation. The bistributyltin derivative SM-XIII was prepared from the corresponding triflate SM-XII followed by fluorination to XIV in 75% yield, (ref. WO 2010059943 and Furuia et al., JACS 2009, 13 (15),1662). Several methods of estrone deoxyfluorination are available (Labrie, Fernand et al. PCT Int. Appl., 9946279, September 16, 1999; Labrie, Fernand et al. PCT Int. Appl., 2004089971, October 21, 2004). Figure Caption: - Estrone Compound XIII:

[00492] In a sealed tube with a screw cap, Compound SM-XII (10.0 g, 20.47 mmol, 100 mol%) and 1,4-dioxane (120 mL) were added. Bistributyltin (230.7 mL, 40.99 mmol, 200 mol %) and LiCl (4.2 g, 102.3 mmol, 500 mol %) were added to the reaction mixture. The reaction mixture was degassed with argon gas for 10 min, then Pd(PPh3)4 (1.41 g, 1.22 mmol, 6 mol %) was added to it. The tube was sealed under nitrogen, and the mixture was stirred and heated to 100 °C in a preheated oil bath for 4 hours. The progress of the reaction was monitored by TLC and LC-MS. The mixture was cooled to room temperature and quenched with water (100 mL), extracted with ethyl acetate (2 x 200 mL), then filtered through celite, washing well with ethyl acetate. The solvents were concentrated under reduced pressure to leave a brown viscous oil. The crude was purified by flash chromatography (40 g pressure) eluting with a gradient of 0 to 10% ethyl acetate in hexanes to yield Compound SM-XIII.

[00493] 1H NMR (400 MHz, CDCl3) δ ppm: 7.29-7.19 (m, 3 H), 3.69 (s, 3 H), 2.95 (bs, 2 H), 2, 42-0.87 (m, 46H). MS m/z (ES+): weak ionization. Compound SM-XIV: Figure Caption: Acetone

[00494] To a stirred solution of Compound SM-XIII (14.0 g, 22.2 mmol, 1.0 eq) in acetone (140 mL) was added AgOTf (11.41 g, 44.4 mmol, 2. 0 eq) at room temperature. The reaction mixture was cooled to 0°C and 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(hexafluorophosphate) (12.53 g, 26.6 mmol, 1.2 eq) added. and the reaction mixture was stirred for 40 min. The progress of the reaction was monitored by TLC. The mass reaction was quenched with water (100 mL) and extracted with ethyl acetate (2 x 150 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the crude compound. The crude Compound was purified by flash chromatography using 40 g of pressure and eluted with 0-20% ethyl acetate in hexane. The combined organic portions were concentrated in vacuo to provide the desired Compound SM-XIV (6.0 g, 75.9%) as a white solid.

[00495] 1H NMR (400 MHz, DMSO-d6) δ ppm: 7.30-7.27 (m, 1 H), 7.10-7.08 (d, 1 H, J = 8 Hz), 6 .94-6.89 (m, 1 H), 3.59 (s, 3 H), 2.87 (bs, 2 H), 2.45-2.07 (m, 8 H), 1.86 -1.32 (m, 8 H), 0.95 (s, 3 H). MS m/z (ES+): weak ionization. SM-XV compound: Figure Caption: Water

[00496] In a stirred solution of Compound SM-XIV (6.0 g, 16.7 mmol, 1.0 eq) in THF (60 mL), water (10.5 mL) and LiOH.H2O (1 .41 g, 33.5, 2.0 eq) at RT. The reaction mixture was stirred at RT for 4 h. The progress of the reaction was monitored by TLC and LC-MS. The reaction mixture was cooled to 10°C, and neutralized with 1N HCl (pH= 6) and extracted with ethyl acetate (2 x 50 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to provide off-white. The Compound was triturated with n-pentane (2 x 10 mL) to yield 5.4 g of white solid, which was purified by prep. HPLC purification to provide Compound SM-XV (2.2 g, 38.19 %) as a white solid.

[00497] 1H NMR (400 MHz, DMSO-d6) δ ppm: 12.06 (s, 1 H), 7.29 7.27 (d, 1 H, J = 8 Hz), 7.16-7, 14 (d, 2 H, J = 8 Hz), 2.87 (bs, 2 H), 2.37-2.12 (m, 8 H), 1.82-1.67 (m, 4 H) , 1.55-1.38 (m, 4 H), 0.84 (s, 3 H). MS m/z (ES+): 343.23 (M - H).

SM-XVII Acid

[00498] Triflate SM-XII in scheme 3 was prepared following methods of Messinger et al, WO 2008065100. SM-XII was converted to chlorine derivative SM-XVI using t-BuBrettPhos in the presence of tris(dibenzylidene-acetone)dipalladium (0) (Pan et al., Organic Letters, 13(18), 4974-4976; 2011) followed by treatment with LiOH in THF:water providing the desired acid SM-XVII. SM-XVI compound:

[00499] In a sealed tube with a screw cap, tris(dibenzylideneacetone)dipalladium(0) (0.084 g, 0.092 mmol, 3 mol%) and t-BuBrettPhos (0.133 g, 0.27 mmol, 9 mol%) were added. ) and 1,4-dioxane (10 mL) and the tube was sealed under nitrogen. The mixture was stirred and heated to 130 °C in a preheated oil bath for 3 minutes. The catalyst mixture was cooled to room temperature and this mixture was added to a solution of Compound SM-XII (1.5 g, 3.04 mmol, 100 mol %) in 1,4-dioxane (11 mL), sodium chloride potassium (0.908 g, 12.28 mmol, 400 mol %) and potassium fluoride (0.178 g, 3.0 mmol, 100 mol %). The mixture was then stirred and heated to 130 °C in a preheated oil bath for 3 hours. The progress of the reaction was monitored by TLC and LC-MS. The mixture was cooled to room temperature and then filtered through celite, washing well with ethyl acetate. The solvents were concentrated under reduced pressure to leave a brown viscous oil. The crude was purified by flash chromatography (40 g pressure) eluting with a 0 to 20% gradient to provide Compound SM-XVI.

[00500] 1H NMR (400 MHz, DMSO-d6) δ ppm: 7.29-7.27 (d, 1 H, J = 8 Hz), 7.16-7.14 (d, 2 H, J = 8 Hz), 3.59 (s, 3 H), 2.87 (bs, 2 H), 2,412.07 (m, 8 H), 1.85-1.38 (m, 8 H), 0, 95 (s, 3 H). MS m/z (ES+): weak ionization. SM-XVII Compound: Figure Caption: Water

[00501] To a stirred solution of Compound SM-XVI (1.7 g, 4.54 mmol, 1.0 eq) in THF:MeOH:Water (12.5 mL, 2:2:1) LiOH was added. H2O (0.572 g, 13.6, 3.0 eq) at RT. The reaction mixture was heated at 80 °C for 1.5 h. The progress of the reaction was monitored by TLC and LC-MS. The reaction mixture was cooled to RT, diluted with 10 mL water and washed with 3 x 3 mL ethyl acetate. The aqueous layer was neutralized with 1N HCl (pH= 6) and extracted with ethyl acetate (2 x 50 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to provide off-white. The Compound was triturated with n-pentane (2 x 10 mL) to provide the desired compound SM-XVII (1.3 g, 79%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm: 12.06 (s, 1 H), 7.29-7.27 (d, 1 H, J = 8 Hz), 7.16-7.14 ( d, 2 H, J = 8 Hz), 2.87 (bs, 2 H), 2.37-2.12 (m, 8 H), 1.82-1.67 (m, 4 H), 1 .55-1.38 (m, 4 H), 0.84 (s, 3 H). MS m/z (ES+): 358.9 (M - H).

Preparation of SM-XXVI Acid starting material:

[00502] Compound SM-XXVI was synthesized from Estrone using the triflate SM-XVIII, which was prepared by methods of Messinger et al, WO 2008065100. C15-C16 SM-XXIII was prepared according to methods described in WO2008065100. The allylation, hydroboration and oxidation of SM-XXIII to SM-XXVI was carried out as in patents WO2005/047303 and WO2006/125800. Figure Caption: Estrone Composite SM-XXVI:

[00503] In a stirred solution of (8R,9S,13S,14S,15R)-15-(3-hydroxypropyl)-13-methyl-7,8,9,11,12,13,14,15,16, 17-decahydro-6H-cyclopenta[a]phenanthren-17-ol (44.0 g 0.140 mol) in acetone (875 mL) and the resulting solution was cooled to 0 °C. In another RBF, Jones reagent was prepared by dissolving chromic acid (35 g, 0.350 mol) in water (350 mL) and conc. sulfuric acid. (41.14 g, 0.420 mol). The prepared Jones reagent was added to the above alcoholic derivative maintaining the temperature at 0-2 °C. The addition was completed in 45 minutes. The reaction mass was maintained at 0-2 °C for 2-3 h. The progress of the reaction was monitored by TLC. The reaction mass was then quenched using ice water (875 mL), the sticky material was filtered and dissolved in 3N NaOH solution (200 mL). The mixture was extracted with ethyl acetate (3 x 200 mL). The aqueous layer was neutralized with 2N aqueous HCl (pH = 6) and extracted with ethyl acetate (3 x 200 ml). The combined organic layer was washed with brine (200 mL), dried over anhydrous sodium sulfate, and the solvent was evaporated under vacuum to obtain the solid acidic compound 3-((8R,9S,13S,14S,15R)-13- methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanoic acid (24 g, 52%) as a white solid.

[00504] 1H NMR (400 MHz, DMSO-d6) δ ppm: 12.0 (s, 1 H), 7.27 7.25 (d, 1 H, J = 8 Hz), 7.13-7, 05 (m, 3 H,), 2.87 (bs, 2 H), 2.41-2.10 (m, 8 H), 1.87-1.36 (m, 8 H), 0.95 (s, 3 H).

[00505] MS m/z (ES+): 325.23 (M - H).

General information

[00506] Commercial grade reagents and solvents were used without further purification. Thin-layer chromatography (TLC) was performed on Merck plates; pre-coated aluminum sheets. Visualization of the plates was done using the following techniques: 1) ultraviolet illumination (254 nm), 2) immersing the plate in anisaldehyde or vanillin solution followed by heating. 1H-NMR spectra were measured with a Bruker DPX spectrometer (200 MHz) with the solvent as indicated.

[00507] Oxime compounds of the invention can be prepared from the corresponding C-17 carbonyl derivatives. Preparation of C-17 carbonyl and oxime compounds Compound 1 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16 ,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide

[00508] In a solution of SM-IX Acid (750 mg, 2.18 mmol, 100 mol%) in dry DCM (10 ml) under nitrogen atmosphere was added 3-amino-5-methylisoxazole (427 mg, 4 .36 mmol, 200 mol %) and pyridine (526 μl, 6.53 mmol, 300 mol %). T3P (50 wt % in EtOAc) (2.6 ml, 4.36 mmol, 200 mol %) was added dropwise, and the reaction mixture stirred at RT for four hours. DCM (10 ml) and 10% NaHCO3 (30 ml) were added. The aqueous phase was extracted twice with DCM (2 x 10 ml). The organic phases were combined and washed with 0.1 N HCl solution (3 x 30 ml), water (3 x 30 ml) and finally with brine (3 x 30 ml) and dried with sodium sulfate. The crude yield of compound 1 was 95% (875 mg).

[00509] 1H NMR (200 MHz, DMSO-d6): 0.97 (s, 3 H), 1.24 - 2.46 (m, 16 H), 2.37 (s, 3 H), 2, 58 - 3.01 (m, 2 H), 6.64 (s, 1 H), 6.88-7.06 (m, 1 H), 7.07 - 7.25 (m, 2 H), 10.88 (s, 1 H). Compound 2 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide

[00510] A suspension of compound 1 (850 mg, 2.00 mmol, 100 mol %), hydroxylamine hydrochloride (278 mg, 4.00 mmol, 200 mol %) and pyridine (0.65 ml, 8, 00 mmol, 400 mol %) in ethanol abs. (15 ml) was stirred at 50 °C under a nitrogen atmosphere for 2.5 hours. The solvent was evaporated. The precipitate was dissolved in ethyl acetate (15 ml) and washed with water (15 ml). The aqueous phase was extracted twice with ethyl acetate (15 ml). The organic phases were combined and washed with dilute 0.1 N HCl solution (3 x 40 ml), 0.25 N HCl (2 x 40 ml), water (3 x 40 ml) and finally with brine (3 x 40 ml), and dried with sodium sulfate. The yield of compound 2 after trituration with heptane:ethanol was 96% (841 mg).

[00511] 1H NMR (200 MHz, DMSO-d6): 1.02 (s, 3 H), 1.24 - 2.47 (m, 15 H), 2.37 (s, 3 H), 2, 57 - 2.99 (m, 3 H), 6.64 (s, 1 H), 6.89 - 7.05 (m, 1 H), 7.07-7.25 (m, 2 H), 10.19 (s, 1 H), 10.89 (s, 1 H). MS m/z (TOF ES+): 462 (M+Na). Compound 3 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide

[00512] In a solution of SM-IX Acid (70 mg, 0.20 mmol, 100 mol%) in dry DMF (2 ml) under nitrogen atmosphere, 1-hydroxybenzotriazole hydrate (HOBt) (60 mg, 0.45 mmol, 220 mol %), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (86 mg, 0.45 mmol, 220 mol %) and 3-amino-6-methoxypyridazine ( 51 mg, 0.41 mmol, 200 mol %). The reaction mixture was stirred at +50°C for 3.5 hours. Water (3 ml) was added to the reaction mixture. The solid precipitate was filtered and washed several times with water and finally with heptane to yield 56 mg of crude product. Purification was done by flash chromatography. The amount of product compound 3 was 36 mg.

[00513] 1H-NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.20-2.47 (m, 16 H), 2.60-2.97 (m, 2 H), 3.98 (s, 3 H), 6.89-7.06 (m, 1 H), 7.08-7.21 (m, 2 H), 7.25 (d, 1 H) , 8.26 (d, 1H), 10.94 (br s, 1H). Compound 4 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide

[00514] A suspension of compound 3 (25 mg, 0.06 mmol, 100 mol %), hydroxylamine hydrochloride (8 mg, 0.11 mmol, 200 mol %) and pyridine (18 μl, 0.22 mmol , 400 mol %) in ethanol abs. (2 ml) was stirred at 40-50 °C under nitrogen atmosphere for 4.5 hours. The solvent was evaporated. The precipitate was dissolved in DCM (5 ml) and washed with water (5 ml). The aqueous phase was extracted twice with DCM (5 ml). The organic phases were combined and washed with 0.1 N HCl solution (3 x 5 ml), water (4 x 5 ml) and finally with brine (3 x 5 ml), and dried with sodium sulfate. The crude product was purified by flash chromatography. The amount of product compound 4 was 15 mg.

[00515] 1H-NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.18-2.45 (m, 15 H), 2.57-3.00 (m, 3 H), 3.98 (s, 3 H), 6.86-7.05 (m, 1 H), 7.07-7.21 (m, 2 H), 7.24 (d, 1 H) , 8.26 (d, 1H), 10.19 (br s, 1H), 10.95 (br s, 1H). MS m/z (TOF ES+): 460 (M+1) Compound 5 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide

[00516] In a solution of SM-IX Acid (50 mg, 0.15 mmol, 100 mol%) in dry DMF (2 ml) 1-hydroxybenzotriazole hydrate (HOBt) (43 mg, 0.32 mmol) was added , 220 mol %) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (61 mg, 0.32 mmol, 220 mol %), and finally 5-methoxypyridine-2-amine (38 mg , 0.29 mmol, 200 mol %). The reaction mixture was stirred at +50°C for two hours. Water (2 ml) was added to the reaction mixture. The solid precipitate was filtered and washed several times with water. The crude yield of compound 5 was 80% (52 mg).

[00517] 1H-NMR (200 MHz, CDCl3): 1.07 (s, 3 H), 1.35-2.53 (m, 16 H), 2.72-3.03 (m, 2 H) , 3.85 (s, 3 H), 6.83-6.92 (m, 1 H), 7.05-7.18 (m, 2 H), 7.24-7.30 (m, 1 H), 7.92-8.01 (m, 2H), 8.15 (d, 1H). Compound 6 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide

[00518] A suspension of compound 5 (30 mg, 0.07 mmol, 100 mol %), hydroxylamine hydrochloride (9.2 mg, 0.13 mmol, 200 mol %) and pyridine (32 μl, 0. 40 mmol, 600 mol %) in ethanol abs. (2 ml) was refluxed under a nitrogen atmosphere for one hour. The solvent was evaporated. The precipitate was dissolved in ethyl acetate (5 ml) and washed with water (5 ml). The aqueous phase was extracted twice with ethyl acetate (5 ml). The organic phases were combined and washed with dilute 0.25N HCl solution (3 x 10 ml), water (3 x 10 ml) and finally with brine (3 x 20 ml), and dried with sodium sulfate. The crude yield of compound 6 was 94% (29 mg).

[00519] 1H-NMR (200 MHz, CDCl3): 1.15 (s, 3 H), 1.34-2.43 (m, 16 H), 2.79-3.03 (m, 3 H) , 3.84 (s, 3 H), 6.81-6.89 (m, 1 H), 7.07-7.16 (m, 2 H), 7.32 (d, 1 H), 7 .94 (br s, 1 H), 8.21 (d, 1 H), 8.83 (br s, 1 H). MS m/z 466 (M +1) Compound 7 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16 ,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide

[00520] In a solution of SM-IX Acid (500 mg, 1.45 mmol, 100 mol%) in dry THF (10 ml) under a nitrogen atmosphere, 2-amino-5-fluoropyridine (325 mg, 2 .90 mmol, 200 mol %) and pyridine (351 μl, 4.36 mmol, 300 mol %). T3P (50 wt % in EtOAc) (1.73 ml, 2.90 mmol, 200 mol %) was added dropwise and the reaction mixture stirred at RT for three hours. The solvent was evaporated, and the residue dissolved in ethyl acetate (15 ml) and washed with 10% NaHCO3 (30 ml). The aqueous phase was extracted twice with ethyl acetate (2 x 15 ml). The organic phases were combined and washed with 0.1 N HCl solution (3 x 30 ml), water (3 x 30 ml) and finally with brine (2 x 30 ml) and dried with sodium sulfate. The Example was used in the next step without further purification. The crude yield of compound 7 was 99% (631 mg).

