Amino guanidine indole derivative, its preparation method and application

Abstract

The present application relates to the technical fields of drug synthesis, in particular to an amino guanidine indole derivative, a preparation method and application thereof. The amino guanidine indole derivative has the following general structure: wherein R1-R5 are independently H, a halogen atom, a trifluoromethyl group or a cyano group. The amino guanidine indole derivative is applied to inhibiting or killing Klebsiella pneumoniae. The amino guanidine indole derivative is applied to preparing a drug for preventing and treating diseases caused by Klebsiella pneumoniae infection.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of drug synthesis, and particularly relates to an amino guanidine indole derivative, a preparation method and application thereof. BACKGROUND

[0002] Klebsiella pneumoniae is a gram-negative short rod that stains diplococally, is facultative anaerobic, has no motility, flagella and spores, and most strains have pili and capsules. Klebsiella pneumoniae can cause various infections or diseases, including pneumonia, urinary tract infection, bacteremia and liver abscess, etc. Klebsiella pneumoniae mainly causes severe infections in individuals with low immune function, but the emergence and spread of high virulence strains make it possible for people with normal immune function to be infected. Klebsiella pneumoniae has virulence factors such as capsule, LPS, pili and siderophore, which can effectively resist the killing of the immune system and help it to colonize, and high virulence strains have high mucoid phenotype capsules.

[0003] Klebsiella pneumoniae is an important opportunistic pathogen that can infect humans and a variety of animals and widely exists in natural environment and organisms. Klebsiella pneumoniae often colonizes various biological and non-biological surfaces, including upper respiratory tract and intestinal tract. According to its habitat and exposure, the colonization rate varies greatly between individuals. When Klebsiella pneumoniae is detected in the blood of patients, accompanied by symptoms such as fever, cough, sputum, white blood cell elevation and pneumonia, it is considered to be Klebsiella pneumoniae infection. The colonization rate of Klebsiella pneumoniae is 18.8% to 87.7% in Asia and 5% to 35% in western countries. In hospitalized patients, the colonization rate in nasopharynx is 19%, and the colonization rate in gastrointestinal tract can be as high as 77%. The colonized Klebsiella pneumoniae can cause infection when the body immunity is low, and the gastrointestinal colonization of Klebsiella pneumoniae is the main source of hospital Klebsiella pneumoniae infection, of which 80% is caused by self-colonization strains.

[0004] Klebsiella pneumoniae is one of the "ESKAPE" pathogens (including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) considered by the US Centers for Disease Control and Prevention as a serious threat, and its drug resistance is serious. The "2022 National Bacterial Drug Resistance Monitoring Report (Brief Version)" points out that drug-resistant Klebsiella pneumoniae ranks second in the isolation rate of gram-negative drug-resistant bacteria, only next to Escherichia coli. Klebsiella pneumoniae shows certain drug resistance to commonly used antibiotics and can acquire drug resistance through multiple pathways. It has natural resistance to penicillin, and the national average of drug resistance rate to the third generation of cephalosporins is 29.8%, the national average of drug resistance rate to carbapenems is 11.3%, and the drug resistance rate to levofloxacin and gentamicin is close to 20%.

[0005] Therefore, it is necessary to find new drugs against Klebsiella pneumoniae. SUMMARY

[0006] The purpose of the present application is to provide an aminoguanidine indole derivative which has inhibitory and killing effects on Klebsiella pneumoniae and can be used for preventing and treating diseases caused by Klebsiella pneumoniae infection.

[0007] To achieve the above-mentioned purpose, the present application provides the following technical solutions.

[0008] An aminoguanidine indole derivative has the following general structure:

[0009]

[0010] wherein R1-R5 are each independently H, a halogen atom, a trifluoromethyl group or a cyano group.

[0011] Preferably, at least one of R1-R5 is a halogen atom, a trifluoromethyl group or a cyano group.

[0012] Preferably, 1-2 of R1-R5 are halogen atoms or trifluoromethyl groups, and the rest are H. Preferably, the halogen is F, Cl or Br.

