Dichloroanthracene compounds with activity of inhibiting helicobacter pylori, and preparation method and application thereof

Abstract

The application provides dichloro-chromone compounds with Helicobacter pylori inhibiting activity and a preparation method and application thereof, and belongs to the field of natural medicines. Compound 1 and compound 2 are separated from 'Reke 1' white agilawood, wherein the compound 1 is (5R, 6R, 7S, 8R)-5, 8-dichloro-6, 7-dihydroxy-2-[2-(4-methoxy) ethyl]-5, 6, 7, 8-tetrahydrochromone; the compound 2 is (5R, 6R, 7S, 8R)-5, 8-dichloro-6, 7-dihydroxy-2-(2-phenylethyl)-5, 6, 7, 8-tetrahydrochromone; the two compounds can effectively inhibit the activity of Helicobacter pylori, and have wide development and application prospects in preparation of medicines or health products for inhibiting excessive production of Helicobacter pylori.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of natural product separation, and particularly relates to two new compounds and a preparation method and application thereof. BACKGROUND

[0002] Chronic gastritis belongs to common diseases of the digestive system, and the pathological change mainly manifests chronic inflammation of gastric mucosa. According to the results published by WHO, the incidence of gastric diseases in the world is as high as 80%, and the most common one is chronic gastritis, accounting for 50% of the total number of gastric diseases. The incidence of gastric diseases in China is higher than that in the world, and the proportion of chronic gastritis in the whole gastric diseases is also higher than that in the world, about 50% to 80%, which has a great impact on people's life and work, and the long-term persistence of the disease can also lead to the occurrence of gastric cancer. Relevant studies have shown that 80% to 95% of chronic gastritis patients have Helicobacter pylori infection in gastric mucosa, and Helicobacter pylori (Hp) infection is the most important pathogenic factor of gastritis and the most important and controllable risk factor for preventing gastric cancer, and almost all Hp current infection exists in different degrees of gastric mucosa inflammation. Therefore, seeking natural, safe and efficient Helicobacter pylori inhibitors has become one of the research hotspots.

[0003] Aquilaria or Gyrinops plant of Thymelaeaceae is formed by resin accumulated and secreted after being damaged by external factors. Aquilaria is known as "the king of incense", has the effects of promoting qi circulation and relieving pain, warming middle and stopping vomiting, and absorbing qi and relieving asthma, and is used for chest and abdominal distending pain, stomach cold vomiting and hiccup, and kidney deficiency and asthma, and is a precious traditional Chinese medicine for treating stomach diseases in clinical practice. The main characteristic components in Aquilaria are sesquiterpenes and 2-(2-phenylethyl) chromone compounds, which have the pharmacological effects of anti-inflammatory, antibacterial, anti-gastric ulcer, promoting gastrointestinal motility, and anti-tumor. SUMMARY

[0004] The present application aims to provide a new compound extracted from 'Reke No. 1' Aquilaria sinensis.

[0005] The present application aims to provide a new compound extracted from 'Reke No. 1' Aquilaria sinensis.

[0006] Another purpose of the present application is to provide that the new compound in 'Reke No. 1' Aquilaria sinensis has the effect of significantly inhibiting the activity of Helicobacter pylori, and further develop the value of Aquilaria.

[0007] Based on the above purpose, the molecular formula of the compound 1 is C 18 H 18Cl2O5, Compound 1: (5R, 6R, 7S, 8R)-5,8-dichloro-6,7-dihydroxy-2-[2-(4- methoxy)ethyl]-5,6,7,8-tetrahydrochromone; having the structure shown below:

[0008]

[0009] Compound 2 has a molecular formula of C 17 H 16 Cl2O4, Compound 2: (5R, 6R, 7S, 8R)-5,8-dichloro-6,7-dihydroxy-2-(2- phenylethyl)-5,6,7,8-tetrahydrochromone;

[0010] having the structure shown below:

[0011]

[0012] The present application provides a preparation method of the new compound with inhibitory activity on Helicobacter pylori, comprising the following steps:

[0013] (1) Extraction and crude separation of ‘Reke No. 1’ white camphor tree sample

[0014] The ‘Reke No. 1’ white camphor tree sample is naturally air-dried, crushed into coarse powder, and then extracted 5-7 times by heating reflux with 8 times / each 95% v / v methanol. All the extraction solutions are combined and concentrated under reduced pressure until no alcohol smell is left to obtain an alcohol extract. The alcohol extract is suspended with 1 times weight of distilled water as an aqueous phase, and then extracted with petroleum ether, ethyl acetate and n-butanol in sequence by liquid-liquid extraction method. The ratio of organic phase to aqueous phase is 3:2 (v / v). After concentration under reduced pressure, three extraction parts of petroleum ether, ethyl acetate and n-butanol are obtained, and the ethyl acetate part is recorded as part A.

