Compound with triazolopyridine structure as well as synthesis method and application of compound

Abstract

The invention discloses a compound with a triazolopyridine structure as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The compound has a brand-new chemical structure, the unique skeleton and the optimized molecular weight endow the compound with excellent patent medicine potential, hydroxyl and other functional groups in the compound provide a wide space for chemical modification, and the development prospect of diversified pharmacological activity derivatives is indicated; the compound significantly inhibits uric acid activity, has efficacy superior to that of a traditional drug benzbromarone, has lower cytotoxicity, and is an ideal uric acid-reducing drug candidate; the synthetic route is simple, the conditions are mild, the raw materials are easy to obtain, industrial production is facilitated, the high purity of the product is ensured through an efficient separation means, a powerful guarantee is provided for clinical medication safety, and novel uric acid lowering drugs are expected to be developed.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to a class of triazolopyridine structure compounds, a synthesis method and an application thereof in the preparation of drugs for treating hyperuricemia. Background Art

[0002] Uric acid is the final product of purine catabolism and is produced by the decomposition of nucleic acids, purine-containing compounds, guanine, and adenine. Under a normal purine diet, if the fasting blood uric acid level is higher than 420 μmol / L for men and higher than 360 μmol / L for women on two different days, it is considered hyperuricemia. At present, the prevalence of hyperuricemia and gout continues to rise worldwide, and is showing a trend of getting younger. Hyperuricemia is not only the direct cause of gout, but is also closely related to a variety of chronic diseases such as cardiovascular disease, diabetes, and kidney disease. It has become one of the important risk factors affecting human health after hypertension, hyperlipidemia, and diabetes.

[0003] At present, the uric acid-lowering drugs used clinically in my country mainly include drugs that promote uric acid excretion, such as benzbromarone, and drugs that inhibit uric acid production, such as allopurinol and febuxostat. However, these drugs have a variety of toxic side effects, which limit their clinical application. Benzbromarone can inhibit the activity of human uric acid transporter 1 (URAT1), inhibit the reabsorption of uric acid in the proximal renal tubules, promote the excretion of uric acid, reduce uric acid levels, reduce the formation and deposition of uric acid crystals, and thus prevent the recurrence of gouty arthritis. However, benzbromarone has poor selectivity for URAT1 and was withdrawn from the market in Europe because it caused fulminant hepatic necrosis. Allopurinol, as a xanthine oxidase inhibitor, can inhibit the production of uric acid. However, allopurinol may cause hypersensitivity reactions in some patients and may also interact with certain drugs, affecting the efficacy or increasing the risk of adverse reactions. Febuxostat is a specific xanthine oxidase inhibitor with a strong uric acid-lowering effect, and can usually reach the target level of blood uric acid in a relatively short period of time. Its efficacy is significant, better than traditional drugs such as allopurinol and benzbromarone, but compared with other uric acid-lowering drugs on the market, the price of febuxostat is relatively high. In addition, its cardiovascular risk is slightly higher than that of allopurinol. It has certain risks for patients with a history of heart disease or stroke, and liver function indicators need to be monitored regularly during use. Therefore, existing uric acid-lowering drugs can no longer meet the needs of the growing number of patients with high uric acid levels, and there is an urgent need to develop a new generation of uric acid-lowering drugs with new structural types, significant uric acid-lowering effects, and stronger safety. Summary of the invention

[0004] In view of the current clinical use of uric acid-lowering drugs, which have many toxic and side effects, poor selectivity, high prices and cardiovascular risks, there is an urgent need to develop a new generation of drugs with new structural types that have higher selectivity, lower toxicity and more significant effects. The purpose of the present invention is to provide a class of triazolopyridine structure compounds, a synthesis method and their use in the preparation of drugs for treating hyperuricemia and anti-liver cancer drugs.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions:

[0006] The present invention provides a triazolopyridine structure compound, the structural formula of the triazolopyridine structure compound is as follows:

[0007]

[0008] Wherein, R1 is selected from any one or combination of hydrogen, halogen, C1-C20 alkyl, and C1-C20 alkoxy groups;

[0009] R2 is selected from any one or a combination of hydrogen, halogen, C1-C20 alkyl, and C1-C20 alkoxy groups.

[0010] The R1 is selected from any one of hydrogen, fluorine, chlorine, bromine, methyl, ethyl, methoxy, and ethoxy groups, and the R2 is selected from any one of hydrogen, fluorine, chlorine, bromine, methyl, ethyl, methoxy, and ethoxy groups.

