KR20220164216A - Novel ergostenol derivatives, and uses thereof - Google Patents

Abstract

The present invention relates to a compound having therapeutic activity for general inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. An ergostenol or cholestenol derivative compound according to the present invention exhibits excellent anti-inflammatory and colitis-alleviating effects, and thus has an excellent therapeutic effect on inflammatory bowel diseases.

Description

Novel ergostenol derivatives and uses thereof {Novel ergostenol derivatives, and uses thereof}

The present invention relates to a compound having therapeutic activity for overall inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. Furthermore, the present invention relates to a synthetic low-molecular compound having an inhibitory activity on cell adhesion molecules induced by TNF-α/IFN-γ.

Collective inflammatory bowel diseases (referred to as IBD), such as Crohn's disease or ulcerative colitis, are chronic, inflammatory diseases of the gastrointestinal tract. Although the clinical features differ somewhat between these two diseases, both are associated with abdominal pain, diarrhea (sometimes bloody), and a distinct variable cluster of 'extra-intestinal' symptoms (e.g., arthritis, uveitis, skin changes, etc.). ), and accumulation of inflammatory cells in the small intestine and colon (found on pathological examination or surgical specimens). IBD affects both children and adults, and has a bimodal age distribution (one peaks around 20 years old and the other peaks around 40 years old). IBD is a chronic, lifelong disease, often present in association with other so-called "autoimmune" diseases (eg, rheumatoid arthritis, type I diabetes, multiple sclerosis, etc.).

Cell adhesion molecules are overexpressed in intestinal epithelial cells of patients suffering from inflammatory bowel disease. In particular, it has been reported that Madcam is overexpressed in the intestinal mucosa of patients with enteropathic disease and the lamina propria of Crohn's disease patients. Therefore, attempts to use antagonists of cell adhesion molecules such as Madcam as therapeutic agents are increasing (Schreiner et al. 2019. Inflamm Intest Dis 4 (3):79-96).

For the treatment of inflammatory bowel disease, 5-aminosalicylic acid (5-ASA) is used as an existing anti-inflammatory agent. However, 5-ASA itself has problems of poor absorption in the intestine when administered orally and side effects when administered for a long time (Pithadia AB et al., 2011. Pharmacol Rep 63(3): 629-642).

As such, unmet needs for novel compounds for the treatment of inflammatory bowel disease, which are non-toxic and can exhibit anti-inflammatory effects in the large intestine, are increasing.

Schreiner et al. 2019. Inflamm Intest Dis 4 (3):79-96 Pithadia AB et al., 2011. Pharmacol Rep 63(3): 629-642

An object of the present invention is to provide an ergostenol derivative compound having a novel structure, or a pharmaceutically acceptable salt thereof.

Another object of the present invention is to provide a method for preparing the ergostenol derivative compound.

Another object of the present invention is to provide a pharmaceutical use of the ergostenol derivative compound, specifically, a pharmaceutical composition for treating or preventing inflammatory bowel disease comprising the ergostenol derivative compound as an active ingredient, and the compound It is to provide a method for treating or preventing inflammatory bowel disease, including the use of the treatment or prevention of inflammatory bowel disease, or administering the compound.

In order to achieve the above object, the present inventors have completed the present invention by confirming the therapeutic effect of ergostenol derivative compounds represented by Formula 1 mentioned below as a result of research efforts by the present inventors on inflammatory bowel disease.

Ergostenol Derivative Compounds

The present invention provides a compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof:

[Formula 1]

R ₁ is -H or -C _1-6 alkyl;

R ₂ is -OR ₃ , -NR ₄ R ₅ , heterocycloalkyl containing one or more N, or heteroaryl containing one or more N, {wherein the heterocycloalkyl and heteroaryl are adjacent to one N is directly connected to the quadruple ring, and at least one H of the heterocycloalkyl is -C _1-6 alkyl, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, =O, -NH ₂ , or -OH, wherein the heteroaryl is -C _1-6 alkyl, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -C _1-6 alkyl-OC(=O)R ₆ , -C(=0)R ₇ , or -NH ₂ , or -OH};

, 또는

이고 {여기서, -C(=O)-아릴의 하나 이상의 H는 -NH₂ 또는 -OH로 치환될 수 있음};R ₃ is -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -C(=O)-(C _1-6 hydroxyalkyl), -C(=O)-(C _1-6 alkyl )-C(=O)OH, -C(=O)-aryl,

, or

and {wherein one or more H of the -C(=O)-aryl may be substituted with -NH ₂ or -OH};

, 또는

이고 {여기서, -C(=O)-아릴의 하나 이상의 H는 -NH₂ 또는 -OH로 치환될 수 있고, R₄ 및 R₅는 동시에 -H일 수 없음};R ₄ and R ₅ are each independently -H, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -C(=O)-(C _1-6 hydroxyalkyl), -C(= O)-(C _1-6 alkyl)-C(=O)OH, -C(=O)-aryl,

, or

and {wherein one or more H of -C(=O)-aryl may be substituted with -NH ₂ or -OH, and R ₄ and R ₅ cannot be -H at the same time};

L ₁ and L ₂ are each independently -(CH ₂ )n- or -C(=0)-;

n is 0, 1, 2, 3, or 4;

A ₁ and A ₂ are each independently a heteroaryl containing one or more N or nothing (null) {wherein, the heteroaryl is one in which one N is directly connected to an adjacent ring};

R ^A is -H or -CH ₂ OH;

R ₆ is -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, or -OH;

R ₇ is -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -NH-(C _1-6 alkyl)-C(=O)OH, -O-(C _1-6 alkyl)-C (=O)OH, or -OH.

According to an embodiment of the present invention, the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof may be in the following range:

R ₁ is -H or -C _1-6 alkyl;

R ₂ is -OR ₃ , -NR ₄ R ₅ , heterocycloalkyl containing one or more N, or heteroaryl containing one or more N, {wherein the heterocycloalkyl and heteroaryl are adjacent to one N is directly connected to the quadruple ring, and at least one H of the heterocycloalkyl is -C _1-6 alkyl, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, =O, -NH ₂ , or -OH, wherein the heteroaryl is -C _1-6 alkyl, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -C _1-6 alkyl-OC(=O)R ₆ , -C(=0)R ₇ , or -NH ₂ , or -OH};

, 또는

이고 {여기서, -C(=O)-아릴의 하나 이상의 H는 -NH₂ 또는 -OH로 치환될 수 있음};R ₃ is -C(=O)-(C _1-6 hydroxyalkyl);

, or

and {wherein one or more H of the -C(=O)-aryl may be substituted with -NH ₂ or -OH};

, 또는

이고 {여기서, -C(=O)-아릴의 하나 이상의 H는 -OH로 치환될 수 있고, R₄ 및 R₅는 동시에 -H일 수 없음};R ₄ and R ₅ are each independently -H, -C _1-6 hydroxyalkyl, -C(=O)-(C _1-6 hydroxyalkyl), -C(=O)-(C _1-6 Alkyl)-C(=O)OH, -C(=O)-aryl,

, or

and {wherein one or more H of -C(=O)-aryl may be substituted with -OH, and R ₄ and R ₅ cannot simultaneously be -H};

L ₁ and L ₂ are each independently -(CH ₂ )n- or -C(=0)-;

n is 0 or 1;

A ₁ and A ₂ are each independently a heteroaryl containing one or more N or nothing (null) {wherein, the heteroaryl is one in which one N is directly connected to an adjacent ring};

R ^A is -H or -CH ₂ OH;

R ₆ is -C _1-6 hydroxyalkyl;

R ₇ is -NH-(C _1-6 alkyl)-C(=O)OH or -OH.

In addition, according to an embodiment of the present invention, the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof may be in the following range:

R ₁ is -H or -C _1-6 alkyl;

R ₂ is -OR ₃ ;

, 또는

이고;R ₃ is -C(=O)-(C _1-6 hydroxyalkyl);

, or

ego;

L ₁ and L ₂ are each independently -(CH ₂ )n- or -C(=0)-;

n is 0, 1, 2, 3, or 4;

A ₁ and A ₂ are each independently a heteroaryl containing one or more N or nothing (null) {wherein, the heteroaryl is one in which one N is directly connected to an adjacent ring};

R ^A is -H or -CH ₂ OH.

In addition, according to an embodiment of the present invention, the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof may be in the following range:

R ₁ is -H or -C _1-6 alkyl;

R ₂ is —NR ₄ R ₅ , a heterocycloalkyl containing one or more N, or a heteroaryl containing one or more N, {wherein the heterocycloalkyl and heteroaryl are in a quadruple ring where one N is adjacent. is directly connected, and at least one H of the heterocycloalkyl is substituted with -C _1-6 alkyl, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, =O, -NH ₂ , or -OH and the heteroaryl is -C _1-6 alkyl, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -C _1-6 alkyl-OC(=O)R ₆ , -C( =O)R ₇ , or -NH ₂ , or -OH};

, 또는

이고 {여기서, -C(=O)-아릴의 하나 이상의 H는 -NH₂ 또는 -OH로 치환될 수 있고, R₄ 및 R₅는 동시에 -H일 수 없음};R ₄ and R ₅ are each independently -H, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -C(=O)-(C _1-6 hydroxyalkyl), -C(= O)-(C _1-6 alkyl)-C(=O)OH, -C(=O)-aryl,

, or

and {wherein one or more H of -C(=O)-aryl may be substituted with -NH ₂ or -OH, and R ₄ and R ₅ cannot be -H at the same time};

L ₁ and L ₂ are each independently -(CH ₂ )n- or -C(=0)-;

n is 0, 1, 2, 3, or 4;

A ₁ and A ₂ are each independently a heteroaryl containing one or more N or nothing (null) {wherein, the heteroaryl is one in which one N is directly connected to an adjacent ring};

R ^A is -H or -CH ₂ OH;

R ₆ is -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, or -OH;

R ₇ is -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -NH-(C _1-6 alkyl)-C(=O)OH, -O-(C _1-6 alkyl)-C (=O)OH, or -OH.