[0015] (2) Separation and purification of ethyl acetate part

[0016] The ethyl acetate part is dissolved with a small amount of methanol, and then 1.4-1.5 times 60-80 mesh silica gel is mixed with the sample. Gradient elution is performed with 30:1, 10:1, 5:1, 2:1 (v / v) petroleum ether-ethyl acetate as the elution system, and then elution is performed with 80:1, 50:1, 25:1, 15:1, 10:1, 5:1, 2:1, 1:1, 0:1 (v / v) chloroform-methanol as the elution system. Through thin layer chromatography analysis detection, 16 flow parts of A1-A16 are obtained.

[0017] (3) Separation of A10 flow part sample

[0018] A10 fraction sample was separated by RP-18 column chromatography, eluted with 3:7, 2:3, 1:1, 3:2, 7:3, 4:1, 9:1, 1:0 (v / v) methanol-distilled water as system gradient, combined by TLC detection and HPLC analysis to obtain 22 fractions of A10-1 to A10-22. A10-17 fraction was further eluted by Sephadex LH-20 gel column with chloroform-methanol (1:1, v / v), detected by thin layer chromatography analysis to obtain 8 fractions of A10-17-1 to A10-17-8. A10-17-6 was further gradient eluted by silica gel column with chloroform-methanol (200:1→0:1, v / v), the specific gradient elution volume ratio of chloroform-methanol was 200:1, 100:1, 80:1, 50:1, 25:1, 10:1, 0:1, detected by thin layer chromatography analysis, combined to obtain 6 fractions of A10-17-6-1 to A10-17-6-6. A10-17-6-4 was eluted by semi-preparative high performance liquid chromatography (C 18 column; acetonitrile-water = 28:72, v / v; flow rate 4.0 mL / min; ultraviolet detection wavelength 210 / 254 nm) to obtain compound 1 and compound 2.

[0019] The MIC and MBC determination method was used to evaluate the activity of inhibiting H. pylori, and the results showed that compound 1 and compound 2 could effectively inhibit the production of H. pylori.

[0020] Based on this, the application provides the use of the above-mentioned compound or the compound prepared by the above-mentioned preparation method to inhibit the activity of H. pylori.

[0021] The application provides the use of the above-mentioned compound or the compound prepared by the above-mentioned preparation method as an inhibitor of the activity of H. pylori.

[0022] An inhibitor for inhibiting the activity of H. pylori, containing compound 1 or / and compound 2.

[0023] The application provides the use of the above-mentioned compound or the compound prepared by the above-mentioned preparation method in the preparation of a medicine for treating and / or relieving the activity of H. pylori.

[0024] The application provides the use of the above-mentioned compound or the compound prepared by the above-mentioned preparation method in the preparation of a health product for relieving the activity of H. pylori.

[0025] Further, the H. pylori infection includes one or more of chronic gastritis, atrophic gastritis, gastric ulcer and other stomach problems.

[0026] The present invention provides a medicament for treating and / or inhibiting Helicobacter pylori activity, comprising compound 1 and / or compound 2, and a pharmaceutically acceptable adjuvant;

[0027] The present invention provides a health product for inhibiting the activity of Helicobacter pylori, comprising compound 1 and / or compound 2, and an excipient acceptable for use in health products.

[0028] Furthermore, the dosage form of the drug or health product is tablet, capsule, powder for injection, or suspension.