[0011] The present invention provides a method for synthesizing the above-mentioned triazolopyridine structure compound, comprising:

[0012] S1, dissolving compound II and N,O-dimethylhydroxylamine hydrochloride, reacting, and separating to obtain intermediate IV. The specific reaction formula is as follows:

[0013]

[0014] The structural formula of compound II is Wherein, R2 is selected from any one or combination of hydrogen, halogen, C1-C20 alkyl, and C1-C20 alkoxy groups;

[0015] The structural formula of the intermediate IV is

[0016] S2, dissolving the intermediate IV and compound V obtained in S1, reacting, and separating to obtain the intermediate VI. The specific reaction formula is as follows:

[0017]

[0018] The structural formula of the compound V is Wherein, R1 is selected from any one or combination of hydrogen, halogen, C1-C20 alkyl, C1-C20 alkoxy group; the structural formula of the intermediate VI is

[0019] S3, dissolving the intermediate VI obtained in S2 and 4-acetylaminobenzenesulfonyl azide, reacting, and separating to obtain the intermediate VIII. The specific reaction is as follows:

[0020]

[0021] The structural formula of the intermediate VIII is:

[0022]

[0023] S4, dissolving the intermediate VIII obtained in S3 with lithium chloride, performing N2 protection reaction, and separating to obtain a triazolopyridine structure compound.

[0024] The molar ratio of compound II to N,O-dimethylhydroxylamine hydrochloride in S1 is 1:1-2, the catalyst is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) and 1-hydroxy-7-azabenzotriazole (HOAt), and the reaction is carried out at room temperature for 12-24 hours; column chromatography is used for separation, and petroleum ether and ethyl acetate in a volume ratio of 50:1 are used as the mobile phase.

[0025] The molar ratio of intermediate IV and compound V in S2 is 1:1-2, and the catalyst is n-butyl lithium.

[0026] The reaction temperature in S2 is 0-5°C and the reaction time is 12-24h. Column chromatography is used for separation, with petroleum ether and ethyl acetate in a volume ratio of 20:1 as the mobile phase.

[0027] The molar ratio of the intermediate VI and 4-acetylaminobenzenesulfonyl azide in S3 is 1:1-2, and the catalyst is 1,8-diazacyclo[5,4,0]undecene-7 (DBU).

[0028] The reaction time at room temperature in S3 is 12 to 24 hours, and column chromatography is used for separation, with petroleum ether and ethyl acetate in a volume ratio of 10:1 as the mobile phase.

[0029] The molar ratio of intermediate VIII to lithium chloride in S4 is 1:2-4, the reaction temperature is 120-140°C, the reaction time is 12-24h, and column chromatography is used for separation, with dichloromethane and anhydrous methanol in a volume ratio of 50:1 as the mobile phase.

[0030] Application of the above-mentioned triazolopyridine structure compound in the preparation of uric acid-lowering drugs.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] The triazolopyridine structure compound provided by the present invention has a brand-new skeleton structure, a smaller molecular weight and better drugability. The hydroxyl groups and other groups contained in the compound provide the possibility for subsequent chemical modification and derivatization, which is helpful to develop more derivatives with different pharmacological activities, which provides a basis for its unique pharmacological activity and drugability. The compound can significantly reduce the activity of uric acid, is better than the positive drug benzbromarone, and has lower cytotoxicity, so it can be used for the development of uric acid-lowering drugs.

[0033] The synthesis method provided by the present invention has clear steps, mild reaction conditions, is easy to operate and control, is conducive to realizing industrial production, and the raw materials required for the synthesis are easily available on the market, which reduces the production cost and the difficulty of obtaining the raw materials. Through efficient separation means such as column chromatography, a high-purity target compound can be obtained, thereby ensuring the quality and stability of the product.

[0034] The application provided by the present invention shows that the triazolopyridine structure compound of the present invention exhibits obvious uric acid lowering activity, and its effect is better than that of the traditional positive drug benzbromarone. This shows that the compound has potential advantages in regulating uric acid metabolism and provides a strong candidate for the development of new uric acid lowering drugs; in toxicity tests, these compounds show lower cytotoxicity than benzbromarone, indicating that they have fewer side effects on patients during use and are safer, providing a strong guarantee for clinical drug safety, and are expected to be developed into new uric acid lowering drugs. DETAILED DESCRIPTION

[0035] The following will clearly and completely describe the concept of the present invention and the technical effects produced in combination with the embodiments, so as to fully understand the purpose, characteristics and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by technicians in this field without creative work are all within the scope of protection of the present invention. The test methods used in the embodiments are all conventional methods unless otherwise specified; the materials, reagents, etc. used, unless otherwise specified, can all be reagents and materials obtained from commercial channels.

