Ursodeoxycholic acid compounds, their preparation methods, pharmaceutical compositions and applications

Abstract

This invention discloses an ursodeoxycholic acid compound, its preparation method, pharmaceutical composition, and applications. The compound has the structure shown in Formula 1 and also includes its stereoisomers, geometric isomers, tautomers, deuterated compounds, pharmaceutically acceptable salts, or mixtures thereof. This class of compounds exhibits highly efficient inhibitory effects on inflammatory cells and significantly inhibits the production of inflammatory mediators, while having no significant impact on the viability of normal cells. It also possesses low cytotoxicity and is suitable for preparation as an anti-inflammatory drug. Furthermore, the preparation method for this class of compounds is highly versatile and facilitates structural expansion.

Description

Technical Field

[0001] This invention relates to an ursodeoxycholic acid compound, its preparation method, pharmaceutical composition, and application, and more particularly to an ursodeoxycholic acid compound with anti-inflammatory activity, its preparation method, pharmaceutical composition, and application. Background Technology

[0002] Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid with low toxicity. Its chemical name is 3α,7β-dihydroxy-5β-cholestane-24-acid, and it has the following structure:

[0003]

[0004] Specifically, UDCA is a steroidal compound consisting of a steroidal skeleton composed of three six-membered rings and one five-membered ring, along with one fatty side chain, totaling 24 carbon atoms. From its stereochemical configuration, it can be seen that rings A and B on the steroidal skeleton are cis-fused, rings B and C are trans-fused, and rings C and D are trans-fused. The hydroxyl group at position 3 is at the α-position, and the hydroxyl group at position 7 is at the β-position; therefore, the molecule exhibits both hydrophilic and lipophilic properties. Because UDCA molecules contain hydroxyl and carboxyl functional groups, they possess broad biological activities and potential medicinal value. Although ursodeoxycholic acid (UDCA) has anti-inflammatory activity, its inherent activity intensity and bioavailability limit its further application and development. Summary of the Invention

[0005] Objectives of the invention: The first objective of this invention is to provide an acylursodeoxycholic acid compound; the second objective is to provide a method for preparing the compound; the third objective is to provide a pharmaceutical composition comprising the compound; and the fourth objective is to provide an application of the compound and the pharmaceutical composition thereof.

[0006] Technical solution: The ursodeoxycholic acid compounds of the present invention have the structure of Formula 1, and further include their stereoisomers, geometric isomers, tautomers, deuterated compounds, pharmaceutically acceptable salts, or mixtures thereof:

[0007]

[0008] in:

[0009] R is selected from

[0010]

[0011] X, Y, and Z are each independently selected from C and N, and are not both C and N;

[0012] n is selected from 0, 1, 2, and 3;

[0013] R1, R2, R3, R4, and R5 are each independently selected from H, hydroxyl, cyano, amino, halogen, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, mercapto, C1-C6 alkoxy, C1-C6 alkylamino, 6-12 aryl, 6-12 aryl-substituted C1-C6 alkyl, 5-7 heteroaryl containing 1-3 N, O, or S, 5-7 heteroaryl-substituted C1-C6 alkyl containing 1-3 N, O, or S, 3-7 heterocyclic group containing 1-2 N, O, or S, 3-7 heterocyclic group substituted C1-C6 alkyl containing 1-2 N, O, or S, 3-7 cycloalkyl containing 0-3 double bonds, or 3-7 cycloalkyl-substituted C1-C6 alkyl containing 0-3 double bonds.

[0014] The 6-12 aryl groups, the 5-7 heteroaryl groups containing 1-3 N, O, and S, and the 3-7 heterocyclic groups containing 1-2 N, O, and S contain the following substituents: H, hydroxyl, cyano, amino, halogen, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, mercapto, C1-C6 alkoxy, and C1-C6 alkylamino.

[0015] Preferably, in the structure:

[0016] X and Y are independently selected from C and N, respectively, and Z is selected from N;

[0017] R1, R2, R3, R4, and R5 are each independently selected from H, hydroxyl, cyano, amino, halogen, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, mercapto, C1-C4 alkoxy, C1-C4 alkylamino, phenyl, naphthyl, phenyl or naphthyl-substituted C1-C4 alkyl, 5-6-membered heteroaryl containing 1-3 N, O, or S, 5-6-membered heteroaryl-substituted C1-C4 alkyl containing 1-3 N, O, or S, 3-6-membered heterocyclic group containing 1-2 N, O, or S, 3-6-membered heterocyclic group substituted C1-C4 alkyl containing 1-2 N, O, or S, 3-6-membered cycloalkyl containing 0-2 double bonds, or 3-6-membered cycloalkyl-substituted C1-C4 alkyl containing 0-2 double bonds.

[0018] The phenyl, naphthyl, 5-6 membered heteroaryl containing 1-3 N, O, S, and 3-6 membered heterocyclic containing 1-2 N, O, S contain the following substituents: H, hydroxyl, cyano, amino, halogen, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, mercapto, C1-C4 alkoxy, and C1-C4 alkylamino.

[0019] Further preferably, in the structure:

[0020] R1, R2, R3, R4, and R5 are each independently selected from H, halogen, cyano, C1-C4 alkyl, C1-C4 alkoxy, phenyl, and phenyl-substituted C1-C4 alkyl.

[0021] The phenyl group contains the following substituents: H, hydroxyl, cyano, amino, halogen, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, mercapto, C1-C4 alkoxy, and C1-C4 alkylamino.

[0022] Preferably, in the structure:

[0023] R is selected from

[0024]

[0025] n is selected from 0 or 1;

[0026] R1, R2, R3, R4, and R5 are each independently selected from H, hydroxyl, cyano, fluorine, chlorine, bromine, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, 2,2,2-trifluoroethoxy, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, phenyl, and benzyl.

[0027] The phenyl and benzyl groups contain the following substituents: H, hydroxyl, cyano, fluorine, chlorine, bromine, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, 2,2,2-trifluoroethoxy, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy.

[0028] Further preferably, in the structure:

[0029] R is selected from

[0030]

[0031] Specifically, when R1, R2, R3, and R4 are each independently selected from fluorine, chlorine, and bromine, the number can be one or two; when it is monosubstituted, the substituent positions are at R2, R3, and R4; when it is disubstituted, the substitution positions are at R2 and R3. When R5 is phenyl or benzyl, the substituent position on its benzene ring is at the para position.

[0032] More preferably, in the structure:

[0033] R is selected from

[0034]

[0035] Preferably, the bio-ursodeoxycholic acid compound is selected from any of the following compounds:

[0036]

[0037]

[0038] This invention modifies and transforms the structure of ursodeoxycholic acid to design a drug molecule with good anti-inflammatory activity and low toxicity.

[0039] Furthermore, the compound forms a pharmaceutically acceptable salt with any of the following acids: hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, citric acid, malic acid, tartaric acid, lactic acid, pyruvic acid, acetic acid, maleic acid, succinic acid, fumaric acid, salicylic acid, phenylacetic acid, or mandelic acid.

[0040] The preparation method of the compound of the present invention is as follows:

[0041] (1) When R is selected Then, it is subjected to Mannich reaction, condensation reaction and alkylation reaction with the intermediate of Formula 3 to obtain the compound of Formula 4;

[0042] (2) When R is selected from When it is alkylated with the intermediate of Formula 3, the compound of Formula 5 is obtained;

[0043] (3) When R is selected When it is alkylated with the intermediate of Formula 3, the compound of Formula 6 is obtained;

[0044]

[0045] The definitions of X, Y, Z, n, R1, R2, R3, R4, and R5 are as described above;

[0046] The corresponding acid is salted with the target compound of formula 1 or formula 2 prepared by the above method to obtain a pharmaceutically acceptable salt of the compound.

[0047] Specifically, the preparation method of the key intermediate is as follows:

[0048] (1) Intermediate containing R structure fragment

[0049] Starting materials are obtained from haloalkanes, benzyl bromo, iodobenzene, etc.

[0050]

[0051] (2) Intermediate of Equation 3

[0052] The intermediate of Formula 3 was obtained from ursodeoxycholic acid:

[0053]

[0054] In a specific implementation, the synthetic route of the target compound is as follows:

[0055]

[0056] The pharmaceutical composition of the present invention comprises the compound and a pharmaceutically acceptable carrier. Specifically, it may be formulated into a pharmaceutical preparation, such as a tablet, capsule, syrup, suspension, or injection, by adding pharmaceutical excipients such as flavorings, sweeteners, liquid / solid fillers, and diluents.

[0057] The compounds and pharmaceutical compositions described in this invention are used to prepare drugs for treating inflammation, specifically for inhibiting or treating inflammation of the digestive tract (colon cancer, rectal cancer, colon tumor, rectal tumor, colon cancer, rectal cancer, ulcerative colitis, polypoid adenoma, familial adenomatous polyposis, etc.), liver inflammation (liver disease, serum biochemical properties of liver function, bile flow, bile secretion of phospholipids or cholesterol, etc.), inflammatory skin diseases or severe pruritus (atopic dermatitis, acne, psoriasis, urticaria, inflammatory skin diseases, seborrheic dermatitis, contact dermatitis, etc.), acute inflammation of the gallbladder or bile ducts, chronic inflammation of the kidneys, and other inflammatory diseases.

