A natural product 3-methylcarbazole derivative, its preparation method, and its application.

Abstract

This invention discloses a natural product 3-methylcarbazole derivative having the general formula A, its preparation method, and its application, relating to the field of organic chemistry. Its substituents R1 and R2 have the definitions given in the specification. This derivative possesses good antibacterial activity against *Escherichia coli* (E. coli). E. coli ), Pseudomonas aeruginosa ( P. aeruginosa It has a significant inhibitory effect on both fluoroquinolone-resistant Escherichia coli (FREC) and can be used to prepare drugs for treating related bacterial infections.

Description

Technical Field

[0001] This invention relates to the field of organic chemistry, specifically to a natural product 3-methylcarbazole derivative, its preparation method, and its applications. Background Technology

[0002] Currently, with the widespread use of antibiotics, various drug-resistant bacteria, multidrug-resistant bacteria, and superdrug-resistant bacteria have emerged, seriously threatening human health. This has led to many infectious diseases in clinical practice being incurable.

[0003] Since naturally derived substances have been used to treat human diseases, their diverse chemical structures and biological activities, as well as their degree of compliance with human body, have become excellent starting points for drug development.

[0004] Therefore, it is of great significance to start with natural products, modify and optimize their structures, and develop novel antibacterial drugs to address these worrying problems. Summary of the Invention

[0005] This invention utilizes knowledge of organic chemistry, medicinal chemistry, and natural product structure modification and optimization to design and synthesize a series of 3-methylcarbazole derivatives for antibacterial activity studies. Results show that some target compounds exhibit good antibacterial activity against *Escherichia coli* (E. coli). E. coli ), Pseudomonas aeruginosa ( P. aeruginosa It has a significant inhibitory effect on both fluoroquinolone-resistant Escherichia coli (FREC) and fluoroquinolone-resistant Escherichia coli (FREC).

[0006] Firstly, to achieve the above objectives, the present invention adopts the following technical solution: a natural product 3-methylcarbazole derivative, whose general chemical structural formula A is shown below: , Wherein, R1 is selected from hydrogen, fluorine, or methoxy; R2 is selected from phenyl, methyl-substituted phenyl, methoxy-substituted phenyl, fluorine-substituted phenyl, trifluoromethyl-substituted phenyl, nitro-substituted phenyl, thiophene, chloro-substituted thiophene, bromo-substituted thiophene, methyl formate thiophene, methyl-substituted isoxazolyl, pyridyl, 2,3-dihydrobenzofuranyl, naphthyl, quinolinyl, coumarinyl, and benzo[1,2,5]thiadiazolyl.

[0007] Preferably, the 3-methylcarbazole derivative is selected from any one of the following: A1: R1 is H, R2 is Ph; A5: R1 is H, R2 is 2-OCH3Ph; A6: R1 is H, R2 is 3-OCH3Ph; A8: R1 is H, R2 is 4-FPh; A9: R1 is H, R2 is 2-CF3Ph; A10: R1 is H, R2 is 3-CF3Ph; A11: R1 is H, R2 is 4-CF3Ph; A12: R1 is H, R2 is 2-NO2Ph; A16: R1 is H, R2 is 5-chlorothiophene-2-yl; A17: R1 is H, R2 is 5-bromothiophene-2-yl; A18: R1 is H, R2 is 2-methoxycarbonyl-3-thiophene-3-yl; A19: R1 is H, R2 is 3,5-dimethylisoxazole-4-yl; A20: R1 is H, R2 is pyridine-3-yl; A21: R1 is H, R2 is 2,3-dihydrobenzofuran-5-yl; A22: R1 is H, R2 is naphthalene-1-yl; A23: R1 is H, R2 is quinoline-8-yl; A24: R1 is H, R2 is coumarin-6-yl; A25: R1 is H, R2 is 2,1,3-benzothiadiazole-4-yl; A26: R1 is 6-F, R2 is quinoline-8-yl; A27: R1 is 6-F, R2 is coumarin-6-yl; A28: R1 is 6-F, R2 is 2,1,3-benzothiadiazole-4-yl; A29: R1 is 8-F, R2 is quinoline-8-yl; A30: R1 is 8-F, and R is coumarin-6-yl; A31: R1 is 8-F, and R is 2,1,3-benzothiadiazole-4-yl; A32: R1 is 6-OCH3, R2 is quinoline-8-yl; A33: R1 is 6-OCH3, R2 is coumarin-6-yl; A34: R1 is 6-OCH3, and R2 is 2,1,3-benzothiadiazole-4-yl.

[0008] In a second aspect, the present invention provides a drug comprising the 3-methylcarbazole derivative described above, wherein the derivative is used as the sole active ingredient or in combination with an antibacterial drug or other antibacterial active ingredients.

[0009] Thirdly, the present invention also provides that the above-mentioned 3-methylcarbazole derivatives, such as any one or more combinations of A1, A8, A32, or drugs containing them, can be used in the preparation of drugs for treating and / or preventing Staphylococcus aureus infections.

[0010] Fourthly, the present invention also provides the above-mentioned 3-methylcarbazole derivatives, such as any one or more combinations of A5, A6, A9, A10, A11, A12, A16, A17, A18, A19, A20, A21, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32 and A34, or drugs containing them, for use in the preparation of drugs for treating and / or preventing Pseudomonas aeruginosa infections.

[0011] Fifthly, the present invention also provides any one or more combinations of the above-mentioned 3-methylcarbazole derivatives, such as A5, A9, A10, A11, A12, A16, A17, A18, A19, A21, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33 and A34, or drugs containing them, for use in the preparation of medicaments for treating and / or preventing fluoroquinolone-resistant Escherichia coli infections.

[0012] In a sixth aspect, the present invention also provides the above-mentioned 3-methylcarbazole derivatives, preferably A5, A6, A9, A10, A11, A12, A16, A17, A18, A19, A20, A21, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33 and A34, or drugs containing them, for use in the preparation of medicaments for treating and / or preventing infectious diseases of Escherichia coli.

[0013] In a seventh aspect, the present invention provides a method for preparing the 3-methylcarbazole derivative, which is prepared according to the following synthetic route: .

[0014] The method specifically includes the following steps: Preparation of compound 1: Phenylhydrazine hydrochloride or substituted phenylhydrazine, acetic acid and 4-methylcyclohexanone were heated and reacted. After cooling, water was added to quench the reaction and the mixture was cooled and crystallized to obtain an intermediate. The intermediate was then heated and reacted with iodine and dimethyl sulfoxide. After cooling, quenching with concentrated hydrochloric acid, stirring with sodium thiosulfate solution, extraction with ethyl acetate, washing, drying and purification by column chromatography were performed to obtain compound 1. Preparation of compound 2: Compound 1, 1,3-dibromopropane, NaH and N,N - The reaction with dimethylformamide was quenched with saturated brine, followed by extraction with ethyl acetate, washing, drying, and purification by column chromatography to obtain compound 2; Preparation of compound 3: Compound 2, 1-Boc-piperazine, triethylamine, KI and anhydrous ethanol were reacted by heating, concentrated and dissolved in ethyl acetate, washed, dried and purified; then reacted with trifluoroacetic acid and dichloromethane at room temperature, and concentrated to obtain compound 3; Preparation of compound A: Compound 3, sulfonyl chlorides with different substitutions, triethylamine, and dichloromethane were reacted at low temperature, concentrated, and purified by column chromatography to obtain compound A.

[0015] Preferably, as an improvement, in the preparation step of compound A, the temperature of the low-temperature reaction is 0~20℃. Detailed Implementation

[0016] The present invention will be further described below with reference to the embodiments. However, the present invention is not limited to the following embodiments. It is foreseeable that various changes may occur in the implementation when those skilled in the art combine it with the prior art.

[0017] The natural product 3-methylcarbazole derivative of this invention has the structure of general formula A, and its synthetic route is as follows: .

[0018] Example 1: Preparation of compound A9 Preparation of Compound 1: 20 mmol of phenylhydrazine hydrochloride, 10.00 mL of acetic acid, and 20 mmol of 4-methylcyclohexanone were weighed and reacted at 100 °C. After 35 min, the reaction was completed, cooled, and quenched with distilled water. After cooling, crystallization occurred, and a white solid was precipitated and set aside. 10 mmol of the above product, 4 mmol of iodine, and 5 mL of dimethyl sulfoxide were weighed and reacted at 90 °C for 11 h. After cooling, the reaction was quenched with concentrated hydrochloric acid, stirred with an appropriate amount of saturated sodium thiosulfate solution for 1 h, extracted with ethyl acetate, washed with saturated saline solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain Compound 1.

[0019] Preparation of compound 2: Weigh 5 mmol of compound 1, 34 mmol of 1,3-dibromopropane, 22 mmol of NaH and 10 mL of...N , N -Dimethylformamide, followed by thin-layer chromatography. After the reaction was completed, saturated brine was added to quench the reaction, followed by extraction with ethyl acetate, washing with saturated brine, drying with anhydrous sodium sulfate, concentrating the solvent under reduced pressure, and purifying by silica gel column chromatography to obtain compound 2.

