Phenyl thiazolyl benzimidazole compound as well as preparation method and application thereof

Abstract

The invention discloses a phenyldihydrothiazolyl benzimidazole compound as well as a preparation method and application thereof, and relates to the technical field of antibacterial drug research. The phenyl dihydrothiazolyl benzimidazole compound prepared by the invention shows broad-spectrum antibacterial activity, has an obvious inhibition effect on staphylococcus aureus, bacillus subtilis, escherichia coli, salmonella and pseudomonas aeruginosa, has the antibacterial effect enhanced along with the increase of the concentration of the compound, shows obvious concentration dependence, and can be used for preparing a compound for treating the pathogenic bacteria. The potential in the development of antibacterial drugs is shown. The compound disclosed by the invention is simple in synthesis process, low in cost, good in repeatability and high in yield, chemical components are easy to control, a new choice is provided for the field of antibacterial drugs, and the compound has important significance for solving the problem of drug resistance of bacteria.

Description

Technical Field

[0001] This invention relates to the field of antibacterial drug research technology, and in particular to a phenyldihydrothiazolylbenzimidazole compound, its preparation method, and its application. Background Technology

[0002] Many antibacterial drugs currently used in clinical practice have reduced efficacy due to drug resistance issues, highlighting the urgent need to develop novel antibacterial drugs with new mechanisms or structures.

[0003] In the pharmaceutical field, benzimidazole compounds exhibit a variety of pharmacological activities, including antibacterial, antiviral, antitumor, anti-inflammatory, and antiparasitic effects, making them a class of drug skeletons with great development potential. Early benzimidazole drugs were mainly used for anthelmintics; for example, thibendazole was widely used to treat gastrointestinal parasites in animals such as cattle, sheep, goats, pigs, horses, and poultry. With structural modifications and optimizations, a new generation of benzimidazole anthelmintics, such as albendazole, oxifendazole, fenbendazole, mebendazole, and flubendazole, have emerged. These anthelmintics possess broad-spectrum anthelmintic activity, good efficacy, and low toxicity, and even have killing effects on larvae and eggs. In the antibacterial field, the potential of benzimidazole compounds is gradually being explored. Studies have shown that benzimidazole compounds not only inhibit various bacteria but also exhibit inhibitory activity against some fungi, such as Blastomyces dermatitidis, Candida albicans, Penicillium, and Trichophyton. This discovery opens up new avenues for the application of benzimidazole compounds in anti-infective therapy and also promotes in-depth research on benzimidazole structural modification and derivative development.

[0004] The antibacterial activity of benzimidazole compounds is closely related to their structural characteristics. Systematic structural modifications can significantly alter their antibacterial spectrum and activity intensity. Heterocyclic fusion is an effective strategy for enhancing the antibacterial activity of benzimidazole compounds. Fusing benzimidazole with heterocycles such as thiazoles, triazoles, and oxadiazoles can produce derivatives with novel structures and enhanced activity. Phenylenol dihydrothiazolylbenzimidazole compounds, as an important subclass of benzimidazole derivatives, possess both the structural features and pharmacological activities of benzimidazole and thiazole rings, exhibiting unique antibacterial properties. These compounds combine benzimidazole with dihydrothiazolyl rings in a rational manner to form new molecular skeletons, potentially possessing mechanisms of action different from traditional antibacterial drugs, providing new insights into overcoming drug resistance. Regarding activity, studies have shown that heterocyclic compounds containing benzimidazole structures, such as 2-phenylimidazo[2,1-b]benzothiazole, exhibit significant inhibitory activity against a variety of pathogens, with effects superior to some commonly used clinical antibacterial drugs. This suggests that phenyldihydrothiazolylbenzimidazole compounds may possess equal or even superior antibacterial potential. Furthermore, research on phenyldihydrothiazolylbenzimidazole compounds will move towards structural diversity, constructing a rich library of compounds by introducing different substituents and combining different heterocycles, thus elucidating their precise molecular targets and antibacterial pathways.

[0005] In view of this, the present invention is proposed. Summary of the Invention

[0006] The purpose of this invention is to provide a phenyldihydrothiazolylbenzimidazole compound, its preparation method, and its application, in order to solve the problems existing in the prior art.