[0013] Preferably, the aminoguanidine indole derivative is:

[0014] (E)-2-((1-(2-fluorobenzyl)-1H-indole-5-)methylene)hydrazino-1-carboxamide;

[0015] (E)-2-((1-(3-fluorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidene-1- amidine;

[0016] (E)-2-((1-(4-fluorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidene-1- amidine;

[0017] (E)-2-((1-(2,4-difluorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidene-1- amidine;

[0018] (E)-2-((1-(2,5-difluorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidene-1- amidine;

[0019] (E)-2-((1-(2,6-difluorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidene-1- amidine;

[0020] (E)-2-((1-(3,5-difluorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidene-1- amidine;

[0021] (E)-2-((1-(3,4-difluorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidene-1- amidine;

[0022] (E)-2-((1-(3-(trifluoromethyl)benzyl)-1H-indol-5-yl)methylene)hydrazin-1- ylidene-1-amidine;

[0023] (E)-2-((1-(4-(trifluoromethyl)benzyl)-1H-indol-5-yl)methylene)hydrazin-1- ylidene-1-amidine;

[0024] (E)-2-((1-(3,5-bis(trifluoromethyl)benzyl)-1H-indol-5-yl)methylene)hydrazin-1- ylidene-1-amidine;

[0025] (E)-2-((1-(2-chlorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidene-1- amidine;

[0026] (E)-2-((1-(3-chlorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidene-1- amidine;

[0027] (E)-2-((1-(4-chlorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidene-1- amidine;

[0028] (E)-2-((1-(2,4-dichlorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidene-1- amidine;

[0029] (E)-2-((1-(3,4-dichlorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidene-1- amidine;

[0030] (E)-2-((1-(2-bromobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidine;

[0031] (E)-2-((1-(3-bromobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidine;

[0032] (E)-2-((1-(4-bromobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidine;

[0033] (E)-2-((1-(2-chloro-4-fluorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidine;

[0034] (E)-2-((1-(3-chloro-4-fluorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidine;

[0035] (E)-2-((1-(4-cyanobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidine.

[0036] More preferably, the aminoguanidine indole derivative is:

[0037] (E)-2-((1-(3,4-dichlorobenzyl)-1H-indol-5-yl)methylene)hydrazin-1-ylidine.

[0038] A method for preparing the aminoguanidine indole derivative as described above, comprising the following steps:

[0039] Step 1: under basic condition, reacting with 5-indolecarboxaldehyde to obtain

[0040] Step 2: under acidic condition, reacting with to obtain the aminoguanidine indole derivative.

[0041] Preferably, in Step 1, the base is potassium hydroxide.

[0042] Preferably, in Step 2, the acid is concentrated hydrochloric acid.

[0043] Use of the aminoguanidine indole derivative as described above in inhibiting or killing Klebsiella pneumoniae.

[0044] Use of the aminoguanidine indole derivative as described above in the preparation of a medicament for preventing or treating diseases caused by Klebsiella pneumoniae infection.

[0045] The diseases are pneumonia, urinary tract infection, bacteremia, liver abscess or other site infection caused by Klebsiella pneumoniae in humans and animals.

[0046] The compound prepared by the application has inhibitory and killing effects on Klebsiella pneumoniae, and can be used for preventing and treating diseases caused by Klebsiella pneumoniae infection. BRIEF DESCRIPTION OF DRAWINGS

[0047] Figure 1 Growth curves of KP2108 under different treatments in Example 5 of the application;

[0048] Figure 2 Time-kill curves of 3P on KP2108 in Example 6 of the application;

[0049] Figure 3 Effect of 3P on survival rate of Klebsiella pneumoniae pneumonia mice (survival curve) in Example 7 of the application. DETAILED DESCRIPTION

[0050] The technical solutions in the embodiments of the application will be clearly and completely described below with reference to the drawings in the embodiments of the application. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments of the application. Based on the embodiments in the application, all other embodiments obtained by a person of ordinary skill in the art without creative work fall within the protection scope of the application.

