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Benzimidazolamines compounds as well as preparation method and application thereof

A technology of benzimidazolamine and benzimidazole, which is applied in the field of preparation of the compound, can solve problems such as narrow antibacterial spectrum, poor water solubility, and ineffective treatment of non-albicans

Active Publication Date: 2012-09-12
SOUTHWEST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the widespread use of fluconazole, its multi-drug resistance occurs frequently, and its therapeutic effect on non-albicans such as Aspergillus fumigatus is not obvious, its antibacterial spectrum is narrow, and its water solubility is poor, which leads to the way of administration. Many researchers at home and abroad are committed to the further development of fluconazole

Method used

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  • Benzimidazolamines compounds as well as preparation method and application thereof
  • Benzimidazolamines compounds as well as preparation method and application thereof
  • Benzimidazolamines compounds as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] The preparation of embodiment 1,2-chloromethyl-1H-benzimidazole (compound VI)

[0061]

[0062] Add 5.412g (0.050mol) of o-phenylenediamine, 7.114g (0.075mol) of chloroacetic acid and 60mL of 5mol / L hydrochloric acid into a 100mL round bottom flask, heat to reflux for 4 hours, cool, neutralize with ammonia water, and keep stirring until yellow The solid precipitated, was filtered by suction, dried, and recrystallized from absolute ethanol to obtain 7.803 g of compound VI, with a yield of 91.2%; a yellow solid with a melting point of 143-144°C.

Embodiment 2

[0063] Embodiment 2, the preparation of N-((1H-benzimidazol-2-yl)methyl)-2-fluoroaniline (compound I-1)

[0064]

[0065] Add 1.669g (0.010mol) of compound VI, 1.110g (0.010mol) of 2-fluoroaniline and an appropriate amount of ethanol (subject to the complete dissolution of the raw materials) into a 100mL round-bottomed flask, and stir at a temperature of 75-90°C for 24-72 hours. , then add 1.272g (0.012mol) of anhydrous sodium carbonate under stirring conditions, and react at a temperature of 10 to 60°C for 2 to 4 hours. TLC traces until the end of the reaction, and then concentrates, extracts, and separates by column chromatography. After crystallization and drying, 1.764 g of compound I-1 was obtained, with a yield of 73.1%; a yellow solid with a melting point of 164-165°C; 1 H NMR (300MHz, CDCl 3 )δ: 4.60 (s, 2H, benzimidazolyl-CH 2 ), 6.46~6.44(m, H, Benzene-6-H), 6.50(m, H, Benzene-4-H), 6.94~6.91(m, H, Benzene-5-H), 7.17~7.14(m , H, benzene-3-H), 7.27~7.23 (m, 2H, ...

Embodiment 3

[0066] Embodiment 3, the preparation of N-((1H-benzimidazol-2-yl)methyl)-3-trifluoromethylaniline (compound 1-2)

[0067]

[0068] Using compound VI 1.665g (0.010mol), 3-trifluoromethylaniline 1.607g (0.010mol) and anhydrous sodium carbonate 1.272g (0.012mol) as starting materials, according to the method described in Example 2, compound I was prepared -2 2.074g, yield 71.2%; yellow solid, melting point 155-156°C; 1 H NMR (300MHz, CDCl 3 )δ: 4.61 (s, 2H, benzimidazolyl-CH 2 ), 6.74~6.71(d, H, benzene-6-H), 6.82(s, H, benzene-2-H), 7.00~6.97(d, H, benzene-4-H), 7.21~7.19(d , H, benzene-5-H), 7.27~7.24 (m, 2H, benzmidazole-5, 6-H), 7.58~7.55 (m, 2H, benzmidazole-4, 7-H) ppm.

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Abstract

The invention discloses benzimidazolamines compounds shown by general formulas I-V, medical salt of the benzimidazolamines compounds, and a preparation method of the benzimidazolamines compounds; the preparation method comprises the following steps of: stirring 2-chloromethyl-1H-benzimidazole and a compound shown by a general formula VII in an organic solvent for reaction, and controlling the temperature to be within the range of 75-90 DEG C; then, adding an alkali reagent under the stirring condition, controlling the temperature to be within the range of 10-60 DEG C, and stirring for reaction, thus obtaining the benzimidazolamines compound shown in the general formula I; stirring the benzimidazolamines compound shown in the general formula I and compound shown in the general formula VIII, IX, X or XI in an organic solvent for reaction, and controlling the temperature to be within the range of 50-70 DEG C; and after the system is acidic, adding the alkali reagent, controlling the temperature to be within the range of 50-70 DEG C, and stirring for reaction, thus obtaining the compound shown in the general formula II, III, IV or V. The benzimidazolamines compounds and the medical salt of the benzimidazolamines compounds have certain inhibitory activity for gram-positive bacteria, gram-negative bacteria and fungi, thus being used for preparing medicines for resisting bacteria and / or fungi.

Description

technical field [0001] The invention belongs to the field of chemistry, relates to a new class of organic compound, and also relates to the preparation method and medical application of the compound. Background technique [0002] Fluconazole has the advantages of strong antibacterial ability, low hepatotoxicity, good oral absorption, high bioavailability, and wide tissue distribution. It is the first drug of choice for the treatment of systemic fungal infections designated by the World Health Organization. It has been used clinically so far. has an irreplaceable role. However, due to the widespread use of fluconazole, its multi-drug resistance occurs frequently, and its therapeutic effect on non-albicans such as Aspergillus fumigatus is not obvious, its antibacterial spectrum is narrow, and its water solubility is poor, which leads to the way of administration. Many researchers at home and abroad are devoted to the further development of fluconazole. At present, many fluco...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D235/14C07D403/12C07D405/12A61K31/4184A61P31/04A61P31/10
CPCY02A50/30
Inventor 周成合张慧珍
Owner SOUTHWEST UNIV