In the present invention, "alkyl" may mean a straight-chain or branched-chain acyclic, cyclic, or saturated hydrocarbon in which they are bonded, unless otherwise specified. For example, "C _1-6 alkyl" may mean an alkyl containing 1 to 6 carbon atoms. Non-cyclic alkyl may include, for example, methyl, ethyl, n -propyl, n -butyl, isopropyl, sec -butyl, isobutyl, or tert -butyl, etc. Not limited to this. Cyclic alkyl may be used interchangeably with "cycloalkyl" herein, and may include, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl, as examples. It doesn't work.

In the present invention, "alkoxy" can mean -(O-alkyl) as an alkyl ether group, where alkyl is as defined above. For example, "C _1-6 alkoxy" may mean C _1-6 alkyl-containing alkoxy, that is, -(OC _1-6 alkyl), and as an example, alkoxy is methoxy. ), ethoxy, n -propoxy, isopropoxy, n - butoxy , isobutoxy , sec - butoxy ), or tert -butoxy ( tert -butoxy), etc., but is not limited thereto.

In the present invention, "halo" can be F, Cl, Br, or I.

For purposes of this invention, "haloalkyl" can mean a straight or branched chain alkyl (hydrocarbon) having carbon atoms substituted with one or more halo as defined herein. Examples of such haloalkyl include, but are not limited to, methyl, ethyl, propyl, isopropyl, isobutyl or n -butyl independently substituted with one or more halogens such as F, Cl, Br, or I .

As used herein, "hydroxyalkyl" may refer to a straight-chain or branched-chain alkyl (hydrocarbon) having a carbon atom substituted with hydroxy (OH).

As used herein, "aminoalkyl" may refer to a straight or branched chain alkyl (hydrocarbon) having a carbon atom substituted with amino (NR'R"), wherein R' and R" are each independently hydrogen; And it may be selected from the group consisting of C _1-6 alkyl, and the selected R' and R" may each independently be substituted or unsubstituted.

As used herein, “cyanoalkyl” may refer to a straight or branched chain alkyl (hydrocarbon) having carbon atoms substituted with cyano (CN).

In the present invention, "heterocycloalkyl" may mean a ring containing at least one selected from N, O, P, P(=O), and S in the ring, and may be saturated or partially unsaturated. Here, when unsaturated, it may be referred to as a heterocycloalkene. Unless otherwise stated, a heterocycloalkyl can be a single ring or multiple rings such as spiro rings, bridged rings or fused rings. In addition, "3 to 12 membered heterocycloalkyl" may mean a heterocycloalkyl containing 3 to 12 atoms forming a ring, and as an example, heterocycloalkyl is pyrrolidine, piperidine, Imidazolidine, pyrazolidine, butyrolactam, valerolactam, imidazolidinone, hydantoin, dioxolane, phthalimide, piperidine, pyrimidine-2,4 (1 H ,3 H ) -Dione, 1,4-dioxane, morpholine, thiomorpholine, thiomorpholine- S -oxide, thiomorpholine- S , S -oxide, piperazine, pyran, pyridone, 3-pyrroline , thiopyran, pyrone, tetrahydrofuran, tetrahydrothiophene, quinuclidine, tropane, 2-azaspiro[3.3]heptane, ( 1R , 5S )-3-azabicyclo[3.2.1 ]octane, ( 1s , 4s )-2- azabicyclo [2.2.2]octane, or (1R, 4R )-2-oxa-5-azabicyclo[2.2.2]octane, etc. It can be done, but is not limited thereto.

In the present invention, "arene" may mean an aromatic hydrocarbon ring. Arenes can be monocyclic arenes or polycyclic arenes. The number of ring carbon atoms of the arene may be 5 or more and 30 or less, 5 or more and 20 or less, or 5 or more and 15 or less. Examples of arenes include benzene, naphthalene, fluorene, anthracene, phenanthrene, bibenzene, terbenzene, quarterbenzene, quinquebenzene, sexybenzene, triphenylene, pyrene, benzofluoranthene, chrysene, etc. , but not limited to these. In the present specification, a residue obtained by removing one hydrogen atom from the above "arene" is referred to as "aryl".

In the present invention, "heteroarene" may be a ring containing one or more of O, N, P, Si, and S as heterogeneous elements. The number of ring carbon atoms of the heteroarene may be 2 or more and 30 or less, or 2 or more and 20 or less. The hetero arene may be a monocyclic hetero arene or a polycyclic hetero arene. Polycyclic heteroarenes may have, for example, a bicyclic or tricyclic structure. Examples of heteroarenes include thiophene, purine, pyrrole, pyrazole, imidazole, thiazole, oxazole, isothiazole, oxadiazole, triazole, pyridine, bipyridyl, triazine, acridyl, pyridazine , pyrazine, quinoline, quinazoline, quinoxaline, phenoxazine, phthalazine, pyrimidine, pyrido pyrimidine, pyrido pyrazine, pyrazino pyrazine, isoquinoline, indole, carbazole, imidazopyridazine, imidazopyridine , imidazopyrimidine, pyrazolopyrimidine, imidazopyrazine or pyrazolopyridine, N -arylcarbazole, N -heteroarylcarbazole, N -alkylcarbazole, benzooxazole, benzoimidazole, benzothiazole , benzocarbazole, benzothiophene, dibenzothiophene, thienothiophene, benzofuran, phenanthroline, isoxazole, oxadiazole, thiadiazole, benzothiazole, tetrazole, phenothiazine , dibenzosilol and dibenzofuran, but are not limited thereto. In one embodiment of the present invention, the heteroarene may also include a bicyclic heterocyclo-arene including an arene ring fused to a heterocycloalkyl ring or a heteroarene fused to a cycloalkyl ring. In the present specification, a residue obtained by removing one hydrogen atom from the "heteroarene" is referred to as "heteroaryl".

또는 쐐기형 점선 결합

을 포함할 수 있다.In the present invention, the term "enantiomer" means a compound of the present invention or a salt thereof having the same chemical formula or molecular formula but sterically different. Each of these optical isomers and mixtures thereof are also included in the scope of the present invention. Unless otherwise specified, the solid bond (-) connecting an asymmetric carbon atom is a wedge-shaped solid bond representing the absolute configuration of the stereogenic center.

or Wedge Dotted Combination

can include

The compound of Formula 1 of the present invention may exist in the form of a "pharmaceutically acceptable salt". As the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. The term "pharmaceutically acceptable salt" of the present invention is a concentration that has a relatively non-toxic and harmless effective effect on patients, and any of the compounds represented by Formula 1 do not reduce the beneficial effects of the compound represented by Formula 1 by side effects caused by the salt. means any organic acid or inorganic acid addition salt of

Acid addition salts are prepared by conventional methods, for example, by dissolving a compound in an excess aqueous acid solution and precipitating the salt using a water-miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. Equimolar amounts of the compound and acid or alcohol in water may be heated, and then the mixture may be evaporated to dryness, or the precipitated salt may be suction filtered.

At this time, organic acids and inorganic acids may be used as the free acid, hydrochloric acid, phosphoric acid, sulfuric acid, or nitric acid may be used as the inorganic acid, and methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, Maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, glue Conic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, or hydroiodic acid, etc. can be used. However, it is not limited to these.

In addition, a pharmaceutically acceptable metal salt may be prepared using a base. The alkali metal salt or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. At this time, as the metal salt, it is particularly suitable for preparing a sodium, potassium, or calcium salt, but is not limited thereto. In addition, the corresponding silver salt can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).

Pharmaceutically acceptable salts of the present invention, unless otherwise indicated, include salts of acidic or basic groups that may be present in the compounds of Formula 1 above. For example, pharmaceutically acceptable salts may include sodium, calcium and potassium salts of a hydroxyl group, and other pharmaceutically acceptable salts of an amino group include hydrobromides, sulfates, hydrogen sulfates, phosphates, hydrogen phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate), and p-toluenesulfonate (tosylate) salts; It can be prepared through a method for preparing a salt known to.

Uses of Ergostenol Derivative Compounds

The present invention provides a use of a compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof.

Formula 1 is as defined above.

Cell adhesion molecules (CAMs) play a role in the process of extravasation, and are known to be involved in mucosal immune homeostasis by being involved in the extravasation of leukocytes from the blood. In particular, CAM is known to be overexpressed in patients with inflammatory bowl disease (IBD), and accordingly, various types of CAM are attracting attention as potential treatment targets for IBD (J. clin Gastroenterol. 2017, 51 (6): 522-527). Since the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof of the present invention exhibits excellent inhibitory activity against cell adhesion molecules such as VCAM-1, E-selectin, and MadCAM, it is mediated by overexpression of cell adhesion molecules. It can be usefully used for the treatment or prevention of inflammatory bowel disease. In particular, the ergostenol derivative compound of the present invention is a material synthesized using phytosterol derived from natural products as a mother core, and has the advantage of being non-toxic and reducing side effects even with long-term administration.

The term of the present invention, "inflammatory bowel disease" includes all diseases of the intestine associated with an inflammatory reaction, and may be caused by, for example, an inflammatory reaction, but is not limited thereto. Specifically, the inflammatory bowel disease may be selected from enteritis, ulcerative colitis, Crohn's disease, intestinal Bechet's disease, hemorrhagic rectal ulcer, and ileum, but is not limited thereto. don't The inflammatory bowel disease may be accompanied by symptoms such as increased expression of inflammatory cytokines, weight loss, decreased colon length, abdominal pain, fever, diarrhea, hemorrhage, and the like, and in particular, cell adhesion molecules may be overexpressed, but is not limited thereto. .