[0020] Preparation of compound 3: Weigh 2 mmol of compound 2, 8 mmol of 1-Boc-piperazine, 8 mmol of Et3N, 1 mmol of KI, and 5 mL of anhydrous ethanol. React at 80 °C, with thin-layer chromatography monitoring the reaction. After the reaction, concentrate the solvent under reduced pressure, dissolve in ethyl acetate, wash with saturated brine, dry with anhydrous sodium sulfate, concentrate the solvent under reduced pressure, and purify by silica gel column chromatography for later use. Add the prepared compound, 25 mmol of trifluoroacetic acid, and 5 mL of dichloromethane to a reaction flask and react at room temperature, with thin-layer chromatography monitoring the reaction. After the reaction, concentrate the solvent under reduced pressure to obtain compound 3.

[0021] Preparation of compound A9: 0.9 mmol of compound 3, 0.9 mmol of o-trifluoromethanesulfonyl chloride, 3 mmol of triethylamine, and 5 mL of dichloromethane were weighed into a reaction flask and reacted at 10 °C. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the solvent was concentrated under reduced pressure, and the mixture was purified by silica gel column chromatography to obtain compound A9.

[0022] Example 2: Preparation of compound A25 Preparation of Compound 1: 20 mmol of phenylhydrazine hydrochloride, 10.00 mL of acetic acid, and 20 mmol of 4-methylcyclohexanone were weighed and reacted at 90 °C. After 40 min, the reaction was completed, cooled, and quenched with distilled water. After cooling, crystallization occurred, and a white solid was precipitated and set aside. 10 mmol of the above product, 4 mmol of iodine, and 5 mL of dimethyl sulfoxide were weighed and reacted at 80 °C for 12 h. After cooling, the reaction was quenched with concentrated hydrochloric acid, stirred with an appropriate amount of saturated sodium thiosulfate solution for 1 h, extracted with ethyl acetate, washed with saturated saline solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain Compound 1.

[0023] Preparation of compound 2: Weigh 5 mmol of compound 1, 34 mmol of 1,3-dibromopropane, 22 mmol of NaH and 10 mL of... N , N -Dimethylformamide, followed by thin-layer chromatography. After the reaction was completed, saturated brine was added to quench the reaction, followed by extraction with ethyl acetate, washing with saturated brine, drying with anhydrous sodium sulfate, concentrating the solvent under reduced pressure, and purifying by silica gel column chromatography to obtain compound 2.

[0024] Preparation of compound 3: Weigh 2 mmol of compound 2, 8 mmol of 1-Boc-piperazine, 8 mmol of Et3N, 1 mmol of KI, and 5 mL of anhydrous ethanol. React at 60 °C, with thin-layer chromatography monitoring the reaction. After the reaction is complete, concentrate the solvent under reduced pressure, dissolve in ethyl acetate, wash with saturated brine, dry with anhydrous sodium sulfate, concentrate the solvent under reduced pressure, and purify by silica gel column chromatography for later use. Add the prepared compound, 25 mmol of trifluoroacetic acid, and 5 mL of dichloromethane to a reaction flask and react at room temperature, with thin-layer chromatography monitoring the reaction. After the reaction is complete, concentrate the solvent under reduced pressure to obtain compound 3.

[0025] Preparation of compound A25: 0.9 mmol of compound 3, 0.9 mmol of benzo[1,2,5]thiadiazole-4-sulfonyl chloride, 3 mmol of triethylamine, and 5 mL of dichloromethane were weighed into a reaction flask and reacted at 5 °C. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the solvent was concentrated under reduced pressure, and the mixture was purified by silica gel column chromatography to obtain compound A25.

[0026] Example 3: Preparation of compound A26 Preparation of Compound 1: 20 mmol of p-fluorophenylhydrazine hydrochloride, 10.00 mL of acetic acid, and 20 mmol of 4-methylcyclohexanone were weighed and reacted at 130 °C. After 20 min, the reaction was completed, cooled, and quenched with distilled water. After cooling, crystallization occurred, and a white solid was precipitated and set aside. 10 mmol of the above product, 4 mmol of iodine, and 5 mL of dimethyl sulfoxide were weighed and reacted at 110 °C. After 10.5 h, the reaction was completed, cooled, quenched with concentrated hydrochloric acid, and stirred with an appropriate amount of saturated sodium thiosulfate solution for 1 h. The mixture was extracted with ethyl acetate, washed with saturated saline solution, dried over anhydrous sodium sulfate, and the solvent was concentrated under reduced pressure. The mixture was then purified by column chromatography on silica gel to obtain Compound 1.

[0027] Preparation of compound 2: Weigh 5 mmol of compound 1, 34 mmol of 1,3-dibromopropane, 22 mmol of NaH and 10 mL of... N , N -Dimethylformamide, followed by thin-layer chromatography. After the reaction was completed, saturated brine was added to quench the reaction, followed by extraction with ethyl acetate, washing with saturated brine, drying with anhydrous sodium sulfate, concentrating the solvent under reduced pressure, and purifying by silica gel column chromatography to obtain compound 2.

[0028] Preparation of compound 3: Weigh 2 mmol of compound 2, 8 mmol of 1-Boc-piperazine, 8 mmol of Et3N, 1 mmol of KI, and 5 mL of anhydrous ethanol. React at 80 °C, with thin-layer chromatography monitoring the reaction. After the reaction, concentrate the solvent under reduced pressure, dissolve in ethyl acetate, wash with saturated brine, dry with anhydrous sodium sulfate, concentrate the solvent under reduced pressure, and purify by silica gel column chromatography for later use. Add the prepared compound, 25 mmol of trifluoroacetic acid, and 5 mL of dichloromethane to a reaction flask and react at room temperature, with thin-layer chromatography monitoring the reaction. After the reaction, concentrate the solvent under reduced pressure to obtain compound 3.

[0029] Preparation of compound A26: 0.9 mmol of compound 3, 0.9 mmol of quinoline-8-sulfonyl chloride, 3 mmol of triethylamine, and 5 mL of dichloromethane were weighed into a reaction flask and reacted at 10 °C. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the solvent was concentrated under reduced pressure, and the mixture was purified by silica gel column chromatography to obtain compound A26.

[0030] Example 4: Preparation of compound A27 Preparation of Compound 1: 20 mmol of p-fluorophenylhydrazine hydrochloride, 10.00 mL of acetic acid, and 20 mmol of 4-methylcyclohexanone were weighed and reacted at 80 °C. After 40 min, the reaction was completed, cooled, and quenched with distilled water. After cooling, crystallization occurred, and a white solid was precipitated and set aside. 10 mmol of the above product, 4 mmol of iodine, and 5 mL of dimethyl sulfoxide were weighed and reacted at 80 °C for 12 h. After cooling, the reaction was quenched with concentrated hydrochloric acid, stirred with an appropriate amount of saturated sodium thiosulfate solution for 1 h, extracted with ethyl acetate, washed with saturated saline solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain Compound 1.

[0031] Preparation of compound 2: Weigh 5 mmol of compound 1, 34 mmol of 1,3-dibromopropane, 22 mmol of NaH and 10 mL of... N , N -Dimethylformamide, followed by thin-layer chromatography. After the reaction was completed, saturated brine was added to quench the reaction, followed by extraction with ethyl acetate, washing with saturated brine, drying with anhydrous sodium sulfate, concentrating the solvent under reduced pressure, and purifying by silica gel column chromatography to obtain compound 2.

[0032] Preparation of compound 3: Weigh 2 mmol of compound 2, 8 mmol of 1-Boc-piperazine, 8 mmol of Et3N, 1 mmol of KI, and 5 mL of anhydrous ethanol. React at 75 °C, with thin-layer chromatography monitoring the reaction. After the reaction is complete, concentrate the solvent under reduced pressure, dissolve in ethyl acetate, wash with saturated brine, dry with anhydrous sodium sulfate, concentrate the solvent under reduced pressure, and purify by silica gel column chromatography for later use. Add the prepared compound, 25 mmol of trifluoroacetic acid, and 5 mL of dichloromethane to a reaction flask and react at room temperature, with thin-layer chromatography monitoring the reaction. After the reaction is complete, concentrate the solvent under reduced pressure to obtain compound 3.

[0033] Preparation of compound A27: 0.9 mmol of compound 3, 0.9 mmol of coumarin-6-sulfonyl chloride, 3 mmol of triethylamine, and 5 mL of dichloromethane were weighed into a reaction flask and reacted at 15 °C. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the solvent was concentrated under reduced pressure, and the mixture was purified by silica gel column chromatography to obtain compound A27.

[0034] Example 5: Preparation of compound A28 Preparation of Compound 1: 20 mmol of p-fluorophenylhydrazine hydrochloride, 10.00 mL of acetic acid, and 20 mmol of 4-methylcyclohexanone were weighed and reacted at 85 °C. After 25 min, the reaction was completed, cooled, and quenched with distilled water. After cooling, crystallization occurred, and a white solid was precipitated and set aside. 10 mmol of the above product, 4 mmol of iodine, and 5 mL of dimethyl sulfoxide were weighed and reacted at 95 °C for 10.5 h. After cooling, the reaction was quenched with concentrated hydrochloric acid, stirred with an appropriate amount of saturated sodium thiosulfate solution for 1 h, extracted with ethyl acetate, washed with saturated saline solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain Compound 1.