[00521] 1H NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.24 - 2.46 (m, 16 H), 2.59 - 3.03 (m, 2 H ), 6.90 - 7.05 (m, 1 H), 7.06 - 7.22 (m, 2 H), 7.73 (td, 1 H), 8.15 (dd, 1 H), 8.32 (d, 1 H), 10.63 (s, 1 H). MS m/z (TOF ES+): 439 (M+1) Compound 8 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11, 12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide

[00522] A suspension of compound 7 (1.07 g, 2.44 mmol, 100 mol %), hydroxylamine hydrochloride (339 mg, 4.88 mmol, 200 mol %) and pyridine (790 μl, 9. 76 mmol, 400 mol %) in ethanol abs. (15 ml) was stirred at 40 °C under a nitrogen atmosphere for 1.5 hours. The solvent was evaporated. The precipitate was dissolved in ethyl acetate (15 ml) and washed with water (15 ml). The aqueous phase was extracted twice with ethyl acetate (15 ml). The organic phases were combined and washed with dilute 0.1 N HCl solution (3 x 40 ml), water (4 x 40 ml) and finally with brine (3 x 40 ml), and dried with sodium sulfate. The crude yield of compound 8 was 92% (1.02 g).

[00523] 1H NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.12 - 2.44 (m, 15 H), 2.58 - 3.01 (m, 3 H ), 6.89 - 7.04 (m, 1 H), 7.05 - 7.24 (m, 2 H), 7.72 (td, 1 H), 8.15 (dd, 1 H), 8.31 (d, 1 H), 10.19 (s, 1 H), 10.64 (s, 1 H). MS m/z (TOF ES+): 454 (M+1) Compound 9 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(oxetan-3-yl)propanamide

[00524] SM-IX acid (56.9 mg, 0.17 mmol, 100 mol%) was dissolved in dry DCM (2 ml). Oxetane-3-amine hydrochloride (30 mg, 0.26 mmol, 150 mmol %), N-methylmorpholino (57 μl, 0.52 mmol, 300 mol%) and HOBt (40 mg, 0.30 mmol , 170 mol %) were added to the reaction mixture, stirred for 5 minutes and then cooled with an ice bath. EDCI (73 mg, 0.38 mmol, 220 mol%) was added and allowed to warm to room temperature. After stirring overnight, the reaction mixture was diluted with DCM, washed with 1N HCl solution (3 x 10 ml), water (3 x 10 ml) and finally with brine (3 x 10 ml). Dried with sodium sulfate. The solvent was evaporated and the crude product was purified by chromatography, yielding compound 9 in 59% yield.

[00525] 1H-NMR (200 MHz, CDCl3): 1.05 (s, 3 H), 1.45 - 2.49 (m, 16 H), 2.71 - 3.06 (m, 2 H) , 4.50 (t, 2 H), 4.95 (t, 2 H), 5.06 (t, 1 H), 6.02 (m, 1 H), 6.84 - 6.92 (m , 1 H), 7.05 - 7.18 (m, 2 H). Compound 10 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(oxetan-3-yl)propanamide

[00526] Compound 10 was prepared in 96% yield from compound 9 by the same method as in Example 2.

[00527] 1H-NMR (200 MHz, CDCl3): 1.11 (s, 3 H), 1.36 - 2.45 (m, 16 H), 2.69 - 3.03 (m, 2 H) , 4.50 (t, 2 H), 4.95 (t, 2 H), 5.07 (t, 1 H), 6.14 (m, 1 H), 6.82 - 6.91 (m , 1 H), 7.04 - 7.20 (m, 2 H), 8.33 (br s, 1H). Compound 11 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-methyl-(oxetan-3-yl)propanamide

[00528] Compound 11 was prepared by the same method as compound 9 using SM-IX acid and N-methyl-3-oxetanamine as the amine. The reaction time was 2 hours, producing the product in 78% yield.

[00529] 1H NMR (200 MHz, DMSO-d6): 0.96 (s, 3 H), 1.15 - 2.47 (m, 16 H), 2.60 - 2.98 (m, 2 H ), 3.00, 3.05 (2 xs, 3 H), 4.50-4.80 (m, 4 H), 5.15-5.40 (m, 1 H), 6.90 - 7 .05 (m, 1 H), 7.10 - 7.25 (m, 2 H). Compound 12 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)- N-methyl-(oxetan-3-yl)propanamide

[00530] Compound 12 was prepared from compound 11 by the same method as compound 2 by stirring at 50 ° C for 2 hours, producing the product in 18% yield after chromatographic purification.

[00531] 1H NMR (200 MHz, CDCl3): 1.12 (s, 3 H), 1.30-2.55 (m, 15 H), 2.60-3.05 (m, 3 H), 3.16 (s, 3H), 4.60-4.92 (m, 4H, isomers), 5.05-5.65 (m, 1H), 6.80-6.95 (m, 1H ), 7.00-7.20 (m, 2H), 7.23 (br s, 1H). Compound 13 (13S,15R)-4-fluoro-13-methyl-15-(3-oxo-3-(pyrrolidin-1-yl)propyl)- 6,7,8,9,11,12,13,14 ,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one

[00532] Compound 13 was synthesized in 54% yield by the method used in the preparation of compound 1 using SM-IX acid and pyrrolidine as starting materials in a reaction time of 5.5 hours.

[00533] 1H NMR (200 MHz, CDCl3): 1.07 (s, 3 H), 1.20 - 2.55 (m, 20 H), 2.70 - 3.10 (m, 2 H), 3.30 - 3.55 (m, 4 H), 6.80-6.95 (m, 1 H), 7.00-7.22 (m, 2 H). Compound 14 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-1-(pyrrolidin-1-yl)propan-1-one

[00534] Compound 14 was prepared in 72% yield from compound 13 by the same method as compound 2 in a reaction time of 3 hours.

[00535] 1H NMR (200 MHz, CDCl3): 1.13 (s, 3 H), 1.25 - 2.55 (m, 19 H), 2.68 - 3.10 (m, 3 H), 3.30 - 3.55 (m, 4 H), 6.80-6.95 (m, 1 H), 7.00-7.22 (m, 2 H), 7.52 (br s, 1H ). Compound 15 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide

[00536] Compound 15 was synthesized in 83% yield by the method used in the preparation of compound 9 in THF using SM-IX acid and 3-amino-6-methylpyridazine as starting materials in a reaction time of 4 hours.

[00537] 1H-NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.20-2.47 (m, 16 H), 2.55 (s, 3 H), 2 .70-2.95 (m, 2 H), 6.89-7.06 (m, 1 H), 7.08-7.25 (m, 2 H), 7.54 (d, 1 H) , 8.23 (d, 1H), 11.05 (s, 1H). Compound 16 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide

[00538] Example 16 was prepared in 59% yield from compound 15 by the same method as in Example 2 in a reaction time of 2.5 hours.

[00539] 1H-NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.15-2.47 (m, 15 H), 2.55 (s, 3 H), 2 .60-2.95 (m, 3 H), 6.89-7.06 (m, 1 H), 7.08-7.25 (m, 2 H), 7.54 (d, 1 H) , 8.23 (d, 1H), 10.20 (s, 1H), 11.06 (s, 1H). Compound 17 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(1,3,4-thiadiazol-2-yl)propanamide

[00540] Compound 17 was synthesized in 61% yield by the method used in the preparation of compound 9 in THF using SM-IX acid and 2-amino-1,3,4-thiadiazole as starting materials in a reaction time of 5 ,5 hours.

[00541] 1H-NMR (200 MHz, CDCl3): 1.03 (s, 3 H), 1.20-3.05 (m, 18 H), 6.80-6.95 (m, 1 H) , 7.03-7.18 (m, 2H), 8.82 (s,1H), 13.67 (br s, 1H). Compound 18 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(1,3,4-thiadiazol-2-yl)propanamide

[00542] Example 18 was prepared in 94% yield from compound 17 by the same method as in Example 2 in a reaction time of 2.5 hours.

[00543] 1H-NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.20-2.47 (m, 15 H), 2.55-2.95 (m, 3 H), 6.90-7.05 (m, 1 H), 7.10-7.23 (m, 2 H), 9.15 (s,1 H), 10.20 (s, 1 H) , 12.59 (br s, 1H). Compound 19 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(pyridazine-3-yl)propanamide

[00544] Compound 19 was synthesized in 42% yield by the method used in the preparation of compound 3 using SM-IX acid and 3-aminopyridazine as starting materials in a reaction time of 2 hours, crystallized from ethanol.

[00545] 1H-NMR (200 MHz, DMSO-d6): 0.99 (s, 3 H), 1.36-2.45 (m, 16 H), 2.78-2.91 (m, 2 H), 6.92-6.97 (m, 1 H), 7.15-7.23 (m, 2 H), 7.67 (dd, 1 H), 8.33 (d, 1 H) , 8.95 (d, 1H), 11.14 (s, 1H). Compound 20 3-((13S,15R,E)-4-fluoro-17-(hydroxyamino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridazine-3-yl)propanamide

[00546] Compound 20 was prepared from Compound 19 by the same method as Compound 2.

[00547] 1H-NMR (200 MHz, CDCl3): 1.12 (s, 3 H), 1.33-3.00 (m, 19 H), 6.81-6.84 (m, 1 H) , 7.04-7.13 (m, 2 H), 7.54 (d, 1 H), 8.63 (dd, 1 H), 8.97 (dd, 1 H), 10.95 (br s, 1H). Compound 21 N-(4,5-dihydrothiazol-2-yl)-3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13 ,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00548] Compound 21 was synthesized in 74% yield by the method used in the preparation of compound 3 using SM-IX acid and 2-amino-2-thiazoline as starting materials in a reaction time of 2 hours.

[00549] 1H-NMR (200 MHz, CDCl3): 1.06 (s, 3 H), 1.39-2.72 (m, 17 H), 2.80-3.05 (m, 2 H) , 3.30 (t, 2 H), 3.94 (t, 2 H), 6.84-6.92 (m, 1 H), 7.05-7.22 (m, 2 H). Compound 22 N-(4,5-dihydrothiazol-2-yl)-3-((13S,15R,E)-4-fluoro-17-(hydroxyamino)-13-methyl-7,8,9,11 ,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00550] Example 22 was prepared from compound 21 by the same method as in Example 2 in a reaction time of 2 hours. Compound 23 N,N-diethyl-3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-deca -hydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00551] Compound 23 was synthesized in 97% yield by the same method as compound 3 using SM-IX acid and diethylamine as an amine in a reaction time of two hours.

[00552] 1H-NMR (200 MHz, DMSO-d6): 0.97 (s, 3 H), 1.01 (t, 3 H), 1.11 (t, 3 H), 1.20-2 .47 (m, 16 H), 2.60-2.99 (m, 2 H), 3.15-3.40 (m, 4 H), 6.90-7.06 (m, 1 H) , 7.08-7.25 (m, 2 H). Compound 24 N,N-diethyl-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16 ,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00553] Example 24 was prepared in 20% yield from compound 23 by the same method as in Example 2 by stirring at 50 ° C for 2.5 hours.

[00554] 1H-NMR (200 MHz, CDCl3): 1.12 (s, 3 H), 1.05-1.24 (m, 6 H), 1.25-2.55 (m, 15 H) , 2.60-3.05 (m, 3 H), 3.20-3.53 (m, 4 H), 6.80-6.92 (m, 1 H), 7.03-7.20 (m, 2H), 8.33 (s, 1H). Compound 25 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide

[00555] Compound 25 was synthesized by the method used in the preparation of compound 1 using SM-XV acid and 2-amino5-fluoropyridine as starting materials. The reaction time was four hours.

[00556] 1H NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.22 - 2.45 (m, 16 H), 2.80 - 2.95 (m, 2 H ), 6.83 - 7.03 (m, 2 H), 7.20 - 7.39 (m, 1 H), 7.73 (td, 1 H), 8.14 (dd, 1 H), 8.31 (d, 1 H), 10.62 (s, 1 H). Compound 26 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide

[00557] Example 26 was prepared in 94% yield from compound 25 by the same method as in Example 2 in a reaction time of three hours.

[00558] 1H NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.12 - 2.48 (m, 15 H), 2.57 - 2.78 (m, 1 H ), 2.80 - 2.95 (m, 2 H), 6.79 - 7.01 (m, 2 H), 7.18 - 7.38 (m, 1 H), 7.72 (td, 1 H), 8.15 (dd, 1 H), 8.31 (d, 1 H), 10.18 (s, 1 H), 10.64 (s, 1 H). MS m/z (TOF ES+): 454 (M+1). Compound 27 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide

[00559] Compound 27 was synthesized in 62% yield by the method used in the preparation of compound 3 using SM-XV acid and 5-methoxypyridine-2-amine as starting materials in a reaction time of three hours.

[00560] 1H-NMR (200 MHz, CDCl3): 1.07 (s, 3 H), 1.39-2.50 (m, 16 H), 2.94 (m, 2 H), 3.85 (s, 3 H), 6.79-6.88 (m, 2 H), 7.19-7.30 (m, 2 H), 7.90 (br s, 1 H), 7.95 ( d, 1H), 8.14 (d, 1H). Compound 28 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide

[00561] Example 28 was prepared in 96% yield from compound 27 by the same method as in Example 2 in a reaction time of one hour.

[00562] 1H-NMR (200 MHz, CDCl3): 1.15 (s, 3 H), 1.40-2.70 (m, 16 H), 2.88-3.02 (m, 3 H) , 3.85 (s, 3 H), 6.77-6.90 (m, 2 H), 7.18-7.32 (m, 2 H), 7.95 (d, 1 H), 8 .16 (d, 1H), 8.37 (br s, 1H), 8.63 (br s, 1H). MS m/z (TOF ES+): 466 (M+1) Compound 29 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide

[00563] Compound 29 was synthesized in a reaction time of four hours by the method used in the preparation of compound 3 using SM-XV acid and 3-amino-6-methoxypyridazine as starting materials.

[00564] 1H-NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.20-2.47 (m, 16 H), 2.75-3.02 (m, 2 H), 3.98 (s, 3 H), 6.83-7.03 (m, 2 H), 7.17-7.39 (m, 2 H), 8.25 (d, 1 H) , 10.94 (br s, 1H). Compound 30 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide

[00565] Example 30 was prepared from compound 29 by the same method as in Example 2 in a reaction time of four hours.

[00566] 1H-NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.11-2.47 (m, 15 H), 2.58-2.78 (m, 1 H), 2.78-2.96 (m, 2 H), 3.98 (s, 3 H), 6.75-7.02 (m, 2 H), 7.13-7.39 (m , 2H), 8.25 (d, 1H), 10.19 (br s, 1H), 10.95 (br s, 1H). MS m/z (TOF ES+): 467 (M+1). Compound 31 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide

[00567] Compound 31 was synthesized in 62% yield by the method used in the preparation of compound 3 using SM-XV acid and 3-amino-6-methylpyridazine as starting materials, using THF as a solvent in the reaction time of five hours.

[00568] 1H-NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.12-2.46 (m, 16 H), 2.55 (s, 3 H), 2 .80-3.00 (m, 2 H), 6.81-7.02 (m, 2 H), 7.21-7.37 (m, 1 H), 7.54 (d, 1 H) , 8.22 (d, 1H), 11.04 (br s, 1H). Compound 32 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide

[00569] Compound 32 was prepared from Compound 31 by the same method as Compound 2 in a reaction time of three hours.

[00570] 1H-NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.11-2.44 (m, 15 H), 2.55 (s, 3 H), 2 .59-2.77 (m, 1 H), 2.78-2.96 (m, 2 H), 6.79-7.03 (m, 2 H), 7.29 (br t, 1 H ), 7.54 (d, 1H), 8.22 (d, 1H), 10.18 (s, 1H), 10.95 (s, 1H). MS m/z (TOF ES+): 451 (M+1) Compound 33 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide

[00571] Compound 33 was synthesized by the method used in the preparation of Compound 1 using SM-XV acid and 3-aminopyridazine as starting materials. Additional amount (70-100 mol %) of reagents was added after 5.5 hours and stirring continued overnight.

[00572] 1H NMR (200 MHz, DMSO-d6): 0.99 (s, 3 H), 1.11 - 2.47 (m, 16 H), 2.80 - 2.95 (m, 2 H ), 6.81 - 7.03 (m, 2 H), 7.20 - 7.38 (m, 1 H), 7.67 (dd, 1 H), 8.32 (dd, 1 H), 8.95 (dd, 1 H), 11.13 (s, 1 H). Compound 34 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide

[00573] Compound 34 was prepared in 96% yield from Compound 33 by the same method as Compound 2 in a reaction time of 1.5 hours.

[00574] 1H-NMR (200 MHz, DMSO-d6): 1.04 (s, 3 H), 1.11-2.47 (m, 15 H), 2.58-2.79 (m, 1 H), 2.78-2.96 (m, 2 H), 6.83-7.02 (m, 2 H), 7.29 (br t, 1 H), 7.66 (dd, 1 H ), 8.33 (dd, 1H), 8.94 (dd, 1H), 10.19 (s, 1H), 11.15 (s, 1H). MS m/z (TOF ES+): 419 (M-H2O +1). Compound 35 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-methyl-N-(oxetan-3-yl)propanamide

[00575] Compound 35 was synthesized in 96% yield by the method used in the preparation of Compound 9 using SM-XV acid and N-methyl-3-oxetanamine as starting materials in a reaction time of 4 hours.

[00576] 1H NMR (200 MHz, DMSO-d6): 0.96 (s, 3 H), 1.12 - 2.45 (m, 16 H), 2.80 - 2.95 (m, 2 H ), 2.95-3.13 (s, 3 H), 4.43-4.84 (m, 4 H), 5.12-5.40 (m, 1 H), 6.82 - 7, 03 (m, 2 H), 7.20 - 7.38 (m, 1 H). Compound 36 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-methyl-N-(oxetan-3-yl)propanamide

[00577] Compound 36 was prepared in 23% yield from Compound 35 by the same method as Compound 2 in a reaction time of four hours.

[00578] 1H NMR (200 MHz, CDCl3): 1.12 (s, 3 H), 1.27 - 2.61 (m, 15 H), 2.75 - 3.09 (m, 3 H), 3.16 (s, 3 H) 4.58 - 4.90 (m, 4 H), 5.05-5.61 (m, 1 H), 6.67 - 6.95 (m, 2 H) , 7.17-7.26 (m, 1 H), 7.91 (br s, 1 H). Compound 37 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(1,3,4-thiadiazol-2-yl)propanamide

[00579] Compound 37 was synthesized in 52% yield by the method used in the preparation of compound 9 using SM-XV acid and 2-amino-1,3,4-thiadiazole as starting materials in a reaction time of 6 hours.

[00580] 1H NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.20 - 2.70 (m, 16 H), 2.80 - 2.95 (m, 2 H ), 6.85 - 7.03 (m, 2 H), 7.22 - 7.38 (m, 1 H), 9.15 (s, 1 H), 12.56 (br s, 1H). Compound 38 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(1,3,4-thiadiazol-2-yl)propanamide

[00581] Compound 38 was prepared in 96% yield from Compound 37 by the same method as Compound 2 in a reaction time of two hours.