[0058] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages:

[0059] These compounds have a highly effective inhibitory effect on inflammatory cells (IC50). 50 It has a concentration <10 μM and significantly inhibits NO production (P <0.01) without affecting normal cell viability. It has low cytotoxicity and can be prepared as an anti-inflammatory drug. Furthermore, the preparation method of this type of compound is simple and versatile. Attached Figure Description

[0060] Figure 1 The results show the effect of the compound on the viability of RAW264.7 cells;

[0061] Figure 2 The effect of the compound on LPS-induced NO production in RAW264.7 cells;

[0062] Figure 3 The effect of compound 4f on LPS-induced IC50 in RAW264.7 cells. 50 value. Detailed Implementation

[0063] The technical solution of the present invention will be further described below with reference to the embodiments.

[0064] Unless otherwise specified, all materials used in this invention are from commercial sources.

[0065] Example 1: Preparation of compound 1-benzyl-7-methylindole (1a)

[0066] 7-Methylindole (200 mg, 1.520 mmol) was dissolved in DMF (2 mL), and sodium cyanide (91.5 mg, 2.287 mmol) was slowly added at 0 °C. After reacting for 10 min, the mixture was allowed to stand at room temperature. Finally, benzyl chloride (289 mg, 2.287 mmol) was added dropwise. After the addition was complete, the mixture was allowed to react at room temperature for 1 h. The reaction was monitored by TLC until complete. The reaction was stopped, and the mixture was extracted with water (40 mL) and ethyl acetate (40 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography with petroleum ether-ethyl acetate = 100:1 (V / V). The final product was compound 1a, yield: 92.9%.

[0067] Example 2: Preparation of compound 1-benzylindole (1b)

[0068] Starting with indole and benzyl chloride, compound 1b was obtained by following the same synthetic method as compound 1a, with a yield of 94.0%.

[0069] Example 3: Preparation of compound 1-phenylindole (1c)

[0070] Starting with indole and iodomethane, the same synthetic method as for compound 1a was followed to obtain yellow liquid compound 1c, with a yield of 62.2%.

[0071] Example 4: Preparation of compound 1-methylindole (1d)

[0072] Starting with indole and p-fluorobenzyl chloride, the same synthetic method as for compound 1a was used to obtain yellow liquid compound 1d, with a yield of 90.7%.

[0073] Example 5: Preparation of compound 1-benzylindole (1e)

[0074] Starting with indole and p-chlorobenzyl chloride, the same synthetic method as for compound 1a was used to obtain yellow liquid compound 1e, with a yield of 94.1%.

[0075] Example 6: Preparation of compound 1-benzylindole (1f)

[0076] Starting with indole and p-bromobenzyl chloride, the same synthetic method as compound 1a was followed to obtain yellow liquid compound 1f, with a yield of 86.8%.

[0077] Example 7: Preparation of compound 1-benzylindole (1g)

[0078] Potassium carbonate (472 mg, 3.418 mmol) and cuprous oxide (73.4 mg, 0.513 mmol) were added to a DMF (4 mL) solution of indole (200 mg, 1.709 mmol), followed by iodobenzene (697 mg, 3.418 mmol). After the addition was complete, the reaction was carried out at 130 °C for 10 h. The reaction was stopped after TLC monitoring until complete. Water (40 mL) was added, and the mixture was extracted with dichloromethane (40 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography with petroleum ether-ethyl acetate = 100:1 (V / V) to give 1 g of the compound as a yellow liquid. Yield: 60.6%.

[0079] Example 8: Preparation of Compound 2

[0080] Piperazine (655.3 mg, 7.62 mmol) was dissolved in dichloromethane (40 mL), and 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (1.448 g, 3.81 mmol) and ursodeoxycholic acid (1.0 g, 2.54 mmol) were added. Finally, N,N-diisopropylethylamine (983 mg, 7.62 mmol) was added. After the addition was complete, the reaction was allowed to proceed at room temperature for 4 h. The reaction was stopped after TLC monitoring showed complete reaction, and water (100 mL) was added. The mixture was extracted with dichloromethane (60 mL × 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography with eluent: dichloromethane-methanol = 10:1 (V / V). The final product was a white compound 2, yield: 90.1%.

[0081] Yield:90.1%.mp:121.1-122.8℃; 1 H NMR(600MHz,CD3OD)δ3.67-3.53(m,4H),3.52-3.44(m,2H),2.97-2.86(m,2H),2.85-2.75(m,2H),2 .45(ddd,J=14.7Hz,10.9Hz,5.2Hz,1H),2.31(ddd,J=14.7Hz,10.6Hz,5.8Hz,1H),2.05(ddd,J=12.6 Hz,3.7Hz,2.8Hz,1H),1.95-1.72(m,5H),1.66-1.53(m,4H),1.52-1.42(m,6H),1.38-1.17(m,6H), 1.16-1.10(m,1H),1.04(td,J=14.2Hz,2.9Hz,1H),0.99(d,J=6.5Hz,3H),0.97(s,3H),0.72(s,3H); 13C NMR(150MHz,CD3OD)δ174.1,72.1,71.9,57.5,56.5,47.1,46.4,46.0,44.8,44.5,44.0,42.7, 41.5,40.7,38.6,38.0,37.0,36.1,35.2,32.8,31.1,31.0,29.8,28.0,23.9,22.4,19.1,12.6;

[0082] HRMS m / z calcd for C 28 H 49 N₂O₃[M+H] + :461.3743; found:461.3743.

[0083] Example 9: Preparation of compound 3a

[0084] HATU (496 mg, 1.304 mmol), indole-3-carboxylic acid (116 mg, 0.71 mmol), and finally DIEA (252 mg, 1.956 mmol) were added to a dichloromethane solution of compound 1 (300 mg, 0.652 mmol). After the addition was complete, the reaction was allowed to proceed at room temperature for 2 h. The reaction was stopped after TLC monitoring until complete. Water (100 mL) was added, and the mixture was extracted with dichloromethane (60 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography with an eluent of dichloromethane-methanol = 10:1 (v / v). The final product was a white compound 3a, with a yield of 52.3%.

[0085] Yield:52.3%.mp:170.6-171.9℃; 1 H NMR (600MHz, CD3OD) δ7.70 (d, J=

[0086] 7.9Hz,1H),7.65(s,1H),7.45(d,J=8.0Hz,1H),7.24-7.18(m,1H),7.17-7.12(m,1H),3.85-3.69(m,4H),3.68- 3.56(m,4H),3.52-3.43(m,2H),2.46(ddd,J=14.5Hz,10.9Hz,5.0Hz,1H),2.32(ddd,J=14.4Hz,10.5Hz,5.7Hz, 1H),2.02(ddd,J=12.5Hz,4.0Hz,2.9Hz,1H),1.94-1.73(m,5H),1.66-1.52(m,4H),1.50-1.40(m,6H),1.34-1. 14(m,6H),1.13-1.08(m,1H),1.01(td,J=14.2Hz,2.9Hz,1H),0.98(d,J=6.5Hz,,3H),0.95(s,3H),0.70(s,3H); 13 C NMR (150MHz, CD3OD) δ174.9,169.4,137.5,129.4,127.0,123.6,122.0,121.1,113.0,110.6,72.1,71.9,57.4,56.4,46. 9,44.8,44.4,44.0,42.9,41.5,40.7,38.6,38.0,37.0,36.1,35.1,32.8,31.2,31.0,29.8,28.0,24.0,22.4,19.2,12.7;

[0087] HRMS m / z calcd for C 37 H 54 N3O4[M+H] + :604.4114; found:604.4114.

[0088] Example 10: Preparation of compound 3b

[0089] Starting with indole-3-acetic acid, compound 3b was obtained by following the same synthetic method as compound 3a, with a yield of 60.3%.

[0090] Yield:60.3%.mp:139.5-140.7℃; 1H NMR(600MHz,CD3OD):~50:50mixture ofrotamers,*indicates amide rotamerδ7.59(d,J=7.9Hz,1H),7.35(dd,J=8.1Hz,3.9Hz,1H),7.15(s,1H),7.13-7.09(m,1H),7.06-6.98(m,1H),3.91(s,2H),3.69-3.54(m,4H),3.53-3.43(m,4H),3.30-3.27(m,1H),3.26-3.23(m,1H),2.42(ddd,J=14.7Hz,10.9Hz,5.0Hz,0.5H),*2.35(ddd,J=14.7Hz,10.9Hz,5.0Hz,0.5H),2.27(ddd,J=14.7Hz,10.5Hz,5.8Hz,0.5H),*2.20(ddd,J=14.7Hz,10.5Hz,5.8Hz,0.5H),2.08-1.97(m,1H),1.94-1.76(m,4H),1.75-1.52(m,5H),1.51-1.38(m,6H),1.36-1.13(m,6H),1.12-1.06(m,1H),1.03(td,J=14.2Hz,2.7Hz,1H),0.99-0.90(m,,3H),0.96(s,6H),0.70(s,1.5H)*0.68(s,1.5H); 13 C NMR(150MHz,CD3OD)δ174.9,174.9,173.1,173.1,138.1,128.3,128.2,124.2,124.2,122.8,122.7,120.1,120.0,119.5,119.4,112.4,112.4,108.9,108.8,72.1,71.9,57.5,56.4,56.4,47.3,47.0,46.6,46.4,44.8,44.5,44.0,43.1,42.7,42.6,42.3,41.5,40.7,38.6,38.0,36.9,36.9,36.1,35.2,32.7,32.7,32.5,31.1,31.1,31.0,29.7,28.0,23.9,22.4,19.1,19.1,12.6;

[0091] HRMS m / z calcd for C 38 H 56 N3O4[M+H] +:618.4271; found:618.4275.

