Unlock instant, AI-driven research and patent intelligence for your innovation.

Application of N-benzylimidamide derivative as polymyxin antibiotic synergist

A technology of benzyl imidamide and synergist, applied in the field of biomedicine, can solve problems such as environmental pollution

Active Publication Date: 2017-05-24
GUANGZHOU INSIGHER BIOTECHNOLOGY CO LTD
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In production practice, a variety of drugs have been used in combination with polymyxin antibiotics in order to increase the efficacy of drugs. Experiments have proved that the therapeutic effects of these compatible drugs combined with polymyxin antibiotics are actually their inhibition of different infection strains. Combined results of effects without any synergistic effect on polymyxin antibiotics
In addition, these compatible drugs are either antibacterial agents or bactericides or chemical reagents with certain toxicity. Long-term combined use may cause new multidrug-resistant strains or cause serious pollution to the environment. Some compatible drugs have been approved by the European Union. Prohibited as a feed additive

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of N-benzylimidamide derivative as polymyxin antibiotic synergist
  • Application of N-benzylimidamide derivative as polymyxin antibiotic synergist
  • Application of N-benzylimidamide derivative as polymyxin antibiotic synergist

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1 Preparation of 1-(2-chloro-6-fluorobenzyl)-1H-imidazole-4,5-diamide (15031)

[0066]

[0067] Step 1: Preparation of dimethyl 1-(2-chloro-6-fluorobenzyl)-1H-imidazole-4,5-dicarboxylate

[0068] Free dimethyl 1H-imidazole-4,5-dicarboxylate (9.2g, 50mmol, 1eq), 2-chloro-6-fluorobenzyl chloride (17.9g, 100mmol, 2eq) and potassium carbonate (17.3g, 125mmol, 2.5eq) were successively dissolved in 70mL N,N-dimethylformamide, stirred and reacted at 100°C for 15h, and monitored by TLC until the end point. The reaction solution was cooled to room temperature, 150 mL of water was added, extracted with ethyl acetate (100 mL×3), the ethyl acetate layers were combined, washed with water (100 mL×3) and saturated brine (100 mL×2), and dried over anhydrous sodium sulfate. Concentrate under reduced pressure to remove the organic solvent to obtain a colorless transparent liquid (dimethyl 1-(2-chloro-6-fluorobenzyl)-1H-imidazole-4,5-dicarboxylate), which is directly used in t...

Embodiment 2

[0072] Example 2 Preparation of 1-(4-chlorobenzyl)-1H-imidazole-4,5-diamide (15037)

[0073]

[0074] Step 1: Preparation of dimethyl 1-(4-chlorobenzyl)-1H-imidazole-4,5-dicarboxylate

[0075] Free dimethyl 1H-imidazole-4,5-dicarboxylate (7.6g, 41mmol, 1eq), p-chlorobenzyl chloride (13.2g, 82mmol, 2eq) and potassium carbonate (14.2g, 103mmol, 2.5eq) were sequentially dissolved In 50mL of N,N-dimethylformamide, the reaction was stirred at 90°C for 16h, and the reaction was monitored by TLC until the end point. The reaction solution was cooled to room temperature, 150 mL of water was added, extracted with ethyl acetate (100 mL×3), the ethyl acetate layers were combined, washed with water (100 mL×3) and saturated brine (100 mL×2), and dried over anhydrous sodium sulfate. Concentration under reduced pressure to remove the organic solvent gave the product as a colorless transparent liquid (1-(4-chlorobenzyl)-1H-imidazole-4,5-dicarboxylic acid dimethyl ester), which was directly...

Embodiment 3

[0079] Example 3 Preparation of 1-(3-chlorobenzyl)-1H-imidazole-4,5-diamide (15041)

[0080]

[0081]Step 1: Preparation of dimethyl 1-(3-chlorobenzyl)-1H-imidazole-4,5-dicarboxylate

[0082] Free dimethyl 1H-imidazole-4,5-dicarboxylate (5.0 g, 27 mmol, 1 eq), 3-chlorobenzyl bromide (11.5 g, 56 mmol, 2 eq) and potassium carbonate (9.3 g, 67.5 mmol, 2.5 eq) Dissolve in 50mL N,N-dimethylformamide successively, stir and react at 90°C for 10h, and monitor the reaction to the end by TLC. The reaction solution was cooled to room temperature, 150 mL of water was added, extracted with ethyl acetate (100 mL×3), the ethyl acetate layers were combined, washed with water (100 mL×3) and saturated brine (100 mL×2), and dried over anhydrous sodium sulfate. The organic solvent was removed by concentration under reduced pressure to obtain a colorless transparent liquid (1-(3-chlorobenzyl)-1H-imidazole-4,5-dicarboxylic acid dimethyl ester), which was directly used in the next reaction.

[...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses application of an N-benzylimidamide derivative as a polymyxin antibiotic synergist. The N-benzylimidamide derivative has a synergetic effect on polymycin antibiotics in aspects of preventing and treating livestock and poultry diseases, promoting the growth and improving the livestock and poultry production performance and is applied to the fields of livestock and poultry disease prevention and treatment, and growth promotion to improve the production performance of animals, thereby improving the economic benefits of livestock and poultry breeding. On the other hand, by combined use of the N-benzylimidamide derivative and the polymycin antibiotics, the using dosage of the polymycin antibiotics can be reduced, so that the toxic and side reaction is reduced, and the use efficiency and the use range of the polymycin antibiotics in the field of human medicines are improved.

Description

[0001] Technical field: [0002] The invention belongs to the field of biomedicine, and relates to the application of N-benzyl imidamide derivatives as synergists of polymyxin antibiotics, such as the preparation of human medicines and their application as animal disease prevention and treatment medicines and feed additives. [0003] Background technique: [0004] Polymyxin is an antibacterial polypeptide found in the culture medium of Bacillus polymyxa. There are five kinds of A, B, C, D, E, etc., which have similar structures, similar antibacterial spectrum and wide range. , especially for Gram-negative bacteria, polymyxin B and polymyxin E (colistin sulfate) are commonly used clinically. Due to their high toxicity, they are mainly used for local treatment of infections caused by sensitive bacteria. Eye, ear, skin, mucous membrane infection and Pseudomonas aeruginosa infection in burns, as well as oral administration for intestinal preoperative preparation. Used as a feed ad...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K31/4174C07D233/64A61P31/04A61P3/00A61P1/12A23K20/137A23K20/195
CPCC07D233/64A23K20/137A23K20/195A61K9/08A61K9/20A61K31/4174
Inventor 彭险峰覃宗华
Owner GUANGZHOU INSIGHER BIOTECHNOLOGY CO LTD