Aryl-containing sulfonamide compound as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of organic matter synthesis, and provides an aryl-containing sulfonamide compound as well as a preparation method and application thereof. The aryl-containing sulfonamide compound provided by the invention is the aryl-containing sulfonamide compound and the racemate, the optical isomer, the pharmaceutically acceptable salt and the hydrate of the aryl-containing sulfonamide compound. The solvate or the prodrug has an effective triglyceride accumulation inhibition effect and excellent protection activity on fatty liver diseases related to in-vivo metabolic dysfunction, is suitable for preparing a medicinal preparation capable of effectively treating liver inflammation related diseases, and provides a more effective and safer treatment choice for the liver inflammation related diseases.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to an aryl sulfonamide compound, its preparation method, and its application. Background Technology

[0002] The innate immune system, as a key defense against endogenous and exogenous foreign stimuli, initiates a moderate inflammatory response to eliminate pathogens and maintain bodily health. However, dysregulation of the inflammatory response is a common pathological basis for many major diseases. Under specific pathological conditions, immune dysregulation can lead to excessive or persistent inflammatory responses, forming harmful "cytokine storms" or chronic inflammatory states, causing widespread damage to the body's own tissues.

[0003] As a core organ for metabolism and immune regulation, the liver is highly susceptible to inflammatory damage. Metabolic dysfunction-associated fatty liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is one of the most common chronic liver diseases worldwide, with a significant progression stage being metabolic dysfunction-associated steatohepatitis (MASH). It is estimated that approximately 20%–30% of MASLD patients will develop MASH. With the increasing severity of obesity and metabolic syndrome, the prevalence of MASLD / MASH continues to rise.

[0004] The core pathological features of MASH are significant inflammatory infiltration in the liver, hepatocellular steatosis, and progressive fibrosis. The persistent inflammatory response in the liver is a key driver of the occurrence, development, and progression of MASH to more severe stages (such as cirrhosis, liver failure, and even hepatocellular carcinoma). This inflammatory state is intertwined with mechanisms such as profound disturbances in hepatic glucose and lipid metabolism and insulin resistance, creating a vicious cycle that accelerates disease progression. However, current treatments for MASLD / MASH face significant challenges: a lack of specific drugs: currently only Resmetirom is approved for the treatment of MASH, but it still has serious side effects. Limitations of existing treatments: lifestyle interventions (diet and exercise) are fundamental, but patient adherence is poor and their effectiveness is limited. Some exploratory drugs (such as PPAR agonists, FXR agonists, and GLP-1 receptor agonists) have shown some potential in clinical trials, but they generally suffer from insufficient efficacy, significant side effects (such as itching and dyslipidemia), limited applicability, or uncertain long-term safety. Urgent clinical need but slow research progress: Despite the large patient population and heavy disease burden of MASLD / MASH, the success rate of new drug development pipelines remains low. Developing novel therapeutics that can effectively block or reverse the progression of liver inflammation, steatosis, and fibrosis, with a good safety profile, represents a significant unmet clinical need.

[0005] Therefore, developing novel anti-inflammatory compounds with novel structures, significant activity, and good safety profiles for MASLD / MASH, which are characterized by liver inflammation as the core pathological feature, and exploring their application in the preparation of drugs for treating such diseases, is of great scientific significance and clinical application value. Summary of the Invention

[0006] In view of this, the present invention provides an aryl sulfonamide compound, its preparation method and application, to solve the problem of poor efficacy of existing drugs for treating inflammation-related diseases.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] This invention provides an aryl sulfonamide compound, wherein the aryl sulfonamide compound is a compound with the structure shown in Formula I or a racemic mixture, optical isomer, pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof;

[0009]

[0010] Wherein: R1 is selected from five-membered heterocycles, six-membered aromatic rings or heteroaromatic rings optionally substituted with 1 to 3 identical or different substituents, wherein the substituents are selected from hydrogen, halogen, alkyl, alkoxy, hydroxyl, alkylthio, monoalkyl-substituted amino, dialkyl-substituted amino, alkylamide, free carboxyl, salt-forming carboxyl, esterified carboxyl, amidated carboxyl, alkylsulfinyl, sulfonyl, alkyl acyl, carbamoyl, monoalkyl-substituted carbamoyl, dialkyl-substituted carbamoyl or alkyldioxy, pyrazole and phenyl;

[0011] R2 is selected from hydrogen, halogen, alkyl, alkoxy, substituted phenyl, substituted benzyl, hydroxyl, nitro, monoalkyl-substituted amino, dialkyl-substituted amino, and cyano.

[0012] Preferably, R1 is

[0013] Preferably, R2 is hydrogen, methyl, ethyl, acetyl, or...

[0014] The present invention also provides a method for preparing the above-mentioned aryl sulfonamide compounds, comprising the following steps:

[0015] 1) Mix amino-containing raw materials, dichloromethane, and 4-chloro-3-nitrobenzenesulfonyl chloride, and react to obtain an intermediate;

[0016] 2) The intermediate is mixed with piperazine-containing raw material, potassium carbonate, sodium iodide and anhydrous tetrahydrofuran, and reacted to obtain aryl sulfonamide compounds;

[0017] The structural formula of the intermediate is as follows:

[0018]

[0019] Preferably, in step 1), the mass ratio of the amino-containing raw material, dichloromethane, and 4-chloro-3-nitrobenzenesulfonyl chloride is 1:25-50:1.1-1.5; the amino-containing raw material is selected from 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one, 4-phenyl-2-aminothiazole, 5-amino-2-methoxypyridine, 1-phenylpyrazole-3-amine, or 4-(pyrazole-1-yl)aniline.

[0020] Preferably, the reaction temperature in step 1) is 0–25°C and the time is 12–20 h.

[0021] Preferably, in step 2), the mass ratio of the intermediate to the piperazine-containing raw material, potassium carbonate, sodium iodide, and anhydrous tetrahydrofuran is 1:1 to 1.5:0.5 to 1.5:0.5 to 1.5:25 to 100; the piperazine-containing raw material is selected from 1-[(2-nitrophenyl)methyl]piperazine, 1-[(3-nitrophenyl)methyl]piperazine, 1-[(4-nitrophenyl)methyl]piperazine, N-methylpiperazine, N-ethylpiperazine, N-acetylpiperazine, piperazine, 1-[(3-fluorophenyl)methyl]piperazine, 1-[(4-fluorophenyl)methyl]piperazine, 1-[(3-cyanophenyl)methyl]piperazine, 1-[(2-cyanophenyl)methyl]piperazine, or 1-[(4-cyanophenyl)methyl]piperazine.

[0022] Preferably, the reaction temperature in step 2) is 65–75°C and the time is 3–6 h.

[0023] The present invention also provides the application of the arylsulfonamide compounds prepared by the above-mentioned method in the preparation of pharmaceutical formulations for treating inflammation-related diseases.

[0024] Preferably, the inflammation-related diseases include hepatitis and / or non-alcoholic fatty liver disease.

[0025] As can be seen from the above technical solution, compared with the prior art, the beneficial effects of the present invention are as follows:

[0026] The aryl sulfonamide compounds of this invention have an effective inhibitory effect on triglyceride accumulation, alleviate cell damage and inflammatory response caused by a high-fat environment, and also have excellent protective activity against fatty liver disease related to metabolic dysfunction in vivo. At the same time, based on the pharmacological mechanism of the aryl sulfonamide compounds of this invention, which can inhibit triglyceride accumulation in cells, drug formulations that can effectively treat inflammation-related diseases can also be prepared, providing a more effective and safer treatment option for inflammation-related diseases. Attached Figure Description

[0027] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0028] Figure 1 This is a schematic diagram illustrating the activity of aryl sulfonamide compounds in Examples 1-39 in inhibiting the accumulation of triglycerides (TG) in HepG2 hepatocytes stimulated by oleic acid (OA) and palmitic acid (PA);

[0029] Figure 2 This is a schematic diagram illustrating the effect of aryl sulfonamide compounds in Example 39 on alleviating the physiological changes caused by impaired lipid metabolism in mouse hepatocytes; wherein, Figure 2 In the image, A represents the result of Oil Red staining; Figure 2 B in the figure represents the quantitative staining statistical bar chart; Figure 2 The 'C' in the diagram represents the triglyceride content. Figure 2 The diagram in the figure shows the expression level of the Fasn gene mRNA. Figure 2 The 'E' in the diagram represents the expression level of the Ehhach gene mRNA. Figure 2 In the image, "A" indicates Oil Red O staining, and "enlarge" enlarges the image. Figure 2 In B, the vertical axis represents the relative positive area; Figure 2 The vertical axis of C represents the triglyceride content; Figure 2 The vertical axes in D and E represent relative mRNA levels;

[0030] Figure 3 This is a schematic diagram illustrating the effect of aryl sulfonamide compounds in Example 39 on alleviating the physiological changes induced by HFD-induced MASLD in mice; wherein, Figure 3 In the diagram, A represents the expression level of alanine aminotransferase in mouse serum. Figure 3 B in the diagram represents the expression level of aspartate aminotransferase in mouse serum; Figure 3 The diagram in Figure C shows the expression level of triglycerides in mouse serum. Figure 3 In the diagram, D represents the total cholesterol expression level in mouse serum; Figure 3 The image shown is of a mouse liver (E). Figure 3 F in the image represents the result of Oil Red staining; Figure 3 In the image, G represents a staining pattern of mouse liver tissue. Figure 3 H in the figure represents the quantitative statistical bar chart of Oil Red staining; Figure 3 The "I" in the diagram represents the mouse NAS score results. Figure 3 The vertical axis in C and D represents the serum triglyceride concentration; Figure 3 In the letter E, "Liver" refers to the liver. Figure 3 In the F section, Oil Red O is used for staining with Oil Red O. Figure 3 In G, the vertical axis represents the relative positive area; Figure 3 The HE in H represents H&E staining, i.e., hematoxylin-eosin staining. Detailed Implementation