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

[0008] One of the technical solutions of this invention is to provide a phenyldihydrothiazolylbenzimidazole compound with the structure shown in Formula I:

[0009]

[0010] The molecular formula of the compound with structure I is C 16 H 13 N3S is specifically named 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole.

[0011] The second technical solution of the present invention provides a method for preparing the above-mentioned phenyldihydrothiazolylbenzimidazole compounds, comprising the following steps:

[0012] 2-Phenylacetic-1,3-thiazolyl-4-carboxylic acid was mixed with o-phenylenediamine and subjected to a condensation and ring-closing reaction under the action of a catalyst to obtain the phenyldihydrothiazolylbenzimidazole compound.

[0013] The structural formula of 2-phenyl-1,3-thiazolyl-4-carboxylic acid is as follows:

[0014]

[0015] The structural formula of the o-phenylenediamine is as follows:

[0016]

[0017] As a further preferred embodiment of the present invention, the molar ratio of 2-phenyl-1,3-thiazolyl-4-carboxylic acid to o-phenylenediamine is 1:(1-2).

[0018] As a further preferred embodiment of the present invention, the temperature of the condensation and ring-closing reaction is 110–180°C, and the time is 4–8 h; the catalyst is polyphosphoric acid.

[0019] As a further preferred embodiment of the present invention, after the ring-closing reaction is completed, a purification step is also included: adding the reaction solution to water, adjusting the pH to 8.0, filtering to obtain a white precipitate, recrystallizing with methanol and then drying.

[0020] In this invention, polyphosphoric acid not only acts as a strong acid catalyst, but also as a dehydrating agent.

[0021] This invention represents the first synthesis of a 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound. Experimental results show that this phenyldihydrothiazole-based benzimidazole compound exhibits inhibitory activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Salmonella, and Pseudomonas aeruginosa, demonstrating that this 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound is a novel antibacterial agent.

[0022] The third technical solution of the present invention provides the application of the above-mentioned phenyldihydrothiazolylbenzimidazole compounds in the preparation of antibacterial drugs.

[0023] As a further preferred embodiment of the present invention, the bacteria include one or more of Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Salmonella, and Pseudomonas aeruginosa.

[0024] The fourth technical solution of the present invention provides an antibacterial drug, the active ingredient of which includes the above-mentioned phenyldihydrothiazolylbenzimidazole compounds.

[0025] As a further preferred embodiment of the present invention, the above-mentioned antibacterial drug further includes pharmaceutically acceptable excipients.

[0026] As a further preferred embodiment of the invention, the pharmaceutically acceptable excipients include one or more of diluents, disintegrants, binders, or lubricants.

[0027] The present invention discloses the following technical effects:

[0028] The phenyldihydrothiazolylbenzimidazole compounds prepared in this invention exhibit broad-spectrum antibacterial activity, showing significant inhibitory effects against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Salmonella, and Pseudomonas aeruginosa. Their antibacterial effect increases with increasing compound concentration, showing a significant concentration dependence and demonstrating their potential in the development of antibacterial drugs.

[0029] The synthesis method of this invention is simple in steps, low in cost, and has good repeatability and high yield, which provides convenient conditions for large-scale production and practical application.

[0030] This invention not only provides new candidate compounds for the field of antibacterial drugs, but also offers a completely new approach and solution to address the increasingly serious problem of bacterial resistance, and has significant research value and broad application prospects. Attached Figure Description

[0031] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0032] Figure 1 The infrared spectrum of the 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound prepared in Example 1 of this invention.

[0033] Figure 2 The 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound prepared in Example 1 of this invention 1 H NMR spectrum.

[0034] Figure 3 The graph shows the inhibition rate of different concentrations of 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compounds on five strains in the efficacy verification example of this invention. Detailed Implementation

[0035] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0036] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0037] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0038] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be readily apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0039] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0040] First aspect of the present invention: to provide a phenyldihydrothiazolylbenzimidazole compound with the structure shown in Formula I:

[0041]

[0042] The molecular formula of the compound with structure I is C 16 H 13 N3S is specifically named 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole.

[0043] A second aspect of the present invention provides a method for preparing the above-mentioned phenyldihydrothiazolylbenzimidazole compounds, comprising the following steps:

[0044] 2-Phenylacetic-1,3-thiazolyl-4-carboxylic acid was mixed with o-phenylenediamine and subjected to a condensation and ring-closing reaction under the action of a catalyst to obtain the phenyldihydrothiazolylbenzimidazole compound.