[0035] Preparation of compound 2: Weigh 5 mmol of compound 1, 34 mmol of 1,3-dibromopropane, 22 mmol of NaH and 10 mL of... N , N -Dimethylformamide, followed by thin-layer chromatography. After the reaction was completed, saturated brine was added to quench the reaction, followed by extraction with ethyl acetate, washing with saturated brine, drying with anhydrous sodium sulfate, concentrating the solvent under reduced pressure, and purifying by silica gel column chromatography to obtain compound 2.

[0036] Preparation of compound 3: Weigh 2 mmol of compound 2, 8 mmol of 1-Boc-piperazine, 8 mmol of Et3N, 1 mmol of KI, and 5 mL of anhydrous ethanol. React at 65 °C, with thin-layer chromatography monitoring the reaction. After the reaction, concentrate the solvent under reduced pressure, dissolve in ethyl acetate, wash with saturated brine, dry with anhydrous sodium sulfate, concentrate the solvent under reduced pressure, and purify by silica gel column chromatography for later use. Add the prepared compound, 25 mmol of trifluoroacetic acid, and 5 mL of dichloromethane to a reaction flask and react at room temperature, with thin-layer chromatography monitoring the reaction. After the reaction, concentrate the solvent under reduced pressure to obtain compound 3.

[0037] Preparation of compound A28: 0.9 mmol of compound 3, 0.9 mmol of benzo[1,2,5]thiadiazole-4-sulfonyl chloride, 3 mmol of triethylamine, and 5 mL of dichloromethane were weighed into a reaction flask and reacted at 8 °C. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the solvent was concentrated under reduced pressure, and the mixture was purified by silica gel column chromatography to obtain compound A28.