[0031] This invention provides an aryl sulfonamide compound, wherein the aryl sulfonamide compound is a compound with the structure shown in Formula I or a racemic mixture, optical isomer, pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof;

[0032]

[0033] Wherein: R1 is selected from five-membered heterocycles, six-membered aromatic rings or heteroaromatic rings optionally substituted with 1 to 3 identical or different substituents, wherein the substituents are selected from hydrogen, halogen, alkyl, alkoxy, hydroxyl, alkylthio, monoalkyl-substituted amino, dialkyl-substituted amino, alkylamide, free carboxyl, salt-forming carboxyl, esterified carboxyl, amidated carboxyl, alkylsulfinyl, sulfonyl, alkyl acyl, carbamoyl, monoalkyl-substituted carbamoyl, dialkyl-substituted carbamoyl or alkyldioxy, pyrazole and phenyl;

[0034] R2 is selected from hydrogen, halogen, alkyl, alkoxy, substituted phenyl, substituted benzyl, hydroxyl, nitro, monoalkyl-substituted amino, dialkyl-substituted amino, and cyano.

[0035] In this invention, R1 is

[0036] In this invention, R2 is hydrogen, methyl, ethyl, acetyl, or...

[0037] The present invention also provides a method for preparing the above-mentioned aryl sulfonamide compounds, comprising the following steps:

[0038] 1) Mix amino-containing raw materials, dichloromethane, and 4-chloro-3-nitrobenzenesulfonyl chloride, and react to obtain an intermediate;

[0039] 2) The intermediate is mixed with piperazine-containing raw material, potassium carbonate, sodium iodide and anhydrous tetrahydrofuran, and reacted to obtain aryl sulfonamide compounds;

[0040] The structural formula of the intermediate is as follows:

[0041] In this invention, the mass ratio of the amino-containing raw material, dichloromethane, and 4-chloro-3-nitrobenzenesulfonyl chloride in step 1) is 1:25-50:1.1-1.5, preferably 1:26-45:1.2-1.4, more preferably 1:28-40:1.25-1.35, and even more preferably 1:30-35:1.3; the amino-containing raw material is selected from 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one, 4-phenyl-2-aminothiazole, 5-amino-2-methoxypyridine, 1-phenylpyrazole-3-amine, or 4-(pyrazole-1-yl)aniline.

[0042] In this invention, the temperature of the reaction in step 1) is 0-25°C, preferably 2-20°C, more preferably 5-18°C, and even more preferably 10-15°C; the reaction time is 12-20h, preferably 13-18h, more preferably 15-17h, and even more preferably 16h.

[0043] In this invention, the mass ratio of the intermediate described in step 2) to the piperazine-containing raw material, potassium carbonate, sodium iodide, and anhydrous tetrahydrofuran is 1:1–1.5:0.5–1.5:0.5–1.5:25–100, preferably 1:1.1–1.4:0.6–1.4:0.6–1.4:30–80, more preferably 1:1.15–1.35:0.8–1.2:0.8–1.2:35–75, and even more preferably 1:1.2–1.3:0.9–1.1:0.9–1. 1:40-60; the piperazine-containing raw material is selected from 1-[(2-nitrophenyl)methyl]piperazine, 1-[(3-nitrophenyl)methyl]piperazine, 1-[(4-nitrophenyl)methyl]piperazine, N-methylpiperazine, N-ethylpiperazine, N-acetylpiperazine, piperazine, 1-[(3-fluorophenyl)methyl]piperazine, 1-[(4-fluorophenyl)methyl]piperazine, 1-[(3-cyanophenyl)methyl]piperazine, 1-[(2-cyanophenyl)methyl]piperazine or 1-[(4-cyanophenyl)methyl]piperazine.

[0044] In this invention, the reaction temperature in step 2) is 65-75°C, preferably 66-74°C, more preferably 68-72°C, and even more preferably 70°C; the reaction time is 3-6 hours, preferably 3.2-5.5 hours, more preferably 3.5-5 hours, and even more preferably 4 hours.

[0045] In this invention, the arylsulfonamide compounds represented by Formula I can react with acids to form their pharmaceutically acceptable salts; the acids may include inorganic or organic acids, and salts formed with the following acids are particularly preferred: hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, benzenesulfonic acid, naphthalenedisulfonic acid, acetic acid, propionic acid, lactic acid, trifluoroacetic acid, maleic acid, citric acid, fumaric acid, tartaric acid, benzenesulfonic acid, benzoic acid, or p-toluenesulfonic acid.

[0046] In this invention, the invention also includes a prodrug containing an aryl sulfonamide compound as shown in Formula I; the prodrug is a derivative of the compound shown in Formula I, which has weak or even no activity on its own, but is converted into the corresponding biologically active form under physiological conditions (e.g., through metabolism, solvation or other means) after administration; the derivatives of the aryl sulfonamide compounds of this invention can be used in combination with other active ingredients, as long as they do not produce other adverse effects, such as allergic reactions.

[0047] The present invention also provides the application of the arylsulfonamide compounds prepared by the above-mentioned method in the preparation of pharmaceutical formulations for treating inflammation-related diseases.

[0048] In this invention, the inflammation-related diseases include hepatitis and / or non-alcoholic fatty liver disease.

[0049] In this invention, the dosage form of the pharmaceutical preparation preferably includes one of the following: injection, tablet, capsule, aerosol, suppository, film, drop pill, external liniment, ointment, controlled-release agent, sustained-release agent, nano-formulation, and enteric-coated tablet; the pharmaceutical preparation can be administered orally or via parenteral route (e.g., intravenous, subcutaneous, intraperitoneal, or local). When the pharmaceutical preparation is unstable under gastric conditions, an enteric-coated tablet dosage form can be used.

[0050] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0051] Example 1

[0052] 1) Dichloromethane (5 g) and 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one (200 mg) were added to a 25 mL round-bottom flask and dissolved. 4-chloro-3-nitrobenzenesulfonyl chloride (277 mg) was added in portions at 0 °C, and the mixture was reacted at room temperature (25 °C) for 16 h. After the reaction was complete, the dichloromethane was evaporated under reduced pressure, and the product was dissolved in water. The aqueous layer was extracted with EtOAc. Finally, the combined organic extracts were dried over anhydrous sodium sulfate, and ethyl acetate was evaporated under reduced pressure. The mixture was then separated by column chromatography (PE:EA = 4:1) to obtain the intermediate.

[0053] 2) In a 25 mL round-bottom flask, the intermediate (50 mg) from step 1), 1-[(2-nitrophenyl)methyl]piperazine (57 mg), potassium carbonate (40 mg), and sodium iodide (44 mg) were added sequentially to anhydrous tetrahydrofuran (5 g), and the reaction was carried out at 70 °C for 4 h. After the reaction, the tetrahydrofuran was evaporated to dryness under reduced pressure, and the mixture was extracted with EA. The organic layer was washed three times with saturated sodium chloride solution and dried over anhydrous magnesium sulfate. Finally, the EA was evaporated to dryness under reduced pressure, and the mixture was separated by column chromatography (DCM:Methanol = 20:1) to obtain an aryl sulfonamide compound named N-(2,3-dimethyl-5-oxoylide-1-phenylpyrazol-4-yl)-3-nitro-4-{4-[(2-nitrophenyl)methyl]piperazine-1-yl}benzenesulfonamide, with the structural formula: The yield was 90%.

[0054] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.08(d,J=2.2Hz,1H),7.84(d,J=8.0Hz,1H),7.70 (dd,J=8.9,2.2Hz,1H),7.60–7.55(m,2H),7.50–7.42(m,3H),7.35(d,J=7.5Hz,1 H),7.31(dd,J=8.5,1.5Hz,3H),6.89(d,J=8.9Hz,1H),3.86(s,2H),3.21(s,3H), 3.02(t,J=4.7Hz,4H),2.53(t,J=4.9Hz,5H),2.41(s,3H).HRMS(ESI,m / z):calcd for C 28 H 30 N7O7S[M+H] + ,608.1927; found,608.1928.

[0055] Example 2

[0056] The only difference between Example 2 and Example 1 is that 1-[(2-nitrophenyl)methyl]piperazine in step 2) is replaced with 1-[(3-nitrophenyl)methyl]piperazine, while other conditions remain unchanged. This yields an aryl sulfonamide compound named N-(2,3-dimethyl-5-oxoylide-1-phenylpyrazol-4-yl)-3-nitro-4-{4-[(3-nitrophenyl)methyl]piperazine-1-yl}benzenesulfonamide, with the structural formula:

[0057] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.26(s,1H),8.17(d,J=8.3Hz,1H),8.11(d,J=2.2H z,1H),7.77(dt,J=8.8,2.9Hz,1H),7.71(d,J=7.6Hz,1H),7.54(t,J=7.9Hz,1H), 7.48(t,J=7.7Hz,2H),7.35(d,J=7.3Hz,1H),7.32(s,2H),6.99–6.93(m,1H),3.6 8(s,2H),3.21(s,3H),3.12(t,J=4.7Hz,4H),2.59(t,J=4.7Hz,4H),2.43(s,3H). 13 C NMR(100MHz,Chloroform-d)δ162.01,154.03,148.53,148.47,139.05,135.16,134.23,132.22,130.48,129.51,1 27.72,126.96,125.09,123.86,122.58,120.09,105.26,61.77,52.45,50.59,35.27,11.15.HRMS(ESI,m / z):calcd for C 28 H 30 N7O7S[M+H] + ,608.1927; found,608.1928.