[00582] 1H NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.20 - 2.80 (m, 16 H), 2.80 - 2.95 (m, 2 H ), 6.85 - 7.03 (m, 2 H), 7.22 - 7.38 (m, 1 H), 9.14 (s, 1 H), 10.19 (s, 1 H), 12.57 (br s, 1H). MS m/z (TOF ES+): 425 (M-H2O +1) Compound 39 N,N-diethyl-3-((13S,15R)-3-fluoro-13-methyl-17-oxo- 7.8, 9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00583] Compound 39 was synthesized in 52% yield by the method used in the preparation of compound 3 using SM-XV acid and diethylamine as starting materials in a reaction time of 4 hours.

[00584] 1H NMR (200 MHz, CDCl3): 1.07 (s, 3 H), 1.08-1.24 (m, 6 H), 1.31 - 2.57 (m, 16 H), 2.78 - 3.11 (m, 2 H), 3.19 - 3.57 (m, 4 H), 6.73 - 6.92 (m, 2 H), 7.20 (br d, 1 H). Compound 40 N,N-diethyl-3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16 ,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00585] Compound 40 was prepared in 76% yield from Compound 39 by the same method as Compound 2 in a reaction time of five hours.

[00586] 1H NMR (200 MHz, CDCl3): 1.13 (s, 3 H), 1.08-1.24 (m, 6 H), 1.31 - 2.57 (m, 15 H), 2.78 - 3.11 (m, 3 H), 3.19 - 3.57 (m, 4 H), 6.73 - 6.92 (m, 2 H), 7.04 (br s, 1 H), 7.18-7.25 (m, 1 H). Compound 41 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide

[00587] Compound 41 was synthesized in 60% yield by the method used in the preparation of compound 1 using SM-XV acid and 2-amino-5-isopropylpyridine as starting materials in overnight reaction time.

[00588] 1H NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.20 (d, 6 H), 1.28 - 2.49 (m, 16 H), 2, 74 - 3.02 (m, 3 H), 6.79 - 7.03 (m, 2 H), 7.19 - 7.39 (m, 1 H), 7.66 (d, 1 H), 8.02 (d, 1H), 8.19 (s, 1H), 10.43 (s, 1H). Compound 42 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide

[00589] Compound 42 was prepared in 64% yield from Compound 41 by the same method as Compound 2 in a reaction time of four hours.

[00590] 1H NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.20 (d, 6 H), 1.28 - 2.49 (m, 15 H), 2, 50-2.74 (m, 1 H), 2.75 - 3.02 (m, 3 H), 6.79 - 7.03 (m, 2 H), 7.19 - 7.39 (m, 1 H), 7.65 (dd, 1 H), 8.02 (d, 1 H), 8.19 (d, 1 H), 10.18 (s, 1 H), 10.45 (s, 1H). Compound 43 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(pyridazine-3-yl)propanamide

[00591] SM-XVII acid (100 mg, 0.28 mmol, 100 mol%) was dissolved in dry DCM (2 ml). SOCI2 (40 μl, 200 mol %) was added under nitrogen atmosphere to the reaction mixture and refluxed for 30 minutes followed by additional amount of SOCl2 (20 μl) with continuous reflux for 1.5 hours. Anhydrous pyridine (112 μl, 500 mol %) and 3-aminopyridazine (54 mg, 200 mol %) were dissolved in dry DCM/DMF (1 ml, vol 1:1) and added dropwise to the reaction mixture. After stirring at room temperature until the reaction was complete, the reaction mixture was diluted with DCM, followed by diluted HCl solution, water and brine, dried with sodium sulfate. The solvents were evaporated, and the precipitate was purified by chromatography, yielding Compound 43 in 25% yield.

[00592] 1H-NMR (200 MHz, CDCl3): 1.06 (s, 3 H), 1.38-2.75 (m, 16 H), 2.90 (m, 2 H), 7.09 -7.22 (m, 3H), 7.54 (dd, 1H), 8.63 (d, 1H), 8.93 (d, 1H), 10.95 (br s, 1H) . Compound 44 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridazine-3-yl)propanamide

[00593] Compound 44 was prepared from Compound 43 by the same method as Compound 2 by stirring at room temperature overnight.

[00594] 1H-NMR (200 MHz, CDCl3): 1.10 (s, 3 H), 1.31-2.99 (m, 16 H), 2.90 (m, 2 H), 7.07 -7.21 (m, 3 H), 7.54 (dd, 1 H), 8.14 (br s, 1 H), 8.61 (d, 1 H), 8.96 (d, 1 H ), 10.75 (br s, 1H). MS m/z (TOF ES+): 475/477 (M + Na) Compound 45 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12, 13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4,5-dihydrothiazol-2-yl)propanamide

[00595] Compound 45 was prepared from SM-XVII acid by the same method as Compound 9 by stirring at room temperature for three hours.

[00596] 1H-NMR (200 MHz, CDCl3): 1.05 (s, 3 H), 1.50-2.56 (m, 17 H), 2.94 (m, 2 H), 3.35 (dd, 2 H), 3.97 (dd, 2 H), 7.09-7.22 (m, 3 H). Compound 46 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)- N-(4,5-dihydrothiazol-2-yl)propanamide

[00597] Compound 46 was prepared from Compound 45 by the same method as Compound 2.

[00598] 1H-NMR (200 MHz, CDCl3): 1.08 (s, 3 H), 1.54-2.41 (m, 18 H), 2.91-3.20 (m, 6 H) , 7.07-7.21 (m, 3 H). MS m/z 460/462 Compound 47 (13S,15R)-3-chloro-13-methyl-15-(3-oxo-3-(8-oxa-2-azaspiro[4.5]decan-2-yl)propyl )-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one

[00599] Compound 47 was prepared in 94% yield from SM-XVII acid by the same method as Compound 9 using 8-oxa-2-aza-spiro(4,5)decane hydrochloride as the amine. The reaction time was 4.5 hours.

[00600] 1H NMR (200 MHz, DMSO-d6): 0.96 (s, 3 H), 1.11 - 2.45 (m, 22 H), 2.75 - 3.00 (m, 2 H ), 3.20 (s, 1 H), 3.30-3.70 (m, 7 H), 7.08 - 7.22 (m, 2 H), 7.25 - 7.38 (m, 1 H). Compound 48 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-1-(8-oxa-2-azaspiro[4.5]decan-2-yl)propan-1-one

[00601] Compound 48 was prepared in 92% yield from Compound 47 by the same method as Compound 2 by refluxing for 5.5 hours.

[00602] 1H NMR (200 MHz, DMSO-d6): 1.01 (s, 3 H), 1.20 - 2.45 (m, 21 H), 2.50-2.75 (m, 1 H ), 2.75 - 3.00 (m, 2 H), 3.20 (s, 1 H), 3.30-3.70 (m, 7 H), 7.08 - 7.22 (m, 2 H), 7.25 - 7.38 (m, 1 H), 10.17 (s, 1H). Compound 49 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide

[00603] Compound 49 was prepared in 56% yield from SM-XVII acid by the same method as Compound 3 by stirring at +50 ° C for several days.

[00604] 1H-NMR (200 MHz, CDCl3): 1.06 (s, 3 H), 1.45-2.43 (m, 15 H), 2.67 (m, 2 H), 2.92 (m, 2 H), 4.07 (s, 3 H), 7.04-7.22 (m, 4 H), 8.47 (d, 1 H), 10.0 (br s, 1H) . Compound 50 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)- N-(6-methoxypyridazin-3-yl)propanamide

[00605] Compound 50 was prepared in 36% yield from Compound 49 by the same method as Compound 2 by refluxing for two hours.

[00606] 1H-NMR (200 MHz, CDCl3): 1.07 (s, 3 H), 1.50-3.03 (m, 20 H), 4.09 (s, 3 H), 7.03 -7.21 (m, 4H), 8.51 (d, 1H), 9.01 (br s, 1H), 10.89 (br s, 1H). MS m/z (TOF ES+): 483/485 (M+) Compound 51 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N,N-diethylpropanamide

[00607] Compound 51 was prepared in 63% yield from SM-XVII acid and diethylamine as an amide by the same method as Compound 9 by stirring at room temperature overnight.

[00608] 1H-NMR (200 MHz, CDCl3): 1.07 (s, 3 H), 1.15 (td, 6 H), 1.44 2.40 (m, 16 H), 2.93 ( m, 2 H), 3.34 (m, 4 H), 7.09-7.23 (m, 3 H). Compound 52 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15- yl)- N,N-diethylpropanamide

[00609] Compound 52 was prepared in 98% yield from Compound 51 by the same method as Compound 2 by refluxing for three hours.

[00610] 1H-NMR (200 MHz, CDCl3): 1.12 (s, 3 H), 1.16 (td, 6 H), 1.34 2.44 (m, 16 H), 2.83- 2.97 (m, 3 H), 3.34 (m, 4 H), 7.08-7.22 (m, 3 H). Compound 53 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide

[00611] Compound 53 was synthesized in 94% yield from SM-XVII acid by the same method as Compound 1 in DCM using 3-amino-5-methylisoxazole as the amine. The reaction time was 6 hours.

[00612] 1H NMR (200 MHz, DMSO-d6): 0.97 (s, 3 H), 1.15 - 2.45 (m, 16 H), 2.37 (s, 3 H), 2, 80 - 3.00 (m, 2 H), 6.64 (s, 1 H), 7.08 - 7.22 (m, 2 H), 7.25 - 7.38 (m, 1 H), 10.88 (br s, 1H). Compound 54 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide

[00613] Compound 54 was prepared in 92% yield from Compound 53 by the same method as Compound 2 by refluxing for 2 hours.

[00614] 1H NMR (200 MHz, DMSO-d6): 1.02 (s, 3 H), 1.15 - 2.45 (m, 15 H), 2.37 (s, 3 H), 2, 55-2.75 (m, 1 H), 2.80 - 3.00 (m, 2 H), 6.64 (s, 1 H), 7.08 - 7.22 (m, 2 H), 7.25 - 7.38 (m, 1 H), 10.19 (s, 1 H), 10.89 (br s, 1H). Compound 55 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide

[00615] Compound 55 was prepared in 51% yield from SM-XVII acid by the same method as Compound 9 using 2-amino-4-methoxypyridine as the amine and stirring the reaction overnight at RT.

[00616] 1H NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.15 - 2.45 (m, 16 H), 2.80 - 3.00 (m, 2 H ), 3.80 (s, 3 H), 6.65-6.75 (dd, 1 H), 7.08 - 7.22 (m, 2 H), 7.25 - 7.38 (m, 1 H), 7.72-7.73 (d, 1 H), 8.12 (d, 1 H), 10.47 (br s, 1H). Compound 56 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide

[00617] Compound 56 was prepared in 84% yield from Compound 55 by the same method as Compound 2 by refluxing for 1.5 hours.

[00618] 1H NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.15 - 2.45 (m, 15 H), 2.55-2.75 (m, 1 H ), 2.80 - 3.00 (m, 2 H), 3.80 (s, 3 H), 6.65-6.75 (dd, 1 H), 7.08 - 7.22 (m, 2 H), 7.25 - 7.38 (m, 1 H), 7.72-7.73 (d, 1 H), 8.12 (d, 1 H), 10.19 (s, 1 H ), 10.48 (br s, 1H). Compound 57 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide

[00619] Compound 57 was synthesized from SM-XVII acid by the same method as Compound 1 in DCM. The reaction time was four hours.

[00620] 1H NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.22 - 2.47 (m, 16 H), 2.75 - 3.02 (m, 2 H ), 7.06 - 7.22 (m, 2 H), 7.22 - 7.37 (m, 1 H), 7.72 (td, 1 H), 8.14 (dd, 1 H), 8.31 (d, 1 H), 10.62 (s, 1 H). Compound 58 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide

[00621] Compound 58 was prepared from Compound 57 by the same method as Compound 2. The reaction time was 2 hours at 50 °C.

[00622] 1H NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.23 - 2.46 (m, 15 H), 2.56 - 2.77 (m, 1 H ), 2.80 - 2.95 (m, 2 H), 7.10 - 7.32 (m, 2 H), 7.23 - 7.36 (m, 1 H), 7.72 (td, 1 H), 8.15 (dd, 1 H), 8.31 (d, 1 H), 10.19 (s, 1 H), 10.63 (s, 1 H). MS m/z (TOF ES+): 470 (M+1) Compound 59 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3-methylpyridin-2-yl)propanamide

[00623] Compound 59 was synthesized in 54% yield from SM-XVII acid by the same method as Compound 1 in DCM using 3-methylpyridin-2-amine as the amine. The reaction was first stirred for 3 hours, then additional amount (100 mol %) of amine and T3P were added, and stirring continued overnight. Finally, the reaction was refluxed for 4 hours.

[00624] 1H NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.15 - 2.45 (m, 16 H), 2.15 (s, 3 H), 2, 80 - 3.00 (m, 2 H), 7.10 - 7.25 (m, 3 H), 7.26 - 7.33 (m, 1 H), 7.66 (d, 1 H), 8.24 (d, 1H), 10.00 (br s, 1H). Compound 60 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(3-methylpyridin-2-yl)propanamide

[00625] Compound 60 was prepared in 93% yield from Compound 59 by the same method as Compound 2 by stirring at 50 ° C for 2 hours.

[00626] 1H NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.15 - 2.45 (m, 15 H), 2.15 (s, 3 H), 2, 60-2.79 (m, 1 H), 2.80 - 3.00 (m, 2 H), 7.10 - 7.25 (m, 3 H), 7.26 - 7.33 (m, 1 H), 7.66 (d, 1 H), 8.24 (d, 1 H), 10.01 (br s, 1 H), 10.20 (s, 1H). Compound 61 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide

[00627] Compound 61 was synthesized from SM-XVII acid by the same method as Compound 1 in DCM. The reaction time was three hours.

[00628] 1H NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.20 - 2.47 (m, 16 H), 2.80 - 2.90 (m, 2 H ), 7.10 - 7.23 (m, 2 H), 7.23 - 7.42 (m, 2 H), 7.76 (dd, 1 H), 8.24 (dd, 1 H), 10.28 (s, 1 H). Compound 62 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide

[00629] Compound 62 was prepared from Compound 61 by the same method as Compound 2. The reaction time was 2.5 hours at 50 °C.

[00630] 1H NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.12 - 2.46 (m, 15 H), 2.56 - 2.77 (m, 1 H ), 2.80 - 2.95 (m, 2 H), 7.10 - 7.22 (m, 2 H), 7.23 - 7.42 (m, 2 H), 7.76 (td, 1 H), 8.24 (dd, 1 H), 10.19 (s, 1 H), 10.29 (s, 1 H). Compound 63 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-methyloxazol-2-yl)propanamide

[00631] Compound 63 was prepared in 52% yield from SM-XVII acid by the same method as Compound 3 using 2-amino-5-methyloxazole as the amine. The reaction time was 3 hours.

[00632] 1H NMR (200 MHz, DMSO-d6): 0.97 (s, 3 H), 1.15 - 2.47 (m, 19 H), 2.80 - 2.90 (m, 2 H ), 6.68 (s, 1 H), 7.10 - 7.23 (m, 2 H), 7.24 - 7.35 (m, 1 H), 10.95 (br s, 1 H) . Compound 64 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methyloxazol-2-yl)propanamide

[00633] Compound 64 was prepared in 89% yield from Compound 63 by the same method as Compound 2. The reaction time was 2.5 hours.

[00634] 1H NMR (200 MHz, DMSO-d6): 1.02 (s, 3 H), 1.15 - 2.47 (m, 18 H), 2.55-2.75 (m, 1 H ), 2.80 - 2.90 (m, 2 H), 6.68 (s, 1 H), 7.10 - 7.23 (m, 2 H), 7.24 - 7.35 (m, 1 H), 10.19 (s, 1 H), 10.96 (br s, 1 H). Compound 65 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide

[00635] Compound 65 was prepared in 62% yield from SM-XVII acid by the same method as Compound 3 by stirring at +50 ° C for two hours.

[00636] 1H-NMR (200 MHz, DMSO-d6): 0.97 (s, 3 H), 1.35-2.42 (m, 16 H), 2.89 (m, 2 H), 3 .80 (s, 3 H), 7.15 (br s, 2 H), 7.31-7.44 (m, 2 H), 8.02 (m, 2 H), 10.37 (br s , 1H). Compound 66 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)- N-(5-methoxypyridin-2-yl)propanamide

[00637] Compound 66 was prepared in 93% yield from Compound 65 by the same method as Compound 2 by refluxing for 2.5 hours.

[00638] 1H-NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.38-2.45 (m, 16 H), 2.86 (m, 2 H), 3 .80 (s, 3 H), 7.14 (br s, 2 H), 7.27-7.44 (2 xm, 2 H), 8.03 (m, 2 H), 10.18 (br s, 1H), 10.38 (br s, 1H). MS m/z (TOF ES+): 482/484 (M+) Compound 67 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide

[00639] Compound 67 was prepared in 41% yield from SM-XVII acid by the same method as Compound 3 by stirring at +50 ° C for 5 hours, and then overnight at room temperature.

[00640] 1H-NMR (200 MHz, CDCl3): 1.05 (s, 3 H), 1.37 - 2.60 (m, 16 H), 2.92 (m, 2 H), 7.03 - 7.15 (m, 4 H), 7.73 (t,1 H), 8.19 - 8.28 (m, 2 H), 8.58 (br s, 1H). Compound 68 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)- N-(pyridin-2-yl)propanamide

[00641] Compound 68 was prepared in 90% yield from Compound 67 by the same method as Compound 2 by refluxing for one hour.

[00642] 1H-NMR (200 MHz, CDCl3): 1.14 (s, 3 H), 1.42 - 2.58 (m, 16 H), 2.88 - 3.03 (m, 3 H) , 7.07 (br s, 3 H), 7.18 (m, 1 H), 7.74 (t, 1 H), 8.26 (d, 2 H), 8.97 (br s, 1 H), 9.66 (br s, 1H). MS m/z (TOF ES+): 452/454 (M+) Compound 69 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide

[00643] Compound 69 was prepared in 40% yield from SM-XVII acid by the same method as Compound 43 by stirring at room temperature for 1.5 hours.

[00644] 1H-NMR (200 MHz, CDCl3): 1.06 (s, 3 H), 1.44- 2.54 (m, 19 H), 2.91 (m, 2 H), 6.89 (d, 1 H), 7.09 - 7.22 (m, 3 H), 8.06 (br s, 1 H), 8.13 (d, 1 H), 8.49 (br s, 1H ). Compound 70 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)- N-(4-methylpyridin-2-yl)propanamide

[00645] Compound 70 was prepared in 46% yield from Compound 69 by the same method as Compound 2 by refluxing for one hour.