[0036] Example 1

[0037] This embodiment provides a triazolopyridine structure compound, and the specific synthesis process is as follows:

[0038] Step 1: Synthesis of intermediate IV-1

[0039]

[0040] In 5 mL of dichloromethane (DCM), add 3,5-dichloro-4-methoxybenzoic acid, i.e., compound II-1 (2.5 g, 11.3 mM), N,O-dimethylhydroxylamine hydrochloride, i.e., compound III (1.3 g, 21.3 mM), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 2.5 g, 5.5 mM), 1-hydroxy-7-azobenzotriazole (HOAt, 1.8 g, 13.5 mM), and stir at room temperature to react overnight. After the reaction is complete, use column chromatography to separate (petroleum ether: ethyl acetate = 50:1) to obtain intermediate IV-1 (3,5-dichloro-N,4-dimethoxy-N-methylbenzamide), 2 g of white solid, and a yield of 37.9%.

[0041] Step 2: Synthesis of intermediate VI-1

[0042]

[0043] Compound IV-1 (1.9 g, 7.2 mM), 2-methylpyridine, i.e., compound V-1 (0.74 g, 8.0 mM), and n-butyl lithium (n-BuLi, 3.4 g, 52.7 mM) were added to 5 mL of anhydrous tetrahydrofuran (THF) and reacted overnight at 0°C. After the reaction was complete, column chromatography was used for separation (petroleum ether: ethyl acetate = 20:1) to obtain intermediate VI-1 (1-(3,5-dichloro-4-methoxyphenyl)-2-(pyridin-2-yl)ethan-1-one), 0.3 g of yellow solid, with a yield of 14.1%.

[0044] Step 3: Synthesis of Intermediate VIII-1

[0045]

[0046] Compound VI-1 (200 mg, 0.68 mM), 4-acetylaminobenzenesulfonyl azide, i.e., compound VII (160 mg, 0.67 mM) and 1,8-diazacyclo[5,4,0]undecene-7 (DBU, 100 mg, 0.65 mM) were added to 3 mL of acetonitrile (MeCN), and the mixture was stirred at room temperature overnight. After the reaction was complete, the mixture was separated and purified by column chromatography (dichloromethane: anhydrous methanol = 10:1) to obtain intermediate VIII-1 ([1,2,3]triazolo[1,5-a]pyridin-3-yl(3,5-dichloro-4-methoxyphenyl)methanone), 170 mg of a yellow solid, with a yield of 81%.

[0047] Step 4: Preparation of triazolopyridine structure compound 1

[0048]

[0049] Compound VIII-1 (130 mg, 0.40 mM) and lithium chloride (LiCl, 51 mg, 1.2 mM) were added to 3 mL of DMF, and the mixture was heated at 130°C under N2 protection overnight. After the reaction was complete, column chromatography was used for separation and purification (dichloromethane: anhydrous methanol = 50:1) to obtain the target compound as a white solid (44 mg) with a yield of 36%.

[0050] The structural formula of triazolopyridine structure compound 1 is as follows:

[0051]

[0052] The compound 1 H NMR and HRMS data are as follows:

[0053] 1 H NMR (DMSO-d6, 400MHz): 7.50 (t, J = 6.7Hz, 1H), 7.90 (t, J = 8.7Hz, 1H), 8.46 (d, J = 8.7Hz, 1H), 8.49 (s, 2H), 9.39 (d, J = 6.9Hz, 1H). 11.30 (s, 1H). HRMS (ESI negative)m / zcalcd for C 13 H7Cl2N3O2(MH):305.9915; found305.9856.