[0038] The relevant data for each 3-methylcarbazole derivative are shown below: 3-Methyl-9-{3-[4-(benzenesulfonyl)piperazin-1-yl]propyl}-9 H - Carbazole (A1): White solid, mp 49.5~50.6 ℃. 1 H NMR (400 MHz, CDCl3) d 8.01 (d, J = 7.8 Hz, 1H, ArH), 7.85 (s,1H, ArH), 7.78 (d, J = 7.2 Hz, 2H, ArH), 7.68-7.55 (m, 3H, ArH), 7.41-7.31 (m,2H, ArH), 7.27-7.17 (m, 3H, ArH), 4.26 (t, J = 6.5 Hz, 2H, Ar-CH2), 2.95 (s,4H, SN-(CH2)2), 2.55 (s, 3H, CH3), 2.35 (t, J = 5.0 Hz, 4H, CN-(CH2)2), 2.24(t, J = 6.7 Hz, 2H, N-CH2), 1.93 (p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d:140.64, 138.74, 135.39, 132.98, 129.14, 128.07, 127.85, 126.88, 125.35,122.92, 122.63, 120.27 (d, J = 4.9 Hz), 118.56, 108.70, 108.46, 54.76, 52.04,45.96, 40.45, 25.62, 21.47. 3-Methyl-9-[3-(2-Toluenesulfonylpiperazin-1-yl)propyl]-9 H -Carbazole (A2): White solid, mp 29.1~29.7 ℃. 1 H NMR (400 MHz, DMSO-) d 6) d 7.96 (d, J = 7.7 Hz, 1H, ArH), 7.81 (s, 1H, ArH), 7.73 (d, J = 8.0 Hz, 1H, ArH), 7.56 (d, J = 8.0 Hz, 1H, ArH), 7.49-7.37 (m,4H, ArH), 7.32 (t, J = 8.0 Hz, 1H, ArH), 7.20-7.16 (m, 1H, ArH), 7.08 (t, J = 7.4Hz, 1H, ArH), 4.32-4.27 (m, 2H, Ar-CH2), 2.86 (s, 4H, SN-(CH2)2), 2.52 (s,3H, CH3), 2.42 (s, 3H, carbazole-CH3), 2.18 (m, 6H, CH2-N-(CH2)2), 1.83-1.79(p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, DMSO-) d 6) d : 140.66, 138.82, 137.79,135.21, 133.62, 133.45, 130.23, 127.69, 127.23, 126.93, 125.74, 122.55,122.25, 120.42 (d, J= 8.5 Hz), 118.74, 109.61, 109.43, 54.65, 52.17, 45.40,25.48, 21.45, 20.83. 3-Methyl-9-[3-(3-toluenesulfonylpiperazin-1-yl)propyl]-9 H -Carbazole (A3): White solid, mp 36.7~37.5 ℃. 1 H NMR (400 MHz, CDCl3) d 7.99 (d, J = 7.7 Hz, 1H, ArH), 7.84 (s, 1H, ArH), 7.58 (d, J = 2.0 Hz, 2H, ArH), 7.47-7.43 (m, 2H, ArH), 7.39-7.31 (m, 2H,ArH), 7.27-7.20 (m, 2H, ArH), 7.19-7.14 (m, 1H, ArH), 4.28 (t, J = 6.5 Hz, 2H,Ar -CH2), 2.95 (s, 4H, SN-(CH2)2), 2.53 (s, 3H, carbazole-CH3), 2.47 (s, 3H,Ar-CH3), 2.38 (t, J = 5.0 Hz, 4H, CN-(CH2)2), 2.27 (t, J = 6.7 Hz, 2H, N-CH2), 1.96 (p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 140.62, 139.28, 138.71,135.20, 133.74, 128.97, 128.14, 128.07, 126.84, 125.31, 125.04, 122.92,122.62, 120.25 (d, J = 5.2 Hz), 118.52, 108.64, 108.38, 54.78, 52.08, 45.96,40.47, 25.66, 21.47, 21.41. 3-Methyl-9-[3-(4-toluenesulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A4): White solid, mp 30.1~30.9 ℃.1 H NMR (400 MHz, CDCl3) d 8.01 (d, J = 7.7 Hz, 1H, ArH), 7.84 (s, 1H, ArH), 7.65 (d, J = 7.9 Hz, 2H, ArH), 7.36 (p, J = 8.0 Hz, 4H, ArH), 7.26-7.15 (m,3H, ArH), 4.27 (t, J = 6.6 Hz, 2H, Ar-CH2), 2.95 (s, 4H, SN-(CH2)2), 2.54 (s,3H, carbazole-CH3), 2.46 (s, 3H, CH3), 2.38 (t, J = 5.0 Hz, 4H, CN-(CH2)2),2.25 (t, J = 6.8 Hz, 2H, N-CH2), 1.95 (p, J = 6.8 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 143.73, 140.63, 138.73, 132.37, 129.73, 128.06, 127.90, 126.86,125.33, 122.92, 122.62, 120.26 (d, J = 5.1 Hz), 118.54, 108.66, 108.42, 54.72,52.06, 45.96, 40.42, 25.66, 21.61, 21.43. 3-Methyl-9-[3-(2-methoxybenzenesulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A5): White solid, mp 55.6~56.5 ℃. 1 H NMR (400 MHz, CDCl3) d 8.04 (d, J = 7.8 Hz, 1H, ArH), 7.92-7.87(m, 2H, ArH), 7.55-7.49 (m, 1H, ArH), 7.43-7.36 (m, 2H, ArH), 7.31 (d, J = 8.3Hz, 1H, ArH), 7.25 (dd,J = 8.3, 1.7 Hz, 1H, ArH), 7.22-7.16 (m, 1H, ArH), 7.09-6.99 (m, 2H, ArH), 4.30 (t, J = 6.5 Hz, 2H, Ar-CH2), 3.92 (s, 3H, Ar-OCH3), 3.22 (s, 4H, SN-(CH2)2), 2.55 (s, 3H, CH3), 2.37 (t, J = 5.1 Hz, 4H, CN-(CH2)2), 2.26 (t, J = 6.7 Hz, 2H, N-CH2), 1.97 (p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101MHz, CDCl3) d : 157.00, 140.67, 138.76, 134.70, 131.76, 128.08, 126.91, 125.89,125.38, 122.93, 122.63, 120.40, 120.28 (d, J = 4.4 Hz), 118.58, 112.35, 108.75,108.52, 55.95, 54.81, 52.71, 45.92, 40.41, 25.75, 21.47. 3-Methyl-9-[3-(3-methoxybenzenesulfonylpiperazin-1-yl)propyl]-9 H -Carbazole (A6): White solid, mp 52.7~53.7 ℃. 1 H NMR (400 MHz, CDCl3) d 8.00 (d, J = 7.8 Hz, 1H, ArH), 7.84 (s,1H, ArH), 7.48 (t, J = 8.0 Hz, 1H, ArH), 7.41-7.31 (m, 3H, ArH), 7.30-7.26 (m,1H, ArH), 7.25-7.21 (m, 2H, ArH), 7.20-7.15 (m, 2H, ArH), 4.26 (t, J= 6.5 Hz,2H, Ar-CH2), 3.88 (s, 3H, Ar-OCH3), 2.94 (s, 4H, SN-(CH2)2), 2.55 (s, 3H,CH3), 2.35 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.24 (t, J = 6.7 Hz, 2H, N-CH2), 1.93(p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 159.95, 140.65, 138.75,136.52, 130.23, 128.05, 126.89, 125.35, 122.92, 122.62, 120.26 (d, J = 4.1 Hz),119.97, 118.93, 118.55, 112.82, 108.72, 108.47, 55.73, 54.78, 52.05, 45.98,40.49, 25.58, 21.46. 3-Methyl-9-[3-(4-methoxybenzenesulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A7): White solid, mp 43.6~44.5 ℃. 1 H NMR (400 MHz, CDCl3) d 8.01 (d, J = 7.8 Hz, 1H, ArH), 7.85 (s,1H, ArH), 7.70 (d, J = 8.9 Hz, 2H, ArH), 7.40-7.31 (m, 2H, ArH), 7.27-7.22 (m,2H, ArH), 7.21-7.15 (m, 1H, ArH), 7.02 (d, J = 8.9 Hz, 2H, ArH), 4.28 (t, J = 6.5Hz, 2H, CH2), 3.88 (s, 3H, Ar-OCH3), 2.94 (s, 4H, SN-(CH2)2), 2.53 (s, 3H,CH3), 2.38 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.26 (t, J= 6.7 Hz, 2H, N-CH2), 1.95(p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 163.10, 140.61, 138.70,129.95, 128.07, 126.98, 126.83, 125.30, 122.90, 122.60, 120.25 (d, J = 5.4 Hz),118.52, 114.23, 108.61, 108.36, 55.65, 54.73, 52.06, 45.95, 40.42, 25.68,21.38. 3-Methyl-9-[3-(4-fluorobenzenesulfonylpiperazin-1-yl)propyl]-9 H -Carbazole (A8): White solid, mp 49.4~50.7 ℃. 1 H NMR (400 MHz, CDCl3) d 8.02 (d, J = 7.8 Hz, 1H, ArH), 7.86 (s, 1H,ArH), 7.79-7.74 (m, 2H, ArH), 7.42-7.32 (m, 2H, ArH), 7.28-7.17 (m, 5H, ArH), 4.26 (t, J = 6.5 Hz, 2H, Ar-CH2), 2.92 (s, 4H, SN-(CH2)2), 2.56 (s, 3H, CH3), 2.35 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.25 (t, J = 6.7 Hz, 2H, N-CH2), 1.94 (p, J =6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 166.56, 164.02, 140.65, 138.75,131.54 (d, J = 3.3 Hz), 130.53 (d, J = 9.3 Hz), 128.09, 126.92, 125.38, 122.92,122.62, 120.29 (d, J= 4.8 Hz), 118.59, 116.52, 116.30, 108.73, 108.49, 54.75,51.97, 45.94, 40.46, 25.62, 21.48. 3-Methyl-9-[3-(2-trifluoromethylbenzenesulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A9): Yellow solid, mp 41.3~42.5 ℃. 1 H NMR (400 MHz, CDCl3) d 8.08 (dd, J = 7.3, 2.1 Hz, 1H, ArH),8.03 (d, J = 7.8 Hz, 1H, ArH), 7.93 (dd, J = 7.0, 2.2 Hz, 1H, ArH), 7.87 (s, 1H,ArH), 7.75-7.67 (m, 2H, ArH)), 7.45-7.36 (m, 2H, ArH), 7.32-7.25 (m, 2H,ArH), 7.22-7.17 (m, 1H, ArH), 4.31 (t, J = 6.4 Hz, 2H, Ar-CH2), 3.20 (s, 4H, SN-(CH2)2), 2.56 (s, 3H, CH3), 2.35 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.25 (t, J =6.6 Hz, 2H, N-CH2), 1.96 (p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d :140.68, 138.77, 137.21, 132.80, 132.28, 131.97, 128.57 (d, J = 6.5 Hz), 128.11,126.92, 125.38, 122.92, 122.63, 120.26 (d, J = 4.7 Hz), 118.57, 108.76, 108.51,54.71, 52.34, 45.64, 40.36, 25.52, 21.44. 