[00646] 1H-NMR (200 MHz, CDCl3): 1.15 (s, 3 H), 1.44- 2.51 (m, 21 H), 2.91 (m, 2 H), 6.89 (d, 1 H), 7.08 - 7.22 (m, 3 H), 8.08 - 8.13 (m, 2 H), 8.54 (br s, 1 H), 8.83 ( br s, 1H). Compound 71 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-cyanopyridin-2-yl)propanamide

[00647] Compound 71 was prepared in 37% yield from SM-XVII acid by the same method as Compound 43 by stirring at room temperature for 1.5 hours.

[00648] 1H-NMR (200 MHz, CDCl3): 1.07 (s, 3 H), 1.46- 2.42 (m, 16 H), 2.93 (m, 2 H), 7.10 - 7.19 (m, 3 H), 7.93 -8.08 (m, 2 H), 8.35 (d, 1 H), 8.56 (s, 1H). Compound 72 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)- N-(5-cyanopyridin-2-yl)propanamide

[00649] Compound 72 was prepared in 96% yield from Compound 71 by the same method as Compound 2 by refluxing for two hours.

[00650] 1H-NMR (200 MHz, CDCl3): 1.14 (s, 3 H), 1.42- 2.70 (m, 17 H), 2.91 (m, 3 H), 7.09 - 7.22(m, 3 H), 7.96 (d, 1 H), 8.38 (d, 1 H), 8.56 (s, 1H). MS m/z (TOF ES+): 477/479 (M+) Compound 73 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide

[00651] Compound 73 was synthesized in 50% yield from SM-XVII acid by the same method as Compound 1 in DCM using aminopyrazine as the amine. The reaction time was 5 hours.

[00652] 1H NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.15 - 2.65 (m, 16 H), 2.80 - 2.90 (m, 2 H ), 7.10 - 7.23 (m, 2 H), 7.24 - 7.35 (m, 1 H), 8.30-8.45 (m, 2 H), 9.35 (s, 1 H), 10.81 (br s, 1 H). Compound 74 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide

[00653] Compound 74 was prepared in 92% yield from Compound 73 by the same method as Compound 2 by stirring at 40 ° C for 2.5 hours.

[00654] 1H NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.15 - 2.79 (m, 16 H), 2.80 - 2.90 (m, 2 H ), 7.10 - 7.23 (m, 2 H), 7.24 - 7.35 (m, 1 H), 8.30-8.45 (m, 2 H), 9.35 (s, 1 H), 10.19 (s, 1 H), 10.82 (br s, 1 H). Compound 75 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide

[00655] Compound 75 was synthesized from SM-XVII acid by the same method as Compound 9 in THF. The reaction time was 5 hours.

[00656] 1H-NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.22-2.47 (m, 16 H), 2.55 (s, 3 H), 2 .80-3.00 (m, 2 H), 7.08-7.22 (m, 2 H), 7.22-7.37 (m, 1 H), 7.54 (d, 1 H) , 8.22 (d, 1H), 11.04 (br s, 1H). Compound 76 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide

[00657] Compound 76 was prepared from Compound 75 by the same method as Compound 2. The reaction time was 4.5 hours at 40 ° C and overnight at RT.

[00658] 1H-NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.12-2.47 (m, 15 H), 2.55 (s, 3 H), 2 .59-2.79 (m, 1 H), 2.78-2.96 (m, 2 H), 7.05-7.22 (m, 2 H), 7.23-7.34 (m , 1H), 7.54 (d, 1H), 8.22 (d, 1H), 10.19 (s, 1H), 11.05 (s, 1H). Compound 77 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide

[00659] Compound 77 was synthesized in 69% yield from SM-XVII acid by the same method as Compound 1 in DCM using triethylamine as the base and 5-morpholinopyridin-2-amine as the amine. The reaction time was 4.5 hours.

[00660] 1H-NMR (200 MHz, DMSO-d6): 0.97 (s, 3 H), 1.15-2.47 (m, 16 H), 2.80-3.00 (m, 2 H), 3.01-3.15 (m, 4 H), 3.70-3.80 (m, 4 H), 7.08-7.22 (m, 2 H), 7.23-7 .35 (m, 1H), 7.37-7.45 (m, 1H), 7.90-8.10 (m, 2H), 10.28 (s, 1H). Compound 78 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide

[00661] Compound 78 was prepared in 66% yield from Compound 77 by the same method as Compound 2. The reaction time was 7 hours at 40-50 ° C and overnight at RT.

[00662] 1H-NMR (200 MHz, DMSO-d6): 1.02 (s, 3 H), 1.15-2.47 (m, 15 H), 2.50-2.75 (m, 1 H), 2.80-2.95 (m, 2 H), 3.01-3.15 (m, 4 H), 3.70-3.80 (m, 4 H), 7.08-7 .22 (m, 2 H), 7.23-7.35 (m, 1 H), 7.37-7.45 (m, 1 H), 7.90-8.10 (m, 2 H) , 10.18 (s, 1H), 10.29 (s, 1H). Compound 79 N-methyl-3-((13S,15R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(tetrahydro-2H-pyran-4-yl)propanamide

[00663] Compound 79 was prepared in 37% yield from SM-XXVI acid by the same method as Compound 9 using methyl-(tetrahydro-pyran-4-yl)-amine hydrochloride as the amine. The reaction time was 4 hours.

[00664] 1H NMR (200 MHz, DMSO-d6): 0.97 (s, 3 H), 1.14 - 2.48 (m, 20 H), 2.60-2.90 (m, 5 H ), 3.26-3.51 (m, 2 H), 3.79-4.04 (m, 2 H), 4.40-4.60 (m, 1 H), 7.00 - 7, 19 (m, 3 H), 7.27 (br d, 1 H). MS m/z (TOF ES+): 424 (M+1) Compound 80 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-methyl-N-(tetrahydro-2H-pyran-4-yl)propanamide

[00665] Compound 80 was prepared in 88% yield from Compound 79 by the same method as Compound 2 using 6 eq of pyridine and refluxing for two hours.

[00666] 1H NMR (200 MHz, DMSO-d6): 1.02 (s, 3 H), 1.10 - 2.45 (m, 19 H), 2.50-2.90 (m, 6 H ), 3.21-3.57 (m, 2 H), 3.76-4.00 (m, 2 H), 4.40-4.60 (m, 1 H), 7.00 - 7, 19 (m, 3H), 7.27 (br d, 1H), 10.16 (m, 1H). Compound 81 3-((13S,15R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren -15-yl)-N-(pyridazin-3-yl)propanamide

[00667] Compound 81 was prepared in 36% yield from SM-XXVI acid by the same method as Compound 43 using 3-aminopyridazine as an amine.

[00668] 1H-NMR (200 MHz, CDCl3): 1.06 (s, 3 H), 1.46 - 3.00 (m, 17 H), 7.10 - 7.18 (m, 3 H) , 7.23 - 7.31 (m, 2 H), 7.51 (dd, 1 H), 8.62 (dd, 1 H), 8.94 (dd, 1 H), 10.73 (br s, 1H). Compound 82 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide

[00669] Compound 82 was prepared in 70% yield from Compound 81 by the same method as in Compound 2

[00670] 1H-NMR (200 MHz, CDCl3): 1.11 (s, 3 H), 1.59 - 2.66 (m, 16 H), 2.87 - 3.00 (m, 2 H) , 7.11 (m, 3 H), 7.24-7.35 (br s, 1 H), 7.53 (dd, 1 H), 8.25 (br s, 1 H), 8.62 (d, 1H), 8.95 (d, 1H), 10.77 (br s, 1H). Compound 83 N-(5-methoxypyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00671] Compound 83 was synthesized in 40% yield from SM-XXVI acid by the same method as Compound 3 by refluxing for two hours.

[00672] 1H-NMR (200 MHz, CDCl3): 1.07 (s, 3 H), 1.40-2.57 (m, 17 H), 2.96 (m, 2 H), 3.85 (s, 3 H), 7.13 - 7.18 (m, 3 H), 7.24 - 7.30 (m, 2 H), 7.96 (d, 1 H), 8.15 (d , 1H). Compound 84 3-((13S,15R,E)-17-(hydroxyamino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide

[00673] Compound 84 was prepared in 82% yield from Compound 83 by the same method as Compound 2 by refluxing for two hours.

[00674] 1H-NMR (200 MHz, CDCl3): 1.15 (s, 3 H), 1.42 - 2.52 (m, 16 H), 2.92 (m, 3 H), 3.84 (s, 3 H), 7.12 - 7.16 (m, 3 H), 7.30 (m, 1 H), 7.96 (d, 1 H), 8.15 (d, 1 H) , 8.44 (br s, 1H), 8.77 (br s, 1H). MS m/z (TOF ES+): 448 (M+1) Compound 85 3-((13S,15R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15, 16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide

[00675] Compound 85 was synthesized in 29% yield from SM-XXVI acid by the same method as Compound 1 in DCM using triethylamine as the base. The reaction time was 3.5 hours.

[00676] 1H NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.10 - 2.50 (m, 23 H), 2.80 - 2.95 (m, 2 H ), 3.01-3.19 (m, 4 H), 7.03 - 7.19 (m, 3 H), 7.27 (br d, 1 H), 7.35-7.43 (m , 1 H), 7.90-8.02 (m, 2 H), 10.26 (s, 1 H). Compound 86 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide

[00677] Compound 86 was prepared in 11% yield from Compound 85 by the same method as Compound 2. The reaction was stirred 2 hours at 50 °C.

[00678] 1H NMR (200 MHz, CDCl3): 1.13 (s, 3 H), 1.25 - 2.55 (m, 19 H), 2.56-2.65 (m, 4 H), 2.80 - 3.07 (m, 2 H), 3.12 - 3.30 (m, 4 H), 7.03 - 7.22 (m, 3 H), 7.25-7.35 ( m, 2 H), 7.91 (d, 1 H), 8.11 (d, 1 H). MS m/z (TOF ES+): 516 (M+1) Compound 87 3-((13S,15R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15, 16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide

[00679] Compound 87 was synthesized in 27% yield from SM-XXVI acid by the same method as Compound 3 in THF using 200 mol% EDCI and HOBT. The reaction time was 6 hours.

[00680] 1H NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.12 - 2.48 (m, 19 H), 2.80 - 2.95 (m, 2 H ), 6.92 (d, 1 H), 7.02 - 7.19 (m, 3 H), 7.27 (br d, 1 H), 7.95 (s, 1 H), 8.15 (d, 1 H), 10.41 (s, 1 H). Compound 88 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide

[00681] Compound 88 was prepared in 48% yield from Compound 87 by the same method as Compound 2. The reaction time was 1.5 hours at 50 ° C.

[00682] 1H NMR (200 MHz, DMSO-d6): 1.04 (s, 3 H), 1.12 - 2.47 (m, 18 H), 2.58-2.76 (m, 1 H ), 2.80 - 2.95 (m, 2 H), 6.92 (d, 1 H), 7.02 - 7.19 (m, 3 H), 7.27 (br d, 1 H) , 7.96 (s, 1 H), 8.15 (d, 1 H), 10.18 (s, 1 H), 10.43 (s, 1 H). MS m/z (TOF ES+): 432 (M+1) Compound 89 3-((13S,15R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15, 16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide

[00683] Compound 89 was synthesized in 29% yield from SM-XXVI acid by the same method as Compound 1 in DCM using triethylamine as the base. The reaction time was five hours.

[00684] 1H NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.10 - 2.46 (m, 16 H), 2.80 - 2.95 (m, 2 H ), 3.01-3.19 (m, 4 H), 3.63-3.84 (m, 4 H), 7.03 - 7.19 (m, 3 H), 7.27 (br d , 1 H), 7.40 (dd, 1 H), 7.88-8.07 (m, 2 H), 10.28 (s, 1 H). Compound 90 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide

[00685] Compound 90 was prepared in 55% yield from Compound 89 by the same method as Compound 2. The reaction time was 5 hours at +50 °C.

[00686] 1H NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.23 - 2.46 (m, 15 H), 2.56-2.75 (m, 1 H ), 2.80 - 2.95 (m, 2 H), 3.02-3.14 (m, 4 H), 3.65-3.84 (m, 4 H), 6.99 - 7, 18 (m, 3 H), 7.26 (br d, 1 H), 7.40 (dd, 1 H), 7.89-8.07 (m, 2 H), 10.17 (s, 1 H), 10.30 (s, 1 H). Compound 91 N,N-dimethyl-6-(3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)propanamido)nicotinamide

[00687] Compound 91 was synthesized in 12% yield from SM-XXVI acid by the same method as Compound 1 in DCM using triethylamine as a base. The reaction time was 6 hours.

[00688] 1H NMR (200 MHz, CDCl3) 1.08 (s, 3 H) 1.13 - 2.67 (m, 16 H) 2.91 - 3.01 (m, 2 H) 3.08 ( br s, 6 H) 7.06 - 7.22 (m, 3 H) 7.23 - 7.39 (m, 1 H) 7.81 (dd, 1 H), 8.15 (br s, 1 H), 8.25 (d, 1 H) 8.39 (d, 1 H) Compound 92 6-(3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7.8 ,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide

[00689] Compound 92 was prepared in quantitative yield from Compound 91 by the same method as Compound 2. The reaction time was 1.5 hours at 50 ° C.

[00690] 1H NMR (200 MHz, CDCl3) 1.15 (s, 3 H) 1.21 - 2.73 (m, 15 H) 2.82 - 3.03 (m, 3 H) 3.09 ( br s, 6 H) 7.05 - 7.23 (m, 3 H) 7.25 - 7.37 (m, 1 H) 7.82 (dd, 1 H), 8.28 (d, 1 H ) 8.40 (d, 1H), 8.61 (br s, 1H). Compound 93 3-((13S,15R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren -15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide

[00691] Compound 93 was synthesized in 22% yield from SM-XXVI acid by the same method as Compound 3. The reaction time was 2.5 hours.

[00692] 1H NMR (200 MHz, DMSO-d6): 0.97 (s, 3 H), 1.10 - 2.48 (m, 24 H), 2.76 - 2.95 (m, 2 H ), 7.02 - 7.19 (m, 3 H), 7.26 (m, 1 H), 8.01 (s, 1 H), 9.15 (s, 1 H), 11.68 ( br s, 1 H). Compound 94 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide

[00693] Compound 94 was prepared in 74% yield from Compound 93 by the same method as Compound 2. The reaction time was 2 hours at 50 °C.

[00694] 1H NMR (200 MHz, CDCl3) 1.13 (s, 3 H), 1.35 - 2.64 (m, 23 H), 2.78 - 3.08 (m, 3 H), 6 .90 (br s, 1 H), 7.06 - 7.21 (m, 3 H), 7.28 - 7.41 (m, 1 H), 8.19 (br s, 1 H) 8, 23 (s, 1H), 9.61 (br s, 1H). Compound 95 N-(5-isopropylpyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00695] Compound 95 was synthesized in 37% yield from SM-XXVI acid by the same method as Compound 9 stirring at room temperature overnight.

[00696] 1H-NMR (200 MHz, CDCl3): 1.07 (s, 3 H), 1.24 & 1.28 (2 xs, 6 H), 1.45-2.58 (m, 16 H ), 2.95 (m, 3 H), 7.13 - 7.18 (m, 3 H), 7.29 - 7.31 (m, 1 H), 7.58 (dd, 1 H), 8.07 (d, 1 H), 8.14 (br s, 2 H). Compound 96 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide

[00697] Compound 96 was prepared in 80% yield from Compound 95 by the same method as Compound 2 by refluxing for two hours.

[00698] 1H-NMR (200 MHz, CDCl3): 1.16 (s, 3 H), 1.24 & 1.27 (2 xs, 6 H), 1.48-2.53 (m, 16 H ), 2.94 (m, 3 H), 7.11 (m, 3 H), 7.26 (m, 1 H), 7.60 (d, 1 H), 8.16 (m, 2 H ), 8.89 (br s, 1H). 9.69 (br s, 1H). MS m/z (TOF ES+): 460 (M+1) Compound 97 N-(5-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7.8, 9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00699] Compound 97 was synthesized in 14% yield from SM-XXVI acid by the same method as Compound 1 in DCM using 2-amino-5-fluoropyridine as the amine. The reaction time was 4.5 hours.

[00700] 1H NMR (200 MHz, CDCl3): 1.07 (s, 3 H), 1.20 - 2.77 (m, 16 H), 2.80 - 3.15 (m, 2 H), 7.06-7.23 (m, 3 H), 7.25-7.37 (m, 1 H), 7.387.52 (m, 1 H), 7.90 (br s, 1 H), 8 .13 (d, 1H), 8.23 (dd, 1H). Compound 98 N-(5-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15 ,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00701] Compound 98 was prepared in 75% yield from Compound 97 by the same method as Compound 2 by stirring at 50 ° C for 3 hours.

[00702] 1H-NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.14 - 2.75 (m, 16 H), 2.80 - 3.00 (m, 2 H), 6.96-7.20 (m, 3 H), 7.21-7.30 (m, 1 H), 7.72 (td, 1 H), 8.15 (dd, 1 H) , 8.31 (d, 1H), 10.18 (s, 1H), 10.63 (s, 1H). Compound 99 N-(5-cyanopyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00703] Compound 99 was synthesized in 39% yield from SM-XXVI acid by the same method as Compound 1 in DCM using 2-amino-5-cyanopyridine as the amine. The reaction time was 5 hours.

[00704] 1H NMR (200 MHz, CDCl3): 1.08 (s, 3 H), 1.20 - 2.70 (m, 16 H), 2.80 - 3.15 (m, 2 H), 7.06-7.23 (m, 3 H), 7.25-7.37 (m, 1 H), 7.95 (dd, 1 H), 8.07 (br s, 1 H), 8 .36 (d, 1H), 8.56 (d, 1H). Compound 100 N-(5-cyanopyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15 ,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00705] Compound 100 was prepared in 33% yield from Compound 99 by the same method as Compound 2 by stirring at 50 ° C for 3 hours.

[00706] 1H NMR (200 MHz, CDCl3): 1.14 (s, 3 H), 1.35 - 2.70 (m, 15 H), 2.80 - 3.15 (m, 3 H), 7.06-7.23 (m, 3 H), 7.25-7.37 (m, 1 H), 7.85 (s, 1 H), 7.95 (dd, 1 H), 8, 28 (br s, 1 H), 8.37 (d, 1 H), 8.56 (d, 1 H). Compound 101 N-(3-hydroxypyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00707] Compound 101 was prepared in 6% yield from SM-XXVI acid by the same method as Compound 9 using 2-amino-3-hydroxypyridine as the amine. The reaction time was 5 hours.