[0054] Example 2

[0055] This embodiment provides a triazolopyridine structure compound based on embodiment 1, and the specific preparation process is as follows:

[0056] The first step is the synthesis of the intermediate 3,5-dichloro-N,4-dimethoxy-N-methylbenzamide

[0057]

[0058] In 5mL of DCM, add 3,5-dichloro-4-methoxybenzoic acid, i.e., compound II-1 (2.5g, 11.3mM), N,O-dimethylhydroxylamine hydrochloride, i.e., compound III (1.3g, 21.3mM), EDCI (2.5g, 5.5mM), 1-hydroxy-7-azobenzotriazole (HOAt, 1.8g, 13.5mM), and stir at room temperature to react overnight. After the reaction is complete, use column chromatography to separate (petroleum ether: ethyl acetate = 50:1) to obtain the intermediate 3,5-dichloro-N,4-dimethoxy-N-methylbenzamide, i.e., compound IV-1, as a white solid of 2g, with a yield of 37.9%.

[0059] Step 2: Synthesis of intermediate VI-2

[0060]

[0061] Compound IV-1 (1.9 g, 7.2 mM), 2-methylpyridine, i.e., compound V-1 (0.74 g, 8.0 mM), and n-butyl lithium (n-BuLi, 3.4 g, 52.7 mM) were added to 5 mL of anhydrous THF and reacted overnight at 0°C. After the reaction was complete, column chromatography was used for separation (petroleum ether: ethyl acetate = 20:1) to obtain intermediate VI-2, 0.3 g of yellow solid, with a yield of 14.1%.

[0062] Step 3: Synthesis of Intermediate VIII-2

[0063]

[0064] Compound VI-1 (200 mg, 0.68 mM), 4-acetylaminobenzenesulfonyl azide, i.e., compound VII (160 mg, 0.67 mM), and 1,8-diazacyclo[5,4,0]undecene-7 (DBU, 100 mg, 0.65 mM) were added to 3 mL of MeCN and stirred at room temperature for overnight reaction. After the reaction was complete, column chromatography was used for separation and purification (dichloromethane: anhydrous methanol = 10:1) to obtain the intermediate [1,2,3]triazolo[1,5-a]pyridin-3-yl(3,5-dichloro-4-methoxyphenyl)methanone, i.e., compound VIII-1, as a yellow solid of 170 mg, with a yield of 81%.

[0065] Step 4: Preparation of triazolopyridine structure compound 2

[0066]

[0067] Compound VIII-2 (130 mg, 0.40 mM) and lithium chloride (LiCl, 51 mg, 1.2 mM) were added to 3 mL of DMF. The mixture was heated at 130°C under N2 protection overnight. After the reaction was complete, the mixture was separated and purified by column chromatography (dichloromethane: anhydrous methanol = 50:1) to obtain the target compound 2 as a white solid (34 mg) with a yield of 36%.

[0068] The chemical structure of the prepared triazolopyridine compound 2 is:

[0069]

[0070] 1 H NMR and HRMS data are as follows:

[0071] 1H NMR (DMSO-d6, 400MHz): 7.58 (dt, J=2.6Hz, 7.3Hz, 1H), 8.20 (d, J=2.4Hz, 8.2Hz, 1H), 8.50 (s, 2H), 9.51 (dd, J=4.7Hz, 7.3Hz, 1H). HRMS (ESI negative) m / z calcdfor C 13 H6Cl2FN3O2(MH):323.9821; found 323.9751.

[0072] Example 3

[0073] In this example, on the basis of Examples 1-2, the triazolopyridine structure compound prepared by the present invention was tested for its in vivo uric acid lowering activity. The triazolopyridine structure compound 1 and the triazolopyridine structure compound 2 prepared by Examples 1 and 2 of the present invention were tested for their in vivo uric acid lowering activity.

[0074] The experimental animals were Kunming mice weighing about 20 g, purchased from the Experimental Animal Center of the Air Force Medical University. Reference J. Med. Chem. 2020, 63, 10829-10854, the uric acid-lowering effect of the compound in mice was tested under the condition of oral administration of 2 mg / kg, and the decrease rate of blood uric acid concentration was calculated.

[0075] The drugs used to establish the hyperuricemia model were hypoxanthine and potassium oxonate, and the solvent used was 0.5% sodium carboxymethyl cellulose (CMC-Na). Hypoxanthine was administered to mice by gavage, and potassium oxonate was injected into the abdomen of mice.

[0076] Sample solution preparation: The compound to be tested was prepared into a 0.2 mg / mL solution with 0.5% CMC-Na, hypoxanthine was prepared into 60 mg / mL, and potassium oxonate was prepared into 40 mg / mL.