The pharmaceutical composition of the present invention may further include at least one active ingredient exhibiting the same or similar efficacy in addition to the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof.

In addition, according to one embodiment of the present invention, inflammatory bowel disease comprising the step of administering a therapeutically effective amount of the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof to a subject in need thereof. A method for treating or preventing a disease is provided. The subject may be a mammal including a human.

The term "therapeutically effective amount" used in the present invention refers to an amount of the compound represented by Formula 1 effective for the treatment or prevention of inflammatory bowel disease. Specifically, "therapeutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type and severity of the subject, age, sex, type of disease, It may be determined according to the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of excretion, the duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, or may be administered sequentially or simultaneously with a commercially available therapeutic agent. And it can be single or multiple administrations. It is important to administer the amount that can obtain the maximum effect with the minimum amount without side effects in consideration of all the above factors, and can be easily determined by those skilled in the art. The dosage of the pharmaceutical composition of the present invention may be determined by an expert according to various factors such as the patient's condition, age, sex, and complications. Since the active ingredient of the pharmaceutical composition of the present invention is excellent in safety, it can be used even at a dose determined or higher.

In addition, according to one embodiment of the present invention, the present invention is a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for use in the treatment or prevention of inflammatory bowel disease. provide a use. The compound represented by Formula 1 for the preparation of a drug may be mixed with an acceptable adjuvant, diluent, carrier, etc., and may be prepared as a combined preparation with other active agents to have a synergistic action of the active ingredients.

Matters mentioned in the use, composition, and treatment method of the present invention are equally applied unless contradictory to each other.

Embodiments of the present invention may be modified in various other forms, and the scope of the present invention is not limited to the embodiments described below. In addition, embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art. Furthermore, "include" a certain component throughout the specification means that other components may be further included without excluding other components unless otherwise stated.

The ergostenol derivative compound or a pharmaceutically acceptable salt thereof according to the present invention has excellent anti-inflammatory and colitis-improving effects, and thus has excellent therapeutic effects on inflammatory bowel disease. In addition, the compound of the present invention or a pharmaceutically acceptable salt thereof is a material synthesized using phytosterol derived from natural products as a mother core, and has the advantage of being non-toxic and reducing side effects even with long-term administration. Therefore, the compound of the present invention or a pharmaceutically acceptable salt thereof can be usefully used for the treatment, improvement and/or prevention of inflammatory bowel disease.

Hereinafter, the present invention will be described in more detail through examples and experimental examples. However, these Examples and Experimental Examples are only for illustrating the present invention, and the scope of the present invention is not limited by these Examples and Experimental Examples.

Preparation Example 1: (3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4 Preparation of 5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-amine

Step 1: (3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4, Preparation of 5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl benzoate

Ergostenol (Δ ⁸⁽¹⁴⁾ -Ergostenol, 2.0 g) and triphenylphosphine (Triphenylphosphine, 3.1 g) was dissolved in 20 mL of tetrahydrofuran. After slowly adding diisopropyl azodicarboxylate (2.6 mL) dropwise at 0 °C, benzoic acid (1.5 g) was added thereto and stirred at room temperature for 4 hours. After completion of the reaction, the concentrate was concentrated under reduced pressure and purified by column chromatography to obtain the title compound as a white solid. (Yield = 100%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.73 (s, 3H), 0.77-0.80 (m, 6H), 0.85-0.87 (m, 6H), 0.94 (d, J = 6.4 Hz, 3H), 5.30 (br s, 1H), 7.45 (t, J = 7.7 Hz, 2H), 7.56 (t, J = 7.1 Hz, 1H), 8.07 (d, J = 7.1 Hz, 2H)

Step 2: (3R,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4,5, Preparation of 6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol

Compound obtained in step 1 (0.50 g) was dissolved in 49.5 mL of dichloromethane, and 4.37 M sodium methoxide in MeOH (4.37 M, 1.1 mL) was added dropwise, followed by stirring at room temperature for 2 hours. After the reaction was completed, it was neutralized with 1 M hydrochloric acid, extracted three times with dichloromethane, washed with saturated sodium bicarbonate and brine, dehydrated with anhydrous sodium sulfate, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give the title compound as a white solid. (Yield = 96.0%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.66 (s, 3H), 0.77-078 (m, 6H), 0.85 (d, J = 7.7 Hz, 6H), 0.93 (d, J = 6.6 Hz, 3H), 4.07 (br s, 1H)

Step 3: (3R,5S,9R,10S,13R,17R)-3-azido-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2 Preparation of 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene

Compound obtained in step 2 (0.60 g) and triphenylphosphine (Triphenylphosphine, 0.79 g) was maintained in a vacuum state for 20 minutes, filled with argon gas, and then dissolved in 6.0 mL of anhydrous tetrahydrofuran. After slowly adding diisopropyl azodicarboxylate (0.59 mL) dropwise at 0 ° C., diphenyl phosphoryl azide (0.39 mL) was added dropwise, followed by stirring at room temperature for 1 hour. After the reaction was completed, the mixture was filtered and concentrated under reduced pressure. The concentrate was purified by column chromatography to give the title compound as a white solid. (Yield = 82.4%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.69 (s, 3H), 0.78 (d, J = 6.8 Hz, 6H), 0.85 (d, J = 7.9 Hz, 6H), 0.93 (d , J = 6.6 Hz, 3H), 3.29 (m, 1H)

Step 4: (3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4, Preparation of 5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-amine

The compound (0.55 g) obtained in step 3 was dissolved in 11.9 mL of tetrahydrofuran, and 1 M lithium aluminum hydride in THF 1.0 M, 14.3 mL was slowly added dropwise at 0 ° C. The mixture was stirred at room temperature for 20 minutes. After the reaction was completed, 0.07 mL of water was slowly added dropwise at 0 ° C. After 10 minutes, 15 wt% of sodium hydroxide (15 wt%, 1.0 mL) was slowly added dropwise. After 10 minutes, water (0.07 mL) was slowly added dropwise and reacted for 1 hour, followed by dehydration with anhydrous sodium sulfate and concentration under reduced pressure to obtain the title compound as a white solid. (Yield = 100%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.62 (s, 3H), 0.77-079 (m, 6H), 0.85 (d, J = 8.6 Hz, 6H), 0.93 (d, J = 6.4Hz, 3H), 2.68 (br s, 1H)

Preparation Example 2: (3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4 Preparation of 5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-amine

Step 1: (3R,5S,9R,10S,13R,17R)-3-azido-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2 Preparation of 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene

Ergostenol (Δ ⁸⁽¹⁴⁾ -Ergostenol, 1.0 g), triphenylphosphine (Triphenylphosphine, 1.3 g) and azodicarboxylate (Diisopropyl azodicarboxylate, 0.98 mL) were reacted in the same manner as in step 3 of Preparation Example 1 to obtain the title compound as a white solid. (Yield = 86.1%)

¹ H NMR (300 MHz, Chloroform- d ) δ (ppm): 0.67 (s, 3H), 0.78 (d, J = 6.6 Hz, 6H), 0.85 (m, 6H), 0.93 (d, J = 6.6 Hz) , 3H), 3.91 (br s, 1H)

Step 2: (3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4, Preparation of 5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-amine

Compound obtained in step 1 (2.0 g) was reacted in the same manner as in Step 4 of Preparation Example 1 to obtain the title compound as a white solid. (Yield = 100%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.66 (s, 3H), 0.77-0.81 (m, 6H), 0.85 (d, J = 7.9 Hz, 6H), 0.93 (dd, J = 6.6, 2.0 Hz, 3H), 3.19 (br s, 1H)

Preparation Example 3: (3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,5,6 Preparation of 7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol

7-dehydrocholesterol (2.0 g) in methylene chloride (Methylene chloride, 52 mL) and methanol (Methanol, 104 mL) were dissolved, palladium/carbon 10 wt% (Pd/C 10 wt%, 0.40 g) was added, hydrogen gas was injected, and the mixture was stirred for 3 hours under hydrogen gas. After the reaction was completed, the filtrate was concentrated under reduced pressure after filtering through Celite. The concentrate was purified by column chromatography to obtain the title compound (Δ ⁸⁽¹⁴⁾ -Cholestenol) as a white solid. (Yield = 85.0 %)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.69 (s, 3H), 0.84 (s, 3H), 0.86 (d, J = 6.6 Hz, 6H), 0.92 (d, J = 6.6 Hz) , 3H), 3.62 (br s, 1H)

Example 1: (2R,3R,4S,5S,6R)-2-(4-((((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6 -Dimethylheptan-2-yl)-10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclo penta[a]phenanthren-3-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4; Preparation of 5-Triol

Step 1: (3S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-3-(prop-2- phosphon-1-yloxy)-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene Produce

Ergostenol (Δ ⁸⁽¹⁴⁾ -Ergostenol, 0.36 g) was diluted in 5.6 mL of toluene, and potassium tert-butoxide (0.30 g) was added thereto, followed by stirring at room temperature for 3 hours. Thereafter, 80% 3-bromo-1-propyne (Propargyl bromide 80% in toluene, 0.27 mL) was added and stirred at room temperature for 48 hours. After completion of the reaction, ethyl acetate:hexane was diluted 1:3, purified water was added to terminate the reaction, and the mixture was extracted with ethyl acetate three times. The organic layer was washed with brine, dehydrated over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give the title compound as a white solid. (Yield = 46.7%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.68 (s, 3H), 0.78 (d, J = 6.8 Hz, 6H), 0.83–0.86 (m, 6H), 0.93 (d, J = 6.4 Hz, 3H), 2.40 (t, J = 2.4 Hz, 1H), 3.47-3.50 (m, 1H), 4.19 (d, J = 2.2 Hz, 2H)