[0058] Example 3

[0059] The only difference between Example 3 and Example 1 is that 1-[(2-nitrophenyl)methyl]piperazine in step 2) is replaced with 1-[(4-nitrophenyl)methyl]piperazine, while other conditions remain unchanged. This yields an aryl sulfonamide compound named N-(1,5-dimethyl-3-oxoylide-2-phenylpyrazol-4-yl)-3-nitro-4-{4-[(4-nitrophenyl)methyl]piperazine-1-yl}benzenesulfonamide, with the structural formula:

[0060] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.23(d,J=8.1Hz,2H),8.12(d,J=2.3Hz,1H),7.83–7.79(m,1H),7.56(d,J=8.3Hz,2H),7.47(t,J=7.8Hz,2H),7.34( t,J=7.5Hz,2H),7.28(s,2H),6.99(t,J=7.8Hz,1H),3.68(s,2H),3.20(s ,3H),3.13(t,J=4.6Hz,4H),2.59(t,J=4.7Hz,4H),2.45(d,J=2.5Hz,4H). 13 C NMR(100MHz,Chloroform-d)δ162.01,154.02,148.43,147.45,139.05,134.20,132.23,129.70,129.51,127.76,126 .96,125.13,123.75,120.13,105.20,61.88,52.53,35.26,11.16.Purity:95.5%,tR=2.66min.HRMS(ESI,m / z):calcd forC 28 H 30 N7O7S[M+H] + ,608.1927; found,608.1928.

[0061] Example 4

[0062] The difference between Example 4 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 4-phenyl-2-aminothiazole, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(3-nitrophenyl)methyl]piperazine. All other conditions remain unchanged, yielding an aryl sulfonamide compound named 3-nitro-4-{4-[(3-nitrophenyl)methyl]piperazine-1-yl}-N-(4-phenylthiazole-2-yl)benzenesulfonamide, with the structural formula:

[0063] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1H NMR (400MHz, Chloroform-d) δ8.27(d,J=9.5Hz,1H),8.16(d,J=8.3Hz,1H),7.83(d,J=7.2Hz,2H),7.72(d,J=7.4Hz,1H),7.60(d,J=2.3Hz,1H),7.53(t,J=7 .9Hz,1H),7.40(d,J=7.3Hz,3H),7.32(d,J=2.4Hz,2H),7.09(d,J=8.7Hz,1H) ,3.69(s,2H),3.09(t,J=4.7Hz,4H),2.65(s,4H).Purity:95.3%,tR=6.09min.

[0064] Example 5

[0065] The difference between Example 5 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 4-phenyl-2-aminothiazole, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(4-nitrophenyl)methyl]piperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 3-nitro-4-{4-[(4-nitrophenyl)methyl]piperazine-1-yl}-N-(4-phenylthiazole-2-yl)benzenesulfonamide, with the structural formula […].

[0066] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.35(s,1H),8.21(d,J=8.2Hz,2H),8.03(d,J=8.8Hz,1H),7.54(dd,J=12.5,7.6Hz,4H),7.44(d,J=7.1Hz,3H), 7.13(d,J=8.8Hz,1H),6.59(s,1H),3.69(s,2H),3.26–3.16(m,4H),2.70–2.57(m,4H).Purity:99.4%,tR=0.40min.HRMS(ESI,m / z):calcdfor C 26 H 25 N6O6S2[M+H] + ,581.1277;found,581.1279.

[0067] Example 6

[0068] The difference between Example 6 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 5-amino-2-methoxypyridine, while other conditions remain unchanged, yielding an aryl sulfonamide compound named N-(2-methoxypyridin-5-yl)-3-nitro-4-{4-[(2-nitrophenyl)methyl]piperazin-1-yl}benzenesulfonamide, with the structural formula:

[0069] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.15(d,J=2.2Hz,1H),7.83(dd,J=5.6,2.6Hz,2H),7.66(dd,J=8.9,2.3Hz,1H),7.56(d,J=4.4Hz,2H),7.50(dd,J=8.8, 2.7Hz,1H),7.44(dt,J=8.6,4.4Hz,1H),7.04(d,J=8.9Hz,1H),6.70(d,J=8 .8Hz,1H),3.88(d,J=2.1Hz,5H),3.17–3.12(m,4H),2.59(t,J=4.7Hz,4H). 13 C NMR(100MHz,Chloroform-d)δ162.92,150.00,148.43,142.95,139.48,136.23,132.53,132.01,12 8.53,126.80,126.07,124.68,120.20,111.54,58.96,53.86,52.45,50.60.HRMS(ESI,m / z):calcd for C 23 H 25 N6O7S[M+H] + ,529.1505;found,529.1506.

[0070] Example 7

[0071] The only difference between Example 7 and Example 1 is that 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one in step 1) is replaced with 1-phenylpyrazole-3-amine, while other conditions remain unchanged. This yields an aryl sulfonamide compound named 3-nitro-4-{4-[(2-nitrophenyl)methyl]piperazin-1-yl}-N-(1-phenylpyrazole-3-yl)benzenesulfonamide, with the structural formula:

[0072] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.26(s,1H),7.82(t,J=6.0Hz,3H),7.54(dd,J=13.3,6.4Hz,4H),7.44(d,J=7.9Hz,3H),7.2 8(d,J=6.9Hz,1H),7.04(d,J=8.9Hz,1H),6.50(d,J=2.6Hz,1H),3.87(s,2H),3.13(t,J=4.7Hz,4H),2.58(t,J=4.7Hz,4H). 13 CNMR(100MHz,Chloroform-d)δ149.99,148.51,146.93,139.48,132.47,131.93,131.13,129.57,128.60,126.92, 126.75,124.64,120.19,118.92,100.34,58.98,52.44,50.62.Purity:99.1%,tR=5.58min.HRMS(ESI,m / z):calcd for C 26 H 26 N7O6S[M+H] + ,564.1665;found,564.1666.

[0073] Example 8

[0074] The difference between Example 8 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 1-phenylpyrazole-3-amine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(3-nitrophenyl)methyl]piperazine. Other conditions remain unchanged, yielding an aryl sulfonamide compound named 3-nitro-4-{4-[(3-nitrophenyl)methyl]piperazine-1-yl}-N-(1-phenylpyrazole-3-yl)benzenesulfonamide, with the structural formula:

[0075] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1H NMR (400MHz, Chloroform-d) δ8.30 (d, J = 2.3Hz, 1H), 8.26 (t, J = 1.9Hz, 1H), 8.16 (dd, J = 8. 3,2.3Hz,1H),7.86(dd,J=8.9,2.3Hz,1H),7.82(d,J=2.6Hz,1H),7.70(d,J=7.6Hz,1H),7. 53(td,J=6.8,6.2,3.5Hz,3H),7.44(t,J=7.9Hz,2H),7.31(d,J=1.4Hz,1H),7.08(d,J=8. 9Hz, 1H), 6.52 (d, J = 2.5Hz, 1H), 3.68 (s, 2H), 3.23 (t, J = 4.8Hz, 4H), 2.63 (t, J = 4.8Hz, 4H). 13 CNMR(100MHz,Chloroform-d)δ148.53,148.48,146.96,139.48,135.14,131.96,129.58,129.46,128.6 3,126.91,126.77,123.86,122.63,120.26,118.94,100.35,61.78,52.48,50.57.HRMS(ESI,m / z):calcd for C 26 H 26 N7O6S[M+H] + ,564.1665;found,564.1666.

[0076] Example 9

[0077] The difference between Example 9 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 1-phenylpyrazole-3-amine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(4-nitrophenyl)methyl]piperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 3-nitro-4-{4-[(4-nitrophenyl)methyl]piperazine-1-yl}-N-(1-phenylpyrazole-3-yl)benzenesulfonamide, with the structural formula […].

[0078] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1H NMR(400MHz,Chloroform-d)δ8.28(d,J=2.3Hz,1H),8.21(d,J=8.2Hz,2H),7.87–7.78(m,2H),7.54(dd,J=8.2,4.7Hz,4H),7.43(t,J=7.8Hz,2 H),7.31(s,2H),7.07(d,J=8.9Hz,1H),6.51(d,J=2.6Hz,1H),3.68(s,2H),3.21(t,J=4.7Hz,4H),2.62(t,J=4.7Hz,4H).HRMS(ESI,m / z):calcd for C 26 H 26 N7O6S[M+H] + ,564.1665;found,564.1666.