[00708] 1H NMR (200 MHz, CDCl3 + MeOH-d4): 1.08 (s, 3 H), 1.20 - 2.72 (m, 16 H), 2.80 - 3.15 (m, 2H), 7.06-7.23 (m, 4H), 7.25-7.38 (m, 2H), 7.84 (dd, 1H). Compound 102 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(3-hydroxypyridin-2-yl)propanamide

[00709] Compound 102 was prepared in 34% yield from Compound 101 by the same method as Compound 2 by stirring at 50 ° C for 3 hours.

[00710] 1H NMR (200 MHz, CDCl3): 1.13 (s, 3 H), 1.20 - 2.72 (m, 15 H), 2.80 - 3.15 (m, 3 H), 7.06-7.23 (m, 4 H), 7.25-7.36 (m, 1 H), 7.39 (dd, 1 H), 7.88 (dd, 1 H), 9, 29 (br s, 1H), 10.31 (br s, 1H). Compound 103 3-((13S,15R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren -15-yl)-N-(pyridin-2-yl)propanamide

[00711] Compound 103 was prepared in 16% yield from SM-XXVI acid by the same method as Compound 3 using 2-aminopyridine as an amine. The reaction time was 6.5 hours.

[00712] 1H-NMR (200 MHz, DMSO-d6): 0.99 (s, 3 H), 1.14 - 2.45 (m, 16 H), 2.80 - 3.00 (m, 2 H), 7.00-7.15 (m, 4 H), 7.21-7.30 (m, 1 H), 7.70-7.82 (m, 1 H), 8.10 (d , 1 H), 8.28-8.33 (m, 1 H), 10.50 (s, 1H). Compound 104 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide

[00713] Compound 104 was prepared in 58% yield from Compound 103 by the same method as Compound 2 by stirring at 50 ° C for 1 hour.

[00714] 1H NMR (200 MHz, CDCl3 + MeOH-d4): 1.15 (s, 3 H), 1.20 - 2.70 (m, 15 H), 2.80 - 3.10 (m, 3 H), 7.00-7.17 (m, 4 H), 7.21-7.35 (m, 1 H), 7.68-7.82 (m, 1 H), 8.20- 8.33 (m, 2H), 8.72 (br s, 1H), 9.16 (br s, 1H). Compound 105 N-(4-methoxypyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00715] Compound 105 was prepared in 17% yield from SM-XXVI acid by the same method as Compound 9 using 2-amino-4-methoxypyridine as an amine. The reaction was stirred overnight.

[00716] 1H NMR (200 MHz, CDCl3): 1.07 (s, 3 H), 1.20 - 2.60 (m, 16 H), 2.80 - 3.15 (m, 2 H), 3.88 (s, 3 H), 6.60 (dd, 1 H), 7.06-7.23 (m, 3 H), 7.25-7.37 (m, 1 H), 7, 83 (d, 1H), 8.05 (d, 1H), 8.09 (br s, 1H). Compound 106 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide

[00717] Compound 106 was prepared in 90% yield from Compound 105 by the modified method that in Compound 2 using methanol as a cosolvent and stirring at RT for 3 hours.

[00718] 1H NMR (200 MHz, CDCl3): 1.15 (s, 3 H), 1.20 - 2.65 (m, 15 H), 2.80 - 3.15 (m, 3 H), 3.88 (s, 3 H), 6.60 (dd, 1 H), 7.06-7.23 (m, 3 H), 7.25-7.37 (m, 1 H), 7, 86 (d, 1H), 8.05 (d, 1H), 8.60 (br s, 1H), 8.78 (br s, 1H). Compound 107 3-((13S,15R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren -15-yl)-N-(5-methyloxazol-2-yl)propanamide

[00719] Compound 107 was prepared in 26% yield from SM-XXVI acid by the same method as Compound 3 using 2-amino-5-methyloxazole as an amine. The reaction time was 2.5 hours.

[00720] 1H-NMR (200 MHz, DMSO-d6): 0.98 (s, 3 H), 1.14 - 2.45 (m, 19 H), 2.80 - 2.98 (m, 2 H), 6.69 (s, 1 H), 7.05-7.20 (m, 3 H), 7.20-7.30 (m, 1 H), 10.96 (br s, 1H) . Compound 108 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-methyloxazol-2-yl)propanamide

[00721] Compound 108 was prepared in quantitative yield from Compound 107 by the same method as Compound 2 by stirring at 50 ° C for 1.5 hours.

[00722] 1H-NMR (200 MHz, DMSO-d6): 1.03 (s, 3 H), 1.20 - 2.75 (m, 19 H), 2.80 - 2.95 (m, 2 H), 6.69 (s, 1 H), 7.05-7.20 (m, 3 H), 7.20-7.30 (m, 1 H), 10.18 (s, 1 H) , 10.96 (br s, 1H). Compound 109 3-((13S,15R,E)- 13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide

[00723] Compound 109 was prepared in 22% yield from Acid XXVI by the same method as Compound 1 in the presence of triethylamine using 3-amino-5-methylisoxazole as an amine. The reaction time was 5 hours.

[00724] 1H-NMR (200 MHz, CDCl3): 0.97 (s, 3 H), 1.29-2.44 (m, 19 H), 2.86 (m, 2 H), 6.63 (s, 1H), 7.09-7.25 (m, 3H), 7.28 (m, 1H), 10.88 (s, 1H). MS m/z (TOF ES+): 407 (M+1), 429 (M + Na). Compound 110 3-((13S,15R,E)-17-(hydroxyamino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide

[00725] Compound 110 was prepared from Compound 109 by the same method as Compound 2.

[00726] 1H-NMR (200 MHz, CDCl3): 1.12 (s, 3 H), 1.37 - 2.66 (m, 18 H), 2.86 - 3.00 (m, 2 H) , 6.76 (s, 1 H), 7.09-7.20 (m, 3 H), 7.30-7.31 (m, 1 H), 7.49 (br s, 1 H), 10.18 (s, 1H), 9.49 (br s, 1H). MS m/z (TOF ES+): 422 (M+1). Compound 111 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide

[00727] Compound 111 was synthesized in 20% yield after chromatographic purification by the method used in the preparation of compound 1 in THF using SM-IX acid and 2-amino-5-isopropylpyridine as starting materials in a reaction time of 4 hours.

[00728] 1H-NMR (200 MHz, CDCl3): 1.07 (s, 3 H), 1.25 (s, 3 H), 1.28 (s, 3 H), 1.34-2.60 (m, 17 H), 2.72-3.05 (m, 2 H), 6.83-6.92 (m, 1 H), 7.05-7.18 (m, 2 H), 7 .57-7.63 (m, 1H), 8.09-8.17 (m, 2H), 8.49 (br s, 1H). Compound 112 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide

[00729] Compound 112 was prepared in 70% yield from compound 111 by the same method as in Example 2 in a reaction time of 1.5 hours.

[00730] 1H-NMR (200 MHz, CDCl3): 1.15 (s, 3 H), 1.24 (s, 3 H), 1.28 (s, 3 H), 1.34-2.60 (m, 16 H), 2.72-3.05 (m, 3 H), 6.82-6.92 (m, 1 H), 7.05-7.18 (m, 2 H), 7 .57-7.64 (m, 1H), 8.09-8.19 (m, 2H), 8.84 (br s, 1H). Compound 113 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide

[00731] Compound 113 was synthesized in 82% yield after chromatographic purification by the method used in the preparation of compound 1 in DCM using SM-IX acid and 5-morpholinopyridin-2-amine as starting materials and triethylamine as a time basis 2 hour reaction time.

[00732] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.46 (m, 16 H), 2.63-2.80 (m, 1 H), 2.81-2.96 (m, 1 H), 3.03-3.15 (m, 4 H), 3.68-3.80 (m, 4 H), 6.90-7 .03 (m, 1 H), 7.10-7.22 (m, 2 H), 7.40 (dd, 1 H), 7.95-8.01 (m, 2 H), 10.29 (s, 1H). Compound 114 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide

[00733] Compound 114 was prepared in 65% yield after chromatographic purification from compound 113 by the same method as in Example 2 in a reaction time of 6.5 hours at 50-80 °C. The reaction required 300 mol% hydroxylamine hydrochloride and 800 mol% pyridine.

[00734] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-2.46 (m, 15 H), 2.63-2.80 (m, 2 H), 2.81-2.96 (m, 1 H), 3.03-3.15 (m, 4 H), 3.68-3.80 (m, 4 H), 6.90-7 .03 (m, 1 H), 7.10-7.22 (m, 2 H), 7.40 (dd, 1 H), 7.95-8.01 (m, 2 H), 10.18 (s, 1H), 10.30 (s, 1H). Compound 115 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide

[00735] Compound 115 was synthesized in 83% yield after chromatographic purification by the method used in the preparation of compound 1 in DCM using SM-IX acid and 1-methyl-4-(6-aminopyridin-3-yl)piperazine as starting materials and triethylamine as a basis for a reaction time of 2 hours.

[00736] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.42 (m, 16 H), 2.21 (s, 3 H), 2 .43-2.48 (m, 4 H), 2.63-2.80 (m, 1 H), 2.81-2.96 (m, 1 H), 3.05-3.15 (m , 4 H), 6.93-7.03 (m, 1 H), 7.10-7.22 (m, 2 H), 7.39 (dd, 1 H), 7.92-8.00 (m, 2H), 10.27 (s, 1H). Compound 116 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide

[00737] Compound 116 was prepared in 90% yield from compound 115 by the same method as in Example 2 in a reaction time of 2 hours.

[00738] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-2.42 (m, 15 H), 2.22 (s, 3 H), 2 .43-2.48 (m, 4 H), 2.63-2.80 (m, 2 H), 2.81-2.96 (m, 1 H), 3.05-3.15 (m , 4 H), 6.93-7.00 (m, 1 H), 7.10-7.22 (m, 2 H), 7.39 (dd, 1 H), 7.92-8.00 (m, 2H), 10.19 (s, 1H), 10.28 (s, 1H). MS m/z (TOF ES+): 534 (M+1) Compound 117 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13, 14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-methylpropanamide

[00739] Compound 117 was synthesized in 44% yield after chromatographic purification by the method used in the preparation of compound 9 using SM-IX acid and methylamine hydrochloride as starting materials in a reaction time of 2 hours.

[00740] 1H-NMR (200 MHz, DMSO-d6): 0.96 (s, 3 H), 1.28-2.42 (m, 16 H), 2.55/2.58 (2 xs, 3 H, isomers), 2.63-2.96 (m, 2 H), 6.93-7.03 (m, 1 H), 7.10-7.25 (m, 2 H), 7, 70-7.80 (m, 1H). Compound 118 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-methylpropanamide

[00741] Compound 118 was prepared in 97% yield from compound 117 by the same method as in Example 2 in a reaction time of 1.5 hours.

[00742] 1H-NMR (200 MHz, DMSO-d6): 1.01 (s, 3 H), 1.28-2.45 (m, 15 H), 2.55/2.57 (2 xs, 3 H, isomers), 2.62-2.96 (m, 3 H), 6.90-7.03 (m, 1 H), 7.10-7.25 (m, 2 H), 7, 70-7.82 (m, 1H), 10.18 (s, 1H). Compound 119 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N,N-dimethylpropanamide

[00743] Compound 119 was synthesized in 85% yield by the method used in the preparation of compound 9 using SM-IX acid and dimethylamine hydrochloride as starting materials in a reaction time of 2 hours.

[00744] 1H-NMR (200 MHz, DMSO-d6): 0.97 (s, 3 H), 1.28-2.40 (m, 16 H), 2.62-2.94 (m, 2 H), 2.82 (s, 3 H), 2.97 (s, 3 H), 6.90-7.03 (m, 1 H), 7.10-7.25 (m, 2 H) . Compound 120 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N,N-dimethylpropanamide

[00745] Compound 120 was prepared in 32% yield from compound 119 by the same method as in Example 2 in a reaction time of 1 hour.

[00746] 1H-NMR (200 MHz, CDCl3): 1.13 (s, 3 H), 1.24-2.60 (m, 15 H), 2.62-3.00 (m, 3 H) , 2.97 (s, 3 H), 3.03 (s, 3 H), 6.80-6.92 (m, 1 H), 7.04-7.18 (m, 2 H), 8 .34 (br s, 1H). Compound 121 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(tetrahydro-2H-pyran-4-yl)propanamide

[00747] Compound 121 was synthesized in 56% yield after chromatographic purification by the method used in the preparation of compound 9 using SM-IX acid and 4-aminotetrahydropyran as starting materials in a reaction time of 5 hours.

[00748] 1H-NMR (400 MHz, DMSO-d6): 0.96 (s, 3 H), 1.30-2.41 (m, 20 H), 2.67-2.76 (m, 1 H), 2.85-2.90 (m, 1 H), 3.29-3.30 (m, 2 H), 3.70-3.77 (m, 1 H), 3.80-3 .83 (m, 2H), 6.94-7.00 (m, 1H), 7.10-7.22 (m, 2H), 7.84 (d, 1H). Compound 122 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(tetrahydro-2H-pyran-4-yl)propanamide

[00749] Compound 122 was prepared in quantitative yield from compound 121 by the same method as in Example 2 in a reaction time of 1.5 hours.

[00750] 1H-NMR (400 MHz, DMSO-d6): 1.01 (s, 3 H), 1.28-2.40 (m, 19 H), 2.60-2.76 (m, 2 H), 2.82-2.90 (m, 1 H), 3.29-3.30 (m, 2 H), 3.70-3.77 (m, 1 H), 3.80-3 .83 (m, 2 H), 6.94-7.00 (m, 1 H), 7.10-7.20 (m, 2 H), 7.86 (d, 1 H), 10.18 (s, 1H). Compound 123 N-cyclohexyl-3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-deca -hydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00751] Compound 123 was synthesized in 64% yield after chromatographic purification by the method used in the preparation of compound 9 using SM-IX acid and cyclohexylamine as starting materials in a reaction time of 2 hours.

[00752] 1H-NMR (400 MHz, DMSO-d6): 0.95 (s, 3 H), 1.10-2.41 (m, 26 H), 2.67-2.76 (m, 1 H), 2.84-2.91 (m, 1 H), 3.50-3.53 (m, 1 H), 6.94-7.00 (m, 1 H), 7.10-7 .22 (m, 2H), 7.71 (br d, 1H). Compound 124 N-Cyclohexyl-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16 ,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00753] Compound 124 was prepared in 73% yield after chromatographic purification from compound 123 by the same method as in Example 2 in a reaction time of 1 hour.

[00754] 1H-NMR (400 MHz, DMSO-d6): 1.00 (s, 3 H), 1.10-2.40 (m, 25 H), 2.59-2.76 (m, 2 H), 2.82-2.90 (m, 1 H), 3.45-3.55 (m, 1 H), 6.94-7.00 (m, 1 H), 7.10-7 .20 (m, 2H), 7.72 (br d, 1H), 10.17 (s, 1H). Compound 125 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide

[00755] Compound 125 was synthesized in 53% yield after chromatographic purification by the method used in the preparation of compound 1 in DCM using SM-IX acid and aminopyrazine as starting materials in a reaction time of 5 hours.

[00756] 1H-NMR (400 MHz, DMSO-d6): 0.99 (s, 3 H), 1.30-2.60 (m, 16 H), 2.69-2.78 (m, 1 H), 2.84-2.92 (m, 1 H), 6.94-7.00 (m, 1 H), 7.12-7.20 (m, 2 H), 8.33-8 .40 (m, 2H), 9.35 (s, 1H), 10.81 (s, 1H). Compound 126 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide

[00757] Compound 126 was prepared in 48% yield from compound 125 by the same method as in Example 2 in a reaction time of 2.5 hours.

[00758] 1H-NMR (400 MHz, CDCl3): 1.15 (s, 3 H), 1.34-2.65 (m, 15 H), 2.72-2.87 (m, 1 H) , 2.90-3.00 (m, 2 H), 6.82-6.90 (m, 1 H), 7.05-7.15 (m, 2 H), 8.15 (s, 1 H), 8.10-8.20 (br s, 1 H), 8.24-8.26 (m, 1 H), 8.368.38 (m, 1 H), 9.56 (s, 1H) . Compound 127 (13S,15R)-4-fluoro-13-methyl-15-(3-oxo-3-(8-oxa-2-azaspiro[4.5]decan-2-yl)propyl)-6,7,8 ,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one

[00759] Compound 127 was synthesized in 93% yield by the method used in the preparation of compound 9 using SM-IX acid and 8-oxa-2-aza-spiro(4,5)decane hydrochloride as starting materials at the time of 4 hour reaction.

[00760] 1H-NMR (400 MHz, DMSO-d6): 0.97 (s, 3 H), 1.30-2.45 (m, 22 H), 2.65-2.76 (m, 1 H), 2.84-2.91 (m, 1 H), 3.19-3.22 (m, 1 H), 3.29-3.42 (m, 2 H), 3.46-3 .65 (m, 5 H), 6.94-7.00 (m, 1 H), 7.10-7.22 (m, 2 H). Compound 128 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-1-(8-oxa-2-azaspiro[4.5]decan-2-yl)propan-1-one

[00761] Compound 128 was prepared in 90% yield from compound 127 by the same method as in Example 2 in a reaction time of 2 hours.

[00762] 1H-NMR (400 MHz, DMSO-d6): 1.02 (s, 3 H), 1.30-2.45 (m, 21 H), 2.60-2.75 (m, 2 H), 2.82-2.91 (m, 1 H), 3.19-3.22 (m, 1 H), 3.29-3.42 (m, 2 H), 3.46-3 .65 (m, 5H), 6.94-7.00 (m, 1H), 7.10-7.22 (m, 2H), 10.17 (s, 1H). Compound 129 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide

[00763] Compound 129 was synthesized in 37% yield after chromatographic purification by the method used in the preparation of compound 3 in THF using 200 mol% EDCI and HOBT and SM-IX acid and 2-amino-4-methylpyridine as starting materials in 4.5 hours reaction time.

[00764] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.48 (m, 16 H), 2.30 (s, 3 H), 2 .65-2.78 (m, 1 H), 2.80-2.92 (m, 1 H), 6.90-6.93 (m, 1 H), 6.94-7.00 (m , 1 H), 7.10-7.21 (m, 2 H), 7.95 (s, 1 H), 8.13-8.17 (m, 1 H), 10.42 (s, 1H ). Compound 130 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide

[00765] Compound 130 was prepared in 81% yield from compound 129 by the same method as in Example 2 in a reaction time of 2 hours.