[0045] The structural formula of 2-phenyl-1,3-thiazolyl-4-carboxylic acid is as follows:

[0046]

[0047] The structural formula of the o-phenylenediamine is as follows:

[0048]

[0049] Further, the molar ratio of 2-phenyl-1,3-thiazolyl-4-carboxylic acid to o-phenylenediamine is 1:(1-2).

[0050] Furthermore, the temperature of the condensation and ring-closing reaction is 110–180°C, and the time is 4–8 h; the catalyst is polyphosphoric acid.

[0051] Furthermore, after the ring-closing reaction is completed, a purification step is also included: the reaction solution is added to water, the pH is adjusted to 8.0, the white precipitate is obtained by filtration, recrystallized with methanol and then dried.

[0052] In this invention, polyphosphoric acid not only acts as a strong acid catalyst, but also as a dehydrating agent.

[0053] A third aspect of the present invention is to provide the use of the above-mentioned phenyldihydrothiazolylbenzimidazole compounds in the preparation of antibacterial drugs.

[0054] Furthermore, the bacteria include one or more of Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Salmonella, and Pseudomonas aeruginosa.

[0055] Fourth aspect of the present invention: to provide an antibacterial drug, wherein the active ingredient comprises the above-mentioned phenyldihydrothiazolylbenzimidazole compounds.

[0056] Furthermore, the aforementioned antibacterial drugs also include pharmaceutically acceptable excipients.

[0057] Furthermore, the pharmaceutically acceptable excipients include one or more of diluents, disintegrants, binders, or lubricants.

[0058] The present invention will be further described in detail below with reference to embodiments. It should be noted that any aspects of the present invention not described in detail are conventional practices in the art and are not the focus of the present invention.

[0059] Example 1

[0060] Synthesis of phenyldihydrothiazolylbenzimidazole compounds (2-(1H-benzo[d]imidazo-2-yl)-4-phenyl-2,3-dihydrothiazolyl):

[0061] 2-Phenylacetic-1,3-thiazolyl-4-carboxylic acid and o-phenylenediamine were mixed at a molar ratio of 1:1 and dissolved in 30 mL of polyphosphoric acid solution. The entire mixture was placed in a glass bottle and reacted at 110 °C for 8 h, yielding a dark-colored solution. This solution was then poured into 100 mL of deionized water, and the pH was adjusted to 8.0 using sodium hydroxide solution. The mixture was filtered to obtain a white precipitate. The precipitate was completely dissolved in methanol, recrystallized, filtered, and dried at room temperature. Yield: 92%.

[0062] Example 2

[0063] Synthesis of phenyldihydrothiazolylbenzimidazole compounds (2-(1H-benzo[d]imidazo-2-yl)-4-phenyl-2,3-dihydrothiazolyl):

[0064] 2-Phenylacetic-1,3-thiazolyl-4-carboxylic acid and o-phenylenediamine were mixed at a molar ratio of 1:1 and dissolved in 30 mL of polyphosphoric acid solution. The entire mixture was placed in a glass bottle and reacted at 180 °C for 4 h, yielding a dark-colored solution. This solution was then poured into 100 mL of deionized water, and the pH was adjusted to 8.0 with sodium hydroxide solution. The mixture was filtered to obtain a white precipitate. The precipitate was then completely dissolved in methanol, recrystallized, filtered, and dried at room temperature. Yield: 94%.

[0065] Example 3

[0066] Synthesis of phenyldihydrothiazolylbenzimidazole compounds (2-(1H-benzo[d]imidazo-2-yl)-4-phenyl-2,3-dihydrothiazolyl):

[0067] 2-Phenylacetic-1,3-thiazolyl-4-carboxylic acid and o-phenylenediamine were mixed at a molar ratio of 1:2 and dissolved in 30 mL of polyphosphoric acid solution. The entire mixture was placed in a glass bottle and reacted at 110 °C for 8 h, yielding a dark-colored solution. This solution was then poured into 100 mL of deionized water, and the pH was adjusted to 8.0 with sodium hydroxide solution. The mixture was filtered to obtain a white precipitate. The precipitate was then completely dissolved in methanol, recrystallized, filtered, and dried at room temperature. Yield: 87%.