[0029] Compared with the prior art, the beneficial effects of the present invention are:

[0030] This invention provides compound 1 (C 18 H 18 Cl2O5), compound 2 (C 17 H 16 Cl2O4) is a novel tetrahydrochromene compound with inhibitory activity against Helicobacter pylori, and can be used to treat or alleviate Helicobacter pylori-related diseases. This invention evaluates the inhibition of Helicobacter pylori production using MIC and MBC assays. Compounds 1 and 2 can inhibit the growth of Helicobacter pylori. Therefore, these compounds can be used to prepare pharmaceuticals for treating and / or inhibiting Helicobacter pylori activity, or to prepare health products that inhibit Helicobacter pylori activity. Attached Figure Description

[0031] Figure 1 It is compound 1 prepared in Example 1. 1 H NMR spectrum;

[0032] Figure 2 It is compound 1 prepared in Example 1. 13 C NMR spectrum;

[0033] Figure 3 This is the DEPT spectrum of compound 1 prepared in Example 1;

[0034] Figure 4 This is the HSQC spectrum of compound 1 prepared in Example 1;

[0035] Figure 5 It is compound 1 prepared in Example 1. 1 H- 1 H COSY spectrum;

[0036] Figure 6 This is the HMBC spectrum of compound 1 prepared in Example 1;

[0037] Figure 7 This is the ROESY spectrum of compound 1 prepared in Example 1;

[0038] Figure 8 This is the HRESIMS spectrum of compound 1 prepared in Example 1;

[0039] Figure 9 It is compound 2 prepared in Example 1. 1 H NMR spectrum;

[0040] Figure 10 It is compound 2 prepared in Example 1. 13 C NMR spectrum;

[0041] Figure 11 This is the DEPT spectrum of compound 2 prepared in Example 1;

[0042] Figure 12 This is the HSQC spectrum of compound 2 prepared in Example 1;

[0043] Figure 13 It is compound 2 prepared in Example 1. 1 H- 1 H COSY spectrum;

[0044] Figure 14 This is the HMBC spectrum of compound 2 prepared in Example 1;

[0045] Figure 15 This is the ROESY spectrum of compound 2 prepared in Example 1;

[0046] Figure 16 This is the HRESIMS spectrum of compound 2 prepared in Example 1. Detailed Implementation

[0047] To better understand the technical content of this invention, specific embodiments are provided below to further illustrate the invention.

[0048] Unless otherwise specified, the experimental methods used in the embodiments of this invention are all conventional methods.

[0049] Unless otherwise specified, all materials and reagents used in the embodiments of this invention are commercially available.

[0050] Example 1

[0051] 1.1 Instruments and Reagents

[0052] Bruker AV-500 superconducting nuclear magnetic resonance spectrometer (Bruker GmbH, Switzerland); Autospec 300 mass spectrometer (VG Corporation, UK); analytical high-performance liquid chromatograph (Agilent Technologies, USA); semi-preparative high-performance liquid chromatograph (Agilent Technologies, USA); N-1000 (2L) vertical rotary evaporator and CA-1111 cooling water circulation system (Shanghai Ailang Instrument Co., Ltd.); SHZ-D (Ⅲ) circulating vacuum pump (Shanghai Longtuo Instrument Equipment Co., Ltd.); AS220.R2 0.0001 g electronic balance (RADWAG Wagi Elektroniczne); Sephadex LH-20 gel (Merck Co. Ltd.); C 18 Reversed silica gel (20–45 μm, Fuji Silysia Chemical Ltd., Japan); Cosmosil C 18 Chromatographic columns (10.0ID×250.0mm, Nacalai Tesque) and Cosmosil πNAP columns (10.0ID×250.0mm, Nacalai Tesque); silica gel for column chromatography and silica gel plates for thin-layer chromatography (Qingdao Ocean Chemical Plant); deuterated reagents and chromatographic methanol (Merck, Germany); commonly used organic reagents such as 95% ethanol, methanol, ethyl acetate, chloroform, petroleum ether, and acetone (Tianjin Kemei, Tianjin Fuchen, Guangzhou Guanghua, etc.).

[0053] 1.2 Preparation and structural identification of compounds

[0054] A 1.98 kg sample of agarwood from 'Reke No. 1' Aquilaria sinensis was collected in Pingding Town, Huazhou City, Guangdong Province in December 2016. The original plant was identified by Researcher Dai Haofu of the Institute of Tropical Biotechnology, Chinese Academy of Tropical Agricultural Sciences as Aquilaria sinensis (Lour.) Spreng. The voucher specimen (No. RK1CL202308) is preserved at the Institute of Tropical Biotechnology, Chinese Academy of Tropical Agricultural Sciences.

