Application of indole triazole derivatives in the preparation of drugs against drug-resistant Candida albicans

Abstract

The present invention discloses the application of indole triazole derivatives in the preparation of drugs against drug-resistant Candida albicans. The indole triazole compounds contain an indole ring and a triazole ring in their structures, and have good inhibitory effects on drug-resistant fungi, especially fluconazole-resistant Candida albicans, and are expected to further solve the problem of infection by drug-resistant strains of Candida albicans.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicinal chemistry, and specifically relates to the application of indole triazole derivatives in the preparation of drugs against drug-resistant Candida albicans. Background Art

[0002] Candida albicans is an opportunistic pathogen, commonly found in the oral cavity, intestines, etc., and is a microorganism in the normal intestinal flora. When the human body's immunity is low, Candida albicans can cause skin or mucosal infections, and can also cause systemic infections, invading tissues such as the blood and heart, that is, causing invasive infections. In most regions of the world, Candida albicans is the most important pathogen of invasive fungal diseases, seriously threatening human life and health. Fluconazole is used clinically for the treatment of fungal infections due to its broad antifungal spectrum, good oral absorption, high bioavailability, etc. However, with the widespread use of fluconazole, the drug resistance of antifungal drugs is becoming stronger and stronger. The emergence of drug resistance makes the problem more urgent and complex, which poses a huge challenge to the clinical treatment of fungal infections such as Candida albicans. Therefore, it is extremely important to discover new antifungal drugs. One of the effective methods is to modify and transform the structures of existing antifungal drugs, and the modification and transformation of fluconazole is a research hotspot. Research shows that the triazole ring, difluorophenyl group, and alcohol hydroxyl group in the fluconazole molecule are important pharmacodynamic structural fragments for fluconazole to exert its antifungal efficacy.

[0003] Indole derivatives have various biological activities, such as anti-inflammatory, bactericidal, and antitumor effects. In recent years, research has shown that indole and its derivatives have good antifungal effects and also show good inhibitory activity against Candida albicans. The present invention retains one triazole ring, difluorophenyl group, and alcohol hydroxyl group of fluconazole, introduces an antibacterial indole structure into its side chain, designs and synthesizes indole triazole derivatives, and conducts in vitro anti-Candida albicans activity tests on all synthesized compounds, hoping to provide new ideas for the research and development of antifungal drugs and the overcoming of drug resistance. Summary of the Invention

[0004] The first object of the present invention is to provide indole triazole derivatives, with the structure:

[0005] .

[0006] The second object of the present invention is to provide the application of indole triazole derivatives in the preparation of drugs against drug-resistant Candida albicans.

[0007] The drug-resistant Candida albicans are drug-resistant Candida albicans ATCC14053, CA6, CA23, CA602, CA550.

[0008] The third object of the present invention is to provide a preparation method of indole triazole derivatives, specifically:

[0009] (1) Add 7 ml of DMF to a dry round-bottom flask, cool it in an ice-water bath, slowly drip 0.44 ml of phosphorus oxychloride with a syringe, and stir in the ice-water bath for 30 minutes. When the solution turns pink, slowly add 4 mmol of substituted indole dissolved in 1.5 ml of DMF to the round-bottom flask and react in the ice-water bath for 1 hour. Pour the reaction solution into ice water, adjust the pH value to 10 with 5 mol / L NaOH, heat at 80 °C for 1 hour, cool to room temperature, adjust the pH value to 4 with dilute hydrochloric acid, a large amount of solid precipitates, filter, and wash the filter cake with water repeatedly. Dry the filter cake to obtain intermediate A.

[0010] (2) Dissolve 0.3 mmol of intermediate A and 0.3 mmol of substituted aniline in 5 ml of ethanol, add 5 drops of piperidine, reflux at 85 °C for 5 hours, cool to room temperature, add 0.3 mmol of NaBH4, react at room temperature for 2 hours. After monitoring the reaction by TLC until it ends, spin-dry the reaction solution, dissolve it in ethyl acetate, and transfer it to a separatory funnel. Wash the organic layer twice with water, once with saturated brine, then dry it with anhydrous Na2SO4, concentrate and spin-dry to obtain intermediate B.

[0011] (3) Add 0.3 mmol of intermediate B, 0.3 mmol of 1-[2-(2,4-difluorophenyl)-2,3-epoxypropane]-1H-1,2,4-triazole methanesulfonate and KOH (50 mg, 0.9 mmol) to a dry round-bottom flask, add dimethyl sulfoxide (5 ml), react at 85 °C. After monitoring the reaction by TLC and showing that it ends, transfer the reaction solution to a separating funnel, add 20 ml of ethyl acetate. Wash the organic layer with water and saturated brine, dry it with anhydrous sodium sulfate, filter, remove the solvent under reduced pressure, and purify it by silica gel column chromatography with petroleum ether / ethyl acetate to obtain the indole triazole derivative.

[0012] The substituted indole is: indole, 4-bromoindole, 5-methoxyindole, 5-fluoroindole, 5-chloroindole, 5-bromoindole, 6-fluoroindole, 6-bromoindole, 4-methylindole.

[0013] The substituted aniline is: aniline, p-methoxyaniline, p-iodoaniline, p-acetylaniline.

[0014] Advantages of the present invention:

[0015] The present invention provides the application of indole triazole derivatives in the preparation of drugs against Candida albicans resistant strains. The indole triazole derivatives alone have antibacterial effects against Candida albicans resistant strains and are expected to further solve the infection of Candida albicans resistant strains. The compounds provided by the present invention are effective against standard drug-resistant Candida albicans and clinical drug-resistant Candida albicans. Description of the Drawings

[0016] Figure 1It is the structural formula of indole triazole derivatives;

[0017] Figure 2 It is the synthetic route of indole triazole derivatives C01 - C28. Detailed implementation manners

[0018] The present invention will be further described below, but it is not limited to the present invention in any way. Any transformation based on the present invention falls within the protection scope of the present invention.

[0019] The indole triazole derivative, the structure is shown in Figure 1 , specifically:

[0020] .

[0021] The application of indole triazole derivatives in the preparation of drugs against drug - resistant Candida albicans.

[0022] The drug - resistant Candida albicans are drug - resistant Candida albicans ATCC14053, CA6, CA 23, CA 602, CA 550. Among them, CA6, CA 23, CA 602, CA 550 are clinical drug - resistant Candida albicans.