[0068] Example 4

[0069] Synthesis of phenyldihydrothiazolylbenzimidazole compounds (2-(1H-benzo[d]imidazo-2-yl)-4-phenyl-2,3-dihydrothiazolyl):

[0070] 2-Phenylacetic-1,3-thiazolyl-4-carboxylic acid and o-phenylenediamine were mixed at a molar ratio of 1:2 and dissolved in 30 mL of polyphosphoric acid solution. The entire mixture was placed in a glass bottle and reacted at 180 °C for 4 h, yielding a dark-colored solution. This solution was poured into 100 mL of deionized water, and the pH of the system was adjusted to 8.0 with sodium hydroxide solution. The mixture was then filtered to obtain a white precipitate. The precipitate was then completely dissolved in methanol, recrystallized, filtered, and dried at room temperature. Yield: 89%.

[0071] The efficacy of the 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound prepared in Example 1 is used as an example for verification and explanation.

[0072] Figure 1 The infrared spectrum of the 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound prepared in Example 1.

[0073] Figure 2 The 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound prepared in Example 1 1 H NMR spectrum.

[0074] In the infrared spectral data of the compound 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole, 3083.94 cm⁻¹ -1 The broad peak (medium intensity) may be attributed to the NH stretching vibration, or the aliphatic CH vibration (2800-3000 cm⁻¹). -1The weak absorption peak is attributed to the saturated CH stretching vibration (-CH3, -CH2-), 1618.68 cm⁻¹. -1 and 1538.37cm -1 The peak (medium intensity) is attributed to the C=C skeletal vibration of the aromatic ring (benzene ring or heteroaromatic ring), 1232.40 cm⁻¹. -1 1099.86cm -1 and 1070.52cm -1 Belongs to CN stretching vibration, fingerprint area 832.15cm -1 and 798.61cm -1 766.36cm -1 The sharp peak is attributed to the out-of-plane bending vibration of the aromatic ring CH. Furthermore, the 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound... 1 In the H NMR spectrum, a chemical shift of 0.97 ppm is attributed to the methyl group (-CH3) of the thiazole ring or side chain, a chemical shift of 2.58 ppm is attributed to the methylene group (-CH2-S-) of the thiazole ring, a chemical shift of 3.62 ppm is attributed to the N-CH2- group of the benzimidazole ring, a chemical shift of 4.08 ppm is attributed to the methine group (-CH-), and a chemical shift of 7.1 ppm is attributed to the hydrogen group of the benzene ring.

[0075] Effect verification example

[0076] The following is an efficacy verification of the 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole prepared in Example 1:

[0077] I. Inhibition Experiment of 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole Compound on Salmonella

[0078] The compound was dissolved in DMSO to prepare a stock solution with a concentration of 20 mM. In the inhibition zone assay, the stock solution was serially diluted with 0.1 M PBS to obtain solutions with concentrations of 50, 100, 200, 400, and 800 μM. Sterile filter paper was immersed in the diluted solutions for 15 minutes. 75 μM gentamicin sulfate was used as a positive control. 100 μL of the diluted Salmonella solution (10 mM) was pipetted into the solution. 8The drug (CFU / mL) was evenly applied to a plate, and then spread evenly with a glass spreader to avoid forming single colonies. The plate was labeled with the time, strain name, drug used, and number. Three parallel controls were set up for each group. Next, filter paper strips soaked in the drug were picked up with tweezers, drained, and placed in the marked positions on the plate. The plate with the filter paper strips was inverted and incubated at 37°C for 12 hours. After incubation, the experimental plates were removed, and the appearance of inhibition zones was observed. The diameter of the inhibition zone was recorded using a vernier caliper with a cross-sectional method; the average of three measurements was taken as the final diameter. The formula for calculating the inhibition rate is as follows:

[0079] Antibacterial rate = (diameter of inhibition zone in treatment group - diameter of inhibition zone in blank group) / diameter of inhibition zone in treatment group × 100%.

[0080] The unit for the diameter of the inhibition zone is millimeters. The inhibitory effect of 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound on Salmonella is as follows: Figure 3 As shown in Table 1, this compound has a significant antibacterial effect against Salmonella, and the inhibitory effect is concentration-dependent.