[0055] The preparation method of the compound includes the following steps:

[0056] 1) Extraction and crude separation of 'Reke No. 1' Aquilaria sinensis sample

[0057] A 1.98 kg sample of agarwood from 'Reke No. 1' Aquilaria sinensis was naturally air-dried, pulverized into coarse powder, and then extracted 5-7 times by reflux with 8 times its weight of 95% v / v methanol. All extracts were combined and concentrated under reduced pressure until no alcohol odor remained, yielding an alcohol extract (244.8 g). The alcohol extract was suspended in an equal volume of distilled water as the aqueous phase, and liquid-liquid extraction was performed sequentially with petroleum ether, ethyl acetate, and n-butanol, with an organic phase to aqueous phase ratio of 3:2 (v / v). After concentration under reduced pressure, three fractions were obtained: petroleum ether, ethyl acetate, and n-butanol. The ethyl acetate fraction was designated as fraction A.

[0058] 2) Separation and purification of ethyl acetate fraction

[0059] The ethyl acetate fraction (202.8 g) was dissolved in a small amount of methanol, mixed with 1.4-1.5 times the volume of 60-80 mesh silica gel, and subjected to reduced pressure column chromatography. First, gradient elution was performed using a petroleum ether-ethyl acetate elution system of 30:1, 10:1, 5:1, 2:1 (v / v), followed by elution using a chloroform-methanol elution system of 80:1, 50:1, 25:1, 15:1, 10:1, 5:1, 2:1, 1:1, 0:1 (v / v). Each gradient elution consisted of 5 column volumes, with each column volume being 2 L. Thin-layer chromatography was used for analysis, and the fractions were combined to obtain 16 fractions, A1 to A16.

[0060] 3) A10 fraction sample separation

[0061] The A10 fraction was separated by RP-18 column chromatography with a methanol-distilled water gradient elution system of 3:7, 2:3, 1:1, 3:2, 7:3, 4:1, 9:1, 1:0 (v / v). Each gradient elution consisted of 15 column volumes, with each column volume being 120 mL. The fractions were then combined by TLC and HPLC analysis to obtain 22 fractions, A10-1 to A10-22.

[0062] The A10-17 fraction was then eluted with 400 mL of chloroform:methanol (1:1, v / v) using a Sephadex LH-20 gel column. The fractions were analyzed by thin-layer chromatography and combined to obtain a total of 8 fractions, A10-17-1 to A10-17-8.

[0063] A10-17-6 was further eluted using a silica gel column with a gradient elution of chloroform-methanol (200:1 → 0:1, v / v). The specific gradient elution volume ratios were 200:1, 100:1, 80:1, 50:1, 25:1, 10:1, and 0:1, with four column volumes eluted for each concentration. Each column volume was 50 mL. The fractions were analyzed by thin-layer chromatography and combined to obtain six fractions: A10-17-6-1 to A10-17-6-6.

[0064] A10-17-6-4 was prepared by high-performance liquid chromatography (C10-17-6-4). 18 The column was eluted with acetonitrile / water, 28:72, v / v; flow rate 4.0 mL / min; UV detection wavelength 210 / 254 nm to obtain compound 1 (5.3 mg, t). R 57.0 min) and compound 2 (7.7 mg, t) R 61.5 min).

[0065] The structure of compound 1 is shown below:

[0066]

[0067] The structure of compound 1 prepared in Example 1 was identified, and the results are as follows: Figures 1-8 The high-resolution mass spectra of the compound are as follows: m / z 385.0599 [M+H] + The molecular formula is C 18 H 18 Cl2O5; compounds 1 H (500MHz) and 13 The C(125MHz) NMR data are shown in Table 1:

[0068] The structure of compound 2 is shown below:

[0069]

[0070] The structure of compound 2 prepared in Example 1 was identified, and the results are as follows: Figures 9-16 The high-resolution mass spectra of the compound are as follows: m / z 355.0497 [M+H] + The molecular formula is C 17 H 16 Cl2O4; compounds 1 H (500MHz) and 13 The C(125MHz) NMR data are shown in Table 1:

[0071] Table 1 Compounds 1 H and 13 C NMR data (δin ppm, J in Hz, in DMSO-d6)

[0072]

[0073]

[0074] Example 2: Assay of the activity of the compound in inhibiting Helicobacter pylori