[0092] Example 11: Preparation of compound 3c

[0093] Starting with 6-methoxyindole-2-carboxylic acid, compound 3c was obtained by following the same synthetic method as compound 3a, with a yield of 77.7%.

[0094] Yield:77.7%.mp:144.8-146.1℃; 1 H NMR (600MHz, CD3OD) δ7.48 (d, J=

[0095] 8.8Hz,1H),6.93(d,J=2.2Hz,1H),6.82(s,1H),6.74(dd,J=8.8Hz,2.2Hz,1H),4.07-3.82(m,4H),3.83(s,3H),3 .72-3.62(m,4H),3.53-3.42(m,2H),2.50(ddd,J=14.8Hz,10.9Hz,5.1Hz,1H),2.35(ddd,J=14.8Hz,10.5Hz,5.8H z,1H),2.04(ddd,J=12.5Hz,3.7Hz,2.9Hz,1H),1.94-1.74(m,5H),1.66-1.53(m,4H),1.52-1.42(m,6H),1.38-1 .16(m,6H),1.16-1.09(m,1H),1.03(td,J=14.2Hz,3.1Hz,1H),1.00(d,J=6.5Hz,,3H),0.96(s,3H),0.72(s,3H); 13 C NMR (150MHz, CD3OD) δ175.0,165.2,159.6,138.9,128.9,123.5,123.0,112.8,107.2,94.6,72.1,71.9,57.5,56.5,55.8,4 6.6,44.8,44.5,44.0,42.7,41.5,40.7,38.6,38.0,37.0,36.1,35.2,32.8,31.2,31.0,29.8,28.0,23.9,22.4,19.1,12.7;

[0096] HRMS m / z calcd for C 38 H 56 N3O5[M+H] + :634.4220; found:634.4222.

[0097] The structures of 3a-3c are shown below:

[0098]

[0099] Example 12: Preparation of compound 4a

[0100] 37% formaldehyde (26.5 mg, 0.326 mmol) was added to a 1:1 (v / v) ethanol-water solution of compound 1 (100 mg, 0.217 mmol), followed by indole (25.4 mg, 0.217 mmol). After the addition was complete, the reaction was carried out at 60 °C for 2 h. The reaction was stopped after TLC monitoring showed complete reaction. Water (100 mL) was added, and the mixture was extracted with dichloromethane (60 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography with dichloromethane-methanol (10:1 (v / v) as eluent. The final product was a white compound 4a, yield: 61.7%.

[0101] Yield:61.7%.mp:122.4-124.2℃; 1 H NMR (600MHz, CD3OD) δ7.65 (ddd, J=

[0102] 7.9Hz,1.1Hz,0.7Hz,1H),7.35(ddd,J=8.1Hz,1.1Hz,0.7Hz,1H),7.21(s,1H),7.14-7.07(m,1H),7.06-7.00(m,1H),3.77(s,2 H),3.65-3.52(m,4H),3.51-3.44(m,2H),2.59-2.47(m,4H),2.41(ddd,J=14.5Hz,10.6Hz,5.1Hz,1H),2.27(ddd,J=14.5Hz,10 .3Hz, 6.1Hz, 1H), 2.02 (ddd, J=12.5Hz, 3.7Hz, 2.9Hz, 1H), 1.93-1.78 (m, 4H), 1.75-1.68 (m, 1H), 1.65-1.54 (m, 4H), 1.51-1.39 (m,6H),1.35-1.14(m,6H),1.12-1.06(m,1H),1.03(td,J=14.2Hz,3.1Hz,1H),0.97(s,3H),0.96(d,J=6.5Hz,3H),0.68(s,3H); 13C NMR (150MHz, CD3OD) δ174.7,138.0,129.3,126.1,122.5,120.0,119.8,112.3,110.8,72.1,71.9,57.5,56.5,54.0,53.9,53.5 ,46.8,44.8,44.5,44.0,42.5,41.5,40.7,38.6,38.0,36.9,36.1,35.2,33.0,31.2,31.0,29.8,28.0,23.9,22.4,19.1,12.6;

[0103] HRMS m / z calcd for C 37 H 56 N3O3[M+H] + :590.4322; found:590.4321.

[0104] Example 13: Preparation of compound 4b

[0105] Starting with 6-fluoroindole, compound 4b was obtained by following the same synthetic method as compound 4a, with a yield of 63.6%.

[0106] Yield:63.6%.mp:134.0-135.8℃; 1 H NMR (600MHz, CD3OD) δ7.61 (dd, J=

[0107] 8.7Hz,5.3Hz,1H),7.19(s,1H),7.05(dd,J=9.8Hz,2.3Hz,,1H),6.82(ddd,J=9.8Hz,8.7Hz,2.3Hz,1H),3.74(s,2H), 3.61-3.44(m,6H),2.59-2.45(m,4H),2.40(ddd,J=14.4Hz,10.7Hz,5.2Hz,1H),2.27(ddd,J=14.4Hz,10.3Hz,6.1Hz,1 H),2.01(ddd,J=12.5Hz,3.7Hz,2.6Hz,1H),1.93-1.77(m,4H),1.75-1.68(m,1H),1.65-1.53(m,4H),1.51-1.38(m,6H ),1.33-1.14(m,6H),1.11-1.06(m,1H),1.03(td,J=14.2Hz,2.9Hz,1H),0.96(s,3H),0.95-0.92(m,3H),0.68(s,3H); 13C NMR (150MHz, CD3OD) δ174.6, 161.1 (d, J = 253.3Hz), 138.0 (d, J = 13.2Hz), 126.5 (d, J =3.3Hz),125.9,120.8(d,J=10.1Hz),111.2,108.5(d,J=24.6Hz),98.2(d,J=26.0Hz ),72.1,71.9,57.5,56.5,54.0,54.0,53.5,46.8,44.8,44.5,44.0,42.5,41.5,40.7,38.6,38.0,36.9,36.1,35.2,32.9,31.2,31.0,29.8,28.0,23.9,22.4,19.1,12.6;

[0108] HRMS m / z calcd for C 37 H 55 FN3O3[M+H] + :608.4227; found:608.4229.

[0109] Example 14: Preparation of compound 4c

[0110] Starting with 7-fluoroindole, compound 4c was obtained by following the same synthetic method as compound 4a, with a yield of 38.9%.

[0111] Yield:38.9%.mp:135.7-137.5℃; 1 H NMR (600MHz, CD3OD) δ7.45 (d, J=

[0112] 7.9Hz,1H),7.26(s,1H),6.97(ddd,J=7.9Hz,7.7Hz,4.6Hz,1H),6.84(dd,J=7.7Hz,3.6Hz,1H),3.94(s,3H),3.78(s,2H ),3.64-3.44(m,6H),2.59-2.47(m,4H),2.40(ddd,J=14.5Hz,10.7Hz,5.2Hz,1H),2.27(ddd,J=14.5Hz,10.3Hz,6.0Hz,1 H),2.00(ddd,J=12.4Hz,3.5Hz,2.8Hz,1H),1.92-1.77(m,4H),1.75-1.68(m,1H),1.65-1.53(m,4H),1.51-1.37(m,6H) ,1.34-1.12(m,6H),1.10-1.05(m,1H),1.02(td,J=14.2Hz,2.9Hz,1H),0.96(s,3H),0.95(d,J=6.6Hz,3H),0.67(s,3H); 13 C NMR(150MHz,CD3OD)δ174.6,151.1(d,J=243.0Hz),133.2(d,J=5.6Hz),127.1,126 .0(d,J=13.3Hz),120.3(d,J=5.6Hz),115.9(d,J=3.0Hz),111.8,107.1,107.0,72 .1,71.9,57.4,56.4,53.9,53.8,53.5,46.7,44.8,44.5,44.0,42.5,41.5,40.7,38.6,38.0,36.9,36.1,35.2,32.9,31.1,31.0,29.8,28.0,23.9,22.4,19.1,12.6;

[0113] HRMS m / z calcd for C 37 H 55 FN3O3[M+H] + :608.4227; found:608.4226.

[0114] Example 15: Preparation of compound 4d

[0115] Starting with 5-chloroindole, compound 4d was obtained by following the same synthetic method as compound 4a, with a yield of 62.0%.

[0116] Yield:62.0%.mp:144.8-146.3℃; 1H NMR (600MHz, CD3OD) δ7.65 (d, J=

[0117] 1.9Hz,1H),7.32(d,J=8.6Hz,1H),7.23(s,1H),7.07(dd,J=8.6Hz,1.9Hz,1H),3.69(s,2H),3.59-3.41(m,6H), 2.56-2.42(m,4H),2.38(ddd,J=14.4Hz,10.8Hz,5.1Hz,1H),2.24(ddd,J=14.4Hz,10.3Hz,6.0Hz,1H),1.98(ddd ,J=12.5Hz,3.7Hz,2.6Hz,1H),1.91-1.76(m,4H),1.74-1.66(m,1H),1.64-1.52(m,4H),1.48-1.36(m,6H),1.3 0-1.10(m,6H),1.08-1.03(m,1H),1.00(td,J=14.2Hz,2.9Hz,1H),0.94(s,3H),0.93-0.90(m,3H),0.66(s,3H); 13 C NMR (150MHz, CD3OD) δ174.5,136.4,130.3,127.7,125.8,122.7,119.4,113.6,111.0,72.1,71.9,57.4,56.4,54.0,53.9,53.5 ,46.8,44.7,44.4,44.0,42.5,41.5,40.6,38.6,38.0,36.9,36.1,35.1,32.9,31.2,31.0,29.8,28.0,24.0,22.4,19.2,12.7;

[0118] HRMS m / z calcd for C 37 H 55 ClN3O3[M+H] + :624.3932; found:624.3936.