3-Methyl-9-[3-(3-trifluoromethylbenzenesulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A10): Yellow solid, mp 47.8~48.5 ℃. 1 H NMR (400 MHz, CDCl3) d : 8.03 (s, 1H, ArH), 7.98-7.89 (m,3H, ArH), 7.83 (s, 1H, ArH), 7.72 (t, J = 7.8 Hz, 1H, ArH), 7.39-7.30 (m, 2H, ArH), 7.26-7.20 (m, 2H, ArH), 7.15 (t, J = 6.8 Hz, 1H, ArH), 4.28 (t, J = 6.4 Hz, 2H, Ar-CH2), 2.93 (s, 4H, SN-(CH2)2), 2.53 (s, 3H, CH3), 2.36 (t, J = 4.9 Hz,4H, CN-(CH2)2), 2.27 (t, J = 6.7 Hz, 2H, N-CH2), 1.96 (p, J = 6.7 Hz, 2H, CH2). 13 CNMR (101 MHz, CDCl3) d : 140.62, 138.68, 136.83, 131.98, 131.64, 131.00, 130.02,129.61 (d, J = 3.6 Hz), 128.14, 126.87, 125.32, 124.69, 122.90, 122.60, 120.23(d, J = 7.1 Hz), 118.55, 108.64, 108.38, 54.80, 51.92, 45.82, 40.48, 25.49,21.39. 3-Methyl-9-[3-(4-trifluoromethylbenzenesulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A11): Yellow solid, mp 42.7~43.2 ℃. 1 H NMR (400 MHz, CDCl3) d 8.00 (d, J = 7.7 Hz, 1H, ArH), 7.84(d,J = 2.2 Hz, 5H, ArH), 7.42-7.31 (m, 2H, ArH), 7.28-7.16 (m, 3H, ArH), 4.27(t, J = 6.5 Hz, 2H, Ar-CH2), 2.90 (s, 4H, SN-(CH2)2), 2.56 (s, 3H, CH3), 2.33(t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.25 (t, J = 6.7 Hz, 2H, N-CH2), 1.94 (p, J = 6.6Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 140.65, 139.21, 138.74, 134.63, 134.30,128.31, 128.11, 126.92, 126.29 (d, J = 3.8 Hz), 125.37, 122.91, 122.61, 120.26(d, J = 5.5 Hz), 118.58, 108.73, 108.47, 54.82, 51.95, 45.87, 40.51, 25.55,21.43. 3-Methyl-9-[3-(2-nitrobenzenesulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A12): Yellow solid, mp 55.8~56.6 ℃. 1 H NMR (400 MHz, CDCl3) d 8.02 (d, J = 7.8 Hz, 1H, ArH), 7.95-7.90(m, 1H, ArH), 7.86 (s, 1H, ArH), 7.72-7.68 (m, 2H, ArH), 7.63-7.58 (m, 1H,ArH), 7.43-7.36 (m, 2H, ArH), 7.30 (d, J = 8.3 Hz, 1H, ArH), 7.27-7.23 (m, 1H, ArH), 7.17 (t, J = 7.9 Hz, 1H, ArH), 4.32 (t, J= 6.4 Hz, 2H, Ar-CH2), 3.25 (t, J =5.0 Hz, 4H, SN-(CH2)2), 2.53 (s, 3H, CH3), 2.38 (t, J = 5.0 Hz, 4H, CN-(CH2)2),2.27 (t, J = 6.6 Hz, 2H, N-CH2), 1.98 (p, J = 6.5 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 148.48, 140.65, 138.74, 133.82, 131.53, 130.92, 128.13, 126.90,125.35, 124.09, 122.91, 122.62, 120.25 (d, J = 5.9 Hz), 118.57, 108.69, 108.45,54.64, 52.27, 45.90, 40.33, 25.55, 21.44. 3-Methyl-9-[3-(3-nitrobenzenesulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A13): Yellow solid, mp 61.2~61.9 ℃. 1 H NMR (400 MHz, CDCl3) d : 8.58 (s, 1H, ArH), 8.49 (d, J = 8.2 Hz, 1H, ArH), 8.06 (d, J = 7.9, 1.4 Hz, 1H, ArH), 7.94 (d, J = 7.8 Hz, 1H, ArH),7.82-7.76 (m, 2H, ArH), 7.36-7.29 (m, 2H, ArH), 7.26-7.20 (m, 2H, ArH), 7.13(t, J = 7.9 Hz, 1H, ArH), 4.29 (t, J = 6.4 Hz, 2H, Ar-CH2), 2.96 (s, 4H, SN-(CH2)2), 2.50 (s, 3H, CH3, 2.38 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.28 (t,J = 6.6Hz, 2H, N-CH2), 1.97 (p, J = 6.5 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 148.36,140.59, 138.66, 138.06, 133.20, 130.53, 128.13, 127.36, 126.83, 125.28,122.87, 122.57, 120.23 (d, J = 1.7 Hz), 120.16, 118.50, 108.28, 54.82, 51.93,45.90, 40.49, 25.51, 21.32. 3-Methyl-9-[3-(4-nitrobenzenesulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A14): Yellow solid, mp 54.8~55.6 ℃. 1 H NMR (400 MHz, CDCl3) d 8.39 (d, J = 8.9 Hz, 1H, ArH), 7.97 (t, J =7.8 Hz, 1H, ArH), 7.90 (d, J = 8.7 Hz, 2H, ArH), 7.81 (s, 1H, ArH), 7.38- 7.29(m, 2H, ArH), 7.26-7.19 (m, 2H, ArH), 7.14 (t, J = 8.0 Hz, 1H, ArH), 4.28 (t, J =6.4 Hz, 2H, Ar-CH2), 2.97 (s, 4H, SN-(CH2)2), 2.51 (s, 3H, CH3), 2.38 (t, J =4.9 Hz, 4H, CN-(CH2)2), 2.27 (t, J = 6.6 Hz, 2H, N-CH2), 1.96 (p, J = 6.4 Hz, 2H,CH2). 13 C NMR (101 MHz, CDCl3) d: 150.20, 141.71, 140.57, 138.66, 128.89, 128.14,126.84, 125.29, 124.37, 122.87, 122.57, 120.24 (d, J = 6.5 Hz), 118.55, 108.56,108.29, 54.76, 51.96, 45.87, 40.42, 25.55, 21.38. 3-Methyl-9-[3-(thiophene-2-sulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A15): White solid, mp 62.1~62.4 ℃. 1 H NMR (400 MHz, CDCl3) d 8.03 (d, J = 7.7 Hz, 1H, ArH), 7.87 (s,1H, ArH), 7.64 (dd, J = 5.0, 1.4 Hz, 1H, ArH), 7.54 (dd, J = 3.8, 1.4 Hz, 1H,ArH), 7.44-7.33 (m, 2H, ArH), 7.30-7.16 (m, 4H, ArH), 4.28 (t, J = 6.5 Hz, 2H,Ar-CH2), 3.00 (s, 4H, SN-(CH2)2), 2.56 (s, 3H, CH3), 2.38 (t, J = 4.8 Hz, 4H,CN-(CH2)2), 2.26 (t, J = 6.7 Hz, 2H, N-CH2), 1.95 (p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 140.67, 138.77, 135.65, 132.65, 132.37, 128.09, 127.85,126.93, 125.39, 122.94, 122.65, 120.31 (d, J = 4.9 Hz), 118.60, 108.76, 108.51,54.71, 51.90, 46.03, 40.47, 25.63, 21.51. 3-Methyl-9-[3-(5-chlorothiophene-2-sulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A16): White solid, mp 52.1~52.8 ℃. 1 H NMR (400 MHz, CDCl3) d 8.02 (d, J = 7.7 Hz, 1H, ArH), 7.86(s, 1H, ArH), 7.43-7.34 (m, 2H, ArH), 7.30 (d, J = 4.0 Hz, 1H, ArH), 7.28-7.24(m, 2H, ArH), 7.21-7.17 (m, 1H, ArH), 7.03 (d, J = 4.0 Hz, 1H, ArH), 4.30 (t, J =6.4 Hz, 2H, Ar-CH2), 2.94 (s, 4H, SN-(CH2)2), 2.55 (s, 3H, CH3), 2.36 (t, J =4.9 Hz, 4H, CN-(CH2)2), 2.28 (t, J = 6.6 Hz, 2H, N-CH2), 1.97 (p, J = 6.5 Hz, 2H,CH2). 13 C NMR (101 MHz, CDCl3) d : 140.67, 138.76, 137.44, 133.83, 131.95, 128.09,127.25, 126.89, 125.35, 122.93, 122.63, 120.25 (d, J = 5.5 Hz), 118.55, 108.69,108.44, 54.81, 51.85, 45.93, 40.56, 25.52, 21.45. 3-Methyl-9-[3-(5-bromothiophene-2-sulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A17): White solid, mp 42.6~43.8 ℃. 1 H NMR (400 MHz, CDCl3) d 8.02 (d, J= 7.8 Hz, 1H, ArH), 7.86(s, 1H, ArH), 7.43-7.33 (m, 2H, ArH), 7.30-7.23 (m, 3H, ArH), 7.22-7.15 (m,2H, ArH), 4.30 (t, J = 6.4 Hz, 2H, Ar-CH2)), 2.93 (s, 4H, SN-(CH2)2), 2.55 (s,3H, CH3), 2.36 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.28 (t, J = 6.6 Hz, 2H, N-CH2), 1.97 (p, J = 6.5 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 140.67, 138.76, 136.63,132.71, 130.88, 128.10, 126.91, 125.37, 122.93, 122.63, 120.28 (d, J = 5.4 Hz),120.13, 118.57, 108.71, 108.45, 54.83, 51.84, 45.91, 40.58, 25.52, 21.49. 3-Methyl-9-{3-[3-(2-methyl carbamate thiophenesulfonyl)piperazin-1-yl]propyl}-9 H - Carbazole (A18): White solid, mp 57.6~58.1 ℃. 1 H NMR (400 MHz, CDCl3) d 8.02 (d, J = 7.6 Hz, 1H, ArH),7.85 (s, 1H, ArH), 7.50 (d, J = 5.3 Hz, 1H, ArH), 7.43 (d, J = 5.3 Hz, 1H, ArH),7.39-7.36 (m, 2H, ArH), 7.29 (d, J = 8.3 Hz, 1H, ArH), 7.26-7.22 (m, 1H, ArH), 7.19-7.15 (m, 1H, ArH), 4.33 (t, J= 6.5 Hz, 2H, Ar-CH2), 3.92 (s, 3H, COOCH3), 3.28 (s, 4H, SN-(CH2)2), 2.52 (s, 3H, CH3), 2.38 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.28 (t, J = 6.6 Hz, 2H, N-CH2), 1.99 (p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101MHz, CDCl3) d : 160.00, 140.64, 140.24, 138.73, 133.99, 131.31 (d, J = 8.0 Hz),129.33-128.87 (m), 128.09, 126.84, 125.30, 122.92, 122.62, 120.46-120.10 (m),118.47, 108.51 (d, J = 24.1 Hz), 54.78, 53.12, 52.47, 46.04, 40.40, 25.63,21.35. 