[0079] Example 10

[0080] The only difference between Example 10 and Example 1 is that 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-3-one in step 1) is replaced with 4-(pyrazol-1-yl)aniline, while other conditions remain unchanged. This yields an aryl sulfonamide compound named 3-nitro-4-{4-[(2-nitrophenyl)methyl]piperazin-1-yl}-N-[4-(pyrazol-1-yl)phenyl]benzenesulfonamide, with the structural formula:

[0081] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.24(d,J=2.3Hz,1H),7.89(d,J=2.4Hz,1H),7. 83(d,J=8.0Hz,1H),7.74–7.68(m,2H),7.63–7.58(m,2H),7.58–7.54(m,2H),7 .45(ddd,J=8.6,5.3,3.6Hz,1H),7.26–7.19(m,2H),7.01(d,J=8.9Hz,1H),6. 48(t,J=2.1Hz,1H),3.88(s,2H),3.14(t,J=4.7Hz,4H),2.58(t,J=4.8Hz,4H). 13C NMR(100MHz,Chloroform-d)δ149.99,148.44,141.39,139.36,138.00,134.35,132.49,131.96,131.16,129.00,128.47,126.91, 126.81,124.64,123.16,120.36,120.16,107.99,58.96,52.44,50.60,29.79.Purity:97.7%,tR=6.87min.HRMS(ESI,m / z):calcd for C 26 H 26 N7O6S[M+H] + ,564.1665;found,564.1665.

[0082] Example 11

[0083] The difference between Example 11 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-3-one is replaced with 4-(pyrazol-1-yl)aniline, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(3-nitrophenyl)methyl]piperazine, with other conditions remaining unchanged, yielding an aryl sulfonamide compound named 3-nitro-4-{4-[(3-nitrophenyl)methyl]piperazine-1-yl}-N-[4-(pyrazol-1-yl)phenyl]benzenesulfonamide, with the structural formula […].

[0084] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.25(s,2H),8.15(d,J=8.2Hz,1H),7.89(d,J=2.6Hz,1H),7.71(q,J=9.1,6.5Hz,3H),7.61(d,J=8.4Hz,2H),7.5 3(t,J=7.9Hz,1H),7.23(d,J=8.4Hz,2H),7.04(d,J=8.9Hz,1H),6.48(d,J=2.7Hz,1H),3.68(s,2H),3.22(t,J=4.8Hz,4H),2.67–2.56(m,4H). 13C NMR(100MHz,Chloroform-d)δ148.54,148.40,141.41,139.46,138.00,135.13,134.35,132.02,129.47,126.93,126.81, 123.86,123.14,122.65,120.38,120.23,108.01,61.76,52.47,50.56.Purity:96.9%,tR=6.10min.HRMS(ESI,m / z):calcd forC 26 H 26 N7O6S[M+H] + ,564.1665;found,564.1666.

[0085] Example 12

[0086] The difference between Example 12 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-3-one is replaced with 4-(pyrazol-1-yl)aniline, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(4-nitrophenyl)methyl]piperazine, with other conditions remaining unchanged, yielding an aryl sulfonamide compound named 3-nitro-4-{4-[(4-nitrophenyl)methyl]piperazine-1-yl}-N-[4-(pyrazol-1-yl)phenyl]benzenesulfonamide, with the structural formula […].

[0087] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.29–8.18(m,3H),7.90(d,J=2.6Hz,1H),7.77–7.68(m,2H),7.63(d,J=8.5Hz,2H),7.55(d,J=8.3Hz,2 H),7.23(d,J=8.4Hz,2H),7.04(d,J=8.9Hz,1H),6.97(s,1H),6.50(s,1H),3.68(s,2H),3.23(t,J=4.7Hz,4H),2.63(t,J=4.7Hz,4H). 13C NMR(100MHz,Chloroform-d)δ148.39,147.45,141.42,139.47,138.02,134.32,132.02,129.65,126.92,126.81, 123.77,123.14,120.38,120.21,108.03,61.88,52.56,50.58.Purity:96.4%,tR=6.22min.HRMS(ESI,m / z):calcd for C 26 H 26 N7O6S[M+H] + ,564.1665;found,564.1665.

[0088] Example 13

[0089] The only difference between Example 13 and Example 1 is that 1-[(2-nitrophenyl)methyl]piperazine in step 2) is replaced with N-methylpiperazine, while other conditions remain unchanged. This yields an aryl sulfonamide compound named N-(2,3-dimethyl-5-oxoylide-1-phenylpyrazol-4-yl)-4-(4-methylpiperazine-1-yl)-3-nitrobenzenesulfonamide, with the structural formula:

[0090] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.15(d,J=2.3Hz,1H),7.84(dd,J=8.8,2.3Hz,1H),7.47(t,J=7.6Hz,2H),7.35(t,J=7.5Hz, 1H),7.28(d,J=7.6Hz,2H),7.02(d,J=8.9Hz,1H),3.20(s,3H),3.17(t,J=5.0Hz,4H),2.66(t,J=4.8Hz,4H),2.45(s,6H). 13 CNMR(100MHz,Chloroform-d)δ162.03,154.00,148.36,139.26,134.21,132.30,130.84,129.52,1 27.75,126.96,125.08,120.31,105.25,54.22,50.23,45.61,35.29,11.17.HRMS(ESI,m / z):calcd forC 22 H 27 N6O5S[M+H] +,487.1758; found,487.1764.

[0091] Example 14

[0092] The only difference between Example 14 and Example 1 is that 1-[(2-nitrophenyl)methyl]piperazine in step 2) is replaced with N-ethylpiperazine, while other conditions remain unchanged. This yields an aryl sulfonamide compound named N-(2,3-dimethyl-5-oxoylide-1-phenylpyrazol-4-yl)-4-(4-ethylpiperazine-1-yl)-3-nitrobenzenesulfonamide, with the structural formula:

[0093] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.13(s,1H),7.77(d,J=8.8Hz,1H),7.48(t,J=7.7Hz,2H),7.36(d,J=7.4Hz,1H),7.30(d,J=6 .7Hz,2H),6.98(d,J=8.8Hz,1H),3.20(s,8H),2.77–2.68(m,4H),2.63(q,J=7.0Hz,2H),2.42(s,3H),1.20(t,J=7.3Hz,3H). 13 C NMR(100MHz,Chloroform-d)δ162.01,153.98,148.27,139.35,134.18,132.33,131.06,129.54,127.79 ,126.91,125.14,120.32,105.20,52.31,51.93,50.09,35.26,11.34,11.16.HRMS(ESI,m / z):calcdfor C 23 H 29 N6O5S[M+H] + ,501.1915; found,501.1921.

[0094] Example 15

[0095] The only difference between Example 15 and Example 1 is that 1-[(2-nitrophenyl)methyl]piperazine in step 2) is replaced with N-acetylpiperazine, while other conditions remain unchanged. This yields an aryl sulfonamide compound named 4-(4-acetylpiperazine-1-yl)-N-(2,3-dimethyl-5-oxoylide-1-phenylpyrazol-4-yl)-3-nitrobenzenesulfonamide, with the structural formula:

[0096] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.17(d,J=2.2Hz,1H),7.85(dd,J=8.8,2.2Hz,1H),7.48(t,J=7.7Hz,2H),7.40–7.33(m,2H),7.28(s,1 H), 6.98 (d, J = 8.8Hz, 1H), 3.74 (t, J = 5.1Hz, 2H), 3.60 (t, J = 5.0Hz, 2H), 3.21 (s, 3H), 3.10 (q, J = 4.9Hz, 4H), 2.45 (s, 3H), 2.15 (s, 3H). 13 C NMR(100MHz,Chloroform-d)δ169.34,154.10,148.38,139.30,134.18,132.38,131.25,129.52,127.83,126.94,125.1 4,120.11,105.06,50.96,50.17,45.98,45.70,40.88,35.24,21.45.Purity:97.1%,tR=1.82min.HRMS(ESI,m / z):calcd for C 23 H 27 N6O6S[M+H] + ,515.1713;found,515.1714.

[0097] Example 16

[0098] The difference between Example 16 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 5-amino-2-methoxypyridine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with piperazine, while other conditions remain unchanged, yielding an aryl sulfonamide compound named N-(2-methoxypyridin-5-yl)-3-nitro-4-(piperazin-1-yl)benzenesulfonamide, with the structural formula as follows:

[0099] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1H NMR(400MHz,Chloroform-d)δ8.18(d,J=2.3Hz,1H),7.80(d,J=2.7Hz,1H),7.67(dd,J=8.9,2.3Hz,1H),7.52(dd,J=8.9,2.8 Hz,1H),7.07(d,J=8.9Hz,1H),6.74(d,J=8.8Hz,1H),3.92(s,3H),3.19(dd,J=6.3,3.4Hz,4H),3.05(dd,J=6.3,3.4Hz,4H). 13 C NMR(100MHz,Chloroform-d)δ162.33,148.46,141.64,139.78,135.52,132.00,130.09,127.09,126 .47,120.37,111.32,53.76,51.21,44.99,29.70.Purity:96.8%,tR=1.80min.HRMS(ESI,m / z):calcd for C 16 H 20 N5O5S[M+H] + ,394.1185; found,394.1186.