[0075] Thaw the frozen Helicobacter pylori strain at room temperature, inoculate the bacterial culture onto solid agar plates for resuscitation, and incubate in an inverted incubator at 37°C (5% O2, 10% CO2, 85% N2) for 5–7 days. Scrape off the cultured colonies and incubate in liquid medium for 4–5 days. Dilute the cultured Hp culture with liquid culture medium (BHI) to adjust the bacterial concentration to 1 × 10⁻⁶. 8 CFU / mL. The compound was dissolved in DMSO, and the initial screening drug concentration was set at 100 μmol·L⁻¹. -1 The anti-Hp activity of all compounds was tested at this concentration. The inhibition rate test method employed microdilution, with secondary screening to remove compounds having an inhibitory concentration greater than 100 μmol·L⁻¹. -1 The concentration of the compound was adjusted to 3.125–100 μmol·L using a serial dilution method. -1 The final volume was 200 μL / well. Clarithromycin (CLA) was used as the positive control, and BHI and DMSO were used as blank controls. Each experimental group was repeated in triplicate. The 96-well plates were incubated at 37°C with microaerophilic conditions and shaken at 150 rpm for 48 h. The absorbance was measured at 600 nm using a microplate reader, combined with the turbidity in the wells. MIC was the lowest concentration at which no bacterial growth was observed; MBC was the lowest concentration at which bacteria in the culture medium could be killed.

[0076] With OD 600 The value reflects the bacterial concentration and is calculated using the following formula:

[0077] Antibacterial rate (%) = (OD) 600 Control bacterial suspension - OD 600 Treatment of bacterial solution / OD 600 Control bacterial suspension ×100.

[0078] Table 2 Results of the inhibitory activity of compounds against Helicobacter pylori

[0079]

[0080] a Positive control, *P<0.05 vs positive control group, *P<0.01 vs positive control group

[0081] As can be seen from the above embodiments, the present invention has discovered a new type of compound with inhibitory activity against Helicobacter pylori; this compound is derived from agarwood produced by 'Reke No. 1' Aquilaria sinensis, and has good application prospects in the development of drugs or health products to solve gastritis caused by Helicobacter pylori infection.

[0082] 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 dichlorochromene compound, characterized in that, The dichlorochrome ketone compound is either compound 1 or compound 2, and compound 1 has the structure shown in formula (1): （1）； Compound 2 has the structure shown in formula (2): （2）。 2. The method for preparing the dichlorochrome ketone compound according to claim 1, characterized in that, Includes the following steps: (1) Extraction and crude separation of Aquilaria sinensis samples to prepare ethyl acetate fraction; (2) The ethyl acetate fraction was separated and purified to obtain 16 fractions, A1 to A16; (3) Separate the A10 fraction sample to obtain the target compound.

3. The method for preparing the dichlorochrome ketone compound according to claim 2, characterized in that, The agarwood mentioned is 'Reke No. 1' agarwood.

4. The method for preparing dichlorochrome ketone compounds according to claim 2, characterized in that, Includes the following steps: (1) Extraction and crude separation of 'Reke No. 1' Aquilaria sinensis sample The 'Reke No. 1' Aquilaria sinensis sample was naturally air-dried, pulverized into coarse powder, and then extracted by heating and reflux with 95% v / v methanol. All extracts were combined and concentrated under reduced pressure until no alcohol odor was detected to obtain the alcohol extract. The alcohol extract was suspended in distilled water at a ratio of 1:1 as the aqueous phase. Liquid-liquid extraction was performed sequentially with petroleum ether, ethyl acetate, and n-butanol. After vacuum concentration, three extract fractions of petroleum ether, ethyl acetate, and n-butanol were obtained. The ethyl acetate fraction was designated as fraction A. (2) Separation and purification of ethyl acetate fraction The ethyl acetate fraction was dissolved in methanol, mixed with silica gel, and subjected to reduced pressure column chromatography. Gradient elution was first performed using a petroleum ether-ethyl acetate elution system with volume ratios of 30:1, 10:1, 5:1, and 2:1, followed by elution using a chloroform-methanol elution system with volume ratios of 80:1, 50:1, 25:1, 15:1, 10:1, 5:1, 2:1, 1:1, and 0:1, yielding 16 fractions from A1 to A16. (3) Separation of A10 fractionated samples The A10 fraction was separated using RP-18 column chromatography with a gradient elution system of methanol-distilled water at volume ratios of 3:7, 2:3, 1:1, 3:2, 7:3, 4:1, 9:1, and 1:

