Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Fatty acid synthetase inhibitor and application for treating bacterial infection

A technology of carboxylic acid and medicinal salt, applied in the field of pyrrole derivatives

Inactive Publication Date: 2008-02-06
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There is no antibacterial drug acting on the fatty acid biosynthesis pathway on the market, therefore, fatty acid synthase inhibitors are expected to develop into new broad-spectrum antibacterial drugs

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
  • Fatty acid synthetase inhibitor and application for treating bacterial infection
  • Fatty acid synthetase inhibitor and application for treating bacterial infection
  • Fatty acid synthetase inhibitor and application for treating bacterial infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0157] Example 1 Preparation of 1-(6-chloro-3,4-methylenedioxybenzyl)-4-(4-(2,6-difluorobenzylamino)phenyl)pyrrole-2-carboxylic acid

[0158] step 1 Preparation of 2-(4-nitrophenyl) Vinamidinium Salt

[0159] Under anhydrous conditions, 110 g (1.5 mol) of anhydrous DMF and 46 g (0.3 mol) of POCl 3 Add it into a 500ml three-necked bottle equipped with a condenser, a magnetic stirrer, and a thermometer, and react with exothermic heat, and the solution becomes colorless and black. Then add 18.1g (0.1mol) 4-nitrophenylacetic acid, heat at 70°C, and react for 7h. After the reaction finished, the reaction solution was cooled and poured into a solution that was dissolved with 15.5g (0.11mol) NaClO 4 200ml of ice-water mixture, placed in an ice bath, precipitated solid, filtered to obtain crude product, washed with a large amount of water to obtain 28.5g of product 2-(4-nitrobenzene) Vinamidinium salt, yield 82%.

[0160] step 2 Preparation of methyl 4-(4-nitrophenyl)pyrro...

Embodiment 2

[0170] Example 2 Preparation of 1-(2-chlorobenzyl)-4-(4-(2,6-dichlorobenzylamino)phenyl)pyrrole-2-carboxylic acid

[0171] step 1 Preparation of methyl 1-(2-chlorobenzyl)-4-(4-nitrophenyl)pyrrole-2-carboxylate

[0172] According to step 3 of Example 1, 2-chlorobenzyl chloride was used instead of 6-chloro-3,4-methylenedioxybenzyl chloride to obtain 2.41 g of a yellow solid product with a yield of 65.1%. 1 H-NMR (d 6 -DMSO) δ: 3.71(s, 3H), 5.69(s, 2H), 6.50(dd, J=7.6Hz, 2Hz, 1H), 7.24-7.32(m, 2H), 7.51(dd, J=7.8Hz , 1.4Hz, 1H), 7.59(d, J=2Hz, 1H), 7.91(d, J=8.7Hz, 2H), 8.03(d, J=2Hz, 1H), 8.19(d, J=8.7Hz, 2H).

[0173] step 2 Preparation of methyl 1-(2-chlorobenzyl)-4-(4-aminophenyl)pyrrole-2-carboxylate

[0174] According to step 4 of Example 1, replace 1-(6-chloro-3,4-methylene with 1-(2-chlorobenzyl)-4-(4-nitrophenyl)pyrrole-2-carboxylic acid methyl ester Dioxybenzyl)-4-(4-nitrophenyl)pyrrole-2-carboxylic acid methyl ester to obtain the product as a brown solid ...

Embodiment 3

[0179] Example 3 Preparation of 1-(3-chlorobenzyl)-4-(4-(2,6-dichlorobenzylamino)phenyl)pyrrole-2-carboxylic acid

[0180] step 1 Preparation of methyl 1-(3-chlorobenzyl)-4-(4-nitrophenyl)pyrrole-2-carboxylate

[0181] According to step 3 of Example 1, 3-chlorobenzyl chloride was used instead of 6-chloro-3,4-methylenedioxybenzyl chloride to obtain 2.37 g of a yellow solid product with a yield of 64.1%. 1 H-NMR (d 6 -DMSO) δ: 3.75(s, 3H), 5.59(s, 2H), 7.12(d, J=7Hz, 1H), 7.25(s, 1H), 7.33-7.39(m, 2H), 7.53(d, J=2Hz, 1H), 7.91(d, J=8.7Hz, 2H), 8.13(d, J=2Hz, 1H), 8.20(d, J=8.7Hz, 2H).

[0182] step 2 Preparation of methyl 1-(3-chlorobenzyl)-4-(4-aminophenyl)pyrrole-2-carboxylate

[0183] According to step 4 of Example 1, replace 1-(6-chloro-3,4-methylene with 1-(3-chlorobenzyl)-4-(4-nitrophenyl)pyrrole-2-carboxylic acid methyl ester Dioxybenzyl)-4-(4-nitrophenyl)pyrrole-2-carboxylic acid methyl ester to obtain the product as a brown solid with a yield of 55.9%. 1 H...

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 relates to a general formula I pyrrole derivation capable of inhibiting the fatty acid synthase, or all possible isomers thereof, or medicated salts or solvates thereof, wherein the definition of each substituting group in general formula I is shown in the instruction; the invention also relates to a preparation process for general formula I pyrrole derivation; the invention comprises the compound, or all possible isomers thereof, or medicated salts or medicine combinations of solvates thereof, and the usage that the compound can be used to prepare the medicaments for the bacteria infection.

Description

technical field [0001] The present invention relates to pyrrole derivatives as fatty acid synthase FabH inhibitors, their pharmaceutically acceptable salts or solvates, their preparation methods, pharmaceutical compositions containing them, and their use in the preparation and treatment of Gram-positive and Gram-negative bacteria Drug use for infections. Background technique [0002] Fatty acid biosynthesis is an essential process in all living organisms. Fatty acid biosynthesis in prokaryotes and eukaryotes is catalyzed by fatty acid synthase (FAS). Although their synthesis pathways are basically the same, the structures of the biosynthesizers are different. The enzyme systems that catalyze fatty acid biosynthesis are of two types (FAS I and FAS II). FAS I exists in mammals and yeast, in which all enzyme activities are coded on one polypeptide chain, and each step of fatty acid synthesis is catalyzed by different functional domains of this large protein. FAS II exists in...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/34A61K31/40A61P31/04
CPCY02P20/55
Inventor 李松张学辉于红王莉莉刘红英郑志兵谢云德钟武肖军海李行舟崔浩
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com