[0023] Substituted indole and phosphorus oxychloride are subjected to formylation in DMF as a solvent to obtain intermediate A. Intermediate A and substituted anilines 3a - 3d are dissolved in an ethanol solution, 5 drops of piperidine are added, and the mixture is heated under reflux at 85°C for 5 hours. After the solution is cooled, sodium borohydride is added, and the reaction is carried out at room temperature for 2 hours to obtain intermediate B. Finally, intermediate B and 1 - [2 - (2,4 - difluorophenyl) - 2,3 - epoxypropane] - 1H - 1,2,4 - triazole methanesulfonate are heated for ring - opening in DMSO as a solvent and KOH as a base at 85°C to obtain indole triazole derivatives C01 - C28. The specific synthetic route is shown in Figure 2 . The specific preparation method is as follows:

[0024] (1) Add 7 ml of DMF to a dry round - bottom flask, cool it in an ice - water bath, slowly drip 0.44 ml of phosphorus oxychloride with a syringe, and stir in the ice - water bath for 30 minutes; when the solution turns pink, slowly add 4 mmol of substituted indole dissolved in 1.5 ml of DMF to the round - bottom flask, and react in the ice - water bath for 1 hour; pour the reaction solution into ice water, adjust the pH value to 10 with 5 mol / L NaOH, and heat at 80°C for 1 hour; cool to room temperature, adjust the pH value to 4 with dilute hydrochloric acid, a large amount of solid precipitates, filter, and wash the filter cake with water repeatedly; dry the filter cake to obtain intermediate A;

[0025] (2) 0.3 mmol of intermediate A and 0.3 mmol of substituted aniline were dissolved in 5 ml of ethanol. 5 drops of piperidine were added, and the mixture was refluxed at 85 °C for 5 hours. After cooling to room temperature, 0.3 mmol of NaBH4 was added and the reaction was carried out at room temperature for 2 hours. After monitoring the reaction by TLC until it was completed, the reaction solution was concentrated by rotary evaporation, dissolved in ethyl acetate, and transferred to a separatory funnel; the organic layer was washed twice with water and once with saturated brine, then dried over anhydrous Na2SO4, concentrated and rotary evaporated to obtain intermediate B;

[0026] (3) 0.3 mmol of intermediate B, 0.3 mmol of 1-[2-(2,4-difluorophenyl)-2,3-epoxypropane]-1H-1,2,4-triazole mesylate and KOH (50 mg, 0.9 mmol) were added to a dry round-bottom flask, dimethyl sulfoxide (5 ml) was added, and the reaction was carried out at 85 °C. After monitoring the reaction by TLC and showing that it was completed, the reaction solution was transferred to a separatory funnel, and 20 ml of ethyl acetate was added; the organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent was removed under reduced pressure, and purified by silica gel column chromatography with petroleum ether / ethyl acetate to obtain the indole triazole derivative.

[0027] The substituted indoles are: indole, 4-bromoindole, 5-methoxyindole, 5-fluoroindole, 5-chloroindole, 5-bromoindole, 6-fluoroindole, 6-bromoindole, 4-methylindole.

[0028] The substituted anilines are: aniline, p-methoxyaniline, p-iodoaniline, p-acetylaniline.

[0029] Indoles with different substituents were formylated with phosphorus oxychloride in DMF as a solvent to obtain intermediates 2a - 2i. Intermediates 2a - 2i and substituted anilines 3a - 3d were dissolved in an ethanol solution, 5 drops of piperidine were added, and the mixture was heated under reflux at 85 °C for 5 hours to obtain intermediates A01 - A28. After the solution was cooled, sodium borohydride was added and the reaction was carried out at room temperature for 2 hours to obtain intermediates B01 - B28. Finally, intermediates B01 - B28 and 1-[2-(2,4-difluorophenyl)-2,3-epoxypropane]-1H-1,2,4-triazole mesylate (CAS No.: 86386-77-8), intermediate 4 were heated and ring-opened at 85 °C in DMSO as a solvent with KOH as a base to obtain indole triazole derivatives C01 - C28. The specific synthetic route is shown in Figure 2 .

[0030] Example 1

[0031] Synthesis of indole triazole derivatives

[0032] Synthesis of Intermediate A: Add DMF (7 ml) to a dry round-bottom flask, cool it in an ice-water bath, slowly drip phosphorus oxychloride (0.44 ml, 4.8 mmol) with a syringe, and stir in the ice-water bath for 30 minutes. When the solution turns pink, slowly add 4-bromoindole (0.5 ml, 4 mmol) dissolved in 1.5 ml of DMF to the round-bottom flask, and react in the ice-water bath for 1 hour. Pour the reaction solution into ice water, adjust the pH value to 10 with 5 mol / L NaOH, and heat at 80 °C for 1 hour. Cool to room temperature, adjust the pH value to 4 with dilute hydrochloric acid, a large amount of solid precipitates, filter, and wash the filter cake with water repeatedly. Finally, dry the filter cake to obtain yellow solid A02, yield: 72%.

[0033] Synthesis of Intermediate B02: Dissolve 4-bromoindole-3-carbaldehyde (A02) (67.2 mg, 0.3 mmol) and aniline (3a) (30 ml, 0.3 mmol) in ethanol (5 ml), add piperidine (5 drops), and reflux at 85 °C for 5 hours. Monitor the reaction by TLC. After the reaction is completed, add NaBH4 (12 mg, 0.3 mmol) to the round-bottom flask and react at room temperature for 2 hours. The reaction process is monitored by TLC. After the reaction is completed, spin-dry the reaction solution, dissolve it in ethyl acetate (15 ml), and transfer it to a separatory funnel. Wash the organic layer twice with water and once with saturated brine, and then dry it with anhydrous Na2SO4. Spin-dry the solvent to obtain B02. B02 is directly used for the next reaction without purification treatment.

[0034] Synthesis of Target Compound C02: Add intermediate B02 (128 mg, 0.3 mmol), 1-[2-(2,4-difluorophenyl)-2,3-epoxypropane]-1H-1,2,4-triazole methanesulfonate (CAS No.: 86386-77-8) Compound 4 (100 mg, 0.3 mmol) and KOH (50 mg, 0.9 mmol) to a dry round-bottom flask, dissolve them in DMSO (5 ml), and react at 85 °C overnight. Monitor the reaction process by TLC. After the reaction is completed, transfer the reaction solution to a separating funnel and add 20 ml of ethyl acetate. Wash the organic layer with water (2×10), then wash it with 10 ml of saturated brine, and dry it with anhydrous sodium sulfate. Filter, remove the solvent under reduced pressure, and purify it by silica gel column chromatography with petroleum ether / ethyl acetate to obtain 85 mg of yellow solid, yield 52.7%, m.p. 71.6 - 74.2 °C.