[0100] Example 17

[0101] The difference between Example 17 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 5-amino-2-methoxypyridine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with N-methylpiperazine, with other conditions remaining unchanged, to obtain an aryl sulfonamide compound named N-(2-methoxypyridin-5-yl)-4-(4-methylpiperazin-1-yl)-3-nitrobenzenesulfonamide, with the structural formula as follows:

[0102] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1H NMR(400MHz,Chloroform-d)δ8.17(d,J=2.3Hz,1H),7.81(d,J=2.7Hz,1H),7.67(dd,J=8.8,2.3Hz,1H),7.52(dd,J=8.8,2.8Hz,1H),7.08(d,J=8.9Hz, 1H),6.73(d,J=8.8Hz,1H),3.90(s,3H),3.23(t,J=4.8Hz,4H),2.60(t,J=4.9Hz,4H),2.38(s,3H).Purity:95.7%,tR=2.75min.HRMS(ESI,m / z):calcd for C17H 22 N5O5S[M+H] + ,408.1342;found,408.1342.

[0103] Example 18

[0104] The difference between Example 18 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 5-amino-2-methoxypyridine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with N-ethylpiperazine. Other conditions remain unchanged, yielding an aryl sulfonamide compound named 4-(4-ethylpiperazin-1-yl)-N-(2-methoxypyridin-5-yl)-3-nitrobenzenesulfonamide, with the structural formula:

[0105] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.15(d,J=2.2Hz,1H),7.82(d,J=2.7Hz,1H),7.67(d d,J=8.8,2.3Hz,1H),7.50(dd,J=8.8,2.7Hz,1H),7.06(d,J=8.9Hz,1H),6.69(d,J= 8.8Hz,1H),3.87(s,3H),3.22(t,J=4.9Hz,4H),2.61(t,J=4.9Hz,4H),2.51(q,J=7. 2Hz,2H),1.12(t,J=7.2Hz,3H).Purity:97.2%,tR=2.40min.HRMS(ESI,m / z):calcd for C 18 H 24 N5O5S[M+H] + ,422.1498; found,422.1494.

[0106] Example 19

[0107] The difference between Example 19 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 5-amino-2-methoxypyridine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with N-acetylpiperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 4-(4-acetylpiperazin-1-yl)-N-(2-methoxypyridin-5-yl)-3-nitrobenzenesulfonamide, with the structural formula as follows:

[0108] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.45(d,J=7.5Hz,1H),8.23(t,J=2.0Hz,1H),7.8 4(t,J=2.3Hz,1H),7.70(dt,J=8.9,2.0Hz,1H),7.53(dt,J=8.9,2.3Hz,1H),7. 08(dd,J=8.9,1.8Hz,1H),6.69(dd,J=8.8,1.7Hz,1H),3.87(d,J=1.8Hz,3H),3 .80(d,J=5.3Hz,2H),3.68(t,J=4.7Hz,2H),3.22(t,J=4.9Hz,4H),2.17(s,3H). 13 C NMR(100MHz,Chloroform-d)δ169.73,162.67,148.16,142.37,139.85,136.23,132.2 6,130.36,126.73,126.51,120.24,111.51,53.98,50.86,50.14,45.73,41.07,21.46.

[0109] Example 20

[0110] The difference between Example 20 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 1-phenylpyrazole-3-amine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with N-methylpiperazine. Other conditions remain unchanged, yielding an aryl sulfonamide compound named 4-(4-methylpiperazin-1-yl)-3-nitro-N-(1-phenylpyrazole-3-yl)benzenesulfonamide, with the structural formula:

[0111] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR (400MHz, Chloroform-d) δ8.28(d,J=2.4Hz,1H),7.84(dd,J=8.8,2.4Hz,1H),7.80(d,J=2.6Hz,1H),7.51(d,J=8.0Hz,2H),7.41(t,J= 7.8Hz,2H),7.28(d,J=7.2Hz,1H),7.07(d,J=8.9Hz,1H),6.49(d,J=2.6Hz,1H),3.22(t,J=4.7Hz,4H),2.64(t,J=4.8Hz,4H),2.40(s,3H). 13 C NMR(100MHz,Chloroform-d)δ148.44,147.28,139.54,131.92,130.19,129.57,128.44,126.80,126. 64,120.27,118.76,100.24,54.31,50.37,45.75.Purity:97.9%,tR=4.70min.HRMS(ESI,m / z):calcd for C 20 H 23 N6O4S[M+H] + ,443.1501;found,443.1502.

[0112] Example 21

[0113] The difference between Example 21 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 1-phenylpyrazole-3-amine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with N-ethylpiperazine. Other conditions remain unchanged, yielding an aryl sulfonamide compound named 4-(4-ethylpiperazine-1-yl)-3-nitro-N-(1-phenylpyrazole-3-yl)benzenesulfonamide, with the structural formula:

[0114] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1H NMR (400MHz, Chloroform-d) δ8.28(s,1H),7.84(d,J=9.1Hz,1H),7.81(d,J=2.6Hz,1H),7.52(d,J=8.0Hz,2H),7.42(t,J=7.7Hz,2H),7.27( s,1H),7.07(d,J=8.9Hz,1H),6.50(d,J=2.5Hz,1H),3.28–3.20(m,4H),2.66(t,J=4.8Hz,4H),2.55(q,J=7.2Hz,2H),1.14(t,J=7.1Hz,3H). 13 C NMR(100MHz,Chloroform-d)δ148.43,147.22,139.52,131.93,130.01,129.57,128.48,12 6.85,126.66,120.17,118.80,100.27,52.22,52.07,50.42,11.64.HRMS(ESI,m / z):calcd for C 21 H 25 N6O4S[M+H] + ,457.1658;found,457.1656.

[0115] Example 22

[0116] The difference between Example 22 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 1-phenylpyrazole-3-amine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with N-acetylpiperazine. Other conditions remain unchanged, yielding an aryl sulfonamide compound named 4-(4-acetylpiperazine-1-yl)-3-nitro-N-(1-phenylpyrazole-3-yl)benzenesulfonamide, with the structural formula:

[0117] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1H NMR(400MHz,Chloroform-d)δ8.35(d,J=2.3Hz,1H),7.90(dd,J=8.9,2.3Hz,1H ),7.83(d,J=2.6Hz,1H),7.57–7.51(m,2H),7.48–7.41(m,3H),7.10(d,J=8.9H z,1H),6.53(d,J=2.6Hz,1H),3.81(t,J=5.2Hz,2H),3.68–3.62(m,2H),3.20(p ,J=4.8Hz,4H),2.15(s,3H).Purity:96.2%,tR=2.89min.HRMS(ESI,m / z):calcd for C 21 H 23 N6O5S[M+H] + ,471.1451;found,471.1451.

[0118] Example 23

[0119] The difference between Example 23 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 4-(pyrazole-1-yl)aniline, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with piperazine, while other conditions remain unchanged, resulting in an aryl sulfonamide compound named 3-nitro-4-(piperazin-1-yl)-N-[4-(pyrazole-1-yl)phenyl]benzenesulfonamide, with the structural formula as follows:

[0120] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.27(d,J=2.3Hz,1H),7.89(d,J=2.5Hz,1H),7.78–7.74(m,1H),7.74–7.72(m,1H),7.65–7.59 (m,2H),7.29–7.25(m,2H),7.05(d,J=9.0Hz,1H),6.49(t,J=2.1Hz,1H),3.18(d,J=4.3Hz,4H),3.04(dd,J=6.0,3.6Hz,4H). 13C NMR(100MHz,Chloroform-d)δ148.11,141.19,140.44,135.28,132.25,131.79,127.25,126.32,122 .42,121.09,120.39,107.83,46.09,44.14,8.53.Purity:95.8%,tR=1.92min.HRMS(ESI,m / z):calcd for C 19 H 21 N6O4S[M+H] + ,429.1345; found,429.1346.

[0121] Example 24

[0122] The difference between Example 24 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 4-(pyrazole-1-yl)aniline, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with N-methylpiperazine. All other conditions remain unchanged, yielding an aryl sulfonamide compound named 4-(4-methylpiperazin-1-yl)-3-nitro-N-[4-(pyrazole-1-yl)phenyl]benzenesulfonamide, with the structural formula:

[0123] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.29(t,J=2.0Hz,1H),7.89(d,J=2.2Hz,1H),7.78 (dt,J=8.9,2.1Hz,1H),7.73(d,J=2.1Hz,1H),7.66–7.58(m,2H),7.29–7.24(m,2 H),7.08(dd,J=8.8,1.8Hz,1H),6.48(q,J=2.2Hz,1H),3.28(t,J=4.8Hz,4H),2. 76–2.66(m,4H),2.46(s,3H).Purity:95.0%,tR=2.07min.HRMS(ESI,m / z):calcd for C 20 H 23 N6O4S[M+H] + ,443.1501;found,443.1502.

[0124] Example 25

[0125] The difference between Example 25 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 4-(pyrazole-1-yl)aniline, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with N-ethylpiperazine, with other conditions remaining unchanged, to obtain an aryl sulfonamide compound named 4-(4-ethylpiperazine-1-yl)-3-nitro-N-[4-(pyrazole-1-yl)phenyl]benzenesulfonamide, with the structural formula as follows:

[0126] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.25(s,1H),7.89(s,1H),7.73(d,J=6.6Hz,2H),7.61(d,J=8.4Hz,2H),7.23(d,J=8.3Hz,2H),7 .05(d,J=8.9Hz,1H),6.48(s,1H),3.24(t,J=4.8Hz,4H),2.65(t,J=4.8Hz,4H),2.54(q,J=7.3Hz,2H),1.15(t,J=7.3Hz,3H). 13 C NMR(100MHz,Chloroform-d)δ148.36,141.37,139.42,137.93,134.48,132.01,129.26,126.9 4,126.80,123.14,120.37,120.23,107.97,52.27,52.12,50.42,11.72.HRMS(ESI,m / z):calcd forC 21 H 25 N6O4S[M+H] + ,457.1658;found,457.1659.