[0051] Example 1

[0052] Preparation of (E)-2-((1-(4-chlorobenzyl)-1H-indol-5-yl)methylene)hydrazino-1-carbamide

[0053] Synthesis of 1-(4-chlorobenzyl)-1H-indole-5-carbaldehyde: 1009 mg (18 mmol) of potassium hydroxide was added to 20 mL of N,N-dimethylformamide, and stirred at room temperature for 5 minutes, then 871 mg (6 mmol) of 5-indolecarboxaldehyde was added, and stirred at room temperature for 45 minutes, then 1234 mg (6 mmol) of 4-chlorobenzyl bromide was added, and stirred at room temperature for 3 h, then the reaction solution was poured into 70 mL of ice water, extracted with ethyl acetate, and the extract was washed with saturated brine twice, then anhydrous sodium sulfate was used for dehydration, and ethyl acetate was removed by reduced pressure distillation to obtain a yellow-brown solid, which was recrystallized in ethanol to obtain white crystals 1442 mg with a yield of 89%.

[0054] Synthesis of (E)-2-((l-(4-bromobenzyl)-lH-indol-5-yl)methylene)hydrazinyl-l- amidine: 269 mg (1 mmol) of l-(4-bromobenzyl)-lH-indole-5-carboxaldehyde and 110 mg (1 mmol) of aminoguanidine hydrochloride were stirred in 15 mL of absolute ethanol, 20 drops of concentrated hydrochloric acid and 3 mL of water were added, and the reaction was stirred at 50 °C in an oil bath for 2-6 hours. Purification was performed by column chromatography using dichloromethane:methanol = 15:1-10:1 to obtain 229 mg of a white solid with a yield of 70%.

[0055] Example 2

[0056] Preparation of (E)-2-((l-(3,4-dichlorobenzyl)-lH-indol-5-yl)methylene)hydrazinyl-l- amidine

[0057] Synthesis of l-(3,4-dichlorobenzyl)-lH-indole-5-carboxaldehyde: 1122 mg (20 mmol) of potassium hydroxide was added to 20 mL of N,N-dimethylformamide, and after stirring for 5 minutes at room temperature, 726 mg (5 mmol) of 5-indolecarboxaldehyde was added. After stirring for 45 minutes at room temperature, 1200 mg (5 mmol) of 3,4-dichlorobenzyl bromide was added, and after stirring for 45 minutes at room temperature, the reaction solution was poured into 70 mL of ice water, extracted with ethyl acetate, washed with saturated brine twice, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove ethyl acetate, thereby obtaining a yellow liquid.

[0058] Synthesis of (E)-2-((l-(3,4-dichlorobenzyl)-lH-indol-5-yl)methylene)hydrazinyl-l- amidine: The resulting entire l-(3,4-dichlorobenzyl)-lH-indole-5-carboxaldehyde and 608 mg (5.5 mmol) of aminoguanidine hydrochloride were stirred in 20 mL of absolute ethanol, 20 drops of concentrated hydrochloric acid and 4 mL of water were added, and the reaction was stirred at 50 °C in an oil bath for 2 hours. Purification was performed by column chromatography using dichloromethane:methanol = 15:1-10:1 to obtain 566 mg of a light red solid with a yield of 31%.

[0059] Example 3

[0060] Preparation of (E)-2-((l-(4-bromobenzyl)-lH-indol-5-yl)methylene)hydrazinyl-l- amidine

[0061] Synthesis of 1-(4-bromobenzyl)-1H-indole-5-carboxaldehyde: 1009 mg (18 mmol) of potassium hydroxide was added to 20 mL of N,N-dimethylformamide, and the mixture was stirred at room temperature for 5 minutes. Then, 871 mg (6 mmol) of 5-indolecarboxaldehyde was added. After stirring at room temperature for 45 minutes, 1500 mg (6 mmol) of 4-bromobenzyl bromide was added. After stirring at room temperature for 45 minutes, the reaction solution was poured into 70 mL of ice water and extracted with ethyl acetate. The extract was washed twice with saturated brine, and then dehydrated with anhydrous sodium sulfate. The ethyl acetate was removed by distillation under reduced pressure to obtain a yellow-brown solid, which was recrystallized from ethanol to obtain 479 mg of white crystals with a yield of 25%.