[0035] The synthesis methods of other derivatives are similar, and the specific data are as follows:

[0036] C01: Yellow solid, yield: 43.7%, m.p. 54.2 - 57.1 °C. 11H NMR (600 MHz, Chloroform- d ) δ 7.77 (s, 1H), 7.75 (s, 1H), 7.64 (d, J J = 7.9 Hz, 1H), 7.47 – 7.40 (m, 2H),7.27 (d, J J = 7.4 Hz, 1H), 7.21 – 7.17 (m, 3H), 7.13 (t, J J = 7.4 Hz, 1H), 6.82 –6.71 (m, 3H), 6.69 (d, J J = 8.0 Hz, 2H), 5.08 (s, 1H), 4.90 (d, J J = 14.2 Hz, 1H),4.62 (d, J J = 15.0 Hz, 1H), 4.45 (s, 2H), 4.34 (d, J J = 15.1 Hz, 1H), 4.06 (d, J J =14.2 Hz, 1H). 13 13C NMR (100 MHz, CDCl3) δ 161.8, 159.8, 152.1, 148.4, 144.1,137.6, 130.4, 129.2, 127.8, 127.1, 123.2, 122.4, 119.7, 119.3, 117.4, 113.6,112.9,112.0, 109.5, 104.3, 77.2, 54.1, 52.6, 39.9.

[0037] CO2: Yellow solid, yield: 52.7%, m.p. 71.6 - 74.2 °C. 1 1H NMR (600 MHz,Chloroform- d ) δ 7.76 (s, 1H), 7.75 (s, 1H), 7.37 (td, J J = 9.0, 6.6 Hz, 1H),7.31 (d, J J = 8.3 Hz, 1H), 7.28 (d, J J = 7.6 Hz, 1H), 7.23 (s, 1H), 7.16 (t, J J = 7.8Hz, 2H), 7.04 (t, J= 7.9 Hz, 1H), 6.79 – 6.66 (m, 5H), 5.14 (s, 1H), 4.83 (d, J = 14.1 Hz, 1H), 4.71 – 4.62 (m, 2H), 4.53 (d, J = 15.0 Hz, 1H), 4.31 (d, J = 15.1Hz, 1H), 3.99 (d, J = 14.1 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 161.7, 159.7,152.1, 148.0, 144.0, 138.9, 130.4, 130.0, 129.1, 125.6, 124.0, 123.0, 122.8,117.5,114.1, 113.5, 113.0, 112.3, 108.9, 104.2, 77.2, 54.0, 52.6, 40.2.

[0038] C03: Yellow solid, yield: 30%, m.p. 68.7 - 71.1 °C. 1 H NMR (600 MHz, Chloroform- d ) δ 7.78 (s, 1H), 7.75 (s, 1H), 7.44 (td, J = 9.0, 6.6 Hz, 1H), 7.30 (d, J = 8.9Hz, 1H), 7.20 (t, J = 7.8 Hz, 2H), 7.16 (s, 1H), 7.04 (d, J = 2.3 Hz, 1H), 6.91(dd, J = 8.9, 2.3 Hz, 1H), 6.82 – 6.70 (m, 5H), 5.07 (s, 1H), 4.88 (d, J = 14.2Hz, 1H), 4.56 (d, J = 15.1 Hz, 1H), 4.40 (s, 2H), 4.32 (d, J = 15.1 Hz, 1H), 4.06(d, J = 14.2 Hz, 1H), 3.82 (s, 3H). 1313C NMR (100 MHz, CDCl3) δ 161.8, 159.7, 154.2, 152.0, 148.5, 144.1, 132.7, 130.3, 129.3, 128.4, 127.5, 123.1, 117.4, 113.1, 112.9, 112.7, 112.2, 110.4, 104.2, 100.8, 77.2, 55.9, 54.1, 52.8, 40.0.

[0039] C04: Yellow solid, yield: 56.6%, m.p. 64.4 - 67.4 °C. 1 1H NMR (600 MHz, Chloroform - d ) δ 7.79 (s, 1H), 7.77 (s, 1H), 7.41 (td, J J = 9.1, 6.5 Hz, 1H), 7.31 (dd, J J = 9.0, 4.1 Hz, 1H), 7.28 (dd, J J = 9.3, 2.4 Hz, 1H), 7.22 – 7.16 (m, 3H), 6.98 (td, J J = 9.0, 2.4 Hz, 1H), 6.79 (ddd, J J = 11.8, 8.3, 2.4 Hz, 1H), 6.73 (q, J J = 8.0, 7.2 Hz, 2H), 6.68 (d, J J = 7.8 Hz, 2H), 5.14 (s, 1H), 4.89 (d, J J = 14.2 Hz, 1H), 4.56 (d, J J = 15.0 Hz, 1H), 4.39 (s, 2H), 4.35 (d, J J = 15.1 Hz, 1H), 4.08 (d, J J = 14.1 Hz, 1H). 1313C NMR (100 MHz, CDCl3) δ 161.7, 159.6, 159.0, 152.1, 148.3, 144.1, 134.1, 130.4, 129.4, 129.3, 127.5, 122.8, 117.6, 113.6, 113.0, 112.1, 110.9, 110.6, 110.4, 104.2, 77.2, 54.1, 52.9, 39.9.

[0040] C05: Yellow solid, yield: 35%, m.p. 72.2 - 75.4 °C. 1 1H NMR (600 MHz, Chloroform - d ) δ 7.78 (s, 1H), 7.77 (s, 1H), 7.61 (s, 1H), 7.40 (q, J J = 8.9 Hz, 1H), 7.31(d, J J = 8.8 Hz, 1H), 7.19 (q, J J = 5.6, 3.6 Hz, 4H), 6.79 (ddd, J J = 11.6, 8.3, 2.1Hz, 1H), 6.73 (t, J J = 7.4 Hz, 2H), 6.68 (d, J J = 7.9 Hz, 2H), 5.17 (s, 1H), 4.88(d, J J = 14.1 Hz, 1H), 4.55 (d, J J = 15.0 Hz, 1H), 4.39 (s, 2H), 4.34 (d, J J = 15.0Hz, 1H), 4.07 (d, J J = 14.1 Hz, 1H). 13 13C NMR (100 MHz, CDCl3) δ 161.9, 159.7, 152.2, 148.2, 144.1, 136.0, 130.4, 129.3, 129.1, 128.1, 125.5, 122.8, 122.7, 118.8, 117.7, 113.3, 113.0, 112.1, 110.7, 104.2, 77.2, 54.1, 52.8, 39.8.