[0119] Example 16: Preparation of compound 4e

[0120] Starting with 7-chloroindole, compound 4e was obtained by following the same synthetic method as compound 4a, with a yield of 62.6%.

[0121] Yield:62.2%.mp:137.2-138.9℃; 1 H NMR (600MHz, CD3OD) δ7.62 (dd, J=

[0122] 7.9Hz,0.7Hz,1H),7.29(s,1H),7.13(d,J=7.5Hz,1H),7.01(dd,J=7.9Hz,7.7Hz,1H),3.78(s,2H),3.64-3.43(m, 6H),2.59-2.46(m,4H),2.40(ddd,J=14.5Hz,10.7Hz,5.2Hz,1H),2.28(ddd,J=14.5Hz,10.3Hz,6.1Hz,1H),2.01(d dd,J=12.5Hz,3.7Hz,2.8Hz,1H),1.94-1.78(m,4H),1.76-1.68(m,1H),1.66-1.53(m,4H),1.52-1.38(m,6H),1.36 -1.13(m,6H),1.10-1.06(m,1H),1.03(td,J=14.2Hz,2.9Hz,1H),0.96(s,3H),0.94(d,J=6.6Hz,3H),0.67(s,3H); 13 C NMR (150MHz, CD3OD) δ174.6,135.0,131.0,127.2,122.0,120.9,118.9,117.7,112.3,72.1,71.9,57.5,56.5,54.0,53.9,53.5 ,46.8,44.8,44.5,44.0,42.5,41.5,40.7,38.6,38.0,36.9,36.1,35.2,32.9,31.1,31.0,29.8,28.0,23.9,22.4,19.1,12.6;

[0123] HRMS m / z calcd for C 37 H 55 ClN3O3[M+H] + :624.3932; found:624.3933.

[0124] Example 17: Preparation of compound 4f

[0125] Starting with 5,6-dichloroindole, compound 4f was obtained by following the same synthetic method as compound 4a, with a yield of 31.8%.

[0126] Yield:31.8%.mp:151.8-153.3℃; 1H NMR(600MHz,CD3OD)δ7.81(s,1H),7.51(s,1H),7.28(s,1H),3.70(s,2H),3.64-3.43(m,6H),2.56-2.43(m, 4H), 2.40 (ddd, J=14.5Hz, 11.0Hz, 5.1Hz, 1H), 2.27 (ddd, J=14.5Hz, 10.4Hz, 6.1Hz, 1H), 1.99 (ddd, J=12.3Hz ,3.5Hz,2.3Hz,1H),1.92-1.77(m,4H),1.75-1.68(m,1H),1.65-1.52(m,4H),1.50-1.37(m,6H),1.31-1.12 (m,6H),1.09-1.04(m,1H),1.02(td,J=14.2Hz,2.9Hz,1H),0.95(s,3H),0.94(d,J=6.6Hz,3H),0.66(s,3H); 13 C NMR (150MHz, CD3OD) δ174.6,136.9,129.0,128.5,126.1,123.8,121.2,113.9,111.3,72.1,71.9,57.4,56.4,54.0,53.8,53.5 ,46.8,44.8,44.5,44.0,42.6,41.5,40.7,38.6,38.0,36.9,36.1,35.2,32.9,31.2,31.0,29.8,28.0,24.0,22.4,19.1,12.6;

[0127] HRMS m / z calcd for C 37 H 55 Cl2N3O3[M+H] + :658.3542; found:658.3541.

[0128] Example 18: Preparation of 4g of compound

[0129] Starting with 5-bromoindole, the same synthetic method as compound 4a was followed to obtain compound 4g, yield: 57.2%.

[0130] Yield:57.2%.mp:147.5-149.0℃; 1 H NMR (600MHz, CD3OD) δ7.81 (d, J=

[0131] 1.8Hz,1H),7.28(d,J=8.6Hz,1H),7.24(s,1H),7.20(dd,J=8.6Hz,1.8Hz,1H),3.72(s,2H),3.65-3.52(m,4H),3. 51-3.44(m,2H),2.57-2.45(m,4H),2.41(ddd,J=14.5Hz,10.6Hz,5.1Hz,1H),2.28(ddd,J=14.5Hz,10.3Hz,6.1Hz ,1H),2.02(ddd,J=12.5Hz,3.7Hz,2.6Hz,,1H),1.95-1.77(m,4H),1.76-1.68(m,1H),1.66-1.52(m,4H),1.51-1. 39(m,6H),1.34-1.14(m,6H),1.13-1.06(m,1H),1.03(td,J=14.2Hz,2.9Hz,1H),1.00-0.90(m,6H),0.69(s,3H); 13 C NMR (150MHz, CD3OD) δ174.7,136.7,130.9,127.5,125.3,122.5,114.0,113.3,110.9,72.1,71.9,57.5,56.5,54.0,53.9,53.6 ,46.8,44.8,44.5,44.0,42.6,41.5,40.7,38.6,38.0,36.9,36.1,35.2,33.0,31.2,31.0,29.8,28.0,23.9,22.4,19.1,12.6;

[0132] HRMS m / z calcd for C 37 H 55 BrN3O3[M+H] + :668.3427; found:668.3422.

[0133] Example 19: Preparation of compound 4h

[0134] Starting with 6-bromoindole, compound 4h was obtained by following the same synthetic method as compound 4a, with a yield of 43.0%.

[0135] Yield:43.0%.mp:148.8-150.6℃; 1 H NMR (600MHz, CD3OD) δ7.55 (d, J=

[0136] 8.5Hz,1H),7.52(d,J=1.7Hz,1H),7.19(s,1H),7.13(d,J=8.5Hz,1.7Hz,1H),3.71(s,2H),3.61-3.43(m,6H),2. 56-2.41(m,4H),2.37(ddd,J=14.5Hz,10.7Hz,5.1Hz,1H),2.24(ddd,J=14.5Hz,10.3Hz,6.0Hz,1H),1.98(ddd,J =12.5Hz,3.9Hz,2.8Hz,1H),1.91-1.76(m,4H),1.73-1.66(m,1H),1.64-1.52(m,4H),1.49-1.34(m,6H),1.32-1 .10(m,6H),1.08-1.03(m,1H),1.00(td,J=14.4Hz,2.9Hz,1H),0.95(s,3H),0.93(d,J=6.5Hz,3H),0.65(s,3H); 13 C NMR (150MHz, CD3OD) δ174.5,138.8,128.2,126.9,123.2,121.4,115.9,115.2,111.4,72.1,71.9,57.4,56.4,53.9,53.8,53.5 ,46.8,44.7,44.4,44.0,42.6,41.5,40.7,38.6,38.0,36.9,36.1,35.1,32.9,31.2,31.0,29.8,28.0,24.0,22.4,19.1,12.7;

[0137] HRMS m / z calcd for C 37 H 54 BrN3O3[M+H] + :668.3427; found:668.3425.

[0138] Example 20: Preparation of compound 4i

[0139] Starting with 7-bromoindole, compound 4i was obtained by following the same synthetic method as compound 4a, with a yield of 59.3%.

[0140] Yield:59.3%.mp:138.0-139.9℃; 1 H NMR (600MHz, CD3OD) δ7.66 (dd, J=

[0141] 7.9Hz,0.8Hz,1H),7.29(s,1H),7.28-7.26(m,1H),6.95(dd,J=7.9Hz,7.7Hz,1H),3.76(s,2H),3.64-3.43(m,6H) ,2.58-2.46(m,4H),2.40(ddd,J=14.5Hz,10.6Hz,5.2Hz,1H),2.27(ddd,J=14.5Hz,10.3Hz,6.1Hz,1H),2.01(ddd ,J=12.5Hz,3.7Hz,2.9Hz,1H),1.92-1.78(m,4H),1.75-1.68(m,1H),1.65-1.53(m,4H),1.51-1.37(m,6H),1.35- 1.13(m,6H),1.10-1.05(m,1H),1.03(td,J=14.2Hz,3.1Hz,1H),0.96(s,3H),0.95(d,J=6.5Hz,3H),0.67(s,3H); 13 C NMR (150MHz, CD3OD) δ174.6,136.5,130.8,127.1,125.1,121.3,119.4,112.4,105.6,72.1,71.9,57.5,56.5,54.0,54.0,53.6 ,46.8,44.8,44.5,44.0,42.5,41.5,40.7,38.6,38.0,36.9,36.1,35.2,32.9,31.1,31.0,29.8,28.0,24.0,22.4,19.1,12.6;

[0142] HRMS m / z calcd for C 37 H 55 BrN3O3[M+H] + :668.3427; found:668.3431.

[0143] Example 21: Preparation of compound 4j

[0144] Starting with 5-cyanoindole, compound 4j was obtained by following the same synthetic method as compound 4a, with a yield of 49.0%.