[0062] Synthesis of (E)-2-((1-(4-bromobenzyl)-1H-indole-5-)methylene)hydrazine-1-amidine: 314 mg (1 mmol) of 1-(4-bromobenzyl)-1H-indole-5-carbaldehyde and 111 mg (1 mmol) of aminoguanidine hydrochloride were dissolved in 15 mL of anhydrous ethanol. 20 drops of concentrated hydrochloric acid and 3 mL of water were added, and the reaction was stirred in an oil bath at 50°C for 2-6 hours. The product was purified by column chromatography using dichloromethane:methanol = 15:1 to 10:1 to obtain 139 mg of a white solid with a yield of 37.5%.

[0063] Using the above-mentioned synthesis method, a series of aminoguanidine indole derivatives were prepared. The structural formula, molecular formula and chemical name of each compound are shown in Table 1, and the corresponding H NMR spectrum, C NMR spectrum and high-resolution mass spectrometry data are shown in Table 2.

[0064] Table 1: Structures, molecular formulas and corresponding chemical names of aminoguanidine indole derivatives

[0065]

[0066]

[0067]

[0068]

[0069]

[0070] Table 2: H NMR, C NMR and HRMS data of aminoguanidine indole derivatives

[0071]

[0072]

[0073]

[0074]

[0075]

[0076]

[0077] Example 4: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) test of aminoguanidine indole derivatives

[0078] Minimum inhibitory concentration and minimum bactericidal concentration of Klebsiella pneumoniae (ATCC 700603) and Klebsiella pneumoniae clinical drug-resistant strains (KP2108, KP2105, KP2109, KP2135, KP2138) were determined by micro-broth dilution method. Compounds 3A-3V were prepared into 2560 μg / mL DMSO solution, 10 μL of compound solution was mixed with 190 μL of MH broth in a 96-well plate, 100 μL of the mixture was serially diluted by two-fold in a 96-well plate, 100 μL of 100-fold diluted bacteria solution was inoculated, and after 16-20 hours of incubation at 37°C, the clarity of the mixture was observed by naked eye. The lowest concentration with clear mixture and no bacterial precipitation at the bottom of the well was the minimum inhibitory concentration of the compound. 100 μL of bacteria solution without bacterial growth was evenly spread on MH agar medium, and after 24 hours of incubation at 37°C, the concentration without bacterial growth was the minimum bactericidal concentration of the compound. MH broth without the addition of the compound was used as a blank control group, and levofloxacin and polymyxin were used as positive control drugs. Klebsiella pneumoniae clinical drug-resistant strains (KP2108, KP2105, KP2109, KP2135, KP2138) were only tested with compounds 3I-3U. The minimum inhibitory concentration results are shown in Table 3, and the minimum bactericidal concentration results are shown in Table 4.

[0079] Table 3: Minimum inhibitory concentration (MIC) of aminoguanidine indole derivatives on 6 strains of Klebsiella pneumoniae

[0080]

[0081]

[0082] Table 4: Minimum bactericidal concentration (MBC) of aminoguanidine indole derivatives on 6 strains of Klebsiella pneumoniae

[0083]

[0084]

[0085] As shown in Table 3, the prepared amino guanidine indole derivatives, compounds 3I-3U, have strong inhibitory effect on Klebsiella pneumoniae, and still have strong inhibitory effect on Klebsiella pneumoniae clinical drug-resistant strains resistant to levofloxacin or polymyxin, wherein the minimum inhibitory concentrations of 3J, 3K, 3N, 3O, 3P, 3Q and 3T to ATCC 700603 are close to that of the control drug polymyxin, and the minimum inhibitory concentrations of 3P and 3O to part of Klebsiella pneumoniae clinical drug-resistant strains can reach 4 μg / mL, and the antibacterial activity is excellent.