[0041] C06: Yellow solid, yield: 45.8%, m.p. 65.0 - 67.9 °C. 1 H NMR (600 MHz, Chloroform- d ) δ 7.79 (s, 1H), 7.78 – 7.74 (m, 2H), 7.39 (td, J J = 9.1, 6.6 Hz, 1H), 7.31 (dd, J J = 8.7, 1.6 Hz, 1H), 7.27 (d, J J = 8.8 Hz, 1H), 7.19 (dd, J J = 13.1, 5.5 Hz, 3H), 6.83 – 6.66 (m, 5H), 5.18 (s, 1H), 4.87 (d, J J = 14.1 Hz, 1H), 4.55 (d, J J = 15.0 Hz, 1H), 4.39 (s, 2H), 4.34 (d, J J = 15.0 Hz, 1H), 4.06 (d, J J = 14.1 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 161.9, 159.7, 152.2, 148.2, 144.1, 136.3, 130.3, 129.3, 128.9, 128.8, 125.2, 122.8, 121.9, 117.7, 113.2, 113.0, 113.0, 112.3, 111.2, 104.2, 77.2, 54.0, 52.7, 39.8.

[0042] C07: Yellow solid, yield: 60%, m.p. 64 - 68.7 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.77 (s, 1H), 7.75 (s, 1H), 7.53 (dd, J J = 8.6, 5.4 Hz, 1H), 7.45 – 7.36 (m, 1H), 7.18 (t, J J = 7.8 Hz, 2H), 7.14 (s, 1H), 7.10 (dd, J J = 10.0, 1.9 Hz, 1H), 6.88 (td, J= 9.2, 1.9 Hz, 1H), 6.80 (ddd, J = 11.8, 8.3, 2.3 Hz, 1H), 6.73 (q, J =7.4, 7.0 Hz, 2H), 6.67 (d, J = 8.3 Hz, 2H), 5.20 (s, 1H), 4.89 (d, J = 14.0 Hz,1H), 4.49 (d, J = 15.0 Hz, 1H), 4.40 (s, 2H), 4.30 (d, J = 15.0 Hz, 1H), 4.08 (d, J = 14.1 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 161.8, 161.4, 159.7, 152.1, 148.3,144.1, 137.6, 130.4, 129.3, 128.1, 123.6, 122.8, 120.1, 117.6, 113.8, 113.0,112.3, 108.3, 104.3,96.5, 77.2, 54.1, 52.9, 39.9.

[0043] C08: Yellow solid, yield: 20%, m.p. 72.6 - 74 °C. 1 H NMR (600 MHz, Chloroform - d )δ 7.81 (s, 1H), 7.77 (s, 1H), 7.53 (d, J = 1.2 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H),7.40 (td, J = 9.1, 6.5 Hz, 1H), 7.22 (dd, J = 8.4, 1.4 Hz, 1H), 7.19 (t, J = 7.8Hz, 2H), 7.14 (s, 1H), 6.80 (ddd, J = 11.2, 8.3, 2.4 Hz, 1H), 6.73 (td, J = 7.1,6.5, 3.0 Hz, 2H), 6.67 (d, J= 8.0 Hz, 2H), 5.20 (s, 1H), 4.91 (d, J = 14.1 Hz,1H), 4.52 (d, J = 15.0 Hz, 1H), 4.41 (s, 2H), 4.32 (d, J = 15.0 Hz, 1H), 4.10 (d, J = 14.1 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 161.8, 159.7, 152.2, 148.3, 144.1,138.4, 130.4, 129.3, 128.4, 125.9, 123.0, 122.7, 120.5, 117.6, 116.1, 113.9,113.0, 112.8, 112.3,104.2, 77.2, 54.1, 52.7, 39.8.

[0044] C09: Yellow solid, yield: 41.7%, m.p. 62.8 - 64.2 °C. 1 H NMR (600 MHz, Chloroform - d ) δ 7.75 (s, 1H), 7.74 (s, 1H), 7.64 (d, J = 7.9 Hz, 1H), 7.46 –7.39 (m, 2H), 7.25 (t, J = 7.6 Hz, 1H), 7.18 (s, 1H), 7.13 (t, J = 7.5 Hz, 1H),6.83 – 6.77 (m, 3H), 6.77 – 6.72 (m, 1H), 6.65 (d, J = 8.8 Hz, 2H), 5.08 (s,1H), 4.88 (d, J = 14.2 Hz, 1H), 4.61 (d, J = 15.0 Hz, 1H), 4.40 (s, 2H), 4.33 (d, J = 15.1 Hz, 1H), 4.04 (d, J = 14.2 Hz, 1H), 3.74 (s, 3H). 1313C NMR (100 MHz, CDCl3) δ 161.8, 159.8, 152.2, 152.0, 144.1, 142.7, 137.6, 130.3, 127.8, 127.1, 123.2, 122.4, 119.7, 119.3, 116.4, 114.9, 114.3, 112.0, 109.5, 104.2, 77.2, 55.8, 54.2, 52.6, 40.9.

[0045] C10: Yellow solid, yield: 25.8%, m.p. 76.6 - 79.0 °C. 1 1H NMR (400 MHz, Chloroform - d ) δ 7.76 (s, 2H), 7.47 (td, J J = 9.0, 6.5 Hz, 1H), 7.18 (s, 1H), 7.17 – 7.12 (m, 1H), 6.89 (d, J J = 7.1 Hz, 1H), 6.85 – 6.73 (m, 5H), 6.67 – 6.63 (m, 2H), 5.03 (s, 1H), 4.93 – 4.85 (m, 1H), 4.62 (d, J J = 15.0 Hz, 1H), 4.45 (s, 2H), 4.30 (d, J J = 15.0 Hz, 1H), 4.03 (d, J J = 14.1 Hz, 1H), 3.75 (s, 3H), 2.68 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 161.5, 157.7, 152.3, 152.1, 144.2, 142.6, 138.2, 131.5, 130.5, 128.8, 123.4, 122.6, 121.5, 116.6, 115.1, 114.5, 114.2, 112.1, 107.4, 104.1, 77.4, 56.0, 54.2, 52.7, 42.3, 19.9.

