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Polyamine derivative medicinal salt and its preparation method and use

A technology of amine derivatives and medicinal salts, which is applied in the fields of polyamine derivatives medicinal salts and preparations, and applications in medicines, can solve problems such as difficulty in comprehensively and effectively treating sepsis, and achieve the effect of improving survival rate.

Active Publication Date: 2016-02-24
GRAND PHARM (CHINA) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] As mentioned above, as the pathogenic factor of sepsis - PAMP molecules come from a wide variety of sources, and the drugs discovered so far can only antagonize one or a few of them, which may be difficult to treat sepsis comprehensively and effectively

Method used

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  • Polyamine derivative medicinal salt and its preparation method and use
  • Polyamine derivative medicinal salt and its preparation method and use
  • Polyamine derivative medicinal salt and its preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Embodiment 1: the preparation of polyamine derivative PAM01 hydrochloride

[0047] 1.1 Experimental method:

[0048]

[0049] (1) Dissolve 6g of bis(2-cyanoethyl)amine (a) in 60ml of dichloromethane, add di-tert-butyl dicarbonate dissolved in dichloromethane dropwise, react at room temperature for 10 hours, spin dry dichloromethane Methane was added to water and ethyl acetate to extract (3×20ml), and the organic layer was dried with anhydrous sodium sulfate, and the solvent was spin-dried to obtain intermediate b11.2g. In an autoclave, dissolve 11.2g of intermediate b in 400ml of methanol ammonia saturated solution, add 1.2g of Raney nickel, fill with hydrogen, pressurize at 4MPa, react at room temperature for 72 hours, filter with diatomaceous earth, and spin dry the solvent to obtain the intermediate c10.4g. Dissolve 5.2g of intermediate c in 40ml of ethanol, add dropwise 3.6ml of acrylonitrile dissolved in ethanol in an ice bath, then heat to 40°C for 10 hours, ...

Embodiment 2

[0054] Embodiment 2: the preparation of polyamine derivative PAM01 sulfate

[0055] 2.1 Experimental method: The preparation method described in Example 1 was adopted, and the reaction was carried out under the same scale and conditions, except that hydrochloric acid was replaced by sulfuric acid.

[0056] 2.2 Experimental results: 1.99g of polyamine derivative PAM01 sulfate was finally obtained, mass spectrum: [M+H] + m / z=630.

Embodiment 3

[0057] Embodiment 3: the preparation of polyamine derivative PAM01 phosphate

[0058] 3.1 Experimental method: The preparation method described in Example 1 was adopted, and the reaction was carried out under the same scale and conditions, except that hydrochloric acid was replaced by phosphoric acid.

[0059] 3.2 Experimental results: 1.85g of polyamine derivative PAM01 phosphate was finally obtained, mass spectrum: [M+H] + m / z=630.

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Abstract

The invention relates to a polyamine derivative medicinal salt and its preparation method and use in preparation of a drug for treating pyemia. The novel compound has good antagonistic action on a plurality of pyemia-causing pathogen-related molecules such as bacterial lipopolysaccharide (endotoxin), bacterial genome DNA, peptidoglycan, teichoic acid, virus RNA and zymosan, and can be used for preparation of a drug for treating pyemia.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a medicinal salt of a polyamine derivative, a preparation method and an application in preparation of a medicine for treating sepsis. Background technique [0002] Sepsis refers to systemic inflammatory response syndrome (systemic inflammatory response syndrome, SIRS) mediated by infectious factors, and the number of cases worldwide is as high as 19 million every year. Although current antibiotics and intensive care technology have made considerable progress, sepsis is still the main cause of death in infected patients, and there is no ideal drug for treatment so far. [0003] Studies have shown that the mechanism of sepsis is that the pathogen-associated molecular pattern (PAMP) released by pathogens such as bacteria, viruses, and fungi is recognized by the pattern recognition receptor (PRR) of the host's natural immune system to mediate an inflammatory response Ce...

Claims

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Application Information

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IPC IPC(8): C07C235/34C07C233/40A61P31/00A61P29/00
CPCC07C233/40C07C235/34A61K31/165A61P29/00A61P31/00A61P31/04Y02A50/30C07C237/42
Inventor 郑玥邓军刘清光
Owner GRAND PHARM (CHINA) CO LTD
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