Step 2: (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(4-((((3S,9R,10S,13R,17R)-17-((2R,5S )-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradeca Hydro-1H-cyclopenta[a]phenanthren-3-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-tri Preparation of monotriacetate

2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylazide under argon gas (0.58 g ) and the compound (0.46 g) obtained in step 1 were added and diluted in 7.0 mL of tert-butyl alcohol and 7.0 mL of tetrahydrofuran. Copper sulfate pentahydrate (0.13 g) and sodium ascorbate (0.206 g) were dissolved in 7.0 mL of water and added dropwise to the mixture, followed by stirring at 40 °C for 24 hours. After the reaction was completed, the mixture was diluted with water, extracted three times with dichloromethane, dehydrated with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give the title compound as a white solid. (Yield = 71.0%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.69 (s, 3H), 0.78 (d, J = 6.78 Hz, 6H), 0.83–0.86 (m, 6H), 0.93 (d, J = 6.6 Hz, 3H), 1.88 (s, 3H), 2.04 (s, 3H), 2.07 (s, 3H), 2.09 (s, 3H), 3.36-3.43 (m, 1H), 3.96-4.02 (m, 1H) ), 4.13 (d, J = 12.45 Hz, 1H), 4.68 (s, 2H), 5.24 (t, J = 9.53 Hz, 1H), 5.38–5.49 (m, 2H), 5.87 (d, J = 8.97 Hz) , 1H), 8.59 (dd, J = 12.54, 5.04 Hz, 1H)

Step 3: (2R,3R,4S,5S,6R)-2-(4-((((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6- Dimethylheptan-2-yl)-10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta [a]phenanthren-3-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5 -Preparation of triols

Compound obtained in step 2 (0.03 g) was diluted in 2.0 mL of dichloromethane and 2.0 mL of methanol, and 4.37 M sodium methoxide in MeOH (4.37 M, 0.066 mL) was added dropwise, followed by stirring at room temperature for 2 hours. After adding Dowex MAC-3 and adjusting the pH to 5.0, the mixture was filtered and concentrated under reduced pressure. The concentrate was purified by column chromatography to give the title compound as a white solid. (Yield = 67.0%)

1H NMR (300 MHz, DMSO ^- _d6 ) δ (ppm): 0.62 (s, 3H), 0.75 ( d , J = 6.42 Hz, 6H), 0.81 (d, J = 6.03 Hz, 6H), 0.90 ( d, J = 6.03 Hz, 3H), 3.16 (d, J = 13.9 Hz, 1H), 3.67–3.74 (m, 2H), 4.52 (s, 2H), 4.63 (br. s, 1H), 5.16 (br s, 1H), 5.34 (d, J = 19.41 Hz, 2H), 5.49 (d, J = 9.36 Hz, 1H), 8.22 (s, 1H).

Example 2: (2R,3R,4S,5R,6R)-2-(4-((((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6 -Dimethylheptan-2-yl)-10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclo penta[a]phenanthren-3-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4; Preparation of 5-Triol

Step 1: (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(4-((((3S,9R,10S,13R,17R)-17-((2R,5S )-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradeca Hydro-1H-cyclopenta[a]phenanthren-3-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-tri Preparation of monotriacetate

2,3,4,6-tetra-O-acetyl-β-D-galactopyranosylazide (2,3,4,6-tetra-O-acetyl-β-D-galactopyranosylazide, 0.13 g) and The compound (0.10 g) obtained in Step 1 of Example 1 was reacted in the same manner as in Step 2 of Example 1 to obtain the title compound as a white solid. (Yield = 85.7%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.69 (s, 3H), 0.78 (d, J = 6.6 Hz, 6H), 0.85 (d, J = 8.61 Hz, 6H), 0.93 (d , J = 6.39 Hz, 3H), 1.89 (s, 3H), 2.01 (s, 3H), 2.05 (s, 3H), 2.22 (s, 3H), 3.31–3.49 (m, 1H), 4.09–4.21 ( m, 3H), 4.69 (s, 2H), 5.24 (dd, J = 11.15, 3.47 Hz, 1H), 5.57 (t, J = 10.07 Hz, 2H), 5.83 (d, J = 9.33 Hz, 1H), 7.82 (s, 1H)

Step 2: (2R,3R,4S,5R,6R)-2-(4-((((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6- Dimethylheptan-2-yl)-10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta [a]phenanthren-3-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5 -Preparation of triols

Compound obtained in step 1 (0.16 g) was reacted in the same manner as in Example 1 step 3 to obtain the title compound as a white solid. (Yield = 75.5%)

1H NMR (300 MHz, DMSO ^- _d6 ) δ (ppm): 0.34 (s, 3H), 0.76 ( d , J = 6.42 Hz, 6H), 0.83 (d, J = 7.14 Hz, 6H), 0.91 ( d, J = 4.92 Hz, 3H), 3.38 (s, 1H), 3.45–3.57 (m, 3H), 3.71 (t, J = 5.67 Hz, 1H), 3.77 (s, 1H), 4.04 (t, J = 9.24 Hz, 1H), 4.54 (s, 2H), 5.47 (d, J = 8.97 Hz, 1H), 8.17 (s, 1H)

Example 3: (2R,3R,4S,5R)-2-(4-((((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethyl Heptan-2-yl) -10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[ Preparation of a] phenanthren-3-yl) oxy) methyl) -1H-1,2,3-triazol-1-yl) tetrahydro-2H-pyran-3,4,5-triol

Step 1: (2R,3R,4S,5R)-2-(4-((((3S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptane-2 -yl) -10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenan Preparation of tren-3-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

2,3,4-tri-O-acetyl-β-D-xylopyranosylazide (2,3,4-tri-O-acetyl-β-D-xylopyranosylazide, 0.11 g) and Example 1 The compound (0.10 g) obtained in Step 1 was reacted in the same manner as in Step 2 of Example 1 to obtain the title compound as a white solid. (Yield = 90.5%)

¹ H NMR (300 MHz, CDCl ₃ ) δ (ppm): 0.65 (s. 3H), 0.78 (d, J = 6.6 Hz, 6H), 0.85 (d, J = 9.15 Hz, 6H), 0.95 (d, J = 7.14 Hz, 3H), 1.89 (s, 3H), 2.05 (s, 3H), 2.08 (s, 3H), 3.37 (m, 1H), 3.58 (t, J = 11.07 Hz, 1H), 4.29 ( dd, J = 11.64, 5.58 Hz, 1H), 4.68 (s, 2H), 5.11–5.19 (m, 1H), 5.40 (t, J = 4.5 Hz, 2H), 5.78 (t, J = 4.40 Hz, 1H) ), 7.72(s, 1H)

Step 2: (2R,3R,4S,5R)-2-(4-((((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptane -2-yl) -10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a Preparation of ]phenanthren-3-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triol

Compound obtained in step 1 of Example 3 (0.16 g) was reacted in the same manner as in Example 1 step 3 to obtain the title compound as a white solid. (Yield = 79.5%)

1H NMR (300 MHz, DMSO ^- _d6 ) δ (ppm): 0.63 (s, 3H), 0.75 ( d , J = 6.24 Hz, 6H), 0.82 (d, J = 6.96 Hz, 6H), 0.91 ( s, 3H), 3.44–3.53 (m, 1H), 3.73–3.85 (m, 2H), 4.53 (s, 2H), 5.19 (d, J = 4.59 Hz, 1H), 5.33 (d, J = 4.41 Hz) , 1H), 5.43 (dd, J = 17.7, 7.52 Hz, 2H), 8.19 (s, 1H)

Example 4: (3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4 ,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxy-2-(hydroxy Preparation of methyl) -2-methylpropanoate

Step 1: (3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4, 5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 2,2,5-trimethyl-1,3 -Preparation of dioxane-5-carboxylate

2,2,5-trimethyl-1,3-dioxane-5-carboxylic acid (2,2,5-trimethyl-1,3-dioxane-5-carboxylic acid, 0.17 g), ergostenol (△ ^{8(14 )} -Ergostenol, 0.20 g) and N,N'-Dicyclohexylcarbodiimide (0.21 g) were diluted in 5.0 mL of dichloromethane, and 4-dimethylaminopyridine (4-Dimethylaminopyridine, 0.012 g) was diluted. g) was added and stirred at room temperature for 24 hours. After the reaction was completed and the precipitate was filtered, the filtrate was concentrated under reduced pressure and purified by column chromatography to obtain the title compound as a white solid. (Yield = 89.2%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.71 (s, 3H), 0.77 (s, 3H), 0.79 (s, 3H), 0.85 (d, J = 7.9 Hz, 6H), 0.93 (d, J = 6.4 Hz, 3H), 3.62 (d, J = 11.8 Hz, 2H), 4.17 (d, J = 11.6 Hz, 2H), 4.79 (br s, 1H)

Step 2: (3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4, 5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxy-2-(hydroxymethyl ) Preparation of 2-methylpropanoate

The compound (0.15 g) obtained in step 1 was diluted in 1.74 mL of tetrahydrofuran, 1 M hydrochloric acid (0.83 mL) was added dropwise, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, extracted three times with dichloromethane, dehydrated over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was slurried with methanol and then filtered to give the title compound as a white solid. (Yield = 96.5%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.72 (s, 3H), 0.77 (s, 3H), 0.79 (s, 3H), 0.85 (d, J = 7.3 Hz, 6H), 0.93 (d, J = 6.6 Hz, 3H), 2.86 (t, J = 6.6 Hz, 2OH), 3.70 (dd, J = 11.3, 6.2 Hz, 2H), 3.89 (dd, J = 11.2, 6.7 Hz, 2H) , 4.80 (br s, 1H)

Example 5: N-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-3-hydroxy- Preparation of 2-(hydroxymethyl)-2-methylpropanamide