[0077] The positive drug benzbromarone was prepared into a drug solution under the same conditions.

[0078] 25 mice were divided into 5 groups, 5 mice in each group, namely compound 1 group, compound 2 group, benzbromarone group, blank control group and modeling group. The blank control group was gavaged and intraperitoneally injected with 0.5% CMC-Na and blank solution, and the other 4 groups were gavaged with hypoxanthine suspension and intraperitoneally injected with potassium oxonate suspension and administered. After 4 hours, the mice were anesthetized, the eyeballs were removed to collect blood and then killed. After 30 minutes of coagulation, the blood was centrifuged, and the supernatant serum was taken. The serum uric acid concentration (SUA) was detected using an automatic biochemical analyzer.

[0079] Blood uric acid concentration reduction rate (DR) % = (model group - experimental value) / (model group - blank value) × 100%

[0080] The uric acid activity of mice after treatment in different groups is shown in Table 2.

[0081] Table 2: Uric acid concentration and decrease rate in mice of different groups

[0082]

[0083] As can be seen from the results in Table 2, the triazolopyridine structure compounds 1 and 2 of the present invention showed excellent performance in the in vivo uric acid lowering activity test. After oral administration, both compounds can effectively reduce SUA in hyperuricemia model mice, and their uric acid lowering effect is better than that of the commonly used positive drug benzbromarone.

[0084] Uric acid lowering effect: The SUA of mice in the compound 1 group dropped to 601 μM, and the blood uric acid concentration decreased by 25.42% compared with the modeling group; the SUA of mice in the compound 2 group dropped to 595 μM, and the blood uric acid concentration decreased by 26.41%; the SUA of mice in the benzbromarone group was 638 μM, and the blood uric acid concentration decreased by 19.72%; in comparison, the uric acid lowering effects of compounds 1 and 2 were more significant, which were 5.7% and 6.69% higher than those of benzbromarone, respectively, indicating that the triazolopyridine structure compounds of the present invention have better performance in lowering uric acid, which provides a strong experimental basis and theoretical basis for further development and research of these compounds as potential anti-hyperuricemia drugs.

[0085] Example 4

[0086] In this example, based on Example 1-2, the triazolopyridine structure compound prepared by the present invention was subjected to a hepatocyte proliferation inhibition experiment.

[0087] The cell line used was HepG2, which was purchased from the cell bank of Shanghai Institutes for Biological Sciences.

[0088] The culture medium was high-glucose DMEM+10% NBS+penicillin and streptomycin double antibodies.

[0089] Sample solution preparation: The test compound was dissolved in DMSO (Merck) to prepare a stock solution with a concentration of 100 mM. The stock solution was diluted with culture medium to prepare final drug concentrations of 1000 μM, 500 μM, 250 μM, 125 μM, 62.5 μM and 31.25 μM, respectively.

[0090] Benzbromarone was prepared as a reference solution under the same conditions.

[0091] The concentration of 8 × 10 4100 μL of cell suspension with a density of 100 cells / mL, i.e. 8000 cells / well, was placed in a 37°C, 5% CO2 incubator. After 24 hours, the upper culture medium was aspirated, and the culture medium containing the sample and the reference solution were added, 100 μL / well, and incubated at 37°C for 72 hours. 10 μL of CKK8 was added to each well and placed in an incubator. After 1 hour, the OD value at 450nm was measured with a MK-2 fully automatic microplate reader to calculate the half inhibitory concentration IC 50 The toxicity of the compounds to HepG2 cells is shown in Table 3 (unit: μM).

[0092] Table 3. In vitro inhibition of HepG2 proliferation by compounds 1 and 2 (IC 50 , μM)

[0093]

[0094] From the results in Table 3, it can be seen that compound 1 and compound 2 showed a certain inhibitory effect on the proliferation of HepG2 cells in vitro, and the half inhibitory concentration IC 50 320.9μM and 384.8μM respectively. Benzbromarone was used as a positive control drug, and its IC 50 The value was 31.68 μM, which was much lower than the IC values ​​of compound 1 and compound 2. 50 The results show that under the same experimental conditions, benzbromarone has a significantly stronger inhibitory effect on the proliferation of HepG2 cells than compound 1 and compound 2. It can be preliminarily judged that compound 1 and compound 2 have relatively low toxicity to HepG2 cells.