[0127] Example 26

[0128] The difference between Example 26 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 4-(pyrazole-1-yl)aniline, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with N-acetylpiperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 4-(4-acetylpiperazin-1-yl)-3-nitro-N-[4-(pyrazole-1-yl)phenyl]benzenesulfonamide, with the structural formula as follows:

[0129] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.31(t,J=2.2Hz,1H),7.89(t,J=2.3Hz,1H),7. 76(dt,J=8.9,2.3Hz,1H),7.72(t,J=2.0Hz,1H),7.65–7.58(m,2H),7.28–7.23 (m,2H),7.06(dd,J=8.9,2.2Hz,1H),6.49(q,J=2.2Hz,1H),3.82(t,J=4.5Hz, 2H), 3.67 (p, J = 2.6Hz, 2H), 3.21 (dt, J = 8.2, 4.7Hz, 4H), 2.17 (d, J = 2.3Hz, 3H). 13 C NMR(100MHz,Chloroform-d)δ169.73,148.17,141.34,139.76,137.79,134.70,132.24,130.46,127.0 1,126.73,123.02,120.41,120.25,108.02,50.83,50.13,45.72,41.07,21.48.HRMS(ESI,m / z):calcd for C 21 H 23 N6O5S[M+H] + ,471.1451;found,471.1451.

[0130] Example 27

[0131] The only difference between Example 27 and Example 1 is that 1-[(2-nitrophenyl)methyl]piperazine in step 2) is replaced with 1-[(3-fluorophenyl)methyl]piperazine, while other conditions remain unchanged. This yields an aryl sulfonamide compound named N-(2,3-dimethyl-5-oxoylide-1-phenylpyrazol-4-yl)-4-{4-[(3-fluorophenyl)methyl]piperazine-1-yl}-3-nitrobenzenesulfonamide, with the structural formula:

[0132] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1H NMR(400MHz,Chloroform-d)δ8.10(s,1H),7.75(d,J=8.7Hz,2H),7.47(t,J=7.9Hz,2H),7.30(s,4H),7. 11(s,2H),6.97(q,J=9.7,9.1Hz,2H),3.56(s,2H),3.20(s,3H),3.10(s,4H),2.55(s,4H),2.43(s,3H). 13 C NMR(100MHz,Chloroform-d)δ162.01,153.99,148.51,138.92,134.25,132.19,130.18,129.94,129.86,129.50,127.69,127.03,125.05 ,124.72,120.08,116.00,115.78,114.47,105.35,62.15,52.42,50.57,35.30,11.18.Purity:97.7%,tR=6.51min.HRMS(ESI,m / z):calcd for C 28 H 30 FN6O5S[M+H] + ,581.1982; found,581.1983.

[0133] Example 28

[0134] The only difference between Example 28 and Example 1 is that 1-[(2-nitrophenyl)methyl]piperazine in step 2) is replaced with 1-[(4-fluorophenyl)methyl]piperazine, while other conditions remain unchanged. This yields an aryl sulfonamide compound named N-(2,3-dimethyl-5-oxoylide-1-phenylpyrazol-4-yl)-4-{4-[(4-fluorophenyl)methyl]piperazine-1-yl}-3-nitrobenzenesulfonamide, with the structural formula:

[0135] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.14(s,1H),7.81(d,J=9.0Hz,1H),7.50(s,3H),7.37(s,5H),7.08 (s,2H),6.99(d,J=8.6Hz,1H),3.57(s,2H),3.23(s,3H),3.14(s,4H),2.58(s,4H),2.47(s,3H). 13C NMR(100MHz,Chloroform-d)δ162.00,153.96,148.50,138.89,134.22,132.19,129.50,127.71,127.04,125.07,120 .09,115.40,115.19,105.33,61.96,52.35,50.54,35.30,11.18.Purity:97.2%,tR=6.19min.HRMS(ESI,m / z):calcd for C 28 H 30 FN6O5S[M+H] + ,581.1982; found,581.1983.

[0136] Example 29

[0137] The difference between Example 29 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 4-phenyl-2-aminothiazole, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(3-fluorophenyl)methyl]piperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 4-{4-[(3-fluorophenyl)methyl]piperazine-1-yl}-3-nitro-N-(4-phenylthiazole-2-yl)benzenesulfonamide, with the structural formula […].

[0138] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ7.82(d,J=7.1Hz,2H),7.60(s,1H),7.40(q,J=7.0,6.6Hz,3H),7.30(d,J=7.1 Hz,3H),7.15–7.04(m,3H),6.98(t,J=8.6Hz,1H),3.58(s,2H),3.07(t,J=4.6Hz,4H),2.61(t,J=4.6Hz,4H).

[0139] Example 30

[0140] The difference between Example 30 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 4-phenyl-2-aminothiazole, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(4-fluorophenyl)methyl]piperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 4-{4-[(4-fluorophenyl)methyl]piperazine-1-yl}-3-nitro-N-(4-phenylthiazole-2-yl)benzenesulfonamide, with the structural formula […].

[0141] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR (400MHz, Chloroform-d) δ7.80 (s, 2H), 7.57 (s, 1H), 7.37 (s, 3H), 7.03 (s, 3H), 3.53 (s, 2H), 3.04 (s, 4H), 2.58 (s, 4H). Purity: 99.5%, tR=3.10min.

[0142] Example 31

[0143] The difference between Example 31 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 5-amino-2-methoxypyridine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(3-fluorophenyl)methyl]piperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 4-{4-[(3-fluorophenyl)methyl]piperazine-1-yl}-N-(2-methoxypyridin-5-yl)-3-nitrobenzenesulfonamide, with the structural formula […].

[0144] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.18(s,1H),7.83(s,1H),7.75–7.61(m,1H),7.53(d,J=8.7Hz,1H ),7.19–6.95(m,5H),6.73(d,J=8.5Hz,1H),3.92(s,3H),3.60(s,2H),3.24(s,4H),2.63(s,4H). 13CNMR(100MHz,Chloroform-d)δ162.93,148.43,142.93,139.42,136.26,132.00,129.99,129.91,126.85,126.0 9,124.71,120.18,115.99,115.78,114.56,114.35,111.55,62.18,53.87,52.45,50.59.HRMS(ESI,m / z):calcd for C 23 H 25 FN5O5S[M+H] + ,502.1560; found,502.1561.

[0145] Example 32

[0146] The difference between Example 32 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 5-amino-2-methoxypyridine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(4-fluorophenyl)methyl]piperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 4-{4-[(4-fluorophenyl)methyl]piperazine-1-yl}-N-(2-methoxypyridin-5-yl)-3-nitrobenzenesulfonamide, with the structural formula […].

[0147] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR (400MHz, Chloroform-d) δ8.18(s,1H),7.81(s,1H),7.67(d,J=8.9Hz,1H),7.53(d,J=8.9Hz,1H),7.32(d,J =10.7Hz,3H),7.05(t,J=8.9Hz,3H),6.74(d,J=8.8Hz,1H),3.92(s,3H),3.57(s,2H),3.23(s,4H),2.61(s,4H). 13 C NMR(100MHz,Chloroform-d)δ162.85,148.41,142.81,139.35,136.16,131.98,130.79,130.71,128.8 3,126.85,126.24,120.12,115.41,115.20,111.49,62.02,53.85,52.39,50.62.HRMS(ESI,m / z):calcd for C 23 H25 FN5O5S[M+H] + ,502.1560; found,502.1561.

[0148] Example 33

[0149] The difference between Example 33 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 1-phenylpyrazole-3-amine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(3-fluorophenyl)methyl]piperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 4-{4-[(3-fluorophenyl)methyl]piperazine-1-yl}-3-nitro-N-(1-phenylpyrazole-3-yl)benzenesulfonamide, with the structural formula […].

[0150] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.29(d,J=2.3Hz,1H),7.92–7.75(m,2H),7.53(d,J=8.0Hz,2H),7.43(t,J=7.8Hz,2H),7.32(d,J=8.3Hz,2H), 7.09(dd,J=14.4,7.7Hz,3H),6.98(td,J=8.5,2.6Hz,1H),6.52(d,J=2.6Hz,1H),3.57(s,2H),3.21(t,J=4.8Hz,4H),2.59(t,J=4.8Hz,4H). 13 C NMR(100MHz,Chloroform-d)δ148.50,147.01,139.50,139.38,131.92,129.96,129.88,129.57,128.57,126.96,126.73,124.72,120 .19,118.91,115.99,115.78,114.52,114.32,100.32,62.17,52.44,50.57,29.78.Purity:98.1%,tR=6.19min.HRMS(ESI,m / z):calcd for C 26 H 26 FN6O4S[M+H] + ,537.1720; found,537.1721.

[0151] Example 34

[0152] The difference between Example 34 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 1-phenylpyrazole-3-amine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(4-fluorophenyl)methyl]piperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 4-{4-[(4-fluorophenyl)methyl]piperazine-1-yl}-3-nitro-N-(1-phenylpyrazole-3-yl)benzenesulfonamide, with the structural formula […].