[0086] As shown in Table 3 and Table 4, the minimum bactericidal concentrations (MBC) of most of the tested compounds to Klebsiella pneumoniae are 1-4 times of the minimum inhibitory concentrations (MIC), indicating that most of the tested compounds have bactericidal activity, and 3P shows excellent bacteriostatic and bactericidal effect.

[0087] Example 5: Effect of 3P on the growth curve of KP2108

[0088] After Klebsiella pneumoniae clinical drug-resistant strain KP2108 was cultured in MH broth medium to logarithmic growth phase, it was diluted to 1×10 6 CFU / mL. Different concentrations of compound 3P (final concentrations were 2, 4, 8 and 16 μg / mL, respectively) and the control drug polymyxin (final concentration was 32 μg / mL) were added to TSB medium, and the same volume of bacterial solution was added. The blank medium without bacterial solution was used as negative control, and the medium without compound and with bacterial solution was used as positive control, and they were cultured at 37°C with shaking. At the specified time intervals (0, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h), the optical density value at 600 nm was detected, and the growth curve of bacteria was drawn with the optical density value at 600 nm as the vertical coordinate and time as the horizontal coordinate, as shown in Figure 1 .

[0089] As shown in Figure 1 , the control drug polymyxin (32 μg / mL) cannot completely inhibit the growth of KP2108; when the concentration of 3P is greater than or equal to 4 μg / mL, i.e. greater than or equal to MIC, the growth of KP2108 is completely inhibited; when the concentration of 3P is 2 μg / mL, i.e. less than MIC, the growth of bacteria cannot be inhibited.

[0090] Example 6: Bactericidal kinetics test of 3P

[0091] The time-bactericidal curve of 3P at different concentrations on Klebsiella pneumoniae clinical drug-resistant strain KP2108 was detected and drawn. After Klebsiella pneumoniae clinical drug-resistant strain KP2108 was cultured in MH broth medium to logarithmic growth phase, it was diluted to 1×10 7CFU / mL bacterial suspension. Compound 3P (final concentrations of 4, 8, 16, and 32 μg / mL, respectively) and polymyxin (final concentration of 32 μg / mL) were added to the bacterial suspension, and cultured at 37°C with shaking. After the specified time intervals (0, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours), 100 μL of culture solution was taken and serially diluted 10 times in 0.9% saline. 100 μL of culture solution was taken for each dilution and spread on MH agar medium. After cultured at 37°C for 24 hours, the number of colonies was counted and the number of bacteria in the culture solution was calculated. The time-sterilization curve was drawn with the logarithm of the number of bacteria per milliliter as the vertical axis and the culture time as the horizontal axis. Figure 2 .

[0092] Depend on Figure 2 As can be seen, the 24-hour bacterial count in the polymyxin (32 μg / mL) group was close to that in the blank control, indicating no antibacterial effect. The bactericidal effect of 3P on KP2108 was concentration-dependent, with different concentrations of 3P (4, 8, 16, and 32 μg / mL, i.e., 1×MIC, 2×MIC, 4×MIC, and 8×MIC) exhibiting significant inhibitory or killing effects on KP2108. The 24-hour bacterial count at 1×MIC was greater than the inoculum size but less than the blank control group, indicating an inhibitory effect. The 24-hour bacterial count at 2×MIC was less than the inoculum size, indicating a bactericidal effect. At 4×MIC and 8×MIC, no bacteria survived after 6 hours, indicating a very significant bactericidal effect.