[0046] C11: Yellow solid, yield: 42.9%, m.p. 57.6 - 59.6 °C. 1 1H NMR (400 MHz, Chloroform - d) δ 7.78 (s, 1H), 7.76 (s, 1H), 7.41 – 7.27 (m, 3H), 7.25 – 7.21(m, 1H), 7.04 (t, J J = 8.0 Hz, 1H), 6.81 – 6.65 (m, 6H), 5.14 (s, 1H), 4.83 (d, J J = 14.1 Hz, 1H), 4.67 – 4.57 (m, 2H), 4.54 (d, J J = 15.0 Hz, 1H), 4.32 (d, J J = 15.0Hz, 1H), 3.95 (d, J J = 14.1 Hz, 1H), 3.71 (s, 3H). 13 C NMR (100MHz, CDCl3) δ161.8, 159.6, 152.3, 152.1, 144.0, 142.2, 138.9, 130.3, 130.0, 125.6, 123.9,122.9, 122.7,119.9, 115.1, 114.7, 114.2, 112.0, 109.0, 104.2, 77.2, 55.7,54.0, 52.6, 41.2.

[0047] C12: Yellow solid, yield: 54.1%, m.p. 71.5 - 73.7 °C. 1 1H NMR (400 MHz,Chloroform- d ) δ 7.77 (s, 1H), 7.75 (s, 1H), 7.43 (td, J J = 9.1, 6.6 Hz, 1H),7.30 (d, J J = 8.9 Hz, 1H), 7.15 (s, 1H), 7.05 (d, J J = 2.3 Hz, 1H), 6.90 (dd, J J =8.9, 2.4 Hz, 1H), 6.82 – 6.72 (m, 4H), 6.67 (d, J J = 8.9 Hz, 2H), 5.05 (s, 1H),4.88 (d, J J = 14.1 Hz, 1H), 4.56 (d, J= 15.0 Hz, 1H), 4.36 (s, 2H), 4.31 (d, J =15.0 Hz, 1H), 4.05 (d, J = 14.1 Hz, 1H), 3.82 (s, 3H), 3.75 (s, 3H). 13 C NMR (100MHz, CDCl3) δ 161.7, 159.8, 154.2, 152.3, 152.0, 144.1, 142.8, 132.7, 130.4,128.4, 127.5, 123.2, 116.4, 114.9, 114.4, 113.3, 112.6,112.0, 104.2, 100.9,77.2, 55.8, 55.7, 54.1, 52.8, 41.0.

[0048] C13: Yellow solid, yield: 20.4%, m.p. 59.2 - 63.2 °C. 1 H NMR (400 MHz, Chloroform- d ) δ 7.82 (s, 1H), 7.77 (s, 1H), 7.44 – 7.38 (m, 1H), 7.31 (dd, J =8.9, 4.2 Hz, 1H), 7.27 (d, J = 2.4 Hz, 1H), 7.23 (s, 1H), 6.98 (td, J = 9.0, 2.5Hz, 1H), 6.84 – 6.72 (m, 4H), 6.70 – 6.65 (m, 2H), 5.14 (s, 1H), 4.89 (d, J =14.2 Hz, 1H), 4.57 (d, J = 15.0 Hz, 1H), 4.38 – 4.32 (m, 3H), 4.06 (d, J = 14.1Hz, 1H), 3.75 (s, 3H). 1313C NMR (100 MHz, CDCl3) δ 159.0, 157.3, 156.6, 152.6, 152.1, 144.1, 142.9, 134.1, 130.3, 129.5, 127.5, 122.9, 120.0, 116.5, 114.9, 114.8, 112.1, 110.8, 110.3, 104.1, 77.2, 55.8, 54.1, 52.9, 41.1.

[0049] C14: Yellow solid, yield: 60.2%, m.p. 56.5 - 59.9 °C. 1 1H NMR (400 MHz, Chloroform - d ) δ 7.80 (s, 1H), 7.77 (s, 1H), 7.61 (d, J J = 1.9 Hz, 1H), 7.44 – 7.36 (m, 1H), 7.31 (d, J J = 8.8 Hz, 1H), 7.20 – 7.16 (m, 2H), 6.83 – 6.71 (m, 4H), 6.68 – 6.62 (m, 2H), 5.17 (s, 1H), 4.88 (d, J J = 14.1 Hz, 1H), 4.55 (d, J J = 15.0 Hz, 1H), 4.37 – 4.31 (m, 3H), 4.05 (d, J J = 14.0 Hz, 1H), 3.74 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 161.9, 159.6, 152.4, 152.1, 144.1, 142.4, 136.0, 130.4, 129.1, 128.2, 125.5, 122.6, 120.0, 118.8, 114.9, 114.5, 113.5, 112.1, 110.7, 104.2, 77.2, 55.8, 54.0, 52.8, 40.8.

[0050] C15: Yellow solid, yield: 34.7%, m.p. 64.0 - 65.7 °C. 1 1H NMR (400 MHz, Chloroform - d ) δ 7.80 – 7.75 (m, 3H), 7.39 (td,J = 9.1, 6.2 Hz, 1H), 7.33 – 7.27 (m, 2H), 7.16 (s, 1H), 6.82 – 6.62 (m, 6H), 5.18 (s, 1H), 4.87 (d, J = 14.1Hz, 1H), 4.55 (d, J = 14.9 Hz, 1H), 4.37 – 4.30 (m, 3H), 4.04 (d, J = 14.0 Hz, 1H), 3.74 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 161.7, 159.6, 152.4, 152.1, 144.1, 142.4, 136.2, 130.4, 128.8, 125.2, 122.7, 121.9, 116.4, 114.9, 114.5, 113.4, 113.0, 112.1, 111.2, 104.2, 77.2, 55.8, 54.0, 52.7, 40.8.