Step 1: 2-(((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)carbamoyl)-2- Preparation of methylpropane-1,3-diyl diacetate

3-acetoxy-2- (acetoxymethyl) -2-methylpropanoic acid (3-acetoxy-2- (acetoxymethyl) -2-methylpropanoic acid, 0.62 g) and the compound obtained in step 2 of Preparation Example 2 ( 1.2 g), filled with argon gas, and diluted with 35.7 mL of anhydrous dichloromethane. Triethylamine (8.6 mL) and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (Bis(2-oxo-3-oxazolidinyl)phosphinic chloride, 0.87 g) were added to the reaction solution and incubated at room temperature for 4 Stir for an hour. After the reaction was completed, purified water was added, extracted three times with dichloromethane, and the organic layer was washed with brine, dehydrated with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give the title compound as a white solid. (Yield = 43.1%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.69 (s, 3H), 0.77-0.79 (m, 6H), 0.84-0.86 (m, 6H), 0.93 (d, J = 6.1 Hz, 3H), 4.16 (br s, 1H), 4.23 (s, 4H), 6.39 (d, J = 6.2 Hz, NH)

Step 2: N-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-3-hydroxy-2 Preparation of (hydroxymethyl)-2-methylpropanamide

Compound obtained in step 1 (0.094 g) was reacted in the same manner as in Example 1 step 3 to obtain the title compound as a white solid. (Yield = 96.8%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.58 (s, 3H), 0.78 (d, J = 6.6 Hz, 6H), 0.85 (d, J = 8.0 Hz, 6H), 0.93 (d , J = 6.4 Hz, 3H), 3.23 (t, J = 5.8 Hz, 2H), 3.75–3.77 (m, 4H), 3.79 (br s, 1H), 7.34 (d, J =7.3 Hz, NH)

Example 6: 1-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1,2 Preparation of 3-triazole-4-carboxylic acid

Step 1: Ethyl 1-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl-1H-1,2, Preparation of 3-triazole-4-carboxylate

Put the compound (0.47 g) obtained in step 1 of Preparation Example 2, dissolve it in tert-butyl alcohol (10.0 mL) and tetrahydrofuran 10.0 mL, and add ethyl propiolate (0.11 mL) dropwise. did Copper sulfate pentahydrate (0.13 g) and sodium ascorbate (0.20 g) were dissolved in 10 mL of water and added dropwise to the mixture. After stirring at 40 °C for 24 hours, the mixture was diluted with water, extracted three times with dichloromethane, dehydrated with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give the title compound as a white solid. (Yield = 89.2%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.77 - 0.79 (m, 9H), 0.85 (d, J = 7.7 Hz, 6H), 0.92 (d, J = 6.6 Hz, 3H), 4.44 (q, J = 7.1 Hz, 2H), 4.73 (br s, 1H), 8.21 (s, 1H)

Step 2: 1-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1,2, Preparation of 3-triazole-4-carboxylic acid

The compound (0.45 g) obtained in step 1 was diluted in 85.9 mL of tetrahydrofuran and 17.2 mL of purified water, and lithium hydroxide (0.041 g) was added thereto and stirred at room temperature for 6 hours. After the reaction was completed, 1 M hydrochloric acid was added to adjust the pH to 4.0, extracted three times with ethyl acetate, dehydrated with anhydrous sodium sulfate, and concentrated under reduced pressure. The concentrate was filtered after slurry with methanol to give the title compound as a white solid. (Yield = 82.6%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.77 (d, J = 5.8 Hz, 6H), 0.85 (d, J = 6.8 Hz, 6H), 0.92 (d, J = 6.6 Hz, 3H) ), 4.76 (br s, 1H), 8.31 (s, 1H)

Example 7: N-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1-((2R ,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazole- Preparation of 4-carboxamide

Step 1: N-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 Preparation of 4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)propinamide

Propioic acid (0.046 mL) and N-Hydroxysuccinimide (0.086 g) were dissolved in 31.3 mL of tetrahydrofuran, and N,N'-dicyclohexylcarbodiyl dissolved in 6.1 mL of tetrahydrofuran. Mead (N,N'-Dicyclohexylcarbodiimide, 0.15 g) was added dropwise and stirred at room temperature for 24 hours. After filtering the precipitate, the compound (0.20 g) obtained in step 2 of Preparation Example 2 was added to the mixture and stirred at room temperature for 24 hours. After completion of the reaction, the concentrate was concentrated under reduced pressure and purified by column chromatography to obtain the title compound as a white solid. (Yield = 48.0%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.69 (s, 3H), 0.77 (s, 3H), 0.79 (s, 3H), 0.85 (d, J = 8.3 Hz, 6H), 0.93 (d, J = 6.6 Hz, 3H), 2.77 (s, 1H), 4.21 (br s, 1H), 6.12 (d, J = 6.6 Hz, 1H)

Step 2: (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((3R,5S,9R,10S,13R,17R)-17-((2R, 5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetra Decahydro-1H-cyclopenta[a]phenanthren-3-yl)carbamoyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-tri Preparation of monotriacetate

Step with 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylazide (2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylazide, 0.074 g) The title compound was obtained as a white solid by reacting in the same manner as in step 2 of Example 1 using the compound (0.090 g) obtained in 1. (Yield = 80.3%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.72 (s, 3H), 0.78 (d, J = 6.6 Hz, 6H), 0.85 (d, J = 6.8 Hz, 6H), 0.93 (d , J = 6.0 Hz, 3H), 1.92 (s, 3H), 2.05 (s, 3H), 2.08 (s, 3H), 2.10 (s, 3H), 4.00–4.03 (m, 1H), 4.16 (d, J = 12.6 Hz, 1H), 4.27–4.32 (m, 2H), 5.27 (t, J = 9.3 Hz, 1H), 5.46 (q, J = 9.5 Hz, 2H), 5.88 (d, J = 8.6 Hz, 2H), 7.41 (d, J = 7.9 Hz, 1H), 8.30 (s, 1H)

Step 3: N-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1-((2R, 3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazole-4 -Manufacture of carboxamides

The compound (0.12 g) obtained in Step 2 was reacted in the same manner as in Step 3 of Example 1 to obtain the title compound as a white solid. (Yield = 99.6%)

1H NMR (300 MHz, DMSO ^- d6) δ (ppm): 0.67 (s, 3H), 0.76 ( d , J = _6.6 Hz, 6H), 0.83 (d, J = 6.4 Hz, 6H), 0.91 ( d.J = 6.1 Hz, 3H), 3.21-3.28 (m, 1OH), 3.38-3.48 (m, 3OH), 3.68-3.80 (m, 2H), 4.14 (br s, 1H), 4.64 (t, J = 5.5 Hz, 1H), 5.20 (d, J = 5.3 Hz, 1H), 5.34 (d, J = 4.6 Hz, 1H), 5.45 (d, J = 5.7 Hz, 1H), 5.60 (d, J = 9.3 Hz, 1H), 7.87 (d, J = 6.9 Hz, 1H), 8.83 (s, 1H)

Example 8: N-((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-3-hydroxy- Preparation of 2-(hydroxymethyl)-2-methylpropanamide

Step 1: 2-(((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)carbamoyl)-2- Preparation of methylpropane-1,3-diyl diacetate

3-acetoxy-2- (acetoxymethyl) -2-methylpropanoic acid (3-acetoxy-2- (acetoxymethyl) -2-methylpropanoic acid, 0.082 g) and the compound obtained in step 4 of Preparation Example 1 (0.15 g) was reacted as in Example 5, step 1. The title compound was obtained as a white solid. (Yield = 50.6%)

Step 2: N-((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-3-hydroxy-2 Preparation of (hydroxymethyl)-2-methylpropanamide

The compound (0.114 g) obtained in Step 1 was reacted in the same manner as in Step 3 of Example 1 to obtain the title compound as a white solid. (Yield = 88.4%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.68 (s, 3H), 0.78 (d, J = 6.8 Hz, 6H), 0.85 (d, J = 9.0 Hz, 6H), 0.93 (d , J = 6.4 Hz), 2.98 (t, J = 5.9 Hz, 2OH), 3.68–3.82 (m, 4H), 6.55 (d, J = 7.7 Hz, NH)

Example 9: 1-((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1,2 Preparation of 3-triazole-4-carboxylic acid

Step 1: Ethyl 1-((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1,2 Preparation of 3-triazole-4-carboxylate

The compound (0.070 g) obtained in Step 3 of Preparation Example 1 was reacted in the same manner as in Step 1 of Example 6 to obtain the title compound as a white solid. (Yield = 86.9%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.77–0.80 (m, 9H), 0.85–0.87 (m, 6H), 0.94 (d, J = 6.4 Hz, 3H), 4.42 (q , J = 7.0 Hz, 2H), 4.52–4.61 (m, 1H), 8.10 (s, 1H)

Step 2: 1-((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyll-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1,2 Preparation of 3-triazole-4-carboxylic acid

The compound (0.050 g) obtained in Step 1 was reacted in the same manner as in Step 2 of Example 6 to obtain the title compound as a white solid. (Yield = 60.9%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.78 (d, J = 6.6 Hz, 9H), 0.85–0.87 (m, 6H), 0.94 (d, J = 6.4 Hz, 3H), 4.58 (br s, 1H), 8.20 (s, 1H)

Example 10: (1-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2 ,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1, Preparation of 2,3-triazole-4-carbonyl) glycine

Step 1: Ethyl (1-((3R,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1,2, Preparation of 3-triazole-4-carbonyl)glycinate

