Vancomycin derivative, preparation method and antibacterial application thereof

A technology of drugs and compounds, applied in the field of preparation of vancomycin derivatives, which can solve the problems of increasing membrane permeability and loss of cell viability

Active Publication Date: 2015-11-25
INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At the same time, due to the long-chain hydrophobic groups connected to vancomycin, the drug can directly act on the plasma membrane of

Method used

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  • Vancomycin derivative, preparation method and antibacterial application thereof
  • Vancomycin derivative, preparation method and antibacterial application thereof
  • Vancomycin derivative, preparation method and antibacterial application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0132] The synthetic route of preparation example 1 intermediate 2b

[0133]

[0134] Preparation of the first step 3-hexylmercaptopropionic acid 2d

[0135] Add 3-mercaptopropionic acid (2.65g, 25mmol) into the reaction flask, add ethanol (25mL), add 25mL of 2M NaOH solution and stir at room temperature for 5min, then add 1-bromohexane (3.31g, 20mmol) TBAB (0.21g , 0.65mmol) was added, reacted at room temperature for 12h, evaporated the ethanol under reduced pressure, adjusted the pH of the solution to 2~3 with 3M HCl solution, extracted with dichloromethane (25mL×2), combined the organic phases, and washed with saturated saline ( 35mL×2) was washed, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain intermediate 2d, 3.62g of colorless oily liquid, with a yield of 94.71%.

[0136] Preparation of the second step 3-hexylsulfone propionic acid 2e

[0137] Dissolve 3-hexylmercaptopropionic acid 2d (3.59g, 18.88mmol) in 30mL of glacial a...

preparation example 2

[0140] The synthetic route of preparation example 2 intermediate 3b

[0141]

[0142] Preparation of the first step 3-heptylmercaptopropionic acid 3d

[0143] Add 3-mercaptopropionic acid (2.65g, 25mmol) into the reaction flask, add ethanol (25mL), add 25mL of 2M NaOH solution and stir at room temperature for 5min, then add 1-bromo-n-heptane (3.58g, 20mmol) TBAB (0.21 g, 0.65mmol) was added, reacted at room temperature for 12h, evaporated the ethanol under reduced pressure, adjusted the pH of the solution to 2~3 with 3M HCl solution, extracted with dichloromethane (25mL×2), combined the organic phases, and washed with saturated saline (35mL×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain intermediate 3d, 3.28g of a colorless oily liquid, with a yield of 80.26%.

[0144] Preparation of the second step 3-heptylsulfone propionic acid 3e

[0145] Dissolve 3-heptylmercaptopropionic acid 3d (3.28g, 16.05mmol) in 25mL of glacial acet...

preparation example 3

[0148] The synthetic route of preparation example 3 intermediate 4b

[0149] Preparation of the first step 3-octylmercaptopropionic acid 4d

[0150] Add 3-mercaptopropionic acid (2.65g, 25mmol) into the reaction flask, add ethanol (25mL), add 25mL of 2M NaOH solution and stir at room temperature for 5min, then add 1-bromo-n-octane (3.86g, 20mmol) TBAB (0.21 g, 0.65mmol) was added, reacted at room temperature for 12h, evaporated the ethanol under reduced pressure, adjusted the pH of the solution to 2~3 with 3M HCl solution, extracted with dichloromethane (25mL×2), combined the organic phases, and washed with saturated saline (35mL×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain intermediate 4d, 1.33g of a colorless oily liquid, with a yield of 30.46%.

[0151] Preparation of the second step 3-octylsulfone propionic acid 4e

[0152] Dissolve 3-octylmercaptopropionic acid 4d (1.32g, 6.05mmol) in 25mL of glacial acetic acid, heat and...

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Abstract

The invention relates to a vancomycin derivative as shown in the formula (I) and a stereisomer, pharmaceutically acceptable salts, a preparation method of the vancomycin derivative and its application in treating and/or preventing diseases or symptoms related to gram negative bacterial infections.

Description

technical field [0001] The invention belongs to the technical fields of medicinal chemistry and medicine. The invention relates to novel vancomycin derivatives represented by the general formula (I), pharmaceutically acceptable salts and isomers thereof, methods for preparing vancomycin derivatives and their use in the treatment and / or prevention of Gram's Positive bacteria infection related diseases or diseases and other applications. Background technique [0002] Bacterial infection is a disease that seriously threatens human health. Among them, Gram-positive bacterial infection is a common and frequently-occurring disease. Now there are many therapeutic drugs for clinical selection, such as cephalosporins, penicillin and so on. However, when people are infected with Gram-positive bacteria (such as staphylococci and enterococci) that are life-threatening, vancomycin is the last line of defense in the clinical treatment of bacterial infections, and it has played a huge rol...

Claims

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Application Information

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IPC IPC(8): C07K9/00A61K38/14A61P31/04
Inventor 冯文化贺娜
Owner INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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