[0145] Yield:49.0%.mp:158.7-160.5℃; 1 H NMR(600MHz,CD3OD)δ8.13(d,J=

[0146] 0.8Hz,1H),7.49(d,J=8.4Hz,1H),7.43-7.29(m,1H),3.76(s,2H),3.62-3.42(m,6H),2.59-2.44(m,4H), 2.40(ddd,J=14.4Hz,10.8Hz,5.1Hz,1H), 2.25(ddd,J=14.4Hz,10.3Hz,5.9Hz,1H), 1.97(ddd,J=12.5Hz, 3.5Hz,2.6Hz,1H),1.89-1.74(m,4H),1.73-1.67(m,1H),1.64-1.52(m,4H),1.47-1.37(m,6H),1.30-1.0 9(m,6H),1.07-1.02(m,1H),1.00(td,J=14.2Hz,2.9Hz,1H),0.94(s,3H),0.93-0.90(m,3H),0.65(s,3H); 13 C NMR (150MHz, CD3OD) δ174.5,139.9,129.0,128.5,126.0,125.3,121.9,113.6,112.6,102.7,72.1,71.8,57.4,56.4,54.0,53.7,5 3.5,46.8,44.7,44.4,43.9,42.6,41.5,40.6,38.6,38.0,36.9,36.1,35.1,32.9,31.2,31.0,29.7,27.9,24.0,22.3,19.2,12.7;

[0147] HRMS m / z calcd for C 38 H 55 N4O3[M+H] + :615.4274; found:615.4275.

[0148] Example 22: Preparation of compound 4k

[0149] Starting with 7-cyanoindole, compound 4k was obtained by following the same synthetic method as compound 4a, with a yield of 46.6%.

[0150] Yield:46.6%.mp:147.3-148.7℃; 1 H NMR (600MHz, CD3OD) δ8.01 (dd, J=

[0151] 8.0Hz,0.8Hz,1H),7.51(d,J=7.7Hz,1H),7.37(s,1H),7.16(dd,J=8.0Hz,7.7Hz,1H),3.78(s,2H),3.63-3.43(m, 6H),2.57-2.44(m,4H),2.40(ddd,J=14.5Hz,10.7Hz,5.1Hz,1H),2.26(ddd,J=14.5Hz,10.5Hz,5.9Hz,1H),2.02-1 .99(ddd,J=12.5Hz,3.7Hz,2.9Hz,1H),1.99(m,4H),1.75-1.67(m,1H),1.65-1.52(m,4H),1.50-1.36(m,6H),1.34 -1.12(m,6H),1.08-1.03(m,1H),1.01(td,J=14.2Hz,2.9Hz,1H),0.95(s,3H),0.94(d,J=6.6Hz,3H),0.66(s,3H); 13 C NMR (150MHz, CD3OD) δ174.6,137.7,130.2,128.0,127.6,125.8,120.1,118.2,112.9,95.4,72.1,71.9,57.4,56.4,54.0,53.6,5 3.5,46.8,44.7,44.4,44.0,42.6,41.5,40.7,38.6,38.0,36.9,36.1,35.1,32.9,31.2,31.0,29.8,27.9,24.0,22.4,19.1,12.6;

[0152] HRMS m / z calcd for C 38 H 55 N4O3[M+H] + :615.4274; found:615.4271.

[0153] Example 23: Preparation of compound 4l

[0154] Starting with 7-methoxyindole, compound 4l was obtained by following the same synthetic method as compound 4a, with a yield of 71.3%.

[0155] Yield:71.3%.mp:131.6-133.2℃; 1 H NMR (600MHz, CD3OD) δ7.23 (dd, J=

[0156] 7.9Hz,0.5Hz,1H),7.16(s,1H),6.96(dd,J=7.9Hz,7.7Hz,1H),6.64(d,J=7.7Hz,1H),3.94(s,3H),3.76(s,2H),3.63 -3.44(m,6H),2.59-2.47(m,4H),2.41(ddd,J=14.5Hz,10.7Hz,5.2Hz,1H),2.27(ddd,J=14.5Hz,10.4Hz,6.1Hz,1H),2 .01(ddd,J=12.5Hz,3.7Hz,2.9Hz,1H),1.93-1.78(m,4H),1.75-1.68(m,1H),1.65-1.53(m,4H),1.52-1.38(m,6H),1 .35-1.13(m,6H),1.11-1.05(m,1H),1.03(td,J=14.2Hz,3.1Hz,1H),0.96(s,3H),0.95(d,J=6.6Hz,3H),0.68(s,3H); 13 C NMR (150MHz, CD3OD) δ174.6,147.8,130.8,128.2,125.7,120.7,112.6,111.1,102.5,72.1,71.9,57.5,56.5,55.7,54.0,53.9,5 3.5,46.7,44.8,44.5,44.0,42.5,41.5,40.7,38.6,38.0,36.9,36.1,35.2,32.9,31.1,31.0,29.8,28.0,23.9,22.4,19.1,12.6;

[0157] HRMS m / z calcd for C 38 H 58 N3O4[M+H] + :620.4227; found:620.4229.

[0158] Example 24: Preparation of compound 4m

[0159] Starting with 7-methylindole, compound 4m was obtained by following the same synthetic method as compound 4a, with a yield of 77.1%.

[0160] Yield:77.1%.mp:119.6-121.3℃; 1 H NMR (600MHz, CD3OD) δ7.46 (d, J=

[0161] 7.9Hz,1H),7.19(s,1H),6.95(dd,J=7.9Hz,7.0Hz,1H),6.90(d,J=7.0Hz,1H),3.73(s,2H),3.63-3.43(m,6H),2.55-2.4 8(m,2H),2.48(s,3H),2.47-2.42(m,2H),2.36(ddd,J=14.4Hz,10.8Hz,5.2Hz,1H),2.22(ddd,J=14.4Hz,10.3Hz,5.9Hz, 1H),1.98(ddd,J=12.5Hz,3.7Hz,2.8Hz,1H),1.91-1.75(m,4H),1.73-1.66(m,1H),1.64-1.52(m,4H),1.49-1.35(m,6H) ,1.30-1.10(m,6H),1.07-1.02(m,1H),1.00(td,J=14.4Hz,3.0Hz,1H),0.94(s,3H),0.93(d,J=6.6Hz,3H),0.66(s,3H); 13 C NMR (150MHz, CD3OD) δ174.5,137.4,128.9,125.9,123.0,121.8,120.3,117.5,111.1,72.1,71.9,57.4,56.4,54.1,53.9,53.5,4 6.7,44.7,44.4,44.0,42.5,41.5,40.6,38.6,38.0,36.9,36.1,35.1,32.9,31.2,31.0,29.8,28.0,24.0,22.4,19.1,17.0,12.7;

[0162] HRMS m / z calcd for C 38 H 58 N3O3[M+H] + :604.4478; found:604.4481.

[0163] Example 25: Preparation of compound 4n

[0164] Starting with compound 1a, compound 4n was obtained by following the same synthetic method as compound 4a, with a yield of 83.7%.

[0165] Yield:83.7%.mp:111.9-113.8℃; 1 H NMR (600MHz, CD3OD) δ7.60 (d, J=

[0166] 7.9Hz,1H),7.32-7.26(m,2H),7.25-7.20(m,1H),7.02(dd,J=7.7Hz,7.4Hz,1H),7.00(s,1H),6.96-6.83(m,3H),5.55(s,2H),3.73(s,2H), 3.66-3.53(m,4H),3.50-3.39(m,2H),2.51(s,3H),2.50-2.43(m,4H),2.35(ddd,J=14.5Hz,11.3Hz,5.0Hz,1H),2.19(ddd,J=14.5Hz,10.9H z,5.5Hz,1H),1.99(ddd,J=12.7Hz,3.7Hz,2.9Hz,1H),1.92-1.87(m,1H),1.85-1.70(m,4H),1.69-1.55(m,4H),1.52-1.38(m,6H),1.35-1. 21(m,5H),1.14(td,J=12.9Hz,3.3Hz,1H),1.10-1.04(m,1H),1.01(td,J=14.2Hz,2.9Hz,1H),0.94(s,3H),0.93-0.88(m,3H),0.67(s,3H); 13 C NMR(150MHz,CD3OD)δ172.1,139.6,135.5,130.0,129.6,128.9,127.4,12 5.5,124.9,121.3,119.8,117.7,110.0,71.4,71.4,55.8,55.0,53.4,53.2 ,52.8,52.1,45.8,43.8,43.8,42.5,41.6,40.2,39.2,37.4,36.9,35.7,35 .0,34.2,31.6,30.4,30.4,29.8,28.8,27.0,23.5,21.2,19,6,18.7,12.2;

[0167] HRMS m / z calcd for C 45 H 64 N3O3[M+H] + :694.4948; found:694.4948.

[0168] Example 26: Preparation of compound 4o

[0169] Starting with compound 1b, compound 4o was obtained by following the same synthetic method as compound 4a, with a yield of 87.8%.