3-Methyl-9-[3-(3,5-dimethylisoxazol-4-sulfonylpiperazine-1-yl)propyl]-9 H - Carbazole (A19): White solid, mp 54.1~54.9 ℃. 1 H NMR (400 MHz, CDCl3) d 7.96 (d, J = 7.8 Hz, 1H, ArH),7.82 (s, 1H, ArH), 7.40-7.32 (m, 2H, ArH), 7.28-7.21 (m, 2H, ArH), 7.16 (t, J =7.9 Hz, 1H, ArH), 4.32 (t, J = 6.2 Hz, 2H, Ar-CH2), 2.72 (s, 4H, SN-(CH2)2), 2.61 (s, 3H, OC-CH3), 2.54 (s, 3H, CH3), 2.39 (s, 3H, N=C-CH3), 2.29 (t, J =6.3 Hz, 2H, N-CH2), 2.22 (t, J= 4.9 Hz, 4H, CN-(CH2)2), 1.98 (p, J = 6.3 Hz, 2H,CH2). 13 C NMR (101 MHz, CDCl3) d : 173.74, 158.10, 140.76, 138.75, 127.99, 126.84,125.25, 122.91, 122.61, 120.15 (d, J = 5.7 Hz), 118.44, 112.78, 108.70, 108.42,55.11, 51.76, 45.16, 40.95, 25.02, 21.41, 13.05, 11.49. 3-Methyl-9-[3-(pyridin-3-sulfonylpiperazin-1-yl)propyl]-9 H - Carbazole (A20): White solid, mp 85.7~86.9 ℃. 1 H NMR (400 MHz, CDCl3) d 8.99 (d, J = 2.3 Hz, 1H, ArH), 8.86 (dd, J =4.9, 1.6 Hz, 1H, ArH), 8.03-7.95 (m, 2H, ArH), 7.81 (s, 1H, ArH), 7.50 (dd, J =8.0, 4.9 Hz, 1H, ArH), 7.40-7.28 (m, 2H, ArH), 7.26-7.19 (m, 2H, ArH), 7.18-7.12 (m, 1H, ArH), 4.26 (t, J = 6.4 Hz, 2H, Ar-CH2), 2.93 (s, 4H, SN-(CH2)2), 2.52 (s, 3H, CH3), 2.33 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.24 (t, J = 6.6 Hz, 2H,N-CH2), 1.93 (p, J = 6.5 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 153.51, 148.53,140.62, 138.70, 135.46 (d,J = 1.8 Hz), 132.38, 128.10, 126.87, 125.33, 123.83,122.89, 122.60, 120.24 (d, J = 5.6 Hz), 118.55, 108.63, 108.38, 54.77, 51.91,45.80, 40.47, 25.48, 21.45. 3-Methyl-9-{3-[4-(2,3-dihydrobenzofuran-5-sulfonyl)piperazin-1-yl]propyl}-9 H - Carbazole (A21): White solid, mp 55.7~56.5 ℃. 1 H NMR (400 MHz, CDCl3) d 8.02 (d, J = 7.8 Hz,1H, ArH), 7.86 (s, 1H, ArH), 7.58-7.55 (m, 1H, ArH), 7.41-7.33 (m, 2H, ArH),7.28-7.22 (m, 3H, ArH), 7.20-7.16 (m, 1H, ArH), 6.89 (d, J = 8.4 Hz, 1H, ArH), 4.67 (t, J = 8.8 Hz, 2H, O-CH2), 4.26 (t, J = 6.5 Hz, 2H, Ar-CH2), 3.27 (t, J = 8.8Hz, 2H, furan-CH2), 2.95 (s, 4H, SN-(CH2)2), 2.54 (s, 3H, CH3), 2.38 (t, J =4.9 Hz, 4H, CN-(CH2)2), 2.25 (t, J = 6.7 Hz, 2H, N-CH2), 1.94 (p, J = 6.6 Hz, 2H,CH2). 13 C NMR (101 MHz, CDCl3) d : 164.06, 140.64, 138.73, 129.47, 128.43, 128.07,126.83 (d, J = 10.8 Hz), 125.35, 125.05, 122.91, 122.61, 120.26 (d,J = 5.6 Hz),118.55, 109.52, 108.70, 108.45, 72.35, 54.75, 52.07, 46.01 (d, J = 3.2 Hz),40.43, 29.13, 25.73, 21.45. 3-Methyl-9-{3-[4-(naphthyl-1-ylsulfonyl)piperazin-1-yl]propyl}-9 H - Carbazole (A22): White solid, mp 45.2~46.3 ℃. 1 H NMR (400 MHz, CDCl3) d 8.83 (d, J = 8.7 Hz, 1H, ArH), 8.24(d, J = 7.4 Hz, 1H, ArH), 8.09 (d, J = 8.2 Hz, 1H, ArH), 7.94 (t, J = 8.3 Hz, 2H, ArH), 7.80 (s, 1H, ArH), 7.74-7.67 (m, 1H, ArH), 7.66-7.54 (m, 2H, ArH), 7.38-7.28 (m, 2H, ArH), 7.26-7.19 (m, 2H, ArH), 7.15 (t, J = 7.3 Hz 1H, ArH), 4.23 (t, J = 6.4 Hz, 2H, Ar-CH2), 3.11 (s, 4H, SN-(CH2)2), 2.54 (s, 3H, CH3), 2.28 (t, J = 5.0 Hz, 4H, CN-(CH2)2), 2.18 (t, J = 6.6 Hz, 2H, N-CH2), 1.89 (p, J =6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 140.67, 138.75, 134.63, 134.43,132.32, 130.72, 129.17, 129.03, 128.14, 128.01, 126.92 (d, J = 8.2 Hz), 125.35(d, J= 3.4 Hz), 124.24, 122.91, 122.61, 120.22 (d, J = 5.4 Hz), 118.53, 108.75,108.51, 54.67, 52.21, 45.59, 40.39, 25.45, 21.50. 3-Methyl-9-{3-[4-(quinoline-8-sulfonyl)piperazin-1-yl]propyl}-9 H - Carbazole (A23): White solid, mp 85.6.5~86.9 ℃. 1 H NMR (400 MHz, CDCl3) d : 9.08 (s, 1H, ArH), 8.46 (s, 1H,ArH), 8.18 (s, 1H, ArH), 7.98 (s, 2H, ArH), 7.83 (s, 1H, ArH), 7.62-7.13 (m,7H, ArH), 4.25 (s, 2H, Ar-CH2), 3.43 (s, 4H, SN-(CH2)2), 2.51 (s, 3H, CH3), 2.36 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.22 (t, J = 6.8 Hz, 2H, N-CH2), 1.92 (p, J =6.7 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 151.24, 144.25, 140.65, 138.74,136.51 (d, J = 5.0 Hz), 133.65, 133.15, 129.04, 128.02, 126.87, 125.41 (d, J =15.2 Hz), 122.89, 122.59, 122.10, 120.22 (d, J = 5.5 Hz), 118.53, 108.64 (d, J =23.0 Hz), 54.77, 52.87, 46.31, 40.36, 25.68, 21.45. 3-Methyl-9-{3-[4-(coumarin-6-sulfonyl)piperazin-1-yl]propyl}-9 H- Carbazole (A24): White solid, mp 55.2~56.3 ℃. 1 H NMR (400 MHz, CDCl3) d 7.93 (t, J = 7.7 Hz, 1H, ArH),7.85 (s, 1H, ArH), 7.82-7.76 (m, 2H, ArH), 7.66 (d, J = 9.8 Hz, 1H, ArH), 7.43-7.38 (m, 1H, ArH), 7.37-7.24 (m, 2H, ArH), 7.22-7.16 (m, 2H, ArH), 7.15-7.10(m, 1H, ArH), 6.47 (d, J = 9.8 Hz, 1H, ArH), 4.22 (t, J = 6.5 Hz, 2H, Ar-CH2),2.92 (s, 4H, SN-(CH2)2), 2.50 (s, 3H, CH3), 2.34 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.22 (t, J = 6.8 Hz, 2H, N-CH2), 1.90 (p, J = 6.7 Hz, 2H, CH2). 13 C NMR (101MHz, CDCl3) d : 159.32, 156.39, 142.45, 140.55, 138.63, 131.84, 130.59, 128.03(d, J = 8.9 Hz), 126.87, 125.33, 122.82, 122.52, 120.20 (d, J = 5.4 Hz), 118.96,118.53, 118.30, 117.84, 108.65, 108.38, 54.72, 51.93, 45.94, 40.40, 25.58,21.42. 3-Methyl-9-[3-(benzo[1,2,5]thiadiazole-4-sulfonylpiperazine-1-yl)propyl]-9 H - Carbazole (A25): Yellow solid, mp 21.2~22.1 ℃. 1 H NMR (400 MHz, CDCl3) d8.24 (d, J = 8.8 Hz, 1H, ArH), 8.19 (d, J = 7.1 Hz, 1H, ArH), 7.91 (d, J = 7.7 Hz, 1H, ArH), 7.78 (s, 1H, ArH), 7.69 (dd, J = 8.8, 7.1 Hz, 1H, ArH), 7.35-7.28 (m, 2H, ArH), 7.25-7.16 (m, 2H,ArH), 7.13-7.08 (m, 1H, ArH), 4.25 (t, J = 6.4 Hz, 2H, Ar-CH2), 3.24 (s, 4H, SN-(CH2)2), 2.51 (s, 3H, CH3), 2.33 (t, J = 5.0 Hz, 4H, CN-(CH2)2), 2.23 (t, J =6.7 Hz, 2H, N-CH2), 1.93 (p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d :155.57, 149.84, 140.59, 138.66, 132.34, 130.03, 128.22, 128.04, 126.84,126.56, 125.27, 122.84, 122.53, 120.17 (d, J = 9.0 Hz), 118.48, 108.67, 108.41,54.81, 52.44, 46.06, 40.43, 25.56, 21.44. 3-Methyl-6-fluoro-9-{3-[4-(quinoline-8-sulfonyl)piperazin-1-yl]propyl}-9 H -Carbazole (A26): White solid, mp 42.7~43.5 ℃. 1 H NMR (400 MHz, CDCl3) d 9.08 (dd, J = 4.3, 1.8 Hz, 1H,ArH), 8.46 (dd, J = 7.4, 1.5 Hz, 1H, ArH), 8.23 ​​(dd, J= 8.3, 1.9 Hz, 1H, ArH),8.02 (dd, J = 8.2, 1.5 Hz, 1H, ArH), 7.73 (s, 1H, ArH), 7.64-7.57 (m, 2H, ArH), 7.52 (dd, J = 8.3, 4.2 Hz, 1H, ArH), 7.27-7.18 (m, 3H, ArH), 7.05 (t, J = 9.0,2.6 Hz, 1H, ArH), 4.25 (t, J = 6.5 Hz, 2H, Ar-CH2), 3.41 (s, 4H, SN-(CH2)2), 2.48 (s, 3H, CH3), 2.36 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.21 (t, J = 6.6 Hz, 2H,N-CH2), 1.93 (p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 158.14, 155.81,151.22, 144.26, 139.53, 137.01, 136.51 (d, J = 3.7 Hz), 133.58, 133.17, 129.03,128.03, 127.48, 125.51, 122.86 (d, J = 9.5 Hz), 122.41 (d, J = 4.2 Hz), 122.09,120.36, 113.06, 112.80, 109.16 (d, J = 9.0 Hz), 108.74, 105.89, 105.65, 54.70,52.88, 46.27, 40.52, 25.64, 21.33. 3-Methyl-6-fluoro-9-{3-[4-(coumarin-6-sulfonyl)piperazin-1-yl]propyl}-9 H - Carbazole (A27): White solid, mp 48.6~49.4 ℃. 1 H NMR (400 MHz, CDCl3) d 7.87 (d, J= 2.1 Hz, 1H, ArH), 7.81 (dd, J = 8.7, 2.2 Hz, 1H, ArH), 7.73-7.68 (m, 2H, ArH), 7.54 (dd, J = 8.9,2.5 Hz, 1H, ArH), 7.43 (d, J = 8.7 Hz, 1H, ArH), 7.22-7.16 (m, 3H, ArH), 7.08-7.01 (m, 1H, ArH), 6.51 (d, J = 9.6 Hz, 1H, ArH), 4.21 (t, J = 6.4 Hz, 2H, Ar-CH2), 2.91 (s, 4H, SN-(CH2)2), 2.47 (s, 3H, CH3), 2.34 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.22 (t, J = 6.6 Hz, 2H, N-CH2), 1.90 (p, J = 6.5 Hz, 2H, CH2). 