A 4-(1H-1,2,3-triazol-1-yl)benzoic acid compound, a preparation method and application thereof

Abstract

The application discloses a 4-(1H-1,2,3-triazole-1-yl) benzoic acid compound and a preparation method and application thereof, a structural formula of the 4-(1H-1,2,3-triazole-1-yl) benzoic acid compound is shown as formula (I), and the preparation method is as follows: 4-(1H-1,2,3-triazole-1-yl) benzoic acid compound (I) is prepared from p-azidobenzoic acid and 3,7,11-trimethyldodecane-3-ol as raw materials. The 4-(1H-1,2,3-triazole-1-yl) benzoic acid compound has antibacterial activity, especially has good antibacterial activity on klebsiella pneumoniae, and can be used as an antibacterial agent.

Description

Technical Field

[0001] This invention belongs to the field of antibacterial drug technology, and particularly relates to a 4-(1H-1,2,3-triazol-1-yl)benzoic acid compound, its preparation method and application. Background Technology

[0002] Klebsiella pneumoniae is a common Gram-negative pathogen that can cause various diseases such as pneumonia, urinary tract infections, and sepsis, posing a significant threat, especially to immunocompromised patients. The increasing drug resistance of this bacterium has led to a sharp decline in available treatment options, highlighting the urgent need to develop novel antibacterial drugs.

[0003] Azole heterocyclic compounds have attracted much attention due to their significant biological activity. These structures are widely found in drug molecules, such as the triazole group in fluconazole and the tetraazole group in cefazolin, serving as side chain groups that enhance the antibacterial efficacy of antibiotics. However, research on the specificity of existing triazole antibacterial agents against Klebsiella pneumoniae remains limited. This invention focuses on 4-(1H-1,2,3-triazol-1-yl)benzoic acid compounds, aiming to develop agents specifically treating Klebsiella pneumoniae by constructing highly effective antibacterial molecules, providing a potential solution for clinical drug-resistant infections. Summary of the Invention

[0004] The purpose of this invention is to provide a novel 4-(1H-1,2,3-triazol-1-yl)benzoic acid compound with good antibacterial activity against Klebsiella pneumoniae, its preparation method, and its application.

[0005] To achieve the above objectives, this application adopts the following technical solution:

[0006] In a first aspect, the present invention provides a 4-(1H-1,2,3-triazol-1-yl)benzoic acid compound, the structural formula of which is shown in formula (I):

[0007] .

[0008] Secondly, the present invention provides a method for preparing the above-mentioned 4-(1H-1,2,3-triazol-1-yl)benzoic acid compounds, comprising the following steps: using p-azidobenzoic acid and 3,7,11-trimethyldodecyn-3-ol as raw materials, the 4-(1H-1,2,3-triazol-1-yl)benzoic acid compounds are prepared, and the synthetic reaction formula is as follows:

[0009] .

[0010] In the above technical solution, p-azidobenzoic acid, 3,7,11-trimethyldodecyn-3-ol, cuprous iodide and N,N-dimethylformamide are added to a reactor and stirred at room temperature to obtain the 4-(1H-1,2,3-triazol-1-yl)benzoic acid compounds.

[0011] In the above technical solution, the molar ratio of azidobenzoic acid, 3,7,11-trimethyldodecyn-3-ol, and cuprous iodide is 1:1.2:0.1.

[0012] In the above technical solutions, the room temperature is 25-35℃.

[0013] Thirdly, the present invention provides the application of the above-mentioned 4-(1H-1,2,3-triazol-1-yl)benzoic acid compounds in the preparation of antibacterial agents.

[0014] In the above technical solution, the antibacterial agent is an agent for treating Klebsiella pneumoniae.

[0015] Fourthly, the present invention provides an antibacterial agent containing the above-mentioned 4-(1H-1,2,3-triazol-1-yl)benzoic acid compounds as active ingredients.

[0016] In the above technical solution, the antibacterial agent is an agent for treating Klebsiella pneumoniae.

[0017] The beneficial effects of this invention are as follows: the synthesis method of the 4-(1H-1,2,3-triazol-1-yl)benzoic acid compound of this invention is simple, and it shows good antibacterial activity, with good antibacterial activity against Klebsiella pneumoniae. As a novel antibacterial 4-(1H-1,2,3-triazol-1-yl)benzoic acid compound, it has great application value in the field of antibacterial technology. Detailed Implementation

[0018] To better illustrate the objectives, technical solutions, and advantages of this invention, the invention will be further described below in conjunction with specific embodiments. This invention can be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the inventive concept to those skilled in the art. This invention will be defined only by the claims.

[0019] Unless otherwise specified, the test methods or experimental methods described in the following examples are conventional methods; unless otherwise specified, the reagents and materials are obtained from conventional commercial sources or prepared by conventional methods.

[0020] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0021] The synthetic reaction formula for the 4-(1H-1,2,3-triazol-1-yl)benzoic acid compound (I) of this invention is as follows:

[0022]

[0023] The following embodiments are further illustrations of the present invention, but not limitations thereof.