Glycine ethyl ester hydrochloride (0.023 g), the compound obtained in step 2 of Example 6 (0.080 g) and 4-dimethylaminopyridine (4-Dimethylaminopyridine, 0.035 g) were dissolved in 3.2 mL of dichloromethane. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.031 g) was slowly added dropwise at 0 °C, followed by 30 minutes at room temperature for 24 hours. Stir. After the reaction was completed, 23.6 mL of 1 M hydrochloric acid was added, extracted three times with dichloromethane, and the organic layer was dehydrated with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give the title compound as a white solid. (Yield = 77.8%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.77 (m, 9H), 0.85 (d, J = 7.7 Hz, 6H), 0.92 (d, J = 6.6 Hz, 3H), 4.22-4.29 (m, 4H), 4.71 (br s, 1H), 7.61 (t, J = 5.1 Hz, 1H), 8.22 (s, 1H)

Step 2: (1-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1,2 Preparation of ,3-triazole-4-carbonyl)glycine

Compound obtained in step 1 (0.18 g) was reacted in the same manner as in Example 6 step 2 to obtain the title compound as a white solid. (Yield = 67.9%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.77–0.81 (m, 9H), 0.85 (d, J = 8.3 Hz, 6H), 0.92 (d, J = 6.2 Hz, 1H), 4.31 (d, J = 5.7 Hz, 2H), 4.72 (br s, 1H), 7.93 (t, J = 5.7 Hz, 1H0, 8.29 (s, 1H)

Example 11: (1-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2 ,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1, Preparation of 2,3-triazol-4-yl)methyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate

Prepared with Prop-2-ynyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate (0.19 g) The title compound was obtained as a white solid by reacting in the same manner as in Example 1, Step 2 using the compound (0.050 g) obtained in Step 1 of Example 2. (Yield = 86.3%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.77-0.79 (m, 9H), 0.83-0.86 (m, 6H), 0.92 (d, J = 6.6 Hz, 3H), 3.13 (br s , 2OH), 3.74-3.92 (m, 4H), 4.64 (br s, 1H), 5.39 (s, 2H), 7.71 (s, 1H)

Example 12: 4-(((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2 ,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)amino)-4- Preparation of oxobutanoic acid

The compound obtained in step 2 of Preparation Example 2 (0.25 g), 4-dimethylaminopyridine (4-Dimethylaminopyridine, 0.19 g), and succinic anhydride (0.15 g, 4.9 eq, 1.526 mmol) were mixed with anhydrous dichloromethane 6.3 It was dissolved in mL and stirred at room temperature for 24 hours. After completion of the reaction, after concentration under reduced pressure, the mixture was dissolved in 30 mL of ethyl acetate, and then 30 mL of saturated sodium bicarbonate and a catalytic amount of 4-dimethylaminopyridine were added thereto, followed by stirring at room temperature for 1 hour. 75 mL of 1 M hydrochloric acid was added, extracted three times with ethyl acetate, dehydrated with anhydrous sodium sulfate, and concentrated under reduced pressure. The concentrate was filtered after slurry with methanol to give the title compound as a white solid. (Yield = 65.0%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.69 (s, 3H), 0.78 (d, J = 6.6 Hz, 6H), 0.85 (d, J = 7.7 Hz, 6H), 0.93 (d , J = 6.4 Hz, 6H), 2.54–2.61 (m, 2H), 2.67–2.74 (m, 2H), 4.15 (br s, 1H), 6.06 (d, J = 7.5 Hz, 1H)

Example 13: 2,2′-(((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13- Dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)azane Preparation of diyl)bis(ethane-1-ol)

Step 1: Di-tert-butyl 2,2′-(((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)- 10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3- 1) Preparation of azanediyl) diacetate

The compound obtained in step 2 of Preparation Example 2 (0.050 g, 1.0 eq, 0.125 mmol) and potassium carbonate (Potassium carbonate, 0.052 g) were dissolved in anhydrous dimethylformamide (Dimethylformamide, 0.41 mL) and tert-butyl-2-broth After adding moacetate (tert-buthyl-2-bromoacetate, 0.055 mL), the mixture was stirred at room temperature for 20 hours. After completion of the reaction, water was added, and after completion, the mixture was extracted three times with dichloromethane, dehydrated with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give the title compound as a white solid. (Yield = 82.6%)

¹ H NMR (300 MHz, Chloroform- d ) δ (ppm): 0.67 (s, 3H), 0.78 (d, J = 6.6 Hz, 6H), 0.83 (s, 3H), 0.85 (d, J = 7.0 Hz, 3H), 0.93 (d, J = 14.3 Hz, 3H), 1.45 (s, 18H), 3.14 (br s, 1H) ), 3.45 (s, 4H)

Step 2: 2,2′-(((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl -2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)acanediyl) Preparation of bis(ethane-1-ol)

The compound (0.050 g) obtained in Step 1 was reacted in the same manner as in Step 4 of Preparation Example 1 to obtain the title compound as a white solid. (Yield = 76.2%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.70 (s, 3H), 0.78 (d, J = 6.8 Hz, 6H), 0.83 (s, 3H), 0.84 (d, J = 6.8 Hz) , 3H), 0.93 (d, J = 6.6 Hz, 3H), 2.83–2.86 (m, 5H), 3.72 (t, J = 5.5 Hz, 4H)

Example 14: N-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-3,4-di Preparation of hydroxybenzamide

Step 1: 4-(((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)carbamoyl)-1, Preparation of 2-phenylene diacetate

3,4-diacetoxybenzoic acid (0.018 g) and The title compound was obtained as a white solid by reacting in the same manner as in Example 5, step 1 using the compound (0.030 g) obtained in step 2 of preparation example 2. (Yield = 36.1%)

Step 2: N-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-3,4-dihydro Preparation of Roxybenzamide

The compound (0.047 g) obtained in step 1 was dissolved in 3.8 mL of dichloromethane and 3.8 mL of methanol, and NaOMe (in MeOH 4.37 M, 0.05 mL) was added dropwise, followed by stirring at room temperature for 12 hours. After the reaction was complete, the mixture was neutralized with 1 M hydrochloric acid and extracted three times with dichloromethane. The organic layer was washed with saturated sodium bicarbonate and brine, then dehydrated with anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate was purified by column chromatography to give the title compound as a white solid. (Yield = 58.6%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.73 (s, 3H), 0.78 (d, J = 6.6 Hz, 6H), 0.86 (d, J = 6.4 Hz, 6H), 0.94 (d , J = 6.4 Hz, 3H), 4.32 (br s, 1H), 6.48 (d, J = 7.5, 1H), 6.90 (d, J = 8.1 Hz, 1H), 7.11 (d, J = 7.9 Hz, 1H) ), 7.77 (s, 1H)

Example 15: 1-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2, 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)piperidin-2- Manufacture of On

Step 1: 5-Bromo-N-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13- Dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)pentana manufacture of amide

After diluting the compound (40 mg, 0.1 mmol) obtained in step 2 of Preparation Example 2 in 334 μL of tetrahydrofuran, triethylamine (21 μL, 0.15 mmol) and 5-bromopentanoyl chloride ( 16 μL, 0.12 mmol) was added and stirred for 10 minutes, followed by further stirring at room temperature for 2 hours. After the reaction was completed, the reaction solution was diluted with ethyl acetate and washed with distilled water. The organic layer was dehydrated with anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 40 mg of the title compound as an off-white solid. (Yield = 71%)

1H NMR (400 MHz, Chloroform ^- d ) δ (ppm): 5.73-5.71 (d, J = 7.2 Hz, 1H), 4.15-4.14 (m, 1H), 3.45-3.42 (t, J = 6.6 Hz, 2H), 2.38-2.37 (m, 1H), 2.24-2.21 (m, 4H), 1.96-1.88 (m, 3H), 1.84-1.77 (m, 3H), 1.70-1.58 (m, 4H), 1.54- 1.48 (m, 3H), 1.45-1.36 (m, 4H), 1.30-1.22 (m, 3H), 1.21-1.17 (m, 1H), 1.16-1.09 (m, 4H), 0.99 (m, 1H), 0.94-0.92 (m, 3H), 0.86-0.77 (m, 12H), 0.69 (s, 3H)

Step 2: 1-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)piperidin-2-one manufacture of

After diluting the compound (38 mg, 0.07 mmol) obtained in step 1 in 225 μL of tetrahydrofuran, sodium hydride (5.4 mg, 0.14 mmol) was added at 0 ° C. After stirring for 30 minutes, the mixture was further stirred for 7 hours at room temperature. Stir. After the reaction was completed, the reaction solution was diluted with ethyl acetate and washed with distilled water. The organic layer was dehydrated with anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 20 mg of the title compound as an off-white solid. (Yield = 61.5%)

¹ H NMR (400 MHz, Chloroform- d ) δ (ppm): 4.67 (m, 1H), 3.51-3.48 (m, 2H), 2.42-2.36 (m, 3H), 2.29-2.16 (m, 2H), 1.96-1.93 (m, 1H), 1.79-1.63 (m, 11H), 1.53-1.49 (m, 3H), 1.45-1.42 (m, 3H), 1.38-1.31 (m, 5H), 1.22-1.19 (m , 1H), 1.14-1.05 (m, 4H), 1.01-0.99 (m, 1H), 0.94-0.77 (m, 12H), 0.69 (s, 1H)

Example 16: (3R,4S,5R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptane-2- yl)-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)oxy Preparation of )-5-(hydroxymethyl)tetrahydrofuran-3,4-diol

Step 1: (2R,3R,4R)-2-(acetoxymethyl)-5-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)- 6-methylheptan-2-yl)-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenan Preparation of tren-3-yl) oxy) tetrahydrofuran-3,4-diylacetate