[00766] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-2.48 (m, 15 H), 2.30 (s, 3 H), 2 .62-2.78 (m, 2 H), 2.80-2.92 (m, 1 H), 6.90-6.93 (m, 1 H), 6.94-7.00 (m , 1 H), 7.10-7.21 (m, 2 H), 7.95 (s, 1 H), 8.13-8.17 (m, 1 H), 10.19 (s, 1 H), 10.43 (s, 1H). Compound 131 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide

[00767] Compound 131 was synthesized in 47% yield after chromatographic purification by the method used in the preparation of compound 3 in THF using SM-IX acid and 2-amino-4-methoxypyridine as starting materials in 10 hours and during night at room temperature. The reaction required 250 mol% of amine, EDCI and HOBT.

[00768] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.48 (m, 16 H), 2.65-2.78 (m, 1 H), 2.80-2.92 (m, 1 H), 3.81 (s, 3 H), 6.68-6.72 (m, 1 H), 6.94-7.00 (m , 1 H), 7.10-7.21 (m, 2 H), 7.73 (s, 1 H), 8.10-8.13 (m, 1 H), 10.47 (s, 1H ). Compound 132 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide

[00769] Compound 132 was prepared in 60% yield from compound 131 by the same method as in Example 2 in a reaction time of 1 hour.

[00770] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-2.48 (m, 15 H), 2.59-2.78 (m, 2 H), 2.80-2.92 (m, 1 H), 3.81 (s, 3 H), 6.68-6.72 (m, 1 H), 6.94-7.00 (m , 1 H), 7.10-7.21 (m, 2 H), 7.74 (s, 1 H), 8.10-8.13 (m, 1 H), 10.19 (s, 1 H), 10.49 (s, 1H). Compound 133 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide

[00771] Compound 133 was synthesized in quantitative yield by the method used in the preparation of compound 1 in DCM using SM-XV acid and 3-amino-5-methylisoxazole as starting materials in 4.5 hours reaction time.

[00772] 1H-NMR (200 MHz, DMSO-d6): 0.97 (s, 3 H), 1.25-2.45 (m, 16 H), 2.36 (s, 3 H), 2 .80-2.95 (m, 2 H), 6.63 (s, 1 H), 6.83-7.00 (m, 2 H), 7.24-7.35 (m, 1 H) , 10.88 (br s, 1H). Compound 134 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylisoxazol-3-yl)propanamide

[00773] Compound 134 was prepared in 78% yield from compound 133 by the same method as in Example 2 in a reaction time of two hours.

[00774] 1H-NMR (200 MHz, DMSO-d6): 1.02 (s, 3 H), 1.25-2.45 (m, 15 H), 2.37 (s, 3 H), 2 .58-2.74 (m, 1 H), 2.80-2.95 (m, 2 H), 6.64 (s, 1 H), 6.87-7.00 (m, 2 H) , 7.24-7.35 (m, 1H), 10.18 (s, 1H), 10.89 (br s, 1H). Compound 135 (13S,15R)-4-fluoro-13-methyl-15-(3-morpholino-3-oxopropyl)- 6,7,8,9,11,12,13,14,15,16-deca- hydro-17H-cyclopenta[a]phenanthren-17-one

[00775] Compound 135 was synthesized in 83% yield by the method used in the preparation of Compound 3 in DMF using SM-IX acid and morpholine as starting materials in a reaction time of two hours.

[00776] 1H-NMR (200 MHz, DMSO-d6): 0.97 (s, 3 H), 1.35-2.37 (m, 15 H), 2.76-2.92 (m, 3 H), 3.45 (br s, 4 H), 3.55 (br s 4 H), 6.93-7.02 (m, 1 H), 7.16-7.23 (m, 2 H ). Compound 136 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-1-morpholinopropan-1-one

[00777] Compound 136 was prepared in 79% yield from compound 135 by the same method as Compound 2 in a reaction time of 1 hour.

[00778] 1H-NMR (200 MHz, CDCl3): 1.13 (s, 3 H), 1.35-3.03 (m, 18 H), 3.46-3.51 (m, 2 H) , 3.66-3.72 (m, 6 H), 6.82-6.90 (m, 1 H), 7.05-7.19 (m, 2 H), 8.23 (br s, 1H). Compound 137 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide

[00779] Compound 137 was synthesized in 51% yield by the method used in the preparation of Compound 3 in DMF using SM-IX acid and 2-aminopyridine as starting materials in overnight reaction time.

[00780] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.34-1.47 (m, 3 H), 1.59-1.68 (m, 4 H), 1.78-1.90 (m, 1 H), 2.17- 2.46 (m, 8 H), 2.68-2.82 (m, 2 H), 6.95-6 .99 (m, 1 H), 7.07-7.13 (m, 1 H), 7.14-7.20 (m, 2 H), 7.76 (dd, 1 H), 8.10 (d, 1H), 8.30 (dd, 1H), 10.50 (s, 1H). Compound 138 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide

[00781] Compound 138 was prepared in 89% yield from compound 137 by the same method as Compound 2 in a reaction time of 1 hour.

[00782] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.36-1.77 (m, 8 H), 2.08-2.45 (m, 7 H), 2.63-2.76 (m, 2 H), 2.82-2.89 (m, 1 H), 6.94-6.98 (m, 1 H), 7.07 (m , 1 H), 7.14-7.19 (m, 2 H), 7.74 (dd, 1 H), 8.10 (d, 1 H), 8.30 (d, 1 H), 10 .19 (s, 1 H), 10.52 (s, 1 H). Compound 139 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide

[00783] Compound 139 was synthesized in 83% yield by the method used in the preparation of Compound 1 in THF using SM-IX acid and 2-amino-4-fluoropyridine as starting materials in overnight reaction time.

[00784] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.36-1.46 (m, 3 H), 1.58-1.74 (m, 4 H), 1.89-1.94 (m, 1 H), 2.16- 2.43 (m, 7 H), 2.68-2.91 (m, 3 H), 6.95-7 .04 (m, 2 H), 7.05-7.20 (m, 2 H), 7.93 (dd, 1 H), 8.34 (dd, 1 H), 10.83 (s, 1 H ). Compound 140 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide

[00785] Compound 140 was prepared in 77% yield from Compound 139 by the same method as Compound 2 in a reaction time of two hours.

[00786] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.35-1.71 (m, 6 H), 1.81-1.91 (m, 2 H), 2.08-2.14 (m, 2 H), 2.30-2.47 (m, 5 H), 2.65-2.90 (m, 3 H), 6.94-7 .04 (m, 2 H), 7.10-7.19 (m, 2 H), 7.93 (dd, 1 H), 8.35 (dd, 1 H), 10.19 (s, 1 H), 10.84 (s, 1H). Compound 141 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide

[00787] Compound 141 was synthesized in 96% yield by the method used in the preparation of Compound 1 in THF using SM-IX acid and 2-amino-3-fluoropyridine as starting materials in overnight reaction time.

[00788] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.34-1.98 (m, 8 H), 2.18- 2.47 (m, 8 H), 2.68-2.77 (m, 1 H), 2.84-2.90 (m, 1 H), 6.97 (m, 1 H), 7.10-7.20 (m , 2H), 7.34 (m, 1H), 7.77 (dd, 1H), 8.24 (d, 1H), 10.28 (s, 1H). Compound 142 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide

[00789] Compound 142 was prepared in 69% yield from Compound 141 by the same method as Compound 2 in a reaction time of 1 hour.

[00790] 1H-NMR (400 MHz, DMSO-d6): 1.04 (s, 3 H), 1.33-1.70 (m, 6 H), 1.88-2.46 (m, 9 H), 2.66-2.90 (m, 3 H), 6.94-6.98 (m, 1 H), 7.10-7.17 (m, 2 H), 7.35 (m , 1H), 7.76 (dd, 1H), 8.24 (d, 1H), 10.19 (s, 1H), 10.28 (s, 1H). Compound 143 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide

[00791] Compound 143 was synthesized in 88% yield by the method used in the preparation of Compound 1 in THF using SM-IX acid and 2-amino-6-fluoropyridine as starting materials in a reaction time of two hours.

[00792] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.35-1.46 (m, 3 H), 1.57-1.77 (m, 4 H), 1.93 (m, 1 H), 2.16-2.47 (m, 8 H), 2.68-2.90 (m, 2 H), 6.83 (dd, 1 H) , 6.97 (dd, 1 H), 7.12-7.20 (m, 2 H), 7.95 (dd, 1 H), 8.01 (d, 1 H), 10.69 (s , 1H). Compound 144 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide

[00793] Compound 144 was prepared in 79% yield from Compound 143 by the same method as Compound 2 in a reaction time of 1 hour.

[00794] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-1.68 (m, 6 H), 1.84-1.91 (m, 2 H), 2.09-2.16 (m, 2 H), 2.31-2.47 (m, 5 H), 2.65-2.88 (m, 3 H), 6.83 (dd , 1 H), 6.96 (m, 1 H), 7.12-7.19 (m, 2 H), 7.94 (dd, 1 H), 8.02 (dd, 1 H), 10 .19 (s, 1H), 10.71 (s, 1H). Compound 145 N-(3,5-difluoropyridin-2-yl)-3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14 ,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00795] Compound 145 was synthesized in 91% yield by the method used in the preparation of Compound 1 in THF using SM-IX acid and 2-amino-3,5-difluoropyridine as starting materials in a reaction time of two hours .

[00796] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.34-1.47 (m, 4 H), 1.58-1.83 (m, 4 H), 1.90-1.95 (m, 1 H), 2.17-2.55 (m, 9 H), 2.67-2.90 (m, 2 H), 6.97 (dd , 1H), 8.01 (dd, 1H), 8.34 (d, 1H), 10.31 (s, 1H). Compound 146 N-(3,5-difluoropyridin-2-yl)-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12 ,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00797] Compound 146 was prepared in 84% yield from Compound 145 by the same method as Compound 2 in a reaction time of 1 hour.

[00798] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-1.68 (m, 6 H), 1.88-1.91 (m, 2 H), 2.13-2.18 (m, 2 H), 2.31-2.45 (m, 5 H), 2.66-2.88 (m, 3 H), 6.96 (m , 1 H), 7.12-7.19 (m, 2 H), 8.01 (dd, 1 H), 8.34 (dd, 1 H), 10.19 (s, 1 H), 10 .32 (s, 1H). Compound 147 N-(5-cyanopyridin-2-yl)-3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15 ,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00799] Compound 147 was synthesized in 85% yield by the method used in the preparation of Compound 1 in THF using SM-IX acid and 2-amino-5-cyanopyridine as starting materials in overnight reaction time.

[00800] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.36-1.97 (m, 8 H), 2.17- 2.43 (m, 7 H), 2.58 (m, 1 H), 2.68-2.90 (m, 2 H), 6.97 (dd, 1 H), 7.12-7.20 (m, 2 H) , 8.25 (m, 2H), 8.78 (d, 1H), 11.04 (s, 1H). Compound 148 N-(5-cyanopyridin-2-yl)-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13 ,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00801] Compound 148 was prepared in 71% yield from compound 147 by the same method as Compound 2 in 1 reaction time.

[00802] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-1.66 (m, 6 H), 1.88-2.43 (m, 8 H), 2.63-2.87 (m, 4 H), 6.94-6.98 (m, 1 H), 7.14-7.19 (m, 2 H), 8.24 (s , 2 H), 8.78 (d, 1 H), 10.19 (s, 1 H), 11.06 (s, 1 H). Compound 149 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide

[00803] Compound 149 was synthesized in 92% yield by the method used in the preparation of Compound 1 in THF using SM-XV acid and 2-amino-3-fluoropyridine as starting materials in overnight reaction time.

[00804] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.35-1.46 (m, 3 H), 1.58-1.75 (m, 4 H), 1.89-1.92 (m, 1 H), 2.11-2.14 (m, 1 H), 2.27-2.48 (m, 7 H), 2.88 (m , 2 H), 6.92 (m, 2 H), 7.27-7.36 (m, 2 H), 7.76 (dd, 1 H), 8.24 (d, 1 H), 10 .27 (s, 1H). Compound 150a 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide

[00805] Compound 150 was prepared from Compound 149 by the same method as Compound 2 in a reaction time of 1 hour. The E and Z isomers (compounds 150a and 150b, respectively) were isolated by chromatographic purification. Compound 150a: E-isomer, yield 58%:

[00806] 1H-NMR (400 MHz, CDCl3): 1.14 (s, 3 H), 1.43-1.75 (m 7 H), 2.00-2.11 (m, 2 H), 2.19 (m, 1 H), 2.27-2.36 (m, 3 H), 2.51 (d, 1 H), 2.59 (m, 1 H), 2.78 (m, 1 H), 2.90-2.97 (m, 3 H), 6.78- 6.84 (m, 2 H), 7.14 (m, 1 H), 7.21 (m, 1 H ), 7.48 (dd, 1H), 8.00 (br s, 1H), 8.20 (d, 1H). Compound 150b: Z isomer, 4% yield: 3-((13S,15R,Z)-3-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15 ,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide

[00807] 1H-NMR (400 MHz, CDCl3): 1.31 (s, 3 H), 1.43-1.87 (m, 7 H), 2.16 (m, 2 H), 2.30 -2.38 (m, 4 H), 2.53 (d, 1 H), 2.60-3.04 (m, 5 H), 6.81-6.85 (m, 2 H), 7 .16-7.24 (m, 2H), 7.53 (m, 1H), 8.17 (d, 1H), 9.74 (br s, 1H). Compound 151 N-(3,5-difluoropyridin-2-yl)-3-((13S,15R)-3-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14 ,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00808] Compound 151 was synthesized in 96% yield by the method used in the preparation of Compound 1 in THF using SM-XV acid and 2-amino-3,5-difluoropyridine as starting materials in a reaction time of 3 hours.

[00809] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.34-1.74 (m, 7 H), 1.88-1.96 (m, 1 H), 2.11-2.48 (m, 8 H), 2.88 (m, 2 H), 6.92 (m, 2 H), 7.29 (dd, 1 H), 8.01 (dd, 1H), 8.34 (d, 1H), 10.31 (s, 1H). Compound 152 N-(3,5-difluoropyridin-2-yl)-3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12 ,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00810] Compound 152 was prepared in 55% yield from Compound 151 by the same method as Compound 2 in 30 minutes reaction time.

[00811] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.35-1.65 (m, 6 H), 1.85-2.44 (m, 9 H), 2.66-2.73 (m, 1 H), 2.86 (m, 2 H), 6.89-6.94 (m, 2 H), 7.29 (m, 1 H) , 8.00 (dd, 1 H), 8.34 (d, 1 H), 10.19 (s, 1 H), 10.32 (s, 1 H). Compound 153 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide

[00812] Compound 153 was synthesized in 63% yield after chromatographic purification by the method used in the preparation of compound 1 in DCM using SM-XV acid and 5-morpholinopyridin-2-amine as starting materials and triethylamine as a base in the reaction time of 2 hours.

[00813] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.47 (m, 16 H), 2.81-2.96 (m, 2 H), 3.06-3.12 (m, 4 H), 3.70-3.78 (m, 4 H), 6.90-6.95 (m, 2 H), 7.25-7 .32 (t, 1H), 7.40 (dd, 1H), 7.95-8.01 (m, 2H), 10.28 (s, 1H). Compound 154 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide

[00814] Compound 154 was prepared in 65% yield after chromatographic purification from compound 153 by the same method as in Example 2 at 50-70 °C in a reaction time of 4 hours.

[00815] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-2.47 (m, 15 H), 2.60-2.70 (m, 1 H), 2.81-2.96 (m, 2 H), 3.06-3.12 (m, 4 H), 3.70-3.78 (m, 4 H), 6.90-6 .95 (m, 2 H), 7.25-7.32 (t, 1 H), 7.40 (dd, 1 H), 7.95-8.01 (m, 2 H), 10.17 (s, 1H), 10.29 (s, 1H). Compound 155 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide

[00816] Compound 155 was synthesized in 90% yield by the method used in the preparation of compound 1 in THF using SM-XVII acid and 2-amino-4-fluoropyridine as starting materials in a reaction time of 4 hours.

[00817] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.47 (m, 16 H), 2.81-2.96 (m, 2 H), 7.00-7.06 (m, 1 H), 7.14-7.17 (m, 2 H), 7.27-7.31 (m, 1 H), 7.92 (dd , 1 H), 8.30-8.37 (m, 1 H), 10.82 (s, 1H). Compound 156 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide

[00818] Compound 156 was prepared in 41% yield after chromatographic purification from compound 155 by the same method as in Example 2 in a reaction time of 2 hours.

[00819] 1H-NMR (400 MHz, CDCl3): 1.15 (s, 3 H), 1.35-2.65 (m, 15 H), 2.81-3.00 (m, 3 H) , 6.80-6.83 (m, 1 H), 7.08-7.11 (m, 2 H), 7.15-7.21 (m, 1 H), 8.04 (dd, 1 H), 8.20-8.25 (m, 1 H), 8.50 (br s, 1 H), 8.52 (br s, 1H). Compound 157 N-(4-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00820] Compound 157 was synthesized in 78% yield by the method used in the preparation of compound 1 in THF using SM-XXVI acid and 290 mol% 2-amino-4-fluoropyridine as starting materials in the reaction time during at night.

[00821] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.47 (m, 16 H), 2.81-2.96 (m, 2 H), 7.00-7.06 (m, 1 H), 7.07-7.16 (m, 3 H), 7.25-7.30 (m, 1 H), 7.92 (dd , 1 H), 8.30-8.37 (m, 1 H), 10.82 (s, 1H). Compound 158 N-(4-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15 ,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00822] Compound 158 was prepared in 68% yield from compound 157 by the same method as in Example 2 in a reaction time of 1.5 hours.

[00823] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-2.45 (m, 15 H), 2.60-2.72 (m, 1 H), 2.81-2.96 (m, 2 H), 7.00-7.06 (m, 1 H), 7.07-7.16 (m, 3 H), 7.25-7 .30 (m, 1 H), 7.92 (dd, 1 H), 8.30-8.37 (m, 1 H), 10.18 (s, 1 H), 10.84 (s, 1 H ). Compound 159 N-(3-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00824] Compound 159 was synthesized in 88% yield by the method used in the preparation of compound 1 in THF using SM-XXVI acid and 2-amino-3-fluoropyridine as starting materials in overnight reaction time.

[00825] 1H-NMR (400 MHz, DMSO-d6): 0.99 (s, 3 H), 1.30-2.47 (m, 16 H), 2.81-2.96 (m, 2 H), 7.05-7.16 (m, 3 H), 7.26-7.28 (m, 1 H), 7.30-7.37 (m, 1 H), 7.73-7 .79 (m, 1H), 8.23-8.25 (m, 1H), 10.27 (s, 1H). Compound 160 N-(3-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15 ,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00826] Compound 160 was prepared in 95% yield from compound 159 by the same method as in Example 2 in a reaction time of 1 hour.