[0051] C16: Yellow solid, yield: 40.1%, m.p. 47.8 - 48.0 °C. 1 H NMR (400 MHz, Chloroform - d ) δ 7.80 (s, 1H), 7.77 (s, 1H), 7.54 (dd, J = 8.6, 5.3 Hz, 1H), 7.44 – 7.37 (m, 1H), 7.16 – 7.13 (m, 1H), 7.10 (dd, J = 10.0, 1.9 Hz, 1H), 6.88 (td, J = 9.4, 2.0 Hz, 1H), 6.85 – 6.75 (m, 4H), 6.65 (d, J = 8.9 Hz, 2H), 5.19 (s, 1H), 4.95 – 4.85 (m, 1H), 4.50 (d, J = 15.0 Hz, 1H), 4.37 (s, 2H), 4.30 (d, J = 15.0 Hz, 1H), 4.11 – 4.04 (m, 1H), 3.74 (s, 3H). 1313C NMR (100 MHz, CDCl3) δ161.4, 159.0, 152.4, 152.1, 144.1, 142.9, 137.6, 130.4, 128.1, 123.6, 122.8,120.0,116.5, 114.9, 114.5, 114.0, 112.0, 108.5, 104.3, 96.2, 77.2, 55.8,54.1, 52.8, 41.0.

[0052] C17: Yellow solid, yield: 42.3%, m.p. 48.4 - 50.1 °C. 1 1H NMR (400 MHz, Chloroform - d ) δ 7.82 (s, 1H), 7.77 (s, 1H), 7.53 (d, J J = 1.3 Hz, 1H), 7.48 (d, J J = 8.4 Hz, 1H), 7.42 – 7.35 (m, 1H), 7.22 (td, J J = 8.3, 1.9 Hz, 1H), 7.14 (s,1H), 6.84 – 6.62 (m, 6H), 5.21 (s, 1H), 4.90 (d, J J = 14.1 Hz, 1H), 4.52 (d, J J =14.9 Hz, 1H), 4.37 (s, 2H), 4.32 (d, J J = 15.0 Hz, 1H), 4.08 (d, J J = 14.0 Hz, 1H),3.74 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 161.9, 159.7, 152.4, 152.1, 144.1,142.9, 138.4, 130.4, 128.4, 126.0, 122.9, 120.5, 119.9, 116.0, 114.9, 114.6,114.0,112.8, 112.1, 104.2, 77.2, 55.8, 54.1, 52.7, 40.9.

[0053] C18: Yellow solid, yield: 33.2%, m.p. 57.5 - 61.3 °C. 1 1H NMR (400 MHz, Chloroform -d ) δ 7.78 (s, 1H), 7.77 (s, 1H), 7.62 (d, J J = 7.9 Hz, 1H), 7.49 –7.36 (m, 5H), 7.19 (s, 1H), 7.14 (t, J J = 7.5 Hz, 1H), 6.85 –6.72 (m, 2H), 6.47(d, J J = 8.7 Hz, 2H), 5.09 (s, 1H), 4.90 (d, J J = 14.1 Hz, 1H), 4.64 (d, J J = 14.9 Hz,1H), 4.41 (s, 2H), 4.34 (d, J J = 15.0 Hz, 1H), 4.05 (d, J J = 13.9 Hz, 1H). 13 C NMR(100 MHz, CDCl3) δ 161.7, 159.7, 152.1, 147.9, 144.0, 137.8, 137.6, 130.3,127.9, 127.0, 123.0, 122.5, 119.8, 119.2, 115.1, 113.0, 112.3, 109.5, 104.3,77.9, 77.2, 54.0, 52.5, 39.8.

[0054] Compound C19: Yellow solid, yield: 44.5%, m.p. 71.2 - 74.1 °C. 1 1H NMR (400 MHz,Chloroform- d ) δ 7.78 (s, 2H), 7.42 – 7.38 (m, 2H), 7.35 – 7.27 (m, 3H), 7.23(s, 1H), 7.05 (t, J J = 8.0 Hz, 1H), 6.82 – 6.70 (m, 2H), 6.50 – 6.44 (m, 2H),5.18 (s, 1H), 4.88 – 4.82 (m, 1H), 4.63 (s, 2H), 4.56 (d, J J = 15.0 Hz, 1H),4.32 (d, J J = 15.0 Hz, 1H), 3.99 (d, J J = 14.0 Hz, 1H).13 13C NMR (100 MHz, CDCl3) δ161.8, 159.6, 152.2, 147.5, 144.0, 138.9, 137.7, 130.4, 130.1, 125.5, 124.0,123.1, 122.6, 115.6,114.1, 113.4, 112.3, 108.9, 104.2, 78.0, 77.2, 54.0,52.5, 39.9.

[0055] C20: Yellow solid, yield: 26.1%, m.p. 73.6 - 76.6 °C. 1 1H NMR (600 MHz, Chloroform - d ) δ 7.76 (s, 2H), 7.46 – 7.39 (m, 3H), 7.30 (d, J J = 8.9 Hz, 1H),7.14 (s, 1H), 7.01 (s, 1H), 6.91 (d, J J = 8.9 Hz, 1H), 6.78 (dt, J J = 27.7, 8.6 Hz,2H), 6.46 (d, J J = 8.4 Hz, 2H), 5.09 (s, 1H), 4.87 (d, J J = 14.2 Hz, 1H), 4.56 (d, J J = 15.1 Hz, 1H), 4.35 (s, 2H), 4.31 (d, J J = 15.1 Hz, 1H), 4.05 (d, J J = 14.1 Hz,1H), 3.82 (s, 3H). 13 13C NMR (150 MHz, CDCl3) δ 162.3, 159.4, 154.4, 152.2,148.1, 144.2, 137.9, 132.9, 130.5, 128.6, 127.5, 123.1,115.2, 112.8, 112.6,112.2, 110.6, 104.4, 100.9, 78.0, 77.3, 56.0, 54.2, 52.9, 40.0.

[0056] C21: Yellow solid, yield: 20.5%, m.p. 79.2 - 81.6 °C. 11H NMR (400 MHz, Chloroform- d ) δ 7.79 (s, 1H), 7.79 (s, 1H), 7.47 – 7.35 (m, 3H), 7.32 (dd, J J = 9.0, 4.2Hz, 1H), 7.25 – 7.22 (m, 1H), 7.20 (s, 1H), 6.99 (td, J J = 9.0, 2.5 Hz, 1H),6.84 – 6.71 (m, 2H), 6.48 – 6.43 (m, 2H), 5.15 (s, 1H),4.89 (d, J J = 14.1 Hz,1H), 4.57 (d, J J = 15.0 Hz, 1H), 4.38 – 4.31 (m, 3H), 4.07 (d, J J = 14.0 Hz, 1H). 13 13C NMR (100 MHz, CDCl3) δ 161.7, 159.6, 159.0, 152.2, 147.8, 144.1, 137.8,134.1, 130.3, 129.4, 127.3,122.8, 115.1, 112.9, 112.1, 110.9, 110.7, 110.4,104.3, 78.1, 77.2, 54.1, 52.8, 39.7.