[0170] Yield:587.8%.mp:237.5-239.0℃; 1 H NMR (600MHz, CDCl3) δ7.74 (d, J=

[0171] 7.9Hz,1H),7.33-7.26(m,4H),7.19(ddd,J=7.9Hz,7.0Hz,0 / 9Hz,1H),7.15-7.10(m,3H),7.09-7.03(m,1H),5.30(s,2H),3.73(s,2H),3 .66-3.54(m,4H),3.49-3.39(m,2H),2.55-2.42(m,4H),2.35(ddd,J=14.7Hz,11.2Hz,5.0Hz,1H),2.19(ddd,J=14.7Hz,10.8Hz,5.5Hz,1 H),1.99(ddd,J=12.7Hz,3.5Hz,2.8Hz,1H),1.94-1.86(m,1H),1.82-1.72(m,4H),1.71-1.61(m,4H),1.52-1.41(m,6H),1.36-1.21(m,5 H),1.14(td,J=12.9Hz,3.7Hz,1H),1.10-1.04(m,1H),1.02(td,J=14.3Hz,3.1Hz,1H),0.94(s,3H),0.93(d,J=6.5Hz,3H),0.66(s,3H); 13 C NMR (150MHz, CDCl3) δ172.2,137.5,136.8,128.9,128.7,128.0,127.8,126.9,122.1,119.8,119.5,111.2,109.9,71.6,71.5,55.8,55.0,53 .6,53.2,52.9,50.1,45.9,43.9,42.5,41.7,40.2,39.3,37.4,36.9,3 5.7,35.0,34.2,31.6,30.4,29.8,28.8,27.0,23.5,21.3,18.7,12.3;

[0172] HRMS m / z calcd for C 44 H 62 N3O3[M+H] + :680.4791; found:680.4789.

[0173] Example 27: Preparation of compound 4p

[0174] Starting with 1g, compound 4p was obtained by following the same synthetic method as compound 4a, with a yield of 55.4%.

[0175] Yield:55.4%.mp:121.9-123.7℃; 1 H NMR (600MHz, CD3OD) δ7.76 (d, J=

[0176] 7.9Hz,1H),7.61-7.47(m,5H),7.44(s,1H),7.41-7.34(m,1H),7.23-7.17(m,1H),7.16-7.11(m,1H),3.83(s,2H),3. 67-3.43(m,6H),2.69-2.47(m,4H),2.40(ddd,J=14.5Hz,10.7Hz,5.2Hz,1H),2.28(ddd,J=14.5Hz,10.3Hz,6.0Hz,1H ),2.00(ddd,J=12.5Hz,3.7Hz,2.9Hz,1H),1.93-1.77(m,4H),1.76-1.68(m,1H),1.66-1.52(m,4H),1.51-1.38(m,6H ),1.32-1.14(m,6H),1.11-1.05(m,1H),1.02(td,J=14.2Hz,2.9Hz,1H),0.95(s,3H),0.94-0.91(m,3H),0.67(s,3H); 13 C NMR (150MHz, CD3OD) δ174.6,141.0,137.5,130.8,130.7,129.2,127.6,125.2,123.7,121.4,120.7,113.3,114.4,72.1,71.9,57.5,56.5,54.8 ,54.1,53.7,53.6,46.8,44.8,44.5,44.0,42.6,41.5,40.7,38.6,38.0 ,36.9,36.1,35.2,33.0,31.2,31.0,29.8,28.0,23.9,22.4,19.1,12.7;

[0177] HRMS m / z calcd for C 43 H 60 N3O3[M+H] + :666.4635; found:666.4633.

[0178] Example 28: Preparation of compound 4q

[0179] Starting with compound 1c, compound 4q was obtained by following the same synthetic method as compound 4a, with a yield of 56.5%.

[0180] Yield:56.5%.mp:122.4-124.2℃; 1 H NMR (600MHz, CD3OD) δ7.63 (d, J=

[0181] 7.9Hz,1H),7.30(d,J=8.3Hz,1H),7.20-7.12(m,1H),7.07(s,1H),7.06-7.03(m,1H),3.73(s,3H),3.70(s,2H),3.59 -3.39(m,6H),2.55-2.38(m,4H),2.35(ddd,J=14.5Hz,10.8Hz,5.1Hz,1H),2.21(ddd,J=14.5Hz,10.3Hz,5.9Hz,1H),1 .98(ddd,J=12.5Hz,3.9Hz,2.6Hz,1H),1.92-1.74(m,4H),1.72-1.65(m,1H),1.64-1.52(m,4H),1.49-1.34(m,6H),1 .29-1.09(m,6H),1.06-1.01(m,1H),0.99(td,J=14.2Hz,2.9Hz,1H),0.94(s,3H),0.93(d,J=6.6Hz,3H),0.66(s,3H); 13 C NMR (150MHz, CD3OD) δ174.3,138.5,130.4,129.7,122.6,120.1,120.1,110.3,110.2,72.0,71.8,57.4,56.4,53.9,53.8,53.4,4 6.7,44.7,44.4,43.9,42.5,41.5,40.6,38.6,38.0,36.9,36.1,35.1,32.9,32.9,31.2,31.1,29.8,28.0,24.0,22.4,19.2,12.7;

[0182] HRMS m / z calcd for C 38 H 58 N3O3[M+H] + :604.4478; found:604.4478.

[0183] Example 29: Preparation of compound 4r

[0184] Starting with 1d, compound 4r was obtained by following the same synthetic method as compound 4a, with a yield of 50.5%.

[0185] Yield:50.5%.mp:104.5-106.2℃; 1 H NMR (600MHz, CD3OD) δ7.73 (d, J=

[0186] 7.9Hz,1H),7.24(d,J=8.2Hz,1H),7.19(dd,J=8.2Hz,7.3Hz,1H),7.13(dd,J=7.9Hz ,7.3Hz,1H),7.09(d,J=8.5Hz,1H),7.08(d,J=8.5Hz,1H),7.05(s,1H),6.99(d,J=8. 5Hz,1H),6.97(d,J=8.5Hz,1H),7.03-6.93(m,2H),5.26(s,2H),3.74(s,2H),3.68- 3.51(m,4H),3.50-3.36(m,2H),2.59-2.40(m,4H),2.34(ddd,J=14.5Hz,11.2Hz,5.0 Hz,1H),2.18(ddd,J=14.5Hz,10.8Hz,5.5Hz,1H),1.98(ddd,J=12.7Hz,3.7Hz,2.6H z,1H),1.93-1.85(m,1H),1.82-1.71(m,4H),1.67-1.55(m,4H),1.52-1.37(m,6H),1 .36-1.26(m,4H),1.24-1.19(m,1H),1.13(td,J=12.9Hz,3.6Hz,1H),1.10-1.04(m,1 H),1.01(td,J=14.2Hz,2.9Hz,1H),0.94(s,3H),0.92(d,J=6.5Hz,3H),0.66(s,3H); 13C NMR (150MHz, CD3OD) δ172.2, 162.3 (d, J = 245.8Hz), 136.6, 133.2 (d, J = 3.2Hz), 128. 7,128.6,128.6,127.9,122.1,119.8,119.6,115.9,115.7,111.1,109.8,71.5,71.4 ,55.8,55.0,53.4,53.1,52.7,49.4,45.7,43.9,43.8,42.5,41.6,40.2,39.2,37.4,36.9,35.7,35.0,34.2,31.6,30.4,30.4,29.8,28.8,27.0,23.5,21.3,18.7,12.2;

[0187] HRMS m / z calcd for C 44 H 61 FN3O3[M+H] + :698.4697; found:689.4692.

[0188] Example 30: Preparation of compound 4s

[0189] Starting with 1e, the same synthetic method as compound 4a was used to obtain compound 4s, with a yield of 52.9%.

[0190] Yield:52.9%.mp:111.6-113.3℃; 1 H NMR (600MHz, CD3OD) δ7.69 (d, J=

[0191] 7.9Hz,1H),7.38-7.19(m,4H),7.18-6.99(m,4H),5.35(s,2H),3.79(s,2H),3.64-3.43(m,6H),2.65-2.44( m, 4H), 2.40 (ddd, J = 14.5Hz, 10.7Hz, 5.2Hz, 1H), 2.27 (ddd, J = 14.5Hz, 10.4Hz, 5.9Hz, 1H), 2.01 (ddd, J = 12. 5Hz,3.7Hz,2.9Hz,1H),1.93-1.77(m,4H),1.75-1.67(m,1H),1.66-1.53(m,4H),1.52-1.39(m,6H),1.33-1 .16(m,6H),1.11-1.06(m,1H),1.03(td,J=14.2Hz,3.2Hz,1H),0.96(s,3H),0.95-0.92(m,3H)0.68(s,3H);13 C NMR (150MHz, CD3OD) δ174.6,138.4,138.0,134.2,130.1,129.9,129.8,129.5,123.0,120.5,120.4,111.1,110.9,72.1,71.9,57.4,56.5,54.0 ,53.7,53.5,49.9,46.8,44.8,44.5,44.0,42.5,41.5,40.7,38.6,38.0 ,37.0,36.1,35.2,33.0,31.2,31.0,29.8,28.0,23.9,22.4,19.1,12.6;

[0192] HRMS m / z calcd for C 44 H 61 ClN3O3[M+H] + :714.4401; found:714.4399.

[0193] Example 31: Preparation of compound 4t

[0194] Starting with 1f, the same synthetic method as compound 4a was used to obtain compound 4t, with a yield of 34.9%.