The compound (50 mg, 0,13 mmol) obtained in Preparation Example 3 was diluted in 1.3 mL of dichloromethane, (3R,4R,5R)-5-(acetoxymethyl)tetrahydrofuran-2,3,4- Triyl triacetate (82 mg, 0.26 mmol) and a 4Å molecular sieve were added. Trimethylsilyl trifluoromethanesulfonate (11.7 μL, 0.07 mmol) was slowly added at 0° C., and the mixture was stirred for 15 minutes and further stirred for 2 hours at room temperature. After the reaction was completed, the reaction solution was neutralized with triethylamine, filtered, and then concentrated under reduced pressure. The concentrated residue was separated by column chromatography to give 30 mg of the title compound as a colorless oil. (Yield = 36%)

¹ H NMR (400 MHz, Chloroform- d ) δ (ppm): 5.35-5.32 (m, 1H), 5.17-5.13 (m, 2H), 4.34-4.30 (m, 1H), 4.27-4.23 (m, 1H) ), 4.14-4.08 (m, 2H), 3.58-3.54 (m, 1H), 2.37-2.18 (m, 2H), 2.10-2.09 (m, 6H), 2.05-2.04 (m, 6H), 2.00-1.74 (m, 5H), 1.69-1.40 (m, 8H), 1.34-1.03 (m, 16H), 0.92-0.79 (m, 12H), 0.66 (s, 3H)

Step 2: (3R,4S,5R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl )-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)oxy) Preparation of -5-(hydroxymethyl)tetrahydrofuran-3,4-diol

After diluting the compound obtained in step 1 (30 mg, 0.05 mmol) in dichloromethane/methanol mixture (1:1, 0.5 mL), a 25% sodium methoxide methanol solution (63.8 μL, 0.28 mmol) was added at 0 °C. It was added and stirred at room temperature for 19 hours. After the reaction was completed, the reaction solution was filtered through AmberLite resin (IR-120), concentrated under reduced pressure, and separated by column chromatography to obtain 7 mg of the title compound as an off-white solid. (Yield = 29%)

¹ H NMR (400 MHz, Chloroform- d ) δ (ppm): 5.13 (m, 1H), 4.45-4.43 (m, 1H), 4.08-4.03 (m, 2H), 3.83-3.80 (m, 1H), 3.70-3.53 (m, 2H), 2.56 (m, 1H), 2.38-2.35 (m, 2H), 2.24-2.19 (m, 2H), 2.01-1.89 (m, 2H), 1.86-1.75 (m, 3H) ), 1.71-1.68 (m, 1H), 1.62 (m, 1H), 1.51-1.39 (m, 6H), 1.36-1.28 (m, 5H), 1.23-1.21 (m, 3H), 1.18-1.02 (m , 6H), 0.93-0.80 (m, 12H), 0.67 (s, 3H)

Example 17: (2R,3R,4S,5S,6R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methyl Heptan-2-yl) -2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3 Preparation of -yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

Step 1: (2R,3R,4S,5R,6R)-2-((benzoyloxy)methyl)-6-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17 -((R)-6-methylheptan-2-yl)-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H- Preparation of cyclopenta[a]phenanthren-3-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate

Obtained from 2,3,4,6-tetra- O -benzoyl-glucopyranosyl trichloroacetimidate (2,3,4,6-tetra- O -benzoyl-glucopyranosyl trichloroacetimidate, 3.5 g) and Preparation Example 3 One compound (0.91 g) was reacted in the same manner as in Step 1 of Example 16 to give the title compound as a white solid. (Yield = 59.0%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.56 (s, 3H), 0.80 - 0.91 (m, 12H), 3.62 (br. s, 1H), 4.14-4.17 (m, 1H), 4.52 (dd, J = 6.33, 12 Hz, 1H), 4.61 (dd, J = 3.39, 12 Hz, 1H), 4.94 (d, J = 7.89 Hz, 1H), 5.49 (dd, J = 8.04, 9.72 Hz) , 1H), 5.62 (t, J = 9.62 Hz, 1H), 5.89 (t, J = 9.51 Hz, 1H), 7.28–7.58 (m, 12H), 7.82–8.03 (m, 8H)

Step 2: (2R,3R,4S,5S,6R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyll-17-((R)-6-methyl Heptan-2-yl) -2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3 Preparation of -yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

The compound (1.33 g) obtained in Step 1 was reacted in the same manner as in Step 3 of Example 1 to obtain the title compound as a white solid. (Yield = 74.0%)

1H NMR (300 MHz, Pyridine ^- d5) δ (ppm): 0.62 (s, 3H), 0.90 ( d , J = 5.31 Hz, 9H), 0.99 (d, J = 6.24 Hz, 3H), _4.03- 4.10 (m, 3H), 4.30 - 4.39 (m, 2H), 4.48 (br. s, 1H), 4.67 (d, J = 11.34 Hz, 1H), 5.10 (dd, J = 7.6 Hz, 1H)

Example 18: (2R,3R,4S,5R,6R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methyl Heptan-2-yl) -2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3 Preparation of -yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

Step 1: (2R,3S,4S,5R,6R)-2-((benzoyloxy)methyl)-6-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17 -((R)-6-methylheptan-2-yl)-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H- Preparation of cyclopenta[a]phenanthren-3-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate

2,3,4,6-tetra- O -benzoyl-galactopyranosyl trichloroacetimidate (2,3,4,6-tetra- O -benzoyl-galactopyranosyl trichloroacetimidate, 2.3 g) and in Preparation Example 3 The obtained compound (0.91 g) was reacted in the same manner as in Step 1 of Example 16 to obtain the title compound as a white solid. (Yield = 71.1%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.58–0.70 (m, 3H), 0.81–0.90 (m, 9H), 0.93 (d, J = 6.78 Hz, 3H), 3.55–3.70 ( br. s, 1H), 4.31 (t, J = 6.96 Hz, 1H), 4.40–4.45 (m, 1H), 4.68 (dd, J = 10.91, 7.14 Hz, 1H), 4.91 (d, J = 7.86 Hz) , 1H), 5.58 (dd, J = 10.05, 3.3 Hz, 1H), 5.76 (dd, J = 10.23, 7.89 Hz, 1H), 5.97 (d, J = 3.48 Hz, 1H), 7.22–7.26 (m, 2H), 7.35–7.61 (m, 10H), 7.79 (d, J = 7.14 Hz, 2H), 7.96 (d, J = 7.5 Hz, 2H), 8.03 (d, J = 8.06 Hz, 2H), 8.10 ( d, J = 7.14 Hz, 2H)

Step 2: (2R,3R,4S,5R,6R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptane -2-yl) -2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3- Preparation of yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

The compound (1.33 g) obtained in Step 1 was reacted in the same manner as in Step 3 of Example 1 to obtain the title compound as a white solid. (Yield = 88.0%)

¹ H NMR (300 MHz, Pyridine- d ₅ ) δ (ppm): 0.61-0.69 (m, 3H), 0.91 (s, 9H), 0.98-1.05 (m, 3H), 4.01 (br. s, 1H) , 4.15–4.24 (m, 2H), 4.49 (s, 3H), 4.60 (s, 1H), 4.97–5.05 (m, 1H).

Example 19: (2S,3R,4S,5R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptane- 2-yl)-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl Preparation of )oxy)tetrahydro-2H-pyran-3,4,5-triol

Step 1: (2S,3R,4S,5R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptane-2 -yl) -2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl) Preparation of oxy) tetrahydro-2H-pyran-3,4,5-triyl tribenzoate

2,3,4-tri- O -benzoyl-xylopyranosyl trichloroacetimidate (2,3,4-tri- O -benzoyl-xylopyranosyl trichloroacetimidate, 2.51 g) and the compound obtained in Preparation Example 3 ( 0.91 g) was reacted in the same manner as in Step 1 of Example 16 to obtain the title compound as a white solid. (Yield = 85.4%)

1H NMR (300 MHz, Chloroform ^- d ) δ (ppm): 0.69 (t, J = 19.32 Hz, 6H), 0.82–0.94 (m, 15H), 3.66–3.75 (m, 2H), 4.45 (d, J = 7.68 Hz, 1H), 4.96 (d, J = 5.13 Hz, 1H), 5.28–5.35 (m, 2H), 5.75 (t, J = 7.14 Hz, 1H), 7.32–7.40 (m, 6H), 7.49-7.54 (m, 3H), 7.96-8.05 (m, 6H)

Step 2: (2S,3R,4S,5R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptane-2 -yl) -2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl) Preparation of oxy)tetrahydro-2H-pyran-3,4,5-triol

The compound (1.33 g) obtained in Step 1 was reacted in the same manner as in Step 3 of Example 1 to obtain the title compound as a white solid. (Yield = 29.0%)

¹ H NMR (300 MHz, Pyridine- d ₅ ) δ (ppm): 0.61-0.73 (m, 3H), 0.88-0.91 (m, 9H), 0.94-1.01 (m, 3H), 3.82 (q, J = 10 Hz, 1H), 3.97-4.05 (m, 2H), 4.28 (br. s, 2H), 4.40-4.48 (m, 1H), 4.94 (t, J = 7.79 Hz, 1H)

Experimental Example 1: Real-time polymerase chain reaction

HaCaT cells were plated at 3 x 10 cells/well in a 6-well cell culture plate using DMEM medium supplemented with 10% FBS.

After culturing for one day, after washing with a serum-free medium, samples were included in the serum-free medium by concentration and cultured for 24 hours. After 24 hours, the solution was removed from each well, washed with D-PBS, and RNA was isolated using an RNA-prep reagent (Bio-Zol, MA500, Bioses). After separation, the concentration was measured to synthesize cDNA using 5 μg of RNA, and real-time PCR was performed with the synthesized cDNA using primers according to each target gene and SYBR GREEN, and the Ct value was calculated.

[Table 1]

Experimental Example 2: Enzyme Immunoassay (ELISA)

In order to confirm the degree of synthesis of each target protein in the cells treated with the sample, ELISA was performed to evaluate efficacy.