[00827] 1H-NMR (400 MHz, DMSO-d6): 1.04 (s, 3 H), 1.30-2.47 (m, 15 H), 2.65-2.74 (m, 1 H), 2.80-2.96 (m, 2 H), 7.05-7.16 (m, 3 H), 7.26-7.28 (m, 1 H), 7.30-7 .37 (m, 1 H), 7.73-7.79 (m, 1 H), 8.23-8.25 (m, 1 H), 10.18 (s, 1 H), 10.28 (s, 1H). Compound 161 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide

[00828] Compound 161 was synthesized in 81% yield by the method used in the preparation of compound 1 in THF using SM-XVII acid and 2-amino-3-fluoropyridine as starting materials in overnight reaction time.

[00829] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.47 (m, 16 H), 2.81-2.94 (m, 2 H), 7.15-7.16 (m, 2 H), 7.28-7.30 (m, 1 H), 7.32-7.36 (m, 1 H), 7.73-7 .79 (m, 1H), 8.23-8.25 (d, 1H), 10.27 (s, 1H). Compound 162 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide

[00830] Compound 162 was prepared in 88% yield from compound 161 by the same method as in Example 2 in a reaction time of 2.5 hours.

[00831] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-2.47 (m, 15 H), 2.65-2.73 (m, 1 H), 2.81-2.94 (m, 2 H), 7.14-7.16 (m, 2 H), 7.28-7.30 (m, 1 H), 7.31-7 .36 (m, 1 H), 7.73-7.77 (m, 1 H), 8.23-8.24 (d, 1 H), 10.19 (s, 1 H), 10.28 (s, 1H). Compound 163 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(3,5-difluoropyridin-2-yl)propanamide

[00832] Compound 163 was synthesized in 90% yield by the method used in the preparation of compound 1 in THF using SM-XVII acid and 2-amino-3,5-difluoropyridine as starting materials in a reaction time of 5 hours.

[00833] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.47 (m, 16 H), 2.80-2.94 (m, 2 H), 7.15-7.16 (m, 2 H), 7.28-7.30 (m, 1 H), 7.98-8.03 (m, 1 H), 8.34-8 .35 (m, 1H), 10.31 (s, 1H). Compound 164 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(3,5-difluoropyridin-2-yl)propanamide

[00834] Compound 164 was prepared in 93% yield from compound 163 by the same method as in Example 2 in a reaction time of 4 hours.

[00835] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-2.47 (m, 15 H), 2.65-2.74 (m, 1 H), 2.80-2.94 (m, 2 H), 7.14-7.16 (m, 2 H), 7.28-7.30 (m, 1 H), 7.98-8 .03 (m, 1H), 8.34-8.35 (m, 1H), 10.19 (s, 1H), 10.32 (s, 1H). Compound 165 N-(3,5-difluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16 ,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00836] Compound 165 was synthesized in 90% yield by the method used in the preparation of compound 1 in THF using SM-XXVI acid and 2-amino-3,5-difluoropyridine as starting materials in overnight reaction time.

[00837] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.47 (m, 16 H), 2.80-2.94 (m, 2 H), 7.05-7.15 (m, 3 H), 7.26-7.28 (m, 1 H), 7.98-8.03 (m, 1 H), 8.34-8 .35 (m, 1H), 10.31 (s, 1H). Compound 166 N-(3,5-difluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14 ,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00838] Compound 166 was prepared in 71% yield after chromatographic purification from compound 165 by the same method as in Example 2 in a reaction time of 3 hours.

[00839] 1H-NMR (400 MHz, DMSO-d6): 1.04 (s, 3 H), 1.30-2.47 (m, 15 H), 2.65-2.74 (m, 1 H), 2.80-2.94 (m, 2 H), 7.05-7.15 (m, 3 H), 7.26-7.28 (m, 1 H), 7.98-8 .03 (m, 1H), 8.34-8.35 (m, 1H), 10.18 (s, 1H), 10.32 (s, 1H). Compound 167 N-(6-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00840] Compound 167 was synthesized in 92% yield by the method used in the preparation of compound 1 in THF using SM-XXVI acid and 2-amino-6-fluoropyridine as starting materials in a reaction time of 4 hours.

[00841] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.47 (m, 16 H), 2.80-2.95 (m, 2 H), 6.83 (dd, 1 H), 7.05-7.15 (m, 3 H), 7.26-7.28 (m, 1 H), 7.91-7.97 (m , 1 H), 8.00-8.03 (m, 1 H), 10.69 (s, 1H). Compound 168 N-(6-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15 ,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide

[00842] Compound 168 was prepared in 85% yield from compound 167 by the same method as in Example 2 in a reaction time of 2 hours.

[00843] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-2.47 (m, 15 H), 2.60-2.71 (m, 1 H), 2.80-2.95 (m, 2 H), 6.83 (dd, 1 H), 7.05-7.15 (m, 3 H), 7.26-7.28 (m , 1 H), 7.91-7.97 (m, 1 H), 8.00-8.03 (m, 1 H), 10.18 (s, 1 H), 10.70 (s, 1H ). Compound 169 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide

[00844] Compound 169 was synthesized in 71% yield by the method used in the preparation of compound 1 in THF using SM-XVII acid and 2-amino-6-fluoropyridine as starting materials in overnight reaction time.

[00845] 1H-NMR (400 MHz, DMSO-d6): 0.97 (s, 3 H), 1.30-2.47 (m, 16 H), 2.80-2.95 (m, 2 H), 6.83 (dd, 1 H), 7.14-7.17 (m, 2 H), 7.28-7.31 (m, 1 H), 7.91-7.97 (m , 1 H), 8.00-8.03 (m, 1 H), 10.68 (s, 1H). Compound 170 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide

[00846] Compound 170 was prepared in 73% yield from compound 169 by the same method as in Example 2 in a reaction time of 3 hours.

[00847] 1H-NMR (400 MHz, DMSO-d6): 1.02 (s, 3 H), 1.30-2.47 (m, 15 H), 2.60-2.70 (m, 1 H), 2.80-2.95 (m, 2 H), 6.83 (dd, 1 H), 7.13-7.17 (m, 2 H), 7.27-7.30 (m , 1 H), 7.90-7.97 (m, 1 H), 8.00-8.03 (m, 1 H), 10.18 (s, 1 H), 10.70 (s, 1H ). Compound 171 6-(3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro- 6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide

[00848] Compound 171 was synthesized in 85% yield by the method used in the preparation of compound 1 in THF using SM-XVII acid and 6-amino-N,N-dimethylpyridine-3-carboxamide as starting materials in the reaction time during the night.

[00849] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.47 (m, 16 H), 2.80-2.95 (m, 2 H), 2.97 (s, 6 H), 7.14-7.17 (m, 2 H), 7.28-7.31 (m, 1 H), 7.85 (dd, 1 H) , 8.14 (d, 1H), 8.38 (d, 1H), 10.71 (s, 1H). Compound 172 6-(3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17- decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide

[00850] Compound 172 was prepared in 78% yield from compound 171 by the same method as in Example 2 in a reaction time of 1 hour.

[00851] 1H-NMR (400 MHz, DMSO-d6): 1.03 (s, 3 H), 1.30-2.47 (m, 15 H), 2.60-2.72 (m, 1 H), 2.80-2.95 (m, 2 H), 2.98 (s, 6 H), 7.14-7.17 (m, 2 H), 7.28-7.31 (m , 1 H), 7.85 (dd, 1 H), 8.14 (d, 1 H), 8.38 (d, 1 H), 10.18 (s, 1 H), 10.73 (s , 1H). Compound 173 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide

[00852] Compound 173 was synthesized in 79% yield by the method used in the preparation of compound 1 in THF using SM-XVII acid and 3-amino-1,2,5,6,7,8-hexahydroquinolin-2 -one as starting materials in the overnight reaction time.

[00853] 1H-NMR (400 MHz, DMSO-d6): 0.97 (s, 3 H), 1.30-2.47 (m, 24 H), 2.80-2.95 (m, 2 H), 7.14-7.17 (m, 2 H), 7.28-7.31 (m, 1 H), 8.01 (s, 1 H), 9.14 (s, 1 H) , 11.68 (s, 1H). Compound 174 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide

[00854] Compound 174 was prepared in 83% yield from compound 173 by the same method as in Example 2 in a reaction time of 3 hours.

[00855] 1H-NMR (400 MHz, DMSO-d6): 1.02 (s, 3 H), 1.29-2.47 (m, 23 H), 2.59-2.68 (m, 1 H), 2.80-2.94 (m, 2 H), 7.14-7.17 (m, 2 H), 7.28-7.31 (m, 1 H), 8.01 (s , 1 H), 9.16 (s, 1 H), 10.17 (s, 1 H), 11.67 (br s, 1H). Compound 175 6-(3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro- 6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide

[00856] Compound 175 was synthesized in quantitative yield by the method used in the preparation of compound 1 in THF using SM-IX acid and 6-amino-N,N-dimethylpyridine-3-carboxamide as starting materials in the reaction time during night.

[00857] 1H-NMR (400 MHz, DMSO-d6): 0.98 (s, 3 H), 1.30-2.47 (m, 16 H), 2.66-2.94 (m, 2 H), 2.98 (s, 6 H), 6.94-7.00 (m, 1 H), 7.12-7.21 (m, 2 H), 7.85 (dd, 1 H) , 8.14 (d, 1H), 8.38 (d, 1H), 10.72 (s, 1H). Compound 176 6-(3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17- decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide

[00858] Compound 176 was prepared in 91% yield from compound 175 by the same method as in Example 2 in a reaction time of 1 hour.

[00859] 1H-NMR (400 MHz, DMSO-d6): 1.04 (s, 3 H), 1.30-2.47 (m, 15 H), 2.63-2.94 (m, 3 H), 2.98 (s, 6 H), 6.93-7.00 (m, 1 H), 7.08-7.21 (m, 2 H), 7.85 (dd, 1 H) , 8.15 (d, 1H), 8.38 (d, 1H), 10.19 (s, 1H), 10.73 (s, 1H). Compound 177 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta [a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide

[00860] Compound 177 was synthesized in 86% yield by the method used in the preparation of compound 1 in THF using SM-IX acid and 3-amino-1,2,5,6,7,8-hexahydroquinolin-2 -one as starting materials in the overnight reaction time.

[00861] 1H-NMR (400 MHz, DMSO-d6): 0.97 (s, 3 H), 1.30-2.47 (m, 24 H), 2.65-2.93 (m, 2 H), 6.94-7.00 (m, 1 H), 7.12-7.21 (m, 2 H), 8.01 (s, 1 H), 9.15 (s, 1 H) , 11.68 (br s, 1H). Compound 178 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro -6H-cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide

[00862] Compound 178 was prepared in 78% yield from compound 177 by the same method as in Example 2 in a reaction time of 2 hours.

[00863] 1H-NMR (400 MHz, DMSO-d6): 1.02 (s, 3 H), 1.30-2.47 (m, 23 H), 2.58-2.93 (m, 3 H), 6.94-7.00 (m, 1 H), 7.10-7.21 (m, 2 H), 8.02 (s, 1 H), 9.17 (s, 1 H) , 10.17 (s, 1H), 11.67 (br s, 1H).

PHARMACOLOGICAL TESTS

[00864] The following tests are provided to demonstrate the present invention in an illustrative manner and should not be considered limiting on the scope of the invention. Furthermore, the compound concentrations in the assays are exemplary and should not be considered limiting. A person skilled in the art can define pharmaceutically relevant concentrations with the method known in the art. Inhibition of the enzyme 17β-hydroxysteroid dehydrogenase type 1

[00865] Production and isolation of 17β-HSD1: The recombinant baculovirus was generated by the "Bac to Bac Expression System" (Invitrogen). The recombinant bacmid was transfected into Sd9 insect cells using "Cellfectin Reagent" (Invitrogen). 60 h later the cells were harvested; the microsomal fraction was isolated as described by Puranen, T.J., Poutanen, M.H., Peltoketo, H.E., Vihko, P.T. and Vihko, R. K. (1994) Site-directed mutagenesis of the putative active site of human 17 β-hydroxysteroid dehydrogenase type 1. Biochem. J. 304: 289-293. Aliquots were stored frozen until determination of enzymatic activity.

[00866] Assay - Inhibition of recombinant human 17β-HSD1: The recombinant protein (1 μg/ml) was incubated in 20 mM KH2PO4, pH 7.4 with 30 nM estrone (including 800,000 cpm/ml 3H-estrone) and 1 mM NADPH for 30 min at room temperature, in the presence of the potential inhibitor at concentrations of 1 μM or 0.1 μM. Inhibitory raw material solutions were prepared in DMSO. The final concentration of DMSO was adjusted to 1% in all samples. The enzymatic reaction was stopped by adding 10% trichloroacetic acid (final concentration). Samples were centrifuged in a microtiter plate at 4000 rpm for 10 min. Supernatants were applied to reversed-phase HPLC on a Waters Symmetry C18 column equipped with a Waters Sentry Guard column. Isocratic HPLC cycles were performed at room temperature at a flow rate of 1 mL/min in 48:52 acetonitrile:water as running solvent. Radioactivity was monitored in the eluate by a Scintillation Analyzer. Total radioactivity for estrone and estradiol was determined in each sample and the percentage conversion of estrone to estradiol was calculated according to the following formula: % conversion = 100 x {(cpm of estradiol in sample with inhibitor) /[(cpm of estrone in sample with inhibitor) + (cpm of estradiol in sample with inhibitor)]} ________________________________________________________ ______ [(cpm of estradiol in sample without inhibitor)/[(cpm of estrone in sample without inhibitor) + (cpm of estradiol in sample without inhibitor )]}.The inhibition percentage was calculated fluidly: % inhibition = 100 - % conversion

[00867] % inhibition values were determined for exemplified compounds and the results are summarized in Table 2. Inhibition of the enzyme 17β-hydroxysteroid dehydrogenase type 2

[00868] Production and isolation of 17β-HSD2: Similar to 17β-HSD1, the recombinant baculovirus was generated by the "Bac to Bac Expression System" (Invitrogen). The recombinant bacmid was transfected into Sd9 insect cells using "Cellfectin Reagent" (Invitrogen). 60 h later, cells were harvested and the supernatant was fractionated by the following protocol:

[00869] - the cells were dissolved in 40 ml of buffer A (40 mM TRIS, pH 8.0, 20% glycerol, 20 μM NAD, 0.4 mM PMSF, 150 mM NaSF, 150 mM NaCl, dodecyl-e -0.5% maltoside + protease inhibitor cocktail)

[00870] - the cells were sonicated

[00871] - the lysate was incubated on ice for 15 min

[00872] - the lysate was centrifuged at 5000 rpm for 15 min, + 4 °C

[00873] - centrifugation of the supernatant 180,000 g 30 min, + 4°C

[00874] - the pellet was dissolved in 8 ml of buffer A

[00875] - non-resuspended material was removed by centrifugation 5000 rpm 15 min, + 4 °C

[00876] - the clear supernatant was divided into 100 μl aliquots and stored frozen until the enzymatic activity was determined.

[00877] The amount of 17β-HSD2 was analyzed by immunoblotting and the total protein concentration of each batch of extract was determined.

[00878] Assay - Inhibition of recombinant human 17β-HSD2: the recombinant protein (4 μg/ml) was incubated in 20 mM KH2PO4 pH 8.5 with 50 nM estradiol (including 800,000 cpm/ml of 3H-estradiol) and NADH 1 mM for 30 min at room temperature, in the presence of potential inhibitor at concentrations of 1 μM or 0.1 μM. Inhibitory raw material solutions were prepared in DMSO. The final concentration of DMSO was adjusted to 1% in all samples. The enzymatic reaction was stopped by adding 10% trichloroacetic acid (final concentration). Samples were centrifuged in a microtiter plate at 4000 rpm for 10 min. Supernatants were applied to reversed-phase HPLC on a Waters Symmetry C18 column equipped with a Waters Sentry Guard column. Isocratic HPLC cycles were performed at room temperature at a flow rate of 1 mL/min in 48:52 acetonitrile:water as running solvent. Radioactivity was monitored in the eluate by a Scintillation Analyzer. Total radioactivity for estrone and estradiol was determined in each sample and the percentage conversion of estradiol to estrone was calculated according to the following formula: % conversion = 100 x {(cpm of estrone in sample with inhibitor) /[(cpm of estradiol in sample with inhibitor) + (cpm of estrone in sample with inhibitor)]} ________________________________________________________ _________________________ [(cpm of estrone in sample without inhibitor)/[(cpm of estradiol in sample without inhibitor) + (cpm of estrone in sample without inhibitor )]}.The inhibition percentage was calculated fluidly: % inhibition = 100 - % conversion

[00879] % inhibition values were determined for exemplified compounds and the results are summarized in Table 2. Inhibition of the conversion of estrone to estradiol in a rabbit tissue homogenate

[00880] The assay is based on an enzymatic reaction in which the HSD1 enzyme, expressed in rabbit placenta tissue, converts its natural substance estrone (E1) into estradiol (E2) in the presence of a cofactor β-NADPH.

[00881] Homogenization of rabbit placenta tissue: Weigh a piece of frozen tissue into a Precellys ck28 bead tube. Add buffer solution (20 mM KH2PO4 with 1 mM EDTA, pH 7.4) in a 1:2 ratio (e.g. 300 mg of tissue : 600 μl of reaction buffer). Insert the bead tubes into the homogenizer and homogenize 2 x 30 s. 6000rpm. Centrifuge for 5 minutes, 2600 rpm at +4°C and collect the supernatant. Aliquots of homogenate are stored at -80 °C.

[00882] Assay - Inhibition of conversion of E1 to E2 in rabbit placenta tissue: A reaction occurs in a buffer solution (20 mM KH2PO4 with 1 mM EDTA, pH 7.4), including appropriate amount of rabbit placenta homogenate , cofactor (β-NADPH 1 μm), Substrate (estrone 30 nM), tracer-labeled substrate (5 nM [3H]-estrone). During a 30-minute incubation, some of the estrone is converted to estradiol. The reaction is stopped by lowering the pH to 1 with 10% trichloroacetic acid (TCA). The substrate and conversion products are analyzed by HPLC and a Scintillation counter analyzer. Total radioactivity for estrone and estradiol was determined in each sample and the percentage of conversion of estrone to estradiol was calculated according to the following formula: % conversion = 100 x {(cpm of estradiol in sample with inhibitor) /[(cpm of estrone in sample with inhibitor) + (cpm of estradiol in sample with inhibitor)]} - ________________________________________________________ _________________________ [(cpm of estradiol in sample without inhibitor)/[(cpm of estrone in sample without inhibitor) + (cpm of estradiol in sample no inhibitor)]}.