13 C NMR (101MHz, CDCl3) d : 159.32, 158.08, 156.43, 155.74, 142.44, 139.45, 136.95, 131.83,130.59, 128.10, 127.98, 127.52, 122.80 (d, J = 9.5 Hz), 122.34 (d, J = 4.1 Hz),120.37, 118.98, 118.40, 117.88, 113.05, 112.80, 109.13 (d, J = 8.9 Hz), 108.64,105.85, 105.61, 54.70, 51.93, 45.91, 40.58, 25.50, 21.35. 3-Methyl-6-fluoro-9-[3-(benzo[1,2,5]thiadiazole-4-sulfonylpiperazine-1-yl)propyl]-9 H - Carbazole (A28): Yellow solid, mp 30.3~31.1 ℃. 1 H NMR (400 MHz, CDCl3) d: 8.26-8.17 (m, 2H,ArH), 7.74-7.67 (m, 2H, ArH), 7.55 (dd, J = 9.0, 2.5 Hz, 1H, ArH), 7.26-7.16(m, 3H, ArH), 7.05 (t, J = 9.0 Hz, 1H, ArH), 4.23 (t, J = 6.4 Hz, 2H, Ar-CH2),3.26 (s, 4H, SN-(CH2)2), 2.48 (s, 3H, CH3), 2.35 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.22 (t, J = 6.7 Hz, 2H, N-CH2), 1.93 (p, J = 6.5 Hz, 2H, CH2). 13 C NMR (101MHz, CDCl3) d : 158.10, 155.77, 155.56, 149.81, 139.47, 136.95, 132.32, 130.05,128.14 (d, J = 13.8 Hz), 127.49, 126.60, 122.83 (d, J = 9.5 Hz), 122.36 (d, J = 4.2Hz), 120.35, 113.07, 112.82, 109.09 (d, J = 9.0 Hz), 108.66, 105.86, 105.63,54.73, 52.46, 46.00, 40.55, 25.51, 21.35. 3-Methyl-8-fluoro-9-{3-[4-(quinoline-8-sulfonyl)piperazin-1-yl]propyl}-9 H -Carbazole (A29): White solid, mp 52.6~53.4 ℃. 1 H NMR (400 MHz, DMSO-) d 6) d : 9.04 (d, 1H, ArH), 8.54 (d, J = 7.0 Hz, 1H, ArH), 8.29 (d, J= 7.4, 2.7 Hz, 2H, ArH), 7.77-7.66 (m, 3H, ArH),7.60 (dd, J = 8.1, 3.4 Hz, 1H, ArH), 7.38 (t, J = 9.2 Hz, 1H, ArH), 7.19-7.02 (m,2H, ArH), 6.95-6.85 (m, 1H, ArH), 4.35 (t, J = 6.2 Hz, 2H, Ar-CH2), 2.98 (s,4H, SN-(CH2)2), 2.36 (s, 3H, CH3), 2.09 (m, 6H, CH2-N-(CH2)2), 1.78 (p, J = 6.6Hz, 2H, CH2). 13 C NMR (101 MHz, DMSO-) d 6) d : 151.78, 150.37, 147.97, 143.87,139.40, 137.29, 136.00, 134.53, 133.21, 129.22, 128.43, 127.97, 126.41 (d, J =5.7 Hz), 126.19, 122.92, 122.48 (d, J = 2.1 Hz), 120.42, 119.06 (d, J = 6.2 Hz),116.50, 111.85, 111.67, 109.80, 54.89, 52.68, 46.13, 43.10, 26.63, 21.33. 3-Methyl-8-fluoro-9-{3-[4-(coumarin-6-sulfonyl)piperazin-1-yl]propyl}-9 H - Carbazole (A30): White solid, mp 50.4~51.4 ℃. 1 H NMR (400 MHz, CDCl3) d 7.85 (d, J = 2.2 Hz, 1H, ArH), 7.80 (dd, J = 8.7, 2.2 Hz, 1H, ArH), 7.71 (s, 1H, ArH), 7.63 (d, J = 7.5 Hz, 1H,ArH), 7.44 (d,J = 8.7 Hz, 1H, ArH), 7.25 (s, 1H, ArH), 7.20 (d, J = 2.2 Hz, 2H,ArH), 7.05-6.93 (m, 2H, ArH), 6.52 (d, J = 9.7 Hz, 1H, ArH), 4.40 (t, J = 6.7 Hz, 2H, Ar-CH2), 2.85 (s, 4H, SN-(CH2)2), 2.48 (s, 3H, CH3), 2.32 (m, 6H, CH2-N-(CH2)2), 1.94 (p, J = 6.7 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 159.29, 156.41,142.42, 139.13, 131.92, 130.64, 128.64, 127.99, 127.55, 120.27, 118.93,118.63 (d, J = 6.5 Hz), 118.38, 117.83, 115.79 (d, J = 3.2 Hz), 111.52, 111.33,108.62, 54.99, 51.90, 45.87, 43.00 (d, J = 5.5 Hz), 26.74, 21.34. 3-Methyl-8-fluoro-9-[3-(benzo[c][1,2,5]thiadiazole-4-sulfonylpiperazine-1-yl)propyl]-9 H - Carbazole (A31): Yellow solid, mp 27.7~28.5 ℃. 1 H NMR (400 MHz, CDCl3) d 8.24 (d, J = 8.9 Hz, 1H, ArH), 8.16 (d, J = 7.2 Hz, 1H, ArH), 7.73-7.66 (m, 2H, ArH), 7.54 (d, J = 7.7Hz, 1H, ArH), 7.26-7.17 (m, 2H, ArH), 6.98 (dd, J= 12.8, 7.9 Hz, 1H, ArH),6.92-6.86 (m, 1H, ArH), 4.41 (t, J = 6.6 Hz, 2H, Ar-CH2), 3.11 (s, 4H, SN-(CH2)2), 2.48 (s, 3H, CH3), 2.29 (m, CH2-N-(CH2)2), 1.94 (p, J = 6.7 Hz, 2H,CH2). 13 C NMR (101 MHz, CDCl3) d : 155.56, 149.87, 148.14, 139.13, 132.29, 129.97,128.59, 128.18, 127.53, 126.49, 122.79 (d, J = 2.2 Hz), 120.23, 118.53 (d, J =6.5 Hz), 115.68 (d, J = 3.3 Hz), 111.45, 111.26, 108.67, 55.12, 52.38, 45.96,43.04 (d, J = 5.5 Hz), 26.66, 21.36. 3-Methyl-6-methoxy-9-{3-[4-(quinoline-8-sulfonyl)piperazin-1-yl]propyl}-9 H - Carbazole (A32): White solid, mp 30.4~31.6 ℃. 1 H NMR (400 MHz, CDCl3) d 9.08 (d, J = 4.2 Hz, 1H,ArH), 8.46 (d, J = 7.4 Hz, 1H, ArH), 8.21 (d, J = 8.4 Hz, 1H, ArH), 8.01 (d, J =8.2 Hz, 1H, ArH), 7.80 (s, 1H, ArH), 7.60 (t, J = 7.8 Hz, 1H, ArH), 7.54-7.47(m, 2H, ArH), 7.28-7.15 (m, 3H, ArH), 6.99 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 4.24(t,J = 6.4 Hz, 2H, Ar-CH2), 3.90 (s, 3H, OCH3), 3.46 (s, 4H, SN-(CH2)2), 2.50(s, 3H, CH3), 2.39 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.22 (t, J = 6.7 Hz, 2H, N-CH2), 1.93 (p, J = 6.5 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 153.28, 151.23,144.25, 139.22, 136.53 (d, J = 9.9 Hz), 135.71, 133.57, 133.16, 129.02, 127.55,126.85, 125.50, 122.82, 122.68, 122.08, 120.18, 114.48, 56.07, 54.72, 52.89,46.29, 40.40, 25.80, 21.38. 3-Methyl-6-methoxy-9-{3-[4-(coumarin-6-sulfonyl)piperazin-1-yl]propyl}-9 H - Carbazole, (A33): white solid, yield: 60%, mp 37.7~38.1 ℃. 1 H NMR (400 MHz, CDCl3) d : 7.90-7.81(m, 2H, ArH), 7.78-7.68 (m, 2H, ArH), 7.48-7.40 (m, 2H, ArH), 7.26-7.14 (m,3H, ArH), 6.97 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 6.51 (d, J = 9.7 Hz, 1H, ArH), 4.21 (t, J = 6.3 Hz, 2H, Ar-CH2), 3.89 (s, 3H, OCH3), 2.98 (s, 4H, SN-(CH2)2), 2.48 (s, 3H, CH3), 2.38 (t, J = 4.9 Hz, 4H, CN-(CH2)2), 2.23 (t, J= 6.6 Hz, 2H,N-CH2), 1.91 (p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 159.30, 156.43,153.30, 142.41, 139.15, 135.61, 131.95, 130.60, 127.97, 127.61, 126.86,122.72 (d, J = 13.8 Hz), 120.19, 118.96, 118.41, 117.91, 114.50, 109.30,108.42, 103.03, 56.07, 54.66, 51.97, 45.96, 40.40, 25.74, 21.37. Elementalanalysis calcd for C 30 H 31 N3O5S (%): C 66.04, H 5.73, N 7.70; found (%): C65.91, H 5.80, N 7.56. 3-Methyl-6-methoxy-9-[3-(benzo[1,2,5]thiadiazole-4-sulfonylpiperazine-1-yl)propyl]-9 H - Carbazole (A34): Yellow solid, mp 30.1~31.0 ℃. 1 H NMR (400 MHz, CDCl3) d : 8.24-8.18 (m, 2H,ArH), 7.77 (s, 1H, ArH), 7.68 (dd, J = 8.7, 7.0 Hz, 1H, ArH), 7.47 (d, J = 2.5Hz, 1H, ArH), 7.26-7.13 (m, 3H, ArH), 6.98 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 4.21(t, J = 6.4 Hz, 2H, Ar-CH2), 3.89 (s, 3H, OCH3), 3.30 (s, 4H, SN-(CH2)2), 2.49(s, 3H, CH3), 2.35 (t, J = 4.8 Hz, 4H, CN-(CH2)2), 2.20 (t, J= 6.7 Hz, 2H, N-CH2), 1.91 (p, J = 6.6 Hz, 2H, CH2). 13 C NMR (101 MHz, CDCl3) d : 155.56, 153.29,149.81, 139.20, 135.67, 132.29, 130.19, 128.18, 127.55, 126.84, 126.54,122.73 (d, J = 15.0 Hz), 120.16, 114.47, 109.33, 108.49, 103.09, 56.08, 54.70,52.50, 46.10, 40.41, 25.74, 21.38. The antibacterial activity test of this invention: using oxacillin as a control drug, the microdilution method was used to determine the antibacterial activity of compound A against Staphylococcus aureus (Staphylococcus aureus). S. aureus ), Escherichia coli ( E. coli ), Pseudomonas aeruginosa ( P. aeruginosa The minimum inhibitory concentrations (MICs) of fluoroquinolone-resistant Escherichia coli (FREC) and other fluoroquinolone-resistant Escherichia coli (FREC) are shown in Table 1.