[0081] II. Inhibition experiment of 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound on Staphylococcus aureus

[0082] The compound was dissolved in DMSO to prepare a stock solution with a concentration of 20 mM. In the inhibition zone assay, the stock solution was serially diluted with 0.1 M PBS to obtain solutions with concentrations of 50, 100, 200, 400, and 800 μM. Sterilized filter paper was immersed in the diluted solutions, shaken well, and soaked for 15 minutes. 75 μM gentamicin sulfate was used as a positive control. 100 μL of the diluted Salmonella solution (10 mM) was pipetted into the solution. 8 The drug (CFU / mL) was evenly applied to a plate and then spread evenly using a glass spreader to avoid forming single colonies. The plate was labeled with the time, strain name, drug used, and number. Three parallel controls were set up for each group. Next, filter paper strips soaked in the drug were picked up with tweezers, drained, and placed in the marked positions on the plate. The plate with the filter paper strips was inverted and incubated at 37°C for 12 hours. After incubation, the experimental plates were removed, and the appearance of inhibition zones was observed. The diameter of the inhibition zone was recorded using a vernier caliper with a cross-sectional method; the average of two measurements was taken as the final diameter. The formula for calculating the inhibition rate is as follows:

[0083] Antibacterial rate = (diameter of inhibition zone in treatment group - diameter of inhibition zone in blank group) / diameter of inhibition zone in treatment group × 100%.

[0084] The unit for the diameter of the inhibition zone is millimeters. The inhibitory effect of 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound on Salmonella is as follows: Figure 3 As shown in Table 1, this compound has a significant antibacterial effect against Staphylococcus aureus, and the inhibitory effect is concentration-dependent.

[0085] III. Inhibition Experiment of 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole Compound on Escherichia coli

[0086] The compound was dissolved in DMSO to prepare a stock solution with a concentration of 20 mM. In the inhibition zone assay, the stock solution was serially diluted with 0.1 M PBS to obtain solutions with concentrations of 50, 100, 200, 400, and 800 μM. Sterilized filter paper was immersed in the diluted solutions, shaken well, and soaked for 15 minutes. 75 μM gentamicin sulfate was used as a positive control. 100 μL of the diluted Salmonella solution (10 mM) was pipetted into the solution. 8 The drug (CFU / mL) was evenly applied to a plate and then spread evenly using a glass spreader to avoid forming single colonies. The plate was labeled with the time, strain name, drug used, and number. Three parallel controls were set up for each group. Next, filter paper strips soaked in the drug were picked up with tweezers, drained, and placed in the marked positions on the plate. The plate with the filter paper strips was inverted and incubated at 37°C for 12 hours. After incubation, the experimental plates were removed, and the appearance of inhibition zones was observed. The diameter of the inhibition zone was recorded using a vernier caliper with a cross-sectional method; the average of two measurements was taken as the final diameter. The formula for calculating the inhibition rate is as follows:

[0087] Antibacterial rate = (diameter of inhibition zone in treatment group - diameter of inhibition zone in blank group) / diameter of inhibition zone in treatment group × 100%.

[0088] The unit for the diameter of the inhibition zone is millimeters. The inhibitory effect of 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound on *Escherichia coli* is as follows: Figure 3 As shown in Table 1, this compound has a significant antibacterial effect against Escherichia coli, and the inhibitory effect is concentration-dependent.

[0089] IV. Inhibition experiment of 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound on Pseudomonas aeruginosa

[0090] The compound was dissolved in DMSO to prepare a stock solution with a concentration of 20 mM. In the inhibition zone assay, the stock solution was serially diluted with 0.1 M PBS to obtain solutions with concentrations of 50, 100, 200, 400, and 800 μM. Sterilized filter paper was immersed in the diluted solutions, shaken well, and soaked for 15 minutes. 75 μM gentamicin sulfate was used as a positive control. 100 μL of the diluted Salmonella solution (10 mM) was pipetted into the solution. 8 The drug (CFU / mL) was evenly applied to a plate and then spread evenly using a glass spreader to avoid forming single colonies. The plate was labeled with the time, strain name, drug used, and number. Three parallel controls were set up for each group. Next, filter paper strips soaked in the drug were picked up with tweezers, drained, and placed in the marked positions on the plate. The plate with the filter paper strips was inverted and incubated at 37°C for 12 hours. After incubation, the experimental plates were removed, and the appearance of inhibition zones was observed. The diameter of the inhibition zone was recorded using a vernier caliper with a cross-sectional method; the average of two measurements was taken as the final diameter. The formula for calculating the inhibition rate is as follows:

[0091] Antibacterial rate = (diameter of inhibition zone in treatment group - diameter of inhibition zone in blank group) / diameter of inhibition zone in treatment group × 100%.