[0195] Yield:34.9%.mp:113.9-115.8℃; 1 H NMR (600MHz, CD3OD) δ7.69 (d, J=

[0196] 7.9Hz,1H),7.42(d,J=8.5Hz,2H),7.28(d,J=8.3Hz,1H),7.26(s,1H),7.16-7.10(m,1H),7.09-7.05(m,1H),7.03(d,J=8.5Hz,2 H),5.34(s,2H),3.81(s,2H),3.64-3.43(m,6H),2.67-2.46(m,4H),2.40(ddd,J=14.4Hz,10.7Hz,5.2Hz,1H),2.27(ddd,J=14.4 Hz,10.5Hz,5.9Hz,1H),2.01(ddd,J=12.5Hz,3.7Hz,2.9Hz,1H),1.91-1.78(m,4H),1.74-1.67(m,1H),1.65-1.53(m,4H),1.51- 1.38(m,6H),1.33-1.14(m,6H),1.11-1.06(m,1H),1.03(td,J=14.2Hz,2.9Hz,1H),0.96(s,3H),0.95-0.91(m,3H),0.68(s,3H); 13 C NMR (150MHz, CD3OD) δ174.6,138.9,138.0,132.8,130.1,130.0,129.8,123.0,122.2,120.6,120.4,110.9,72.1,71.9,57.4,56.5,53.9,53 .7,53.4,50.0,46.7,44.8,44.5,44.0,42.5,41.5,40.7,38.6,38.0,3 7.0,36.1,35.2,33.0,31.2,31.0,29.8,28.0,23.9,22.4,19.1,12.6;

[0197] HRMS m / z calcd for C 44 H 61 BrN3O3[M+H] + :758.3896; found:758.3899.

[0198] The structure of 4a-4t is shown below:

[0199]

[0200] Example 32: Preparation of compound 5a

[0201] Potassium carbonate (150 mg, 1.085 mmol) was added to an ethanol solution of compound 1 (100 mg, 0.217 mmol), followed by 3-(chloromethyl)pyridine hydrochloride (0.543 mg, 89 mmol). After the addition was complete, the mixture was refluxed for 4 h. The reaction was stopped after TLC monitoring until complete, and the mixture was extracted with water (100 mL) and dichloromethane (60 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography with dichloromethane-methanol = 10:1 (V / V). The final product was a white compound 5a, with a yield of 54.6%.

[0202] Yield:54.6%.mp:127.6-129.4℃; 1 H NMR (600MHz, CD3OD) δ8.52 (d, J=

[0203] 1.7Hz,1H),8.46(dd,J=4.9Hz,1.5Hz,1H),7.86(ddd,J=7.9Hz,1.7Hz,1.5Hz,1H),7.43(dd,J=7.9Hz,4.9Hz,1H),3 .61(s,2H),3.60-3.53(m,4H),3.53-3.44(m,2H),2.54-2.39(m,5H),2.29(ddd,J=14.5Hz,10.4Hz,5.9Hz,1H),2.04 (ddd,J=12.7Hz,3.7Hz,2.9Hz,1H),1.95-1.79(m,4H),1.78-1.71(m,1H),1.65-1.53(m,4H),1.52-1.42(m,6H),1.3 6-1.16(m,6H),1.14-1.08(m,1H),1.03(td,J=14.2Hz,3.0Hz,1H),0.98(d,J=6.5Hz,3H),0.97(s,3H),0.71(s,3H); 13 C NMR (150MHz, CD3OD) δ174.6,150.8,149.1,139.3,135.4,125.2,72.1,71.9,60.5,57.5,56.5,54.2,53.7,46.9,44. 8,44.5,44.0,42.7,41.5,40.7,38.6,38.0,37.0,36.1,35.2,32.9,31.1,31.0,29.8,28.0,24.0,22.4,19.1,12.7;

[0204] HRMS m / z calcd for C 34 H 54N3O3[M+H] + :552.4165; found:552.4167.

[0205] Example 33: Preparation of compound 5b

[0206] Starting with 2-chloromethylquinoline hydrochloride, compound 5b was obtained by following the same synthetic method as compound 5a, with a yield of 68.9%.

[0207] Yield:68.9%.mp:107.5-109.3℃; 1 H NMR (600MHz, CD3OD) δ8.34 (d, J=

[0208] 8.5Hz,1H),8.02(d,J=8.5Hz,1H)),7.93(d,J=8.2Hz,1H),7.76(ddd,J=8.5Hz,7.0Hz,1.4Hz,1H),7.73(d,J=8.5Hz,1H),7.60(ddd,J =8.2Hz,7.0Hz,1.0Hz,1H),3.86(s,2H),3.68-3.56(m,4H),3.53-3.43(m,2H),2.62-2.49(m,4H),2.44(ddd,J=14.5Hz,10.7Hz,5.1Hz ,1H),2.30(ddd,J=14.5Hz,10.4Hz,5.9Hz,1H),2.02(ddd,J=12.5Hz,3.7Hz,2.9Hz,1H),1.94-1.71(m,5H),1.65-1.53(m,4H),1.51- 1.41(m,6H),1.33-1.16(m,6H),1.13-1.06(m,1H),1.02(td,J=14.2Hz,2.9Hz,1H),0.97(d,J=6.5Hz,,3H),0.96(s,3H),0.70(s,3H); 13 C NMR (150MHz, CD3OD) δ174.7,160.3,148.3,138.7,131.1,129.0,128.9,127.8,122.6,72.1,71.9,65.2,57.5,56.5,54.6,54.2 ,47.0,44.8,44.5,44.0,42.7,41.5,40.7,38.6,38.0,37.0,36.1,35.2,33.0,31.2,31.0,29.8,28.0,23.9,22.4,19.1,12.7;

[0209] HRMS m / z calcd for C38 H 56 N3O3[M+H] + :602.4322; found:602.4322.

[0210] Example 34: Preparation of compound 5c

[0211] Starting with 2-(chloromethyl)benzimidazole, compound 5c was obtained by following the same synthetic method as compound 5a, with a yield of 60.1%.

[0212] Yield:60.1%.mp:157.5-158.9℃; 1 H NMR (600MHz, CD3OD) δ7.54 (dd, J=

[0213] 5.9Hz, 3.2Hz, 2H), 7.23 (dd, J=5.9Hz, 3.2Hz, 2H), 3.84 (s, 2H), 3.72-3.55 (m, 4H), 3.54-3.42 (m, 2H), 2.67-2. 47(m,4H),2.43(ddd,J=14.5Hz,10.7Hz,5.1Hz,1H),2.30(ddd,J=14.5Hz,10.4Hz,6.0Hz,1H),2.02(ddd,J=12. 7Hz,3.9Hz,2.4Hz,1H),1.95-1.78(m,4H),1.77-1.70(m,1H),1.66-1.53(m,4H),1.51-1.39(m,6H),1.36-1.1 4(m,6H),1.13-1.07(m,1H),1.03(td,J=14.2Hz,2.9Hz,1H),0.97(d,J=6.5Hz,,3H),0.96(s,3H),0.69(s,3H); 13 C NMR (150MHz, CD3OD) δ174.7,153.0,123.6,115.7,72.1,71.9,57.5,56.5,56.5,54.4,54.0,46.9,44.8,44.5 ,44.0,42.7,41.5,40.7,38.6,38.0,37.0,36.1,35.2,32.9,31.1,31.0,29.8,28.0,23.9,22.4,19.1,12.6;

[0214] HRMS m / z calcd for C 35 H 52 N4O3[M+H] + :591.4274; found:591.4276.

[0215] Example 35: Preparation of compound 5d

[0216] Starting with 1-bromomethylnaphthalene, compound 5d was obtained by following the same synthetic method as compound 5a, with a yield of 67.0%.

[0217] Yield:67.0%.mp:124.5-126.3℃; 1 H NMR (600MHz, CD3OD) δ8.31 (d, J=

[0218] 8.3Hz,1H),7.86(d,J=8.3Hz,1H),7.81(d,J=7.7Hz,1H),7.56-7.46(m,2H),7.45-7.38(m,2H),3.94(s,2H),3.61-3. 42(m,6H),2.58-2.46(m,4H),2.42(ddd,J=14.5Hz,10.9Hz,5.1Hz,1H),2.28(ddd,J=14.4Hz,10.5Hz,5.9Hz,1H),2.0 3(ddd,J=12.5Hz,3.7Hz,2.9Hz,1H),1.94-1.78(m,4H),1.77-1.70(m,1H),1.65-1.53(m,4H),1.52-1.40(m,6H),1.3 6-1.15(m,6H),1.13-1.07(m,1H),1.03(td,J=14.2Hz,2.9Hz,1H),0.97(d,J=6.5Hz,,3H),0.96(s,3H),0.71(s,3H); 13 C NMR (150MHz, CD3OD) δ174.6,135.5,134.6,133.9,129.4,129.4,129.0,126.8,126.8,126.1,125.9,72.1,71.9,61.8,57.5,56.4,54. 5,54.1,47.0,44.8,44.5,44.0,42.8,41.5,40.7,38.6,38.0,37.0,36.1,35.2,33.0,31.2,31.0,29.8,28.0,23.9,22.4,19.1,12.7;

[0219] HRMS m / z calcd for C 39 H 57 N₂O₃[M+H] + :601.4369; found:601.4371.

[0220] Example 36: Preparation of compound 5e

[0221] Starting with 2-bromomethylnaphthalene, compound 5e was obtained by following the same synthetic method as compound 5a, with a yield of 62.1%.