[0153] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.28(d,J=2.3Hz,1H),7.88–7.79(m,2H),7.53(d,J=8.0Hz,2H),7.44(d,J=7.6Hz,2H),7.31(d d,J=8.4,6.2Hz,5H),7.04(q,J=8.5Hz,3H),6.51(d,J=2.6Hz,1H),3.55(s,2H),3.20(t,J=4.8Hz,4H),2.58(t,J=4.8Hz,4H). 13 C NMR(100MHz,Chloroform-d)δ148.48,146.99,139.49,139.39,131.91,129.57,128.59,126.94,126.74,120. 20,118.92,115.44,115.23,100.33,61.95,52.35,50.51.Purity:97.2%,tR=5.87min.HRMS(ESI,m / z):calcd for C 26 H 26 FN6O4S[M+H] + ,537.1720; found,537.1721.

[0154] Example 35

[0155] The difference between Example 35 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-3-one is replaced with 4-(pyrazol-1-yl)aniline, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(3-fluorophenyl)methyl]piperazine, with other conditions remaining unchanged, yielding an aryl sulfonamide compound named 4-{4-[(3-fluorophenyl)methyl]piperazine-1-yl}-3-nitro-N-[4-(pyrazol-1-yl)phenyl]benzenesulfonamide, with the structural formula […].

[0156] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.25(d,J=2.3Hz,1H),7.89(d,J=2.5Hz,1H),7.7 2(d,J=9.2Hz,2H),7.61(d,J=8.4Hz,2H),7.32(d,J=7.4Hz,1H),7.23(d,J=8.4H z,2H),7.15–7.07(m,2H),7.04(d,J=8.9Hz,1H),6.98(td,J=8.5,2.5Hz,1H),6 .49(d,J=2.2Hz,1H),3.58(s,2H),3.21(t,J=4.6Hz,4H),2.60(t,J=4.8Hz,4H). 13 C NMR(100MHz,Chloroform-d)δ148.43,141.40,139.36,138.00,134.35,131.97,129.98,129.90,126.92,126.84,124.71,123.13, 120.38,120.17,115.99,115.78,114.56,114.35,108.00,62.15,52.42,50.55.Purity:99.6%,tR=7.59min.HRMS(ESI,m / z):calcd for C 26 H 26 FN6O4S[M+H] + ,537.1720; found,537.1721.

[0157] Example 36

[0158] The difference between Example 36 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-3-one is replaced with 4-(pyrazol-1-yl)aniline, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(4-fluorophenyl)methyl]piperazine, with other conditions remaining unchanged, yielding an aryl sulfonamide compound named 4-{4-[(4-fluorophenyl)methyl]piperazine-1-yl}-3-nitro-N-[4-(pyrazol-1-yl)phenyl]benzenesulfonamide, with the structural formula […].

[0159] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.25(d,J=2.3Hz,1H),7.89(d,J=2.6Hz,1H),7.73(s,1H),7.70(dd,J=8.9,2.3Hz,1H),7.63(d,J=8.4Hz,2H),7. 35–7.30(m,2H),7.23(d,J=8.4Hz,2H),7.04(t,J=8.0Hz,3H),6.50(d,J=2.5Hz,1H),3.55(s,2H),3.21(t,J=4.8Hz,4H),2.59(t,J=4.8Hz,4H). 13 C NMR(100MHz,Chloroform-d)δ148.42,141.40,139.32,137.99,134.37,131.95,130.82,130.74,128.92,126.92,126.85, 123.12,120.37,120.13,115.42,115.21,108.00,61.97,52.35,50.56.Purity:99.0%,tR=7.01min.HRMS(ESI,m / z):calcd forC 26 H 26 FN6O4S[M+H] + ,537.1720; found,537.1721.

[0160] Example 37

[0161] The difference between Example 37 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 5-amino-2-methoxypyridine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(3-cyanophenyl)methyl]piperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 4-{4-[(3-cyanophenyl)methyl]piperazine-1-yl}-N-(2-methoxypyridin-5-yl)-3-nitrobenzenesulfonamide, with the structural formula […].

[0162] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.18(s,1H),7.82(s,1H),7.68(d,J=13.6Hz,2H),7.60(s,2H),7.55–7.39(m,2H),7.12–7.00(m, 1H),6.79–6.65(m,1H),3.89(s,3H),3.62(s,2H),3.23(s,4H),2.62(s,4H).Purity:98.4%,tR=4.57min.HRMS(ESI,m / z):calcd for C 24 H 25 N6O5S[M+H] + ,509.1607; found,509.1608.

[0163] Example 38

[0164] The difference between Example 38 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 5-amino-2-methoxypyridine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(2-cyanophenyl)methyl]piperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 4-{4-[(2-cyanophenyl)methyl]piperazine-1-yl}-N-(2-methoxypyridin-5-yl)-3-nitrobenzenesulfonamide, with the structural formula […].

[0165] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1H NMR(400MHz,Chloroform-d)δ8.18(s,1H),7.85(s,1H),7.69(t,J=6.5Hz,2H ),7.60(t,J=7.5Hz,1H),7.56–7.49(m,2H),7.41(t,J=7.6Hz,1H),7.07(d,J= 8.9Hz,1H),6.71(d,J=8.9Hz,1H),3.89(s,3H),3.78(s,2H),3.22(d,J=6.2Hz,4H),2.74–2.58(m,4H).Purity:96.0%,tR=3.44min.HRMS(ESI,m / z):calcd for C 24 H 25 N6O5S[M+H] + ,509.1607; found,509.1608.

[0166] Example 39

[0167] The difference between Example 39 and Example 1 is only that: in step 1), 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one is replaced with 5-amino-2-methoxypyridine, and in step 2), 1-[(2-nitrophenyl)methyl]piperazine is replaced with 1-[(4-cyanophenyl)methyl]piperazine, with other conditions remaining unchanged, resulting in an aryl sulfonamide compound named 4-{4-[(4-cyanophenyl)methyl]piperazine-1-yl}-N-(2-methoxypyridin-5-yl)-3-nitrobenzenesulfonamide, with the structural formula […].

[0168] The spectral data of the aryl sulfonamide compounds in this embodiment are as follows: 1 H NMR(400MHz,Chloroform-d)δ8.23(d,J=12.9Hz,1H),7.85(d,J=11.8Hz,1H),7.78–7.65(m,3H),7.56(dt,J=18.0,9.8Hz,3H),7.17–7.0 3(m,1H),6.99–6.85(m,1H),6.78(q,J=9.0Hz,1H),4.06–3.83(m,3H),3.70(d,J=13.2Hz,2H),3.28(d,J=12.9Hz,4H),2.78–2.58(m,4H). 13CNMR(100MHz,Chloroform-d)δ162.94,148.39,143.58,142.90,139.50,136.30,132.35,132.01,129.58,129.03,126.82 ,126.09,120.14,118.92,111.57,111.27,62.26,53.87,52.56,50.66.Purity:98.5%,tR=2.95min.HRMS(ESI,m / z):calcd for C 24 H 25 N6O5S[M+H] + ,509.1607; found,509.1605.

[0169] Pharmacological studies:

[0170] (1) The activity of aryl sulfonamide compounds in Examples 1-39 in inhibiting the accumulation of triglycerides (TG) in HepG2 hepatocytes stimulated by oleic acid (OA) and palmitic acid (PA) was tested. The specific test methods are as follows:

[0171] 1.2×10 6 One HepG2 hepatocyte was used in 100 μL DMEM culture medium was used to culture in 96-well plates and placed in an incubator containing 5% CO2 at 37°C. After 24 hours, the culture medium was replaced, and the test compounds—aryl sulfonamide compounds prepared in Examples 1-39 (with a final molar concentration of 10 μmol / L in the culture medium)—were added for pretreatment for 0.5 hours. Pretreatment involved dissolving the aryl sulfonamide compounds in DMSO, then adding a certain amount of the compound solution to the cell-containing culture medium to achieve a final concentration of 10 μmol / L, and culturing for 0.5 hours. Then, 1 μL of OA and PA at a mass ratio of 2:1 was added, and treatment continued for 24 hours. The culture medium was collected, and the culture medium was finally tested using the triglyceride enzyme method. Simultaneously, the same test method was used to test the blank group (con, with only the same volume of DMSO added) and the control group (OAPA) with only OA and PA added. A schematic diagram of the activity of different aryl sulfonamide compounds in inhibiting the accumulation of triglycerides in HepG2 hepatocytes stimulated by OA mixed with PA was obtained, as shown in the figure. Figure 1 As shown. From Figure 1 As can be seen from the results, the aryl sulfonamide compounds prepared in Examples 1 to 39 of this invention have a good inhibitory effect on OAPA-induced TG accumulation, indicating that the aryl sulfonamide compounds prepared in this invention have a good regulatory effect on lipid metabolism.