[0024] Example 1:

[0025] Preparation steps of 4-(4-(2-hydroxy-6,10-dimethylundecane-2-yl)-1H-1,2,3-triazol-1-yl)benzoic acid (abbreviated as 4-(1H-1,2,3-triazol-1-yl)benzoic acid compounds, I):

[0026]

[0027] 10 mmol of azidobenzoic acid was dissolved in 10 mL of N,N-dimethylformamide, followed by the addition of 12 mmol of 3,7,11-trimethyldodecyn-3-ol and 1 mmol of cuprous iodide. The mixture was stirred at 25-35 °C for 3 hours. After the reaction was complete, 50 mL of water was added to precipitate the solid. The solid was filtered, air-dried, and the target product (I) was obtained with a yield of 70%. 1 H NMR (600 MHz, DMSO-d6, δ): 13.19 (s, 1H, -COOH), 8.80 (s, 1H, triazole), 8.26 (d, 2H, benzene), 7.87 (d,2H, benzene), 5.37 (s, 1H, -OH), 1.71 (m, 3H, alkane), 1.40 (m, 4H, alkane), 1.22 (m, 10H, alkane), 0.91 (m, 9H, alkane). HRMS (ESI): m / z calcd forC 22 H 32 N3O3 + 386.2449 [M-H] + ; found: 386.2476.

[0028] Example 2:

[0029] Antibacterial activity test of the target compound:

[0030] The MIC of the target compound was determined by microdilution, and the antibacterial activity of the target compound (4-(1H-1,2,3-triazol-1-yl)benzoic acid compound prepared in Example 1) against Klebsiella pneumoniae ATCC 4352 was determined.

[0031] The experimental steps for the microdilution method are as follows:

[0032] Add 200 μL of a 1024 μg / mL aqueous solution of the test sample (4-(1H-1,2,3-triazol-1-yl)benzoic acid compound prepared in Example 1) to column 1 of a 96-well plate. Add 100 μL of nutrient broth medium (3g beef extract, 5g peptone, 1000mL deionized water) to columns 2-12 respectively. Then, take 100 μL from column 1 and add it to column 2, then take 100 μL from column 2 and add it to column 3, and so on. Finally, take 100 μL from column 9 and add it to column 10, then discard the excess 100 μL. Take 100 μL of a 10... 6 Add CFU / mL bacterial culture to each well in columns 1-11, and add 100 μL of culture medium to each well in column 12, for a final volume of 200 μL per well. Column 11 represents bacterial growth control (without culture medium), and column 12 represents sterile control (without culture medium). The concentrations of the test samples in columns 1-10 are 512, 256, 128, 64, 32, 16, 8, 4, 2, and 1 μg / mL, respectively. Each test sample is performed in triplicate. After incubating the 96-well plate at 37°C for 24 hours, the OD is measured using a microplate reader. 600 Value, OD 600 The concentration of wells with values ​​close to those of the sterile blank control is the minimum inhibitory concentration (MIC).

[0033] The results show:

[0034] 4-(4-(2-hydroxy-6,10-dimethylundecane-2-yl)-1H-1,2,3-triazol-1-yl)benzoic acid (abbreviated as 4-(1H-1,2,3-triazol-1-yl)benzoic acid compound, I) has a MIC of 128 μg / mL against Klebsiella pneumoniae, and has good antibacterial activity against Klebsiella pneumoniae.

[0035] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A 4-(1H-1,2,3-triazol-1-yl)benzoic acid compound, characterized in that: Its structural formula is shown in equation (I): 。 2. The method for preparing the 4-(1H-1,2,3-triazol-1-yl)benzoic acid compound according to claim 1, characterized in that: The process includes the following steps: using p-azidobenzoic acid and 3,7,11-trimethyldodecyn-3-ol as raw materials, the 4-(1H-1,2,3-triazol-1-yl)benzoic acid compounds are synthesized, and the synthetic reaction formula is as follows: 。 3. The preparation method according to claim 2, characterized in that: p-Azide benzoic acid, 3,7,11-trimethyldodecyn-3-ol, cuprous iodide and N,N-dimethylformamide were added to a reactor and stirred at room temperature to obtain the 4-(1H-1,2,3-triazol-1-yl)benzoic acid compounds.

4. The preparation method according to claim 3, characterized in that: The molar ratio of azidobenzoic acid, 3,7,11-trimethyldodecyn-3-ol, and cuprous iodide is 1:1.2:0.

1.

5. The preparation method according to claim 3, characterized in that: The room temperature is 25-35℃.

6. The use of the 4-(1H-1,2,3-triazol-1-yl)benzoic acid compound according to claim 1 in the preparation of antibacterial agents, characterized in that: The antibacterial agent is an agent for treating Klebsiella pneumoniae.

7. An antibacterial agent, characterized in that: The active ingredient is a 4-(1H-1,2,3-triazol-1-yl)benzoic acid compound as described in claim 1, and the antibacterial agent is an agent against Klebsiella pneumoniae.

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