[0222] Yield:62.1%.mp:117.7-113.2℃; 1 H NMR(600MHz,CD3OD)δ7.90-7.80(m,3H),7.78(s,1H),7.52(dd,J=8.4Hz,1.6Hz,1H),7.50-7.42(m,2H),3.71(s,2H),3.66 -3.53(m,4H),3.52-3.43(m,2H),2.59-2.45(m,4H),2.42(ddd,J=14.5Hz,10.8Hz,5.2Hz,1H),2.29(ddd,J=14.4Hz,10.4Hz ,6.0Hz,1H),2.02(ddd,J=12.5Hz,3.7Hz,2.9Hz,1H),1.95-1.78(m,4H),1.77-1.70(m,1H),1.66-1.33(m,4H),1.52-1.40( m,6H),1.35-1.14(m,6H),1.13-1.07(m,1H),1.03(td,J=14.2Hz,2.9Hz,1H),1.00-0.96(m,3H),0.96(s,3H),0.69(s,3H); 13 C NMR (150MHz, CD3OD) δ174.7,136.0,134.8,134.4,129.3,129.1,128.8,128.7,128.5,127.2,126.9,72.1,71.9,63.8,57.5,56.5,54. 3,53.9,46.9,44.8,44.5,44.0,42.6,41.5,40.7,38.6,38.0,37.0,36.1,35.2,33.0,31.2,31.0,29.8,28.0,23.9,22.4,19.1,12.6;

[0223] HRMS m / z calcd for C 39 H 57 N₂O₃[M+H] + :601.4369; found:601.4369.

[0224] Example 37: Preparation of compound 5f

[0225] Starting with 4-bromomethyl-7-methoxycoumarin, compound 5f was obtained by following the same synthetic method as compound 5a, with a yield of 66.4%.

[0226] Yield:66.4%.mp:125.1-126.7℃; 1 H NMR (600MHz, CD3OD) δ7.89 (d, J=

[0227] 8.9Hz,1H),6.94(dd,J=8.9Hz,2.5Hz,1H),6.91(d,J=2.5Hz,1H),6.39(s,1H),3.89(s,3H),3.72(s,2H),3.68-3.53 (m,4H),3.52-3.44(m,2H),2.65-2.49(m,4H),2.45(ddd,J=14.5Hz,10.9Hz,5.1Hz,1H),2.30(ddd,J=14.5Hz,10.5H z,5.8Hz,1H),2.04(ddd,J=12.7Hz,3.7Hz,2.6Hz,1H),1.94-1.72(m,5H),1.65-1.53(m,4H),1.52-1.42(m,6H),1.3 6-1.16(m,6H),1.15-1.08(m,1H),1.03(td,J=14.2Hz,2.9Hz,1H),0.99(d,J=6.5Hz,3H),0.97(s,3H),0.71(s,3H); 13 C NMR (150MHz, CD3OD) δ174.7,164.5,163.5,156.9,154.5,127.6,113.5,112.3,101.7,72.1,71.9,59.5,57.5,56.4,54.5,54.1 ,47.1,44.8,44.5,44.0,42.9,41.5,40.7,38.6,38.0,37.0,36.1,35.2,32.9,31.2,31.0,29.8,28.0,23.9,22.4,19.1,12.7;

[0228] HRMS m / z calcd for C 39 H 57 N₂O₆[M+H] + :649.4217; found:649.4214.

[0229] Example 38: Preparation of 5g of compound

[0230] Starting with 1-benzyl-3-(chloromethyl)-1H-indazole, the same synthetic method as compound 5a was followed to obtain compound 5g, yield: 43.8%.

[0231] Yield:43.8%.mp:104.8-106.3℃; 1 H NMR (600MHz, CD3OD) δ7.90 (d, J=

[0232] 8.2Hz,1H),7.48(d,J=8.5Hz,1H),7.43-7.33(m,1H),7.30-7.19(m,3H),7.18-7.11(m,3H),5.60(s,2H),3.95(s,2H), 3.67-3.40(m,6H),2.69-2.44(m,4H),2.40(ddd,J=14.5Hz,10.7Hz,5.0Hz,1H),2.26(ddd,J=14.5Hz,10.3Hz,5.9Hz,1 H),2.01(ddd,J=12.5Hz,3.9Hz,2.8Hz,1H),1.94-1.76(m,4H),1.75-1.67(m,1H),1.66-1.53(m,4H),1.52-1.37(m,6H ),1.34-1.13(m,6H),1.10-1.05(m,1H),1.02(td,J=14.0Hz,2.4Hz,1H),0.96(s,3H),0.95-0.88(m,3H),0.68(s,3H); 13 C NMR (150MHz, CD3OD) δ174.6,142.5,142.1,138.6,129.7,128.7,128.2,128.1,124.8,122.1,121.9,110.8,72.1,71.9,57.4,56.4,55.0,54 .2,53.8,53.3,46.8,44.8,44.4,44.0,42.6,41.5,40.7,38.6,38.0,3 6.9,36.1,35.2,33.0,31.2,31.0,29.8,28.0,24.0,22.4,19.1,12.7;

[0233] HRMS m / z calcd for C 43 H 61 N4O3[M+H] + :681.4744; found:681.4745.

[0234] The structure of 5a-5g is shown below:

[0235]

[0236] Example 39: Anti-inflammatory activity of the compound against LPS-induced RAW264.7 cells

[0237] 1. Effects on RAW264.7 cell viability

[0238] RAW264.7 cells in the logarithmic growth phase were used to prepare a single-cell suspension (2×10⁻⁶ cells / cells). 6 Cells (cells / mL) were seeded at 100 μL / well in 96-well plates. 100 μL of the compound was added to each well to achieve a final concentration of 20 μmol / L. An equal volume of complete culture medium containing DMSO was added to the normal control. After incubation for 24 h, 20 μL of CCK-8 was added to each well, and the cells were incubated for another 1 h. The absorbance of each well was then measured at 540 nm. Cell viability (%) = (drug group - blank group) / (control group - blank group) × 100%. Data are shown below. Figure 1 .

[0239] Figure 1 In this study, RAW264.7 cells were seeded in 96-well plates and treated with the indicated concentration of the compound for 24 h. Cell viability was determined by the CCK-8 assay. Data are expressed as mean ± standard deviation of three independent experiments. **P < 0.001 compared with the control group.

[0240] The results showed that, at a concentration of 20 μmol / L, only compounds 4a, 4d, 4m, and 4q exhibited significant cytotoxicity, while the other compounds showed no cytotoxicity or only weak cytotoxicity.

[0241] 2. Effects of LPS on NO content in RAW264.7 cells

[0242] The experimental groups were set as follows: normal control group (equal volume of complete culture medium containing DMSO), LPS (10 ng / mL) model group, and drug group (20 μmol / L). Dexamethasone (DEX, 10 μmol / L) was used as a positive control. RAW264.7 cells were introduced at a rate of 2 × 10⁻⁶ cells / year. 6 Cells were seeded at a density of [number] cells / mL in 96-well plates, followed by the addition of DEX, the drug group, and LPS. After culturing in a CO2 cell incubator for 24 h, 50 μL of cell culture supernatant was transferred to a new 96-well plate, and 50 μL each of Griess I and Griess II were added. The plates were shaken for 10 min to allow for complete reaction, and the absorbance of each well was measured at 540 nm. Specific data are shown below. Figure 2 and Figure 3 .

[0243] Figure 2In this study, RAW264.7 cells were treated with a synthetic compound (10 μM) and LPS (10 ng / mL) for 24 h, with the DEX group (10 μM) serving as a positive control. Data are expressed as mean ± standard deviation of three independent experiments. Compared with the normal control group, ## P < 0.01.

[0244] Figure 3 In comparison with the normal control group, ## P < 0.01; compared with the LPS model group, *P < 0.05, **P < 0.01.

[0245] Experimental results showed that at a concentration of 10 μM, most derivatives exhibited significant inhibitory effects (inhibition rate greater than 50%), and the inhibitory effect was stronger than that of the parent compound ursodeoxycholic acid. Among them, compound 4f showed the highest inhibitory effect (IC50). 50 The value is less than 5 μM.

Claims

1. A ursodeoxycholic acid compound, characterized in that, Selected from any of the following compounds, and also containing a pharmaceutically acceptable salt thereof:

2. The ursodeoxycholic acid compound according to claim 1, characterized in that, The pharmaceutically acceptable salt is a salt formed by the compound with any of the following acids: hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, citric acid, malic acid, tartaric acid, lactic acid, pyruvic acid, acetic acid, maleic acid, succinic acid, fumaric acid, salicylic acid, phenylacetic acid, or mandelic acid.

3. A method for preparing the ursodeoxycholic acid compound according to claim 1, characterized in that, (1) When R is selected When the intermediate containing the R-structure fragment is subjected to Mannich reaction, condensation reaction and alkylation reaction with the intermediate of Formula 3, the compound of Formula 4 is obtained. (2) When R is selected from When the intermediate containing the R structure fragment is alkylated with the intermediate of Formula 3, the compound of Formula 5 is obtained. (3) When R is selected At that time, the intermediate containing the R structure fragment is alkylated with the intermediate of Formula 3 to obtain the compound of Formula 6; Wherein, X, R1, R2, R3, R4, and R5 are defined as the substituents at the corresponding positions in the compound structure as described in claim 1; The target compound of Formula 1 prepared by the above method is salted with the corresponding acid to obtain a pharmaceutically acceptable salt of the compound.

4. A pharmaceutical composition, characterized in that, It comprises the ursodeoxycholic acid compound of claim 1 and a pharmaceutically acceptable carrier.

5. The use of a ursodeoxycholic acid compound of claim 1 or a pharmaceutical composition of claim 4 in the preparation of a medicament for treating inflammation.

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