[0057] C22: Yellow solid, yield: 25.4%, m.p. 80.6 - 82.1 °C. 1 1H NMR (400 MHz,Chloroform- d ) δ 7.79 (s, 1H), 7.78 (s, 1H), 7.57 (d, J J = 1.8 Hz, 1H), 7.45 –7.35 (m, 3H), 7.31 (d, J J = 8.8 Hz, 1H), 7.23 – 7.16 (m, 2H), 6.83 – 6.70 (m,2H), 6.48 – 6.42 (m, 2H), 5.19 (s, 1H), 4.88 (d, J J = 14.1 Hz, 1H), 4.56 (d, J= 14.9 Hz, 1H), 4.38 – 4.30 (m, 3H), 4.06 (d, J = 14.0 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 161.7, 159.5, 152.2, 147.7, 144.0, 137.8, 136.0, 130.3, 129.1, 128.0, 125.6, 122.7, 122.6, 118.6, 115.2, 112.7, 112.3, 110.8, 104.3, 78.2, 77.2, 54.1, 52.7, 39.6.

[0058] C23: Yellow solid, yield: 30.6%, m.p. 100.4 - 104.4 °C. 1 H NMR (400 MHz, Chloroform - d ) δ 7.79 (s, 1H), 7.78 (s, 1H), 7.74 – 7.72 (m, 1H), 7.46 – 7.27 (m, 5H), 7.16 (s, 1H), 6.84 – 6.70 (m, 2H), 6.45 (d, J = 8.8 Hz, 2H), 5.19 (s, 1H), 4.88 (d, J = 14.1 Hz, 1H), 4.56 (d, J = 14.9 Hz, 1H), 4.38 – 4.30 (m, 3H), 4.05 (d, J = 14.0 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 161.8, 159.5, 152.2, 147.7, 144.1, 137.8, 136.3, 130.2, 129.0, 128.6, 125.3, 122.8, 121.7, 117.3, 115.2, 113.1, 112.1, 111.2, 104.3, 78.2, 77.2, 54.1, 52.7, 39.6.

[0059] C24: Yellow solid, yield: 35.5%, m.p. 103.6 - 106.6 °C. 1 H NMR (400 MHz, Chloroform - d) δ 7.80 (s, 1H), 7.78 (s, 1H), 7.50 (dd, J = 8.6, 5.3 Hz, 1H),7.43 (dd, J = 8.7, 5.2 Hz, 3H), 7.14 (s, 1H), 7.10 (dd, J = 9.9, 2.0 Hz, 1H),6.89 (td, J = 9.2, 2.1 Hz, 1H), 6.81 (ddd, J = 11.8, 8.3, 2.3 Hz, 1H), 6.78 –6.71 (m, 1H), 6.45 (d, J = 8.7 Hz, 2H), 5.20 (s, 1H), 4.90 (d, J = 14.1 Hz, 1H),4.51 (d, J = 15.0 Hz, 1H), 4.37 (s, 2H), 4.30 (d, J = 15.0 Hz, 1H), 4.08 (d, J =14.0 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 161.9, 159.1, 152.2, 147.8, 144.1,137.8, 137.7, 130.3, 128.2, 123.4, 122.8, 120.0, 119.9,115.1, 113.2, 112.1,108.7, 104.3, 96.5, 78.1, 77.2, 54.1, 52.8, 39.7.

[0060] C25: Yellow solid, yield: 30.6%, m.p. 76.8 - 81.25 °C. 1 H NMR (400 MHz,Chloroform- d ) δ 7.85 (s, 1H), 7.83 (s, 1H), 7.76 (s, 2H), 7.61 (d, J = 7.9 Hz,1H), 7.43 (dq, J = 9.1, 3.0 Hz, 2H), 7.29 (d, J = 7.2 Hz, 1H), 7.21 (s, 1H), 7.15(t, J= 7.4 Hz, 1H), 6.86 – 6.72 (m, 2H), 6.63 (d, J = 8.7 Hz, 2H), 5.15 (s, 1H),4.90 (d, J = 14.2 Hz, 1H), 4.69 – 4.60 (m, 1H), 4.50 (s, 2H), 4.35 (d, J = 15.0Hz, 1H), 4.09 (d, J = 14.1 Hz, 1H), 2.50 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ196.5, 161.8, 159.8, 152.2, 152.0, 144.1, 137.6, 130.8, 130.4, 128.1, 126.9,126.7, 123.1, 122.6, 119.9, 119.1, 112.3, 112.2, 111.5, 109.6, 104.3, 77.2,54.2, 52.5, 39.3, 26.0.

[0061] C26: Yellow solid, yield: 30.7%, m.p. 62.7 - 66.7 °C. 1 1H NMR (400 MHz, Chloroform - d ) δ 7.84 (d, J = 8.7 Hz, 2H), 7.80 (s, 1H), 7.78 (s, 1H), 7.40 (td, J = 9.1, 6.5 Hz, 1H), 7.33 (dd, J = 9.0, 4.2 Hz, 1H), 7.26 – 7.21 (m, 2H), 7.00(td, J = 9.0, 2.5 Hz, 1H), 6.84 – 6.70 (m, 2H), 6.63 (d, J = 8.8 Hz, 2H), 5.22(s, 1H), 4.89 (d, J = 14.1 Hz, 1H), 4.59 (d, J = 14.9 Hz, 1H), 4.45 (s, 2H), 4.36(d, J= 15.0 Hz, 1H), 4.15 – 4.07 (m, 1H), 2.50 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 196.4, 161.7, 159.7, 159.0, 152.1, 152.0, 144.1, 134.2, 130.8, 130.3, 129.6, 127.1, 126.9, 122.8, 112.3, 112.1, 111.5, 111.1, 110.8, 110.6, 104.2, 77.2, 54.1, 52.8, 39.2, 26.0.