[0093] Example 7: In vivo antibacterial activity test of compound 3P

[0094] The effects of 3P and the control drug polymyxin on the survival rate of mice with Klebsiella pneumoniae pneumonia were measured to evaluate their in vivo efficacy. The specific process was as follows: After the purchased SPF-grade BALB / c female mice were adaptively raised for one week, the mice were completely randomly divided into 4 groups (blank control group, model group, polymyxin group and 3P group), with 6 mice in each group, weighing 20±2g. Each group of mice was given the same food and water and allowed to eat freely. Each group of mice was given different intervention measures, among which the blank control group was not given any intervention; the model group, polymyxin group and 3P group were given Klebsiella pneumoniae cultured in MH broth medium through the nasal cavity to create a Klebsiella pneumoniae pneumonia model, and then different intervention measures were given by intraperitoneal injection, among which the model group was injected with blank solvent every day, the polymyxin group was injected with polymyxin solution (1mg / Kg) every day, and the 3P group was injected with 3P solution (4mg / Kg) every day. The experimental results are as follows. Figure 3 .

[0095] Depend on Figure 3It can be seen that the mortality of the model group mice was 100% after 2 days of infection; the survival rates of the mice treated with 3P and polymyxin were significantly improved, and the survival rate of the 3P treatment group was 10% higher than that of polymyxin, indicating that the anti-Klebsiella pneumoniae activity of 3P in BALB / c mice was better than that of polymyxin.

[0096] The embodiments of the present application are described above in conjunction with the drawings, but the present application is not limited to the specific embodiments described above, and the specific embodiments described above are only illustrative, not restrictive, and those of ordinary skill in the art can make many forms under the inspiration of the present application without departing from the purpose of the present application and the scope protected by the claims, which all belong to the protection of the present application.

Claims

1. An aminoguanidine indole derivative having the following general structural formula: ， in, R1 to R5 are each independently H, a halogen atom, a trifluoromethyl group or a cyano group.

2. An aminoguanidine indole derivative according to claim 1, characterized in that: At least one of R1 to R5 is a halogen atom, a trifluoromethyl group or a cyano group.

3. An aminoguanidine indole derivative according to claim 2, characterized in that: Among the R1 to R5, 1-2 are halogen atoms or trifluoromethyl groups, and the remaining are H.

4. Any one of the aminoguanidine indole derivatives according to claim 3, characterized in that: The halogen is F, Cl or Br.

5. An aminoguanidine indole derivative according to claim 4, characterized in that The aminoguanidine indole derivative is: (E)-2-((1-(2-fluorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; (E)-2-((1-(3-fluorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; (E)-2-((1-(4-fluorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; (E)-2-((1-(2,4-difluorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; (E)-2-((1-(2,5-difluorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(2,6-difluorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(3,5-difluorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(3,4-difluorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(3-(trifluoromethyl)benzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(4-(trifluoromethyl)benzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(3,5-bis(trifluoromethyl)benzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(2-chlorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(3-chlorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(4-chlorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(2,4-dichlorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(3,4-dichlorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(2-bromobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(3-bromobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(4-bromobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(2-chloro-4-fluorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(3-chloro-4-fluorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine; ( E )-2-((1-(4-cyanobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine.

6. An aminoguanidine indole derivative according to claim 5, characterized in that The aminoguanidine indole derivative is: ( E )-2-((1-(3,4-dichlorobenzyl)-1H-indol-5-)methylene)hydrazino-1-amidine.

7. A method for preparing any one of the aminoguanidine indole derivatives according to claims 1 to 6, comprising the following steps: Step 1: Under alkaline conditions, Reaction with 5-indolecarboxaldehyde to obtain ; Step 2: Under acidic conditions, and The reaction yields the aminoguanidine indole derivative.

8. The method for preparing an aminoguanidine indole derivative according to claim 7, wherein: In step 1, the base is potassium hydroxide; in step 2, the acid is concentrated hydrochloric acid.

9. Use of any one of the aminoguanidine indole derivatives according to claims 1 to 6 in the preparation of a medicament for inhibiting or killing Klebsiella pneumoniae.

10. Use of any one of the aminoguanidine indole derivatives according to claims 1 to 6 in the preparation of a medicament for preventing and treating diseases caused by Klebsiella pneumoniae infection; the diseases are pneumonia, urinary tract infection, bacteremia, liver abscess or other infections caused by Klebsiella pneumoniae in humans and animals.

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