0. The fractions were then combined by TLC and HPLC analysis to obtain 22 fractions, A10-1 to A10-22. The A10-17 fraction was then eluted using a Sephadex LH-20 gel column with a chloroform:methanol volume ratio of 1:1 to obtain 8 fractions, A10-17-1 to A10-17-8. A10-17-6 was further eluted using a silica gel column with a chloroform:methanol volume ratio of 200:1 to 0:1 to obtain 6 fractions, A10-17-6-1 to A10-17-6-6. A10-17-6-4 was eluted by semi-preparative high-performance liquid chromatography to obtain the target compound.

5. The method for preparing dichlorochrome ketone compounds according to claim 4, characterized in that, Includes the following steps: (1) Extraction and crude separation of 'Reke No. 1' Aquilaria sinensis sample The 'Reke No. 1' Aquilaria sinensis sample was naturally air-dried, pulverized into coarse powder, and then extracted 5-7 times by heating and reflux with 8 times the volume of 95% v / v methanol. All extracts were combined and concentrated under reduced pressure until no alcohol odor was detected, yielding an alcohol extract. The alcohol extract was suspended in one volume of distilled water as the aqueous phase, and extracted sequentially with petroleum ether, ethyl acetate, and n-butanol using a liquid-liquid extraction method. The volume ratio of organic phase to aqueous phase was 3:

2. After concentration under reduced pressure, three extraction fractions were obtained: petroleum ether, ethyl acetate, and n-butanol. The ethyl acetate fraction was designated as fraction A. (2) Separation and purification of ethyl acetate fraction The ethyl acetate fraction was dissolved in methanol, and mixed with 1.4-1.5 times the volume of 60-80 mesh silica gel. Reduced pressure column chromatography was used. Gradient elution was first performed using a petroleum ether-ethyl acetate elution system with volume ratios of 30:1, 10:1, 5:1, and 2:

1. Elution was then performed using a chloroform-methanol elution system with volume ratios of 80:1, 50:1, 25:1, 15:1, 10:1, 5:1, 2:1, 1:1, and 0:

1. Thin-layer chromatography analysis was performed, and the fractions were combined to obtain 16 fractions, A1 to A16. (3) Separation of A10 fractionated samples The A10 fraction was separated using RP-18 column chromatography with a methanol-distilled water gradient elution system at volume ratios of 3:7, 2:3, 1:1, 3:2, 7:3, 4:1, 9:1, and 1:

0. The fractions were then analyzed by TLC and HPLC, yielding 22 fractions from A10-1 to A10-22. The A10-17 fraction was then processed using Sephadex. LH-20 gel column elution with chloroform-methanol at a volume ratio of 1:1 yielded eight fractions (A10-17-1 to A10-17-8) by thin-layer chromatography. A10-17-6 was further eluted using a silica gel column with gradient elution of chloroform-methanol at volume ratios of 200:1, 100:1, 80:1, 50:1, 25:1, 10:1, and 0:1, yielding six fractions (A10-17-6-1 to A10-17-6-6) by thin-layer chromatography. A10-17-6-4 was eluted by semi-preparative high-performance liquid chromatography (HPLC) to yield compounds 1 and 2. The semi-preparative HPLC used C10-17-6-4. 18 Column; acetonitrile-water ratio of 28:72; flow rate of 4.0 mL / min; UV detection wavelength of 210 / 254 nm.

6. The use of the compound of claim 1 or the compound prepared by the preparation method of claim 2 in the preparation of inhibitors that inhibit the activity of Helicobacter pylori.

7. The use of the compound of claim 1 or the compound prepared by the method of claim 2 in the preparation of medicaments for treating and / or alleviating diseases related to Helicobacter pylori.

8. The application according to claim 7, characterized in that, The diseases caused by Helicobacter pylori include chronic gastritis, atrophic gastritis, and gastric ulcers.

9. A drug for inhibiting the production of Helicobacter pylori, comprising the compound of claim 1 or the compound prepared by the method of claim 2 and pharmaceutically acceptable excipients.

10. The drug for inhibiting Helicobacter pylori production according to claim 9, characterized in that, Dosage forms include tablets, capsules, powder for injection, or suspensions.

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