[0039] Table 1

[0040] The experimental results above clearly demonstrate that the compounds of general formula A protected by this invention possess potential antibacterial activity. These compounds are effective against... E. coli , P. aeruginosa It has a significant inhibitory effect on FREC, among which compounds A9, A18, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33 and A34 have a significant inhibitory effect on FREC. E. coli The MIC was ≤16 μg / mL, and the antibacterial activity of some compounds was comparable to or better than that of the control drug; compounds A9, A18, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32 and A34 showed antibacterial activity against the control drug. P. aeruginosaThe MICs of these compounds are ≤16 μg / mL, and some compounds exhibit antibacterial activity comparable to or better than the control drug. Simultaneously, most compounds also show significant efficacy against resistant FRECs. For example, compounds A9, A10, A11, A18, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33, and A34 have MICs ≤32 μg / mL against FRECs, demonstrating antibacterial activity far superior to the control drug. These compounds exhibit significant antibacterial activity and possess a certain broad antibacterial spectrum, particularly effective against Gram-negative bacteria. Their potential antibacterial activity can be used for… E. coli , P. aeruginosa And the application of FREC. At the same time, these derivatives can also be used in combination with other antibacterial active substances.

[0041] The above descriptions are merely embodiments of the present invention, and common knowledge such as specific technical solutions and / or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solutions of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A natural product 3-methylcarbazole derivative characterized in that, The general chemical structure A is shown below: ， wherein R1is selected from hydrogen, fluorine or methoxy; R2is selected from one of phenyl, methyl-substituted phenyl, methoxy-substituted phenyl, fluorine-substituted phenyl, trifluoromethyl-substituted phenyl, nitro-substituted phenyl, thienyl, chlorine-substituted thienyl, bromine-substituted thienyl, methylformate thienyl, methyl-substituted isoxazolyl, pyridyl, 2,3-dihydrobenzofuranyl, naphthyl, quinolyl, coumarinyl, benzo[1,2,5]thiadiazolyl.

2. The 3-methylcarbazole derivative according to claim 1, characterized by selected from any one of: A1: R1is H, R2is Ph; A5: R1is H, R2is 2-OCH3Ph; A6: R1is H, R2is 3-OCH3Ph; A8: R1is H, R2is 4-FPh; A9: R1is H, R2is 2-CF3Ph; A10: R1is H, R2is 3-CF3Ph; A11: R1is H, R2is 4-CF3Ph; A12: R1is H, R2is 2-NO2Ph; A16: R1is H, R2is 5-chlorothiophene-2-yl; A17: R1is H, R2is 5-bromothiophene-2-yl; A18: R1is H, R2is 2-methoxycarbonyl-3-thiophene-3-yl; A19: R1is H, R2is 3,5-dimethylisoxazole-4-yl; A20: R1is H, R2is pyridine-3-yl; A21: R1is H, R2is 2,3-dihydrobenzofuran-5-yl; A22: R1is H, R2is naphthalene-1-yl; A23: R1is H, R2is quinoline-8-yl; A24: R1is H, R2is coumarin-6-yl; A25: R1is H, R2is 2,1,3-benzothiadiazole-4-yl; A26: R1is 6-F, R2is quinoline-8-yl; A27: R1is 6-F, R2is coumarin-6-yl; A28: R1is 6-F, R2is 2,1,3-benzothiadiazole-4-yl; A29: R1is 8-F, R2is quinoline-8-yl; A30: R1is 8-F, R2is coumarin-6-yl; A31: R1is 8-F, R2is 2,1,3-benzothiadiazole-4-yl; A32: R1is 6-OCH3, R2is quinoline-8-yl; A33: R1is 6-OCH3, R2is coumarin-6-yl; A34: R1is 6-OCH3, R2is 2,1,3-benzothiadiazole-4-yl.

3. A medicament, characterized by comprising a compound of the formula (I) or a pharmaceutically acceptable salt thereof. A 3-methylcarbazole derivative according to claim 1, used as the sole active ingredient or in combination with an antibacterial drug or other antibacterial active ingredients.

4. Use of the 3-methylcarbazole derivative according to claim 2 or the medicament according to claim 3 for the manufacture of a medicament for the treatment and / or prevention of Staphylococcus aureus infectious diseases, characterized in that, The derivative is selected from any one or more combinations of A1, A8, A32.

5. Use of the 3-methylcarbazole derivative according to claim 2 or the medicament according to claim 3 in the manufacture of a medicament for the treatment and / or prevention of a Pseudomonas aeruginosa infectious disease, characterized in that, The derivative is selected from any one or more combinations of A5, A6, A9, A10, A11, A12, A16, A17, A18, A19, A20, A21, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33 and A34.

6. Use of the 3-methylcarbazole derivative according to claim 2 or the pharmaceutical according to claim 3 in the manufacture of a medicament for the treatment and / or prevention of a fluoroquinolone-resistant E. coli infectious disease, characterized in that, The derivative is selected from any one or more combinations of A5, A9, A10, A11, A12, A16, A17, A18, A19, A21, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33 and A34.

7. Use of the 3-methylcarbazole derivative according to claim 2 or the pharmaceutical according to claim 3 in the manufacture of a medicament for the treatment and / or prevention of an E. coli infectious disease, characterized in that, The derivative is preferably any one or more combinations of A5, A6, A9, A10, A11, A12, A16, A17, A18, A19, A20, A21, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33 and A34.

8. The method for preparing the 3-methylcarbazole derivative according to claim 1, characterized in that: Prepared according to the following synthetic route: 。 9. The production method according to claim 8, characterized by, Comprising the following steps: Preparation of compound 1: heating reaction of phenylhydrazine hydrochloride or substituted phenylhydrazine, acetic acid and 4-methylcyclohexanone, after cooling, quenching with water, cooling and crystallization to obtain an intermediate; heating reaction of the intermediate with iodine and dimethyl sulfoxide, after cooling, quenching with concentrated hydrochloric acid, stirring with sodium thiosulfate solution, extraction with ethyl acetate, washing, drying, column chromatography purification to obtain compound 1; Preparation of compound 2: Compound 1, 1,3-dibromopropane, NaH and dimethylformamide were reacted, and after quenching with saturated brine, compound 2 was obtained by extraction with ethyl acetate, washing, drying, column chromatography purification. N,N dimethylformamide, and after quenching with saturated brine, compound 2 was obtained by extraction with ethyl acetate, washing, drying, column chromatography purification. Preparation of compound 3: heating reaction of compound 2, 1-Boc-piperazine, triethylamine, KI and anhydrous ethanol, after concentration, dissolving in ethyl acetate, washing, drying and purification; Then, reaction with trifluoroacetic acid and dichloromethane at room temperature, after concentration to obtain compound 3; Preparation of compound A: low-temperature reaction of compound 3, different substituted sulfonyl chloride, triethylamine and dichloromethane, after concentration, column chromatography purification to obtain compound A.

10. The method of claim 9, wherein: In the preparation steps of compound A, the temperature of the low-temperature reaction is 0-20 ℃.

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