[0092] The unit for the diameter of the inhibition zone is millimeters. The inhibitory effect of 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound on Pseudomonas aeruginosa is as follows: Figure 3 As shown in Table 1, this compound has a significant inhibitory effect on Pseudomonas aeruginosa, and the inhibitory effect is concentration-dependent.

[0093] V. Inhibition experiment of 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound on Bacillus subtilis:

[0094] The compound was dissolved in DMSO to prepare a stock solution with a concentration of 20 mM. In the inhibition zone assay, the stock solution was serially diluted with 0.1 M PBS to obtain solutions with concentrations of 50, 100, 200, 400, and 800 μM. Sterilized filter paper was immersed in the diluted solutions, shaken well, and soaked for 15 minutes. 75 μM gentamicin sulfate was used as a positive control. 100 μL of the diluted Salmonella solution (10 mM) was pipetted into the solution. 8The drug (CFU / mL) was evenly applied to a plate and then spread evenly using a glass spreader to avoid forming single colonies. The plate was labeled with the time, strain name, drug used, and number. Three parallel controls were set up for each group. Next, filter paper strips soaked in the drug were picked up with tweezers, drained, and placed in the marked positions on the plate. The plate with the filter paper strips was inverted and incubated at 37°C for 12 hours. After incubation, the experimental plates were removed, and the appearance of inhibition zones was observed. The diameter of the inhibition zone was recorded using a vernier caliper with a cross-sectional method; the average of two measurements was taken as the final diameter. The formula for calculating the inhibition rate is as follows:

[0095] Antibacterial rate = (diameter of inhibition zone in treatment group - diameter of inhibition zone in blank group) / diameter of inhibition zone in treatment group × 100%.

[0096] The unit for the diameter of the inhibition zone is millimeters. The inhibitory effect of 2-(1H-benzo[d]imidazol-2-yl)-4-phenyl-2,3-dihydrothiazole compound on Bacillus subtilis is as follows: Figure 3 As shown in Table 1, this compound has a significant inhibitory effect on Bacillus subtilis, and the inhibitory effect is concentration-dependent.

[0097] Table 1. Diameter of inhibition zones (mm) under different concentrations of the compound.

[0098]

[0099] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A phenyldihydrothiazolylbenzimidazole compound, characterized in that, The structure is shown in Equation I:

2. The method for preparing phenyldihydrothiazolylbenzimidazole compounds as described in claim 1, characterized in that, Includes the following steps: 2-Phenylacetic-1,3-thiazolyl-4-carboxylic acid was mixed with o-phenylenediamine and subjected to a condensation and ring-closing reaction under the action of a catalyst to obtain the phenyldihydrothiazolylbenzimidazole compound.

3. The preparation method according to claim 2, characterized in that, The molar ratio of 2-phenyl-1,3-thiazolyl-4-carboxylic acid to o-phenylenediamine is 1:(1-2).

4. The preparation method according to claim 2, characterized in that, The condensation and ring-closing reaction is carried out at a temperature of 110–180°C for 4–8 hours; the catalyst is polyphosphoric acid.

5. The preparation method according to claim 2, characterized in that, After the condensation and ring-closing reaction is completed, a purification step is also included: the reaction solution is added to water, the pH is adjusted to 8.0-10.0, the precipitate is obtained by filtration, recrystallized with methanol and then dried.

6. The use of the phenyldihydrothiazolylbenzimidazole compound as described in claim 1 in the preparation of antibacterial drugs.

7. The application according to claim 6, characterized in that, The bacteria include one or more of Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Salmonella, and Pseudomonas aeruginosa.

8. An antibacterial drug, characterized in that, The active ingredient includes the phenyldihydrothiazolylbenzimidazole compound as described in claim 1.

9. The antibacterial drug as described in claim 8, characterized in that, It also includes pharmaceutically acceptable excipients.

10. The antibacterial drug according to claim 9, characterized in that, Pharmaceutically acceptable excipients include one or more of diluents, disintegrants, binders, or lubricants.

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