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A kind of synthetic method of metronidazole-sulfonamide derivative

A derivative, the technology of metronidazole, is applied in the field of synthesis of a class of metronidazole-sulfonamide derivatives, which can solve the problems of no bactericidal effect, easy drug resistance, and limited application range

Inactive Publication Date: 2017-04-26
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Metronidazole has a broad-spectrum anti-anaerobic and antiprotozoal effect. It is mainly used clinically to prevent and treat infections caused by anaerobic bacteria. In addition, it is also widely used to prevent and treat oral anaerobic infections. Currently, metronidazole is still on the market. However, it has been reported in recent years that metronidazole has drug resistance and adverse reactions clinically, such as elevated transaminases, pseudomembranous colitis, black urine, neutropenia, nausea, vomiting, diarrhea, thrombophlebitis, Headache, dizziness, ataxia, rash, etc. Therefore, modifying metronidazole to enhance its antibacterial effect and reduce adverse reactions is a hot topic in the field of medicinal chemistry.
[0003] Sulfonamides have a variety of biological activities and have always been a research hotspot in the field of medicinal chemistry. They are widely used in antibacterial, hypotensive, diuretic, etc. However, these drugs are bacteriostatic agents without bactericidal effect, and are prone to drug resistance Sexuality and frequent use will produce many adverse reactions, which greatly limits its application range. However, due to its easy drug resistance, the use range has gradually decreased.

Method used

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  • A kind of synthetic method of metronidazole-sulfonamide derivative
  • A kind of synthetic method of metronidazole-sulfonamide derivative
  • A kind of synthetic method of metronidazole-sulfonamide derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0013] Example 1: Preparation of 3-(2-(2-methyl-5-nitro-1-imidazole)ethoxy)-benzaldehyde (compound 3)

[0014]

[0015] Under stirring, 3-(2-(2-methyl-5-nitro-1-imidazole)ethoxy)-4-methylbenzenesulfonate (4.0g, 12.1mmol), DMF (150mL) , anhydrous potassium carbonate (8.0g, 58mmol), 3-hydroxybenzaldehyde (1.9g, 15.7mmol) were added in a 250mL round-bottomed flask, and stirred at a constant temperature of 80°C for 20 hours (TLC followed the reaction; developer: V 二氯甲烷 :V 乙酸乙酯 =2:1), the reaction solution was poured into distilled water (300mL), extracted with ethyl acetate, the organic layers were combined, dried over anhydrous magnesium sulfate, the solvent was removed under reduced pressure, column chromatography (eluent: V 二氯甲烷 :V 乙酸乙酯 =2:1) ​​to obtain 1.7 g of light yellow solid. Yield 51.3%. m.p.41~43°C; 1 H NMR (DMSO-d 6 , 300MHz) δ: 9.95(s, 1H, CHO), 7.91(s, 1H, CH), 7.96(s, 1H, ArH), 7.47~7.05(m, 3H, ArH), 4.75(t, J=4.7 Hz, 2H, -CH 2 ), 4.39 (t, J=5.0Hz, 2H, -CH...

Embodiment 2

[0016] Example 2: Preparation of 4-(3-(2-(2-methyl-5-nitro-1-imidazole)ethoxy)-benzaldehyde)sulfonamide (compound 4)

[0017]

[0018] The compound 4-(2-(2-methyl-5-nitro-1-imidazole)ethoxy)-benzaldehyde (0.25g, 0.78mmol), ethanol (15mL), sulfonamide (0.22g , 0.78mmol), glacial acetic acid (0.3mL) was added to a 25mL round bottom flask, heated at 50°C for 8h (reaction monitored by TLC; developer: V 二氯甲烷 :V 乙酸乙酯 =1:1), after the reaction was completed, part of the solvent was removed under reduced pressure, a small amount of distilled water was added, filtered, and dried to obtain 0.21 g of an orange-yellow solid, with a yield of 66.5%. m.p.195-197°C; 1 H NMR (DMSO-d 6 , 300MHz) δ: 8.52(s, 1H, CH), 8.03(s, 1H, CH), 7.88~7.03(m, 8H, ArH), 7.04(s, 1H, NH), 7.02(s, 1H, NH ), 4.75(t, J=4.7Hz, 2H, -CH 2 ), 4.39 (t, J=5.0Hz, 2H, -CH 2 ), 2.48(s, 3H, CH 3 ).

Embodiment 3

[0019] Example 3: Preparation of 4-(3-(2-(2-methyl-5-nitro-1-imidazole)ethoxy)-benzaldehyde)sulfathiazole (compound 5)

[0020]

[0021] The preparation method is the same as that in Example 2. Sulfathiazole is used instead of sulfonamide to obtain the orange-yellow target compound. The yield is 50.0%. m.p.258-259°C; 1 H NMR (DMSO-d 6 , 300MHz) δ: 8.49(s, 1H, CH), 8.02(s, 1H, CH), 7.85~7.77(m, 4H, ArH), 7.29(d, J=5.0Hz, 2H, ArH), 7.23( d, J=2.7Hz, 1H, CH), 7.02(d, J=5.2Hz, 2H, ArH), 6.81(d, J=2.7Hz, 1H, CH), 4.75(t, J=4.7Hz, 2H ,-CH 2 ), 4.39 (t, J=5.0Hz, 2H, -CH 2 ), 2.48(s, 3H, CH 3 ).

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Abstract

The invention provides a synthesis method of metronidazole-sulfanilamide derivatives. The metronidazole-sulfanilamide derivatives are characterized by having a formula, which is shown in the description. The invention discloses a preparation method of metronidazole-sulfanilamide derivatives.

Description

technical field [0001] The object of the invention is to provide a class of synthetic methods containing metronidazole-sulfonamide derivatives. Background technique [0002] Metronidazole has a broad-spectrum anti-anaerobic and antiprotozoal effect. It is mainly used clinically to prevent and treat infections caused by anaerobic bacteria. In addition, it is also widely used to prevent and treat oral anaerobic infections. Currently, metronidazole is still on the market. However, it has been reported in recent years that metronidazole has drug resistance and adverse reactions clinically, such as elevated transaminases, pseudomembranous colitis, black urine, neutropenia, nausea, vomiting, diarrhea, thrombophlebitis, Headache, dizziness, ataxia, rash, etc. Therefore, modifying metronidazole to enhance its antibacterial effect and reduce adverse reactions is a hot topic in the field of medicinal chemistry. [0003] Sulfonamides have a variety of biological activities and have al...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D233/94C07D417/12C07D403/12C07D413/12
Inventor 朱海亮王忠长段永涛秦亚娟文晴
Owner NANJING UNIV