[0095] The above is only a preferred embodiment of the present invention, and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment as above, it is not used to limit the present invention. Any technician familiar with this patent can still use the technical content suggested above to make some changes or modify it into an equivalent embodiment with equivalent changes without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiment based on the technical essence of the present invention without departing from the content of the technical solution of the present invention still falls within the scope of the solution of the present invention.

[0096] The above contents are only for explaining the technical idea of ​​the present invention and cannot be used to limit the protection scope of the present invention. Any changes made on the basis of the technical solution in accordance with the technical idea proposed by the present invention shall fall within the protection scope of the claims of the present invention.

Claims

1. A triazolopyridine structure compound, characterized in that: The structural formula of the triazolopyridine structure compound is as follows: Wherein, R1 is selected from any one or combination of hydrogen, halogen, C1-C20 alkyl, and C1-C20 alkoxy groups; R2 is selected from any one or a combination of hydrogen, halogen, C1-C20 alkyl, and C1-C20 alkoxy groups.

2. A triazolopyridine structure compound according to claim 1, characterized in that: The R1 is selected from any one of hydrogen, fluorine, chlorine, bromine, methyl, ethyl, methoxy, and ethoxy groups, and the R2 is selected from any one of hydrogen, fluorine, chlorine, bromine, methyl, ethyl, methoxy, and ethoxy groups.

3. A method for synthesizing a triazolopyridine structure compound according to any one of claims 1 to 2, characterized in that: include: S1, dissolving compound II and N,O-dimethylhydroxylamine hydrochloride, reacting, and separating to obtain intermediate IV; The structural formula of compound II is Wherein, R2 is selected from any one or combination of hydrogen, halogen, C1-C20 alkyl, and C1-C20 alkoxy groups; The structural formula of the intermediate IV is S2, dissolving the intermediate IV and compound V obtained in S1, reacting, and separating to obtain the intermediate VI; The structural formula of the compound V is Wherein, R1 is selected from any one or combination of hydrogen, halogen, C1-C20 alkyl, and C1-C20 alkoxy groups; The structural formula of the intermediate VI is S3, dissolving the intermediate VI obtained in S2 and 4-acetylaminobenzenesulfonyl azide, reacting, and separating to obtain the intermediate VIII; The structural formula of the intermediate VIII is S4, dissolving the intermediate VIII obtained in S3 with lithium chloride, performing N2 protection reaction, and separating to obtain a triazolopyridine structure compound.

4. The method for synthesizing a triazolopyridine structure compound according to claim 3, characterized in that: The molar ratio of compound II and N,O-dimethylhydroxylamine hydrochloride in S1 is 1:1-2, the catalyst is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 1-hydroxy-7-azabenzotriazole, and the reaction is carried out at room temperature for 12-24 hours; column chromatography is used for separation, and petroleum ether and ethyl acetate in a volume ratio of 50:1 are used as the mobile phase.

5. The method for synthesizing a triazolopyridine structure compound according to claim 3, characterized in that: The molar ratio of intermediate IV and compound V in S2 is 1:1-2, and the catalyst is n-butyl lithium.

6. The method for synthesizing a triazolopyridine structure compound according to claim 3, characterized in that: The reaction temperature in S2 is 0-5°C and the reaction time is 12-24h. Column chromatography is used for separation, with petroleum ether and ethyl acetate in a volume ratio of 20:1 as the mobile phase.

7. The method for synthesizing a triazolopyridine structure compound according to claim 3, characterized in that: The molar ratio of the intermediate VI and 4-acetylaminobenzenesulfonyl azide in S3 is 1:1-2, and the catalyst is 1,8-diazacyclo[5,4,0]undecene-7.

8. The method for synthesizing a triazolopyridine structure compound according to claim 3, characterized in that: The reaction time at room temperature in S3 is 12 to 24 hours, and column chromatography is used for separation, with dichloromethane and anhydrous methanol in a volume ratio of 10:1 as the mobile phase.

9. The method for synthesizing a triazolopyridine structure compound according to claim 3, characterized in that: The molar ratio of intermediate VIII to lithium chloride in S4 is 1:2-4, the reaction temperature is 120-140°C, the reaction time is 12-24h, and column chromatography is used for separation, with dichloromethane and anhydrous methanol in a volume ratio of 50:1 as the mobile phase.

10. Use of the triazolopyridine structure compound according to any one of claims 1 to 2 in the preparation of uric acid-lowering drugs.

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