To this end, HaCaT cells were dispensed in a 6-well plate at 6 x 10 ⁴ cells/well and cultured for 24 hours. After 24 hours, the test substance was diluted in the cell culture medium, treated with cells at each concentration, and cultured for 24 hours. Then, the medium of the cultured cells was collected and the amount was measured using VCAM-1, E-selectin, and MadCAM ELISA kit (R&D system, Korea).

Table 2 summarizes the activities of the compounds of the examples of the present invention.

[Table 2]

<110> ST PHARM CO., LTD. <120> Novel ergostenol and cholestenol derivatives <130> P21010-STP <160> 6 <170> KoPatentIn 3.0 <210> 1 <211> 20 <212> DNA <213> artificial sequence <220> <223> VCAM-1 primer forward <400> 1 tggaaaaagg aatccaggtg 20 <210> 2 <211> 20 <212> DNA <213> artificial sequence <220> <223> VCAM-1 primer reverse <400> 2 ccagcctgtc aaatgggtat 20 <210> 3 <211> 20 <212> DNA <213> artificial sequence <220> <223> E-selectin primer forward <400> 3 ggacacagca aatcccagtt 20 <210> 4 <211> 20 <212> DNA <213> artificial sequence <220> <223> E-selectin primer reverse <400> 4 cacattggag ccttttggat 20 <210> 5 <211> 20 <212> DNA <213> artificial sequence <220> <223> MadCAM primer forward <400> 5 ttgcctcttt ggagaagctc 20 <210> 6 <211> 20 <212> DNA <213> artificial sequence <220> <223> MadCAM primer reverse <400> 6 aagtacgtgg ttccgtccag 20

Claims (6)

A compound represented by Formula 1 or a pharmaceutically acceptable salt thereof:
[Formula 1]

R ₁ is -H or -C _1-6 alkyl;
R ₂ is -OR ₃ , -NR ₄ R ₅ , heterocycloalkyl containing one or more N, or heteroaryl containing one or more N, {wherein the heterocycloalkyl and heteroaryl are adjacent to one N is directly connected to the quadruple ring, and at least one H of the heterocycloalkyl is -C _1-6 alkyl, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, =O, -NH ₂ , or -OH, wherein the heteroaryl is -C _1-6 alkyl, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -C _1-6 alkyl-OC(=O)R ₆ , -C(=0)R ₇ , or -NH ₂ , or -OH};
R ₃ is -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -C(=O)-(C _1-6 hydroxyalkyl), -C(=O)-(C _1-6 alkyl )-C(=O)OH, -C(=O)-aryl,

, or

and {wherein one or more H of the -C(=O)-aryl may be substituted with -NH ₂ or -OH};
R ₄ and R ₅ are each independently -H, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -C(=O)-(C _1-6 hydroxyalkyl), -C(= O)-(C _1-6 alkyl)-C(=O)OH, -C(=O)-aryl,

, or

and {wherein one or more H of -C(=O)-aryl may be substituted with -NH ₂ or -OH, and R ₄ and R ₅ cannot be -H at the same time};
L ₁ and L ₂ are each independently -(CH ₂ )n- or -C(=0)-;
n is 0, 1, 2, 3, or 4;
A ₁ and A ₂ are each independently a heteroaryl containing one or more N or nothing (null) {wherein, the heteroaryl is one in which one N is directly connected to an adjacent ring};
R ^A is -H or -CH ₂ OH;
R ₆ is -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, or -OH;
R ₇ is -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -NH-(C _1-6 alkyl)-C(=O)OH, -O-(C _1-6 alkyl)-C (=O)OH, or -OH. According to claim 1,
R ₁ is -H or -C _1-6 alkyl;
R ₂ is -OR ₃ , -NR ₄ R ₅ , heterocycloalkyl containing one or more N, or heteroaryl containing one or more N, {wherein the heterocycloalkyl and heteroaryl are adjacent to one N is directly connected to the quadruple ring, and at least one H of the heterocycloalkyl is -C _1-6 alkyl, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, =O, -NH ₂ , or -OH, wherein the heteroaryl is -C _1-6 alkyl, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -C _1-6 alkyl-OC(=O)R ₆ , -C(=0)R ₇ , or -NH ₂ , or -OH};
R ₃ is -C(=O)-(C _1-6 hydroxyalkyl);

, or

and {wherein one or more H of the -C(=O)-aryl may be substituted with -NH ₂ or -OH};
R ₄ and R ₅ are each independently -H, -C _1-6 hydroxyalkyl, -C(=O)-(C _1-6 hydroxyalkyl), -C(=O)-(C _1-6 Alkyl)-C(=O)OH, -C(=O)-aryl,

, or

and {wherein one or more H of -C(=O)-aryl may be substituted with -OH, and R ₄ and R ₅ cannot simultaneously be -H};
L ₁ and L ₂ are each independently -(CH ₂ )n- or -C(=0)-;
n is 0 or 1;
A ₁ and A ₂ are each independently a heteroaryl containing one or more N or nothing (null) {wherein, the heteroaryl is one in which one N is directly connected to an adjacent ring};
R ^A is -H or -CH ₂ OH;
R ₆ is -C _1-6 hydroxyalkyl;
R ₇ is -NH-(C _1-6 alkyl)-C(=0)OH or -OH;
A compound or a pharmaceutically acceptable salt thereof. According to claim 1,
R ₁ is -H or -C _1-6 alkyl;
R ₂ is -OR ₃ ;
R ₃ is -C(=O)-(C _1-6 hydroxyalkyl);

, or

ego;
L ₁ and L ₂ are each independently -(CH ₂ )n- or -C(=0)-;
n is 0, 1, 2, 3, or 4;
A ₁ and A ₂ are each independently a heteroaryl containing one or more N or nothing (null) {wherein, the heteroaryl is one in which one N is directly connected to an adjacent ring};
R ^A is -H or -CH ₂ OH;
A compound or a pharmaceutically acceptable salt thereof. According to claim 1
R ₁ is -H or -C _1-6 alkyl;
R ₂ is —NR ₄ R ₅ , a heterocycloalkyl containing one or more N, or a heteroaryl containing one or more N, {wherein the heterocycloalkyl and heteroaryl are in a quadruple ring where one N is adjacent. is directly connected, and at least one H of the heterocycloalkyl is substituted with -C _1-6 alkyl, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, =O, -NH ₂ , or -OH and the heteroaryl is -C _1-6 alkyl, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -C _1-6 alkyl-OC(=O)R ₆ , -C( =O)R ₇ , or -NH ₂ , or -OH};
R ₄ and R ₅ are each independently -H, -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -C(=O)-(C _1-6 hydroxyalkyl), -C(= O)-(C _1-6 alkyl)-C(=O)OH, -C(=O)-aryl,

, or

and {wherein one or more H of -C(=O)-aryl may be substituted with -NH ₂ or -OH, and R ₄ and R ₅ cannot be -H at the same time};
L ₁ and L ₂ are each independently -(CH ₂ )n- or -C(=0)-;
n is 0, 1, 2, 3, or 4;
A ₁ and A ₂ are each independently a heteroaryl containing one or more N or nothing (null) {wherein, the heteroaryl is one in which one N is directly connected to an adjacent ring};
R ^A is -H or -CH ₂ OH;
R ₆ is -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, or -OH;
R ₇ is -C _1-6 aminoalkyl, -C _1-6 hydroxyalkyl, -NH-(C _1-6 alkyl)-C(=O)OH, -O-(C _1-6 alkyl)-C (=0)OH, or -OH;
A compound or a pharmaceutically acceptable salt thereof. According to claim 1,
At least one compound selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof:
(1) (2R,3R,4S,5S,6R)-2-(4-((((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6- Dimethylheptan-2-yl) -10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta [a]phenanthren-3-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5 -triol;
(2) (2R,3R,4S,5R,6R)-2-(4-((((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6- Dimethylheptan-2-yl) -10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta [a]phenanthren-3-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5 -triol;
(3) (2R,3R,4S,5R)-2-(4-((((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptane -2-yl) -10,13-dimethyl-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a ]phenanthren-3-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triol;
(4) (3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3,4; 5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-hydroxy-2-(hydroxymethyl )-2-methylpropanoate;
(5) N-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-3-hydroxy-2 -(hydroxymethyl)-2-methylpropanamide;
(6) 1-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1,2, 3-triazole-4-carboxylic acid;
(7) N-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1-((2R, 3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazole-4 -carboxamides;
(8) N-((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-3-hydroxy-2 -(hydroxymethyl)-2-methylpropanamide;
(9) 1-((3S,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1,2, 3-triazole-4-carboxylic acid;
(10) (1-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2; 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1,2 ,3-triazole-4-carbonyl)glycine;
(11) (1-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2; 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-1H-1,2 ,3-triazol-4-yl)methyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate;
(12) 4-(((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2; 3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)amino)-4-oxo butanoic acid;
(13) 2,2'-(((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl -2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)azanediyl ) bis(ethane-1-ol);
(14) N-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-3,4-dihydro oxybenzamide;
(15) 1-((3R,5S,9R,10S,13R,17R)-17-((2R,5S)-5,6-dimethylheptan-2-yl)-10,13-dimethyl-2,3 ,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)piperidin-2-one ;
(16) (3R,4S,5R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl )-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)oxy) -5-(hydroxymethyl)tetrahydrofuran-3,4-diol;
(17) (2R,3R,4S,5S,6R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptane -2-yl) -2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3- yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;
(18) (2R,3R,4S,5R,6R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptane -2-yl) -2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3- yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; and
(19) (2S,3R,4S,5R)-2-(((3S,5S,9R,10S,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptane-2 -yl) -2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl) oxy)tetrahydro-2H-pyran-3,4,5-triol. A pharmaceutical composition for preventing or treating inflammatory bowel disease, comprising the compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof as an active ingredient.