[0172] (2) To test the ability of the aryl sulfonamide compounds in Example 39 to alleviate hepatocyte lipid metabolism disorders. The specific test method is as follows:

[0173] HepG2 cell lines were induced for 24 h by exposing them to PA, OA, or a mixture of PA and OA at a volume ratio of 1:2. PCR was then performed to determine the expression of relevant genes, along with triglyceride enzyme assay and Oil Red staining. The experiments were repeated in triplicate. Additionally, the same assays were used to test the blank group (con) and the control group (OAPA) with only OA and PA. The test results are as follows: Figure 2 As shown in A to E, where, Figure 2 In the image, A represents the result of Oil Red O staining. Figure 2 The top row of line A shows the Oil Red O staining results at 200× magnification, and the bottom row shows the Oil Red O staining results at 400× magnification. Figure 2 As can be seen from A, the OAPA group exhibits a large number of red lipid droplets, while the number of lipid droplets in the treatment group containing the aryl sulfonamide compound in Example 39, especially the treatment group containing the aryl sulfonamide compound with a molar concentration of 0.5 μmol / L, is significantly reduced, and the lipid deposition is close to the level of the blank group. Figure 2 In the B to E columns, the "-" in the OAPA column indicates no OAPA treatment, and the "+" indicates OAPA treatment. The "-" in the 39 column indicates no treatment with aryl sulfonamide compounds as described in Example 39. The numbers correspond to the final concentration of aryl sulfonamide compounds in the culture medium in Example 39. Figure 2 B in the figure represents the bar chart for quantitative statistical analysis using Oil Red O staining, from... Figure 2 As can be seen from B in the figure, the percentage of the relative positive area of ​​Oil Red staining in the drug-treated group was significantly lower than that in the OAPA group, which confirms that the aryl sulfonamide compounds in Example 39 can significantly reduce the number of lipid droplets in hepatocytes. Figure 2 The 'C' in the diagram represents the triglyceride content. Figure 2 As can be seen from C in Example 39, the aryl sulfonamide compounds can effectively regulate blood lipid levels and significantly reduce the increase in serum TG caused by OAPA. Figure 2 The diagram shows the expression level of the Fasn gene mRNA under the symbol D. Figure 2 The 'E' in the diagram represents the mRNA expression level of the Ehhach gene. Figure 2As can be seen from D to E, in terms of molecular mechanism, the aryl sulfonamide compounds in Example 39 can downregulate the expression of the fatty acid synthesis-related gene Fasn, inhibit lipid synthesis, and upregulate the expression of the key fatty acid oxidation gene Ehhach, promoting lipid breakdown. These results indicate that the aryl sulfonamide compounds in Example 39 of this invention exhibit significant anti-lipid deposition activity, and can effectively alleviate OAPA-induced hepatocyte steatosis by regulating lipid synthesis and breakdown pathways, demonstrating good potential for combating metabolic dysfunction-related fatty liver disease.

[0174] (3) To test the ability of the aryl sulfonamide compounds in Example 39 to alleviate fatty liver disease associated with metabolic dysfunction in mice. The specific test method is as follows:

[0175] Eight-week-old male C57BL / 6 mice were fed either a standard diet (CON) or a high-fat diet (HFD) (containing 60% fat, 20% carbohydrates, and 20% protein) for 12 weeks to establish the glucose tolerance model. Glucose tolerance and insulin tolerance were measured at weeks 6, 9, and 12 to assess glucose tolerance impairment and model progression. A suspension was prepared using 0.5% sodium carboxymethyl cellulose and the aryl sulfonamide compound from Example 39, with a concentration of 2 mg / mL, for gavage administration. Experimental results are as follows: Figure 3 As shown in A to I, the con group is the blank group, i.e., the standard diet group; CON+39(H) is the standard diet + Example 39 gavage administration group, with a dosage of 20 mg / kg; HFD is the model group, i.e., the MASH model group induced by high-fat diet; HFD+39(L) is the high-fat diet + Example 39 gavage administration group, with a dosage of 10 mg / kg; HFD+39(H) is the high-fat diet + Example 39 gavage administration group, with a dosage of 20 mg / kg.

[0176] Figure 3 In the diagram, A represents the expression level of alanine aminotransferase in mouse serum. Figure 3 B in the diagram represents the expression level of aspartate aminotransferase (AST) in mouse serum. Figure 3 As can be seen from A to B in the table, compared with the con group, the serum ALT and AST levels of mice in the HFD model group were significantly increased, indicating significant liver damage. However, the treatment group containing the aryl sulfonamide compound in Example 39, especially the high-dose group (HFD+39(H)), showed significantly reduced ALT and AST levels, which were close to normal levels, indicating that it has a good liver-protective effect. Figure 3 The diagram shows the level of triglycerides expressed in mouse serum, represented by the number C. Figure 3 The diagram shows the expression level of total cholesterol in mouse serum, starting from... Figure 3As can be seen from C to D in Example 39, the aryl sulfonamide compounds can significantly improve dyslipidemia caused by HFD and effectively reduce serum TG and total cholesterol (TCH) levels. Figure 3 The image shown is of a mouse liver. Figure 3 F in the image represents the result of Oil Red staining. Figure 3 As can be seen from E to F in the figures, histological analysis of the liver showed that the livers of mice in the HFD group exhibited significant steatosis and lipid droplet deposition, while the livers treated with aryl sulfonamide compounds in Example 39 showed improved morphology and a significant reduction in lipid droplets. Figure 3 H in the figure represents the bar chart for quantitative statistical analysis using Oil Red staining, from... Figure 3 As can be seen from the H in the image, HE staining further confirms the restoration of tissue structure; Figure 3 In the image, G represents a staining pattern of mouse liver tissue. Figure 3 The "I" in the diagram represents the mouse NAS score results. Figure 3 As can be seen from the G and I values, the quantitative results showed a significant decrease in both the percentage of Oil Red O staining positive area and the NAS score, indicating that the aryl sulfonamide compound in Example 39 can effectively alleviate liver inflammation and steatosis. These results demonstrate that the aryl sulfonamide compound in Example 39 of this invention exhibits significant pharmacological activity in the HFD-induced MASLD model through multiple mechanisms, including improving liver function indicators, regulating lipid metabolism, and reducing hepatic steatosis, thus possessing good therapeutic potential.

[0177] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A compound containing an aryl sulfonamide, characterized in that, The aryl sulfonamide compounds are compounds with structures as shown in Formula I or their racemates, optical isomers, pharmaceutically acceptable salts, hydrates, solvates or prodrugs; Wherein: R1 is selected from five-membered heterocycles, six-membered aromatic rings or heteroaromatic rings optionally substituted with 1 to 3 identical or different substituents, wherein the substituents are selected from hydrogen, halogen, alkyl, alkoxy, hydroxyl, alkylthio, monoalkyl-substituted amino, dialkyl-substituted amino, alkylamide, free carboxyl, salt-forming carboxyl, esterified carboxyl, amidated carboxyl, alkylsulfinyl, sulfonyl, alkyl acyl, carbamoyl, monoalkyl-substituted carbamoyl, dialkyl-substituted carbamoyl or alkyldioxy, pyrazole and phenyl; R2 is selected from hydrogen, halogen, alkyl, alkoxy, substituted phenyl, substituted benzyl, hydroxyl, nitro, monoalkyl-substituted amino, dialkyl-substituted amino, and cyano.

2. The arylsulfonamide compound according to claim 1, characterized in that, R1 is R2 is hydrogen, methyl, ethyl, acetyl, 3. A method for preparing an aryl sulfonamide compound according to any one of claims 1 to 2, characterized in that, It includes the following steps: 1) Mix amino-containing raw materials, dichloromethane, and 4-chloro-3-nitrobenzenesulfonyl chloride, and react to obtain an intermediate; 2) The intermediate is mixed with piperazine-containing raw material, potassium carbonate, sodium iodide and anhydrous tetrahydrofuran, and reacted to obtain aryl sulfonamide compounds; The structural formula of the intermediate is as follows:

4. The method for preparing an aryl sulfonamide compound according to claim 3, characterized in that, In step 1), the mass ratio of the amino-containing raw material, dichloromethane, and 4-chloro-3-nitrobenzenesulfonyl chloride is 1:25-50:1.1-1.

5. The amino-containing raw material is selected from 4-amino-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazole-3-one, 4-phenyl-2-aminothiazole, 5-amino-2-methoxypyridine, 1-phenylpyrazole-3-amine or 4-(pyrazole-1-yl)aniline.

5. The method for preparing an aryl sulfonamide compound according to claim 4, characterized in that, The reaction in step 1) is carried out at a temperature of 0–25°C for 12–20 hours.

6. The method for preparing an aryl sulfonamide compound according to claim 5, characterized in that, The mass ratio of the intermediate described in step 2) to the piperazine-containing raw material, potassium carbonate, sodium iodide and anhydrous tetrahydrofuran is 1:1~1.5:0.5~1.5:0.5~1.5:25~100; The piperazine-containing raw material is selected from 1-[(2-nitrophenyl)methyl]piperazine, 1-[(3-nitrophenyl)methyl]piperazine, 1-[(4-nitrophenyl)methyl]piperazine, N-methylpiperazine, N-ethylpiperazine, N-acetylpiperazine, piperazine, 1-[(3-fluorophenyl)methyl]piperazine, 1-[(4-fluorophenyl)methyl]piperazine, 1-[(3-cyanophenyl)methyl]piperazine, 1-[(2-cyanophenyl)methyl]piperazine or 1-[(4-cyanophenyl)methyl]piperazine.

7. The method for preparing an aryl sulfonamide compound according to claim 6, characterized in that, The reaction in step 2) is carried out at a temperature of 65–75°C for 3–6 hours.

8. The use of the arylsulfonamide compound prepared by the method of any one of claims 3 to 7 in the preparation of pharmaceutical formulations for treating inflammation-related diseases.

9. The use of an aryl sulfonamide compound according to claim 8 in the preparation of a pharmaceutical formulation for treating inflammation-related diseases, characterized in that, The inflammation-related diseases include hepatitis and / or non-alcoholic fatty liver disease.

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