[00883] The percentage of inhibition was calculated fluidly: % inhibition = 100 - % conversion. % inhibition values were determined for exemplified compounds and the results are summarized in Table 2.

Metabolic Stability Assay

[00884] The in vitro metabolic stability of compounds of the invention was determined for exemplified compounds using human hepatocyte incubations. The study compouds were incubated 0, 10, 20, 40 and 60 min at 37 °C. Samples were collected at all time points and compounds were detected by LC-MS/MS analysis. The percentage of compound remaining is calculated by comparing the peak area of the parent compound at each time point to time zero. In vitro metabolic stability was determined as half-life (T1/2), which was determined by regression analysis of the percentage of disappearance origin versus time curve. The results are summarized in Table 2. RESULTS OF PHARMACOLOGICAL TESTS Table 2

UTILITY OF THE INVENTION

[00885] The compounds of the invention show selective inhibitory potential for the 17β-HSD1 enzyme and little or no inhibitory activity for the 17β-HSD2 enzyme and, therefore, may be useful for the treatment of a steroid hormone-dependent disease or disorder, in particular for the treatment and prevention of various diseases and conditions which include, but are not limited to, breast cancer, prostate carcinoma, ovarian cancer, uterine cancer, endometrial cancer, endometrial hyperplasia, endometriosis, uterine fibroids, adenomyosis, polycystic ovary syndrome, dysmenorrhea, menorrhagia, metrorrhagia, contraception, prostadynia, benign prostatic hyperplasia, urinary dysfunction, lower urinary tract symptoms, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), systemic lupus erythematosus (SLE), sclerosis multiple, obesity, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), lung cancer, colon cancer, tissue wounds, wrinkles and cataracts.

[00886] Furthermore, the compounds of the present invention may be useful for the treatment of diseases and disorders associated with increased levels of estradiol and which can be prevented, treated and/or improved by an inhibitor of the 17β-HSD1 enzyme.

[00887] "Treatment or prevention", when used herein, includes prophylaxis or prevention, as well as reducing the risk of the individual becoming ill with the named disorder or condition, or alleviating, improving, eliminating or curing said disorder once established.

[00888] The compounds of the present invention can be administered in an effective amount within the dosage range of about 0.1 μg/kg to about 300 mg/kg, preferably between 1.0 μg/kg to 10 mg/kg of body weight. The compounds of the present invention can be administered in a single daily dose, or the total daily dose can be administered in divided doses two, three or four times a day.

[00889] "An effective amount" refers to an amount of a compound that confers a therapeutic effect on the treated individual. The therapeutic effect can be objective (that is, measurable by some test or marker) or subjective (that is, the individual gives an indication or feels an effect). This treatment does not necessarily need to completely improve the condition of the disease. Furthermore, this treatment or prevention can be used in conjunction with other traditional treatments to reduce the condition known to those skilled in the art.

[00890] The compounds of the invention are more preferably used alone or in combination, that is, administered simultaneously, separately or sequentially with other active ingredients, for example, pharmaceutically active compounds or biological products. The amounts of the compound(s) of the invention, particularly a compound of Formula (I), (Ia) or (Ib), or pharmaceutically acceptable salts thereof, and the other active ingredient(s) (s) and relative times of administration will be selected to obtain the desired combined therapeutic effect. The compounds of the invention can be administered by various routines, for example, parenteral, subcutaneous, intravenous, intra-articular, intrathecal, intramuscular, intraperitoneal, topical and by intradermal injections, and by transdermal, rectal, buccal, oromucosal, nasal, ocular route. and via inhalation and via implant.

[00891] The compounds can be formulated into a suitable composition; Suitable forms of administration include, for example, solutions, dispersions, suspensions, powders, capsules, tablets, pills, controlled-release capsules, controlled-release tablets and controlled-release pills. In addition to the pharmacologically active compounds, the pharmaceutical compositions of the compounds may contain suitable pharmaceutically acceptable carriers comprising excipients and auxiliaries that facilitate the processing of the active compounds into preparations that can be used pharmaceutically.

[00892] Those skilled in the art have the knowledge and skill in the art to allow them to select suitable pharmaceutically acceptable excipients in appropriate amounts for use in the invention. Furthermore, there are a number of resources that are available to those skilled in the art that describe pharmaceutically acceptable excipients and may be useful in selecting suitable pharmaceutically acceptable excipients.

[00893] Suitable pharmaceutically acceptable excipients include, but are not limited to, the following types of excipients: diluents (e.g., starches, mannitol), fillers (e.g., lactose, microcrystalline cellulose or calcium hydrogen phosphate), binders (e.g., starch pregelatinized corn, polyvinylpyrrolidone or methylcellulose), additives (e.g. magnesium stearate, talc, silica), disintegrants (e.g. potato starch), lubricants (e.g. sodium lauryl sulfate), glidants (e.g. , fumed silica, talc, magnesium carbonate), granulating agents (e.g. water, ethanol), coating agents (e.g. hydroxypropyl methylcellulose, gelatin, waxes, shellac, plastics, plant fibers), wetting agents ( e.g. sorbitan monopalmitate, poloxamer 407), solvents (e.g. water), co-solvents (e.g. ethanol, propylene glycol), suspending agents (e.g. sorbitol, cellulose derivatives, hydrogenated edible fats), emulsifiers (e.g. , lecithin or acacia), sweeteners (e.g. sucrose), flavoring agents (e.g. cherry, lemon), flavor masking agents (e.g. vanilla, citrus), coloring agents (e.g. titanium oxide), anticaking agents (e.g. silicon dioxide), humectants (e.g. glycerin, sorbitol), chelating agents (e.g. EDTA salts, histidine, aspartic acid), plasticizers (e.g. tributyl citrate, diethyl phthalate), viscosity increasing agents (e.g. methylcellulose), antioxidants (e.g. ascorbic acid, cysteine), preservatives (e.g. methyl or propyl p-hydroxybenzoates, sorbic acid or ascorbic acid), stabilizers (e.g. polysorbate 20 and 80, poloxamer 407), surfactants (e.g. polyethylene glycol, polysorbate 80) and buffering agents (e.g. sodium and potassium phosphate buffers, citrate, acetate, carbonate or glycine depending on the targeted pH range). The person skilled in the art will appreciate that certain pharmaceutically acceptable excipients may serve more than one function and may serve alternative functions depending on how much of the excipient is present in the composition and what other ingredients are present in the composition.

[00894] The pharmaceutical compositions of the invention are prepared using techniques and methods known to those skilled in the art. The pharmaceutical compositions of the invention include, but are not limited to, parenteral and topical administration, which include, but are not limited to, sterile aqueous or non-aqueous solvents, suspensions and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oil, fish oil and injectable organic esters. Aqueous vehicles include, but are not limited to, water, water-alcohol solutions, including saline and buffered medial parenteral vehicles, including sodium chloride solution, Ringer's dextrose solution, dextrose plus sodium chloride solution, Ringer's containing lactose or fixed oils. Intravenous vehicles include, but are not limited to, fluid and nutrient replenishers, electrolyte replenishers such as those based on Ringer's dextrose and the like. Aqueous compositions according to the invention may comprise suitable buffering agents, such as sodium and potassium phosphates, citrate, acetate, carbonate or glycine buffers, depending on the desired pH range. The use of sodium chloride as a tonicity adjuster is also helpful. The compositions may include other excipients, such as stabilizing agents or preservatives. Useful stabilizing excipients include surfactants (polysorbate 20 and 80, poloxamer 407), polymers (polyethylene glycols, povidones), carbohydrates (sucrose, mannitol, glucose, lactose), alcohols (sorbitol, glycerol propylene glycol, ethylene glycol), suitable proteins (albumin), suitable amino acids (glycine, glutamic acid), fatty acids (ethanolamine), antioxidants (ascorbic acid, cysteine etc.), chelating agents (EDTA salts, histidine, aspartic acid) or metal ions (Ca, Ni, Mg, Mn). Useful preservatives include benzyl alcohol, chlorbutanol, benzalkonium chloride, and possibly parabens. The pharmaceutical composition according to the present invention can be supplied in concentrated form or in the form of a powder to be reconstituted on demand. In such cases, the injection/infusion excipient powder-to-solution formulations mentioned above may be used. In the case of freeze-drying, certain cryoprotectants are preferred, including polymers (povidones, polyethylene glycol, dextran), sugars (sucrose, glucose, lactose), amino acids (glycine, arginine, glutamic acid) and albumin. If the solution for reconstitution is added to the packaging, it may consist, for example, of pure water for injection or sodium chloride solution or dextrose or glucose solutions.

[00895] Furthermore, compounds of Formula (I) can be used as synthetic intermediates for the preparation of other compounds, in particular other pharmaceutically active ingredients, which are obtained from compounds of Formula (I), e.g. , by introducing substituents or modifying functional groups.

[00896] It will be obvious to a person skilled in the art that, as technology advances, the inventive concept can be implemented in a variety of ways. The invention and its embodiments are not limited to the examples described above, however, they may vary within the scope of the claims.

Claims (21)

1. Compound, characterized by the fact that it presents Formula (I), in which R1 and R2 are each independently selected from the group consisting of H and halogen; R3 is selected from the group consisting of H and C1-3-alkyl; and R4 is a 6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl)2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, or two adjacent substituents can form a saturated 5- or 6-membered fused ring; or a pharmaceutically acceptable salt thereof. 2. Compound, according to claim 1, characterized by the fact that it has Formula (Ia), in which R1 is selected from the group consisting of H and halogen; (1) R3 is selected from the group consisting of H and C1-3-alkyl; and R4 is a 6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl)2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, or two adjacent substituents can form a saturated 5- or 6-membered fused ring; or a pharmaceutically acceptable salt thereof. 3. Pharmaceutically acceptable compound or salt according to claim 2, characterized in that R1 is selected from the group consisting of H, F and Cl, preferably F and Cl. 4. Pharmaceutically acceptable compound or salt according to any one of claims 1 to 3, characterized in that R3 is H or methyl. 5. Pharmaceutically acceptable compound or salt according to claim 4, characterized by the fact that R3 is H. 6. Pharmaceutically acceptable compound or salt according to any one of claims 1 to 5, characterized in that R4 is selected from the group consisting of pyridinyl, fluoropyridinyl, cyanopyridinyl, methylpyridinyl, dimethylpyridinyl, isopropylpyridinyl, hydroxypyridinyl, methoxypyridinyl, morpholinopyridinyl, methylpiperazinylpyridinyl, pyrazinyl, methylpyridazinyl, and methoxypyridazinyl; in particular from the group consisting of fluoropyridinyl, methoxypyridinyl, methylpyridazinyl, and methoxypyridazinyl. 7. Compound, according to claim 1, characterized by the fact that it has Formula (Ib), in which R1 is selected from the group consisting of H and halogen; and R4 is a 6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl)2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, or two adjacent substituents can form a saturated 5- or 6-membered fused ring; or a pharmaceutically acceptable salt thereof. 8. Pharmaceutically acceptable compound or salt according to claim 7, characterized in that R4 is a 6-membered aromatic heterocycle of Formula (A), in which X is CR9 or N; one of R6, R7, R8 is H, and the others are independently selected from the group consisting of H, halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, C1-3- alkoxy, and morpholine ring; and R9 is H or C1-3-alkyl. 9. Compound according to claim 1, characterized by the fact that it is selected from the group consisting of: 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyamino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(pyridazine-3-yl)propanamide; 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide; 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide; 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide; 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide; 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide; 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(pyridazine-3-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(3-methylpyridin-2-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-cyanopyridin-2-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide; 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(pyridazin-3-yl)propanamide; 3-((13S,15R,E)-17-(hydroxyamino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide; 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide; 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide; 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide; 6-(3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide; 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide; 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide; N-(5-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16 ,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; N-(5-cyanopyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16 ,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(3-hydroxypyridin-2-yl)propanamide; 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide; 3-((13S,15R,E)-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide; N-(3,5-difluoropyridin-2-yl)-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13 ,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; N-(5-cyanopyridin-2-yl)-3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14 ,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide; N-(3,5-difluoropyridin-2-yl)-3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13 ,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; 3-((13S,15R,E)-3-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide; N-(4-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16 ,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; N-(3-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16 ,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(3,5-difluoropyridin-2-yl)propanamide; N-(3,5-difluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)- 13-methyl-7,8,9,11,12,13,14,15 ,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; N-(6-fluoropyridin-2-yl)-3-((13S,15R,E)-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16 ,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide; 6-(3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide; 3-((13S,15R,E)-3-chloro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide; 6-(3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-deca- hydro-6H-cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide; or a pharmaceutically acceptable salt thereof. 10. Compound according to claim 9, characterized by the fact that it is selected from the group consisting of: 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide; 3-((13S,15R,E)-4-fluoro-17-(hydroxyimino)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H -cyclopenta[a]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide; or a pharmaceutically acceptable salt thereof. 11. Compound, characterized by the fact that it presents Formula (II), in which R1 and R2 are each independently selected from the group consisting of H and halogen; R3 is selected from the group consisting of H and C1-3-alkyl; and R4 is a 6-membered unsaturated or aromatic heterocycle comprising 1 nitrogen atom and optionally 1 to 2 other heteroatom(s) independently selected from the group consisting of nitrogen, sulfur and oxygen, and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, oxo, C1-3-alkoxy, C(O)N(C1-3-alkyl)2, and 6-membered saturated heterocycle comprising 1 to 2 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur and is optionally substituted with one or two substituent(s) independently selected from the group consisting of halogen, CN, C1-3-alkyl, C1-3-(per)haloalkyl, OH, and C1-3-alkoxy, or two Adjacent substituents can form a saturated 5- or 6-membered fused ring. 12. Compound according to claim 11, characterized by the fact that R1 and R2 are each independently selected from the group consisting of H and halogen, preferably F and Cl. 13. Compound according to claim 11 or 12, characterized by the fact that R3 is H or methyl. 14. Compound according to any one of claims 11 to 13, characterized in that R4 is selected from the group consisting of pyridinyl, fluoropyridinyl, cyanopyridinyl, methylpyridinyl, dimethylpyridinyl, isopropylpyridinyl, hydroxypyridinyl, methoxypyridinyl, morpholinopyridinyl, methylpiperazinylpyridinyl, pyrazinyl, methylpyridazinyl, and methoxypyridazinyl; in particular from the group consisting of fluoropyridinyl, methoxypyridinyl, methylpyridazinyl, and methoxypyridazinyl. 15. Compound according to claim 11, characterized in that it is selected from the group consisting of: 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8 ,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(6-methoxypyridazin-3-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(5-methoxypyridin-2-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(5-fluoropyridin-2-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(6-methylpyridazin-3-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(5-isopropylpyridin-2-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(pyrazin-2-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(4-methylpyridin-2-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(4-methoxypyridin-2-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(pyridin-2-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide; 3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide; N-(3,5-difluoropyridin-2-yl)-3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15 ,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; N-(5-cyanopyridin-2-yl)-3-((13S,15R)-4-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16 ,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide; N-(3,5-difluoropyridin-2-yl)-3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15 ,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; 3-((13S,15R)-3-fluoro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(5-morpholinopyridin-2-yl)propanamide; 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(4-fluoropyridin-2-yl)propanamide; N-(4-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-deca -hydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; N-(3-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-deca -hydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(3-fluoropyridin-2-yl)propanamide; 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(3,5-difluoropyridin-2-yl)propanamide; N-(3,5-difluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17 -decahydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; N-(6-fluoropyridin-2-yl)-3-((13S,15R)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-deca -hydro-6H-cyclopenta[a]phenanthren-15-yl)propanamide; 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(6-fluoropyridin-2-yl)propanamide; 6-(3-((13S,15R)-3-chloro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide; 3-((13S,15R)-3-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a ]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin-3-yl)propanamide; 6-(3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H- cyclopenta[a]phenanthren-15-yl)propanamido)-N,N-dimethylnicotinamide, and 3-((13S,15R)-4-fluoro-13-methyl-17-oxo- 7,8,9,11,12 ,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(2-oxo-1,2,5,6,7,8-hexahydroquinolin -3-yl)propanamide. 16. Compound according to any one of claims 1 to 10, characterized by the fact that it is for use as a medicine. 17. Use of a compound as defined in any one of claims 1 to 10, characterized in that it is for preparing a medicament for treating or preventing a disease selected from a group consisting of breast cancer, carcinoma prostate cancer, ovarian cancer, uterine cancer, endometrial cancer, endometrial hyperplasia, endometriosis, uterine fibroids, adenomyosis, polycystic ovary syndrome, dysmenorrhea, menorrhagia, metrorrhagia, contraception, prostadinia, benign prostatic hyperplasia, urinary dysfunction, lower urinary tract symptoms , chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), systemic lupus erythematosus (SLE), multiple sclerosis, obesity, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), lung cancer, colon cancer, tissue wounds, skin wrinkles and cataracts. 18. Use of a compound as defined in any one of claims 1 to 10, characterized in that it is for preparing a medicament for treating a disease selected from a group consisting of breast cancer, prostate carcinoma , ovarian cancer, uterine cancer, endometrial cancer, endometrial hyperplasia, endometriosis, uterine fibroids, adenomyosis, polycystic ovary syndrome, dysmenorrhea, menorrhagia, metrorrhagia, contraception, prostadinia, benign prostatic hyperplasia, urinary dysfunction, lower urinary tract symptoms, prostatitis chronic/chronic pelvic pain syndrome (CP/CPPS), systemic lupus erythematosus (SLE), multiple sclerosis, obesity, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), lung cancer, colon cancer, tissue wounds, skin wrinkles skin and cataracts. 19. Pharmaceutical composition, characterized by the fact that it comprises an effective amount of one or more compounds, as defined in any one of claims 1 to 10, together with one or more pharmaceutically acceptable excipient(s). 20. Pharmaceutical composition according to claim 19, characterized by the fact that it comprises one or more compounds, as defined in any one of claims 1 to 10, in combination with one or more other active ingredients. 21. Method for preparing a compound of Formula (I), as defined in any one of claims 1 to 10, characterized in that it comprises the steps of: reacting a compound of Formula (III), in which R1 and R2 are each independently selected from the group consisting of H and halogen; with the compound of Formula (IV), NR3R4 (IV), in which R3 and R4 are as defined for the compound of Formula (I), in the presence of amide bond-forming reagents, in particular T3P and a base, preferably pyridine , to obtain a compound of Formula (II), and react the compound obtained with NH2-OH (V) or hydrogen halide thereof, in the presence of a base, preferably pyridine, to obtain a compound of Formula (I); and optionally converting the compound of Formula (I) to a pharmaceutically acceptable salt thereof.