[0062] C27: Yellow solid, yield: 28.1%, m.p. 89.8 - 92.9 °C. 1 1H NMR (400 MHz, Chloroform - d ) δ 7.84 (d, J J = 8.7 Hz, 2H), 7.79 (s, 1H), 7.78 (s, 1H), 7.56 (d, J J = 1.9 Hz, 1H), 7.39 (td, J J = 9.1, 6.5 Hz, 1H), 7.33 (d, J J = 8.8 Hz, 1H), 7.24 – 7.17 (m, 2H), 6.84 – 6.70 (m, 2H), 6.63 (d, J J = 8.8 Hz, 2H), 5.23 (s, 1H), 4.89 (d, J J = 14.1 Hz, 1H), 4.58 (d, J J = 14.9 Hz, 1H), 4.45 (s, 2H), 4.36 (d, J J = 15.0 Hz, 1H), 4.10 (d, J J = 14.0 Hz, 1H), 2.50 (s, 3H). 1313C NMR (100 MHz, CDCl3) δ196.5, 161.8, 159.7, 152.2, 152.0, 144.1, 136.0, 130.8, 130.4, 129.3, 127.9,126.9, 125.7, 122.9, 122.7, 118.5, 112.3, 112.0,111.6, 110.9, 104.3, 77.2,54.0, 52.7, 39.1, 26.0.

[0063] C28: Yellow solid, yield: 22.4%, m.p. 85.2 - 88.2 °C. 1 1H NMR (400 MHz,Chloroform- d ) δ 7.84 (d, J J = 8.7 Hz, 2H), 7.79 (s, 1H), 7.78 (s, 1H), 7.73 (d, J J = 1.6 Hz, 1H), 7.43 – 7.27 (m, 3H), 7.19 (s, 1H), 6.83 – 6.70 (m, 2H), 6.63(d, J J = 8.8 Hz, 2H), 5.24 (s, 1H), 4.89 (d, J J = 14.1 Hz, 1H), 4.58 (d, J J = 15.0 Hz,1H), 4.45 (s, 2H), 4.36 (d, J J = 15.0 Hz, 1H), 4.09 (d, J J = 14.1 Hz, 1H), 2.50 (s,3H). 13 13C NMR (100 MHz, CDCl3) δ 196.5, 161.8, 159.7, 152.2, 151.9, 144.1,136.3, 130.8, 130.3, 129.1, 128.5, 127.0, 125.4, 122.7, 121.6, 113.2, 112.1,112.0, 111.6, 111.3, 104.3, 77.2, 54.1, 52.7, 39.1, 26.0.

[0064] Example 2

[0065] Antifungal Activity Test

[0066] I. Materials and Methods

[0067] 1. Drugs and Samples

[0068] The indole triazole derivative C01 - C28 was prepared in Example 1.

[0069] The positive control drug fluconazole (FLC) was dissolved in DMSO, sonicated for 10 min, centrifuged, and the supernatant was taken. The storage concentration was 50 mM / mL, and it was stored sealed in a 4°C refrigerator. All compounds were dissolved in DMSO at a concentration of 50 mM / mL and stored sealed in a 4°C refrigerator.

[0070] 2. Culture Media and Strains

[0071] (1) Culture Media

[0072] Sabouraud liquid culture medium, Sabouraud solid medium.

[0073] (2) Strains

[0074] Candida albicans fluconazole - sensitive strain SC5314, Candida albicans fluconazole - resistant strain ATCC14053, Candida albicans fluconazole clinical strains CA6, CA23, CA602, CA550, Candida albicans fluconazole - sensitive strain ATCC - 10231. CA6, CA23, CA602, CA550 are clinical fluconazole - resistant Candida albicans.

[0075] 3. Experimental Methods

[0076] Take a 96 - well culture plate. The samples and fluconazole were both diluted to an initial concentration of 200 μM / mL, 100 μL per well, and serially diluted 5 - fold with 6 concentration gradients, with 3 replicate wells for each concentration gradient. After the strains were activated twice, a bacterial suspension was prepared. 100 μL of the fungal bacterial suspension was added to each well in the 96 - well plate to make the final concentration of Candida albicans 1×10 5 CFU / mL, and incubated in a 37°C constant - temperature incubator for 24 h. The OD value at 625 nm was measured using a microplate reader. At the same time, a medium blank control, a bacterial suspension control, and a fluconazole positive drug control were set up in the experiment.

[0077] 4. Calculation Formula

[0078] Fungal activity inhibition rate (%) = (1 - OD value of sample / OD value of experimental control well) × 100%

[0079] II. Results

[0080] Table 1 Summary of the antibacterial activity experiments of the samples to be tested and fluconazole against Candida albicans

[0081]

[0082] Table 2 In vitro Antifungal Activity of Target Compounds C04 and C08

[0083]

[0084] III. Conclusion

[0085] 1. Samples that have an effect on both sensitive and resistant strains of Candida albicans with single drugs are: C02, C04, C05, C06, C07, C08, C10, C11, C13, C14, C15, C17, C19, C20, C21;

[0086] 2. Samples that have an effect only on sensitive strains of Candida albicans with single drugs are: C09, C12, C16, C23, C24, C26;

[0087] 3. Samples that have an effect only on resistant strains of Candida albicans with single drugs are: None;

[0088] In Table 1, most indole triazole derivatives have antibacterial effects on both sensitive and resistant strains of Candida albicans alone. The activity of compound C08 against sensitive strains of Candida albicans is better than that of fluconazole, and the activity of compound C04 against the resistant strain ATCC14053-FR of Candida albicans is the best. In Table 2, the two representative compounds C04 and C08 show strong activities against several fungal pathogens. In particular, compound C08 shows very strong activities against the fluconazole-sensitive strain SC5314 of Candida albicans, the fluconazole-resistant strain ATCC14053-FR of Candida albicans, the clinical fluconazole strains CA6, CA23, CA602, CA550 of Candida albicans, and the fluconazole-sensitive strain ATCC-10231 of Candida albicans.

Claims

1. The use of indoletriazole derivatives in the preparation of drugs against drug-resistant Candida albicans, characterized in that: The structure of indoletriazole derivatives is:

2. The use according to claim 1, characterized in that The drug-resistant Candida albicans are drug-resistant Candida albicans ATCC14053, CA6, CA23, CA602, and CA550, among which CA6, CA23, CA602, and CA550 are clinically drug-resistant Candida albicans.

Images