NO (nitric oxide) donor type polydatin (PD) derivative as well as preparation method and medical application thereof

A technology of nitric oxide and polygoside, which is used in the preparation of sugar derivatives, sugar derivatives, sugar derivatives, etc.

Inactive Publication Date: 2012-02-01
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

This combination of new drugs includes nitrosoalcohol sulfur / drug conjugates, nitrosalt / drug conjugates, etc., many of which have been patented and used clinically

Method used

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  • NO (nitric oxide) donor type polydatin (PD) derivative as well as preparation method and medical application thereof
  • NO (nitric oxide) donor type polydatin (PD) derivative as well as preparation method and medical application thereof
  • NO (nitric oxide) donor type polydatin (PD) derivative as well as preparation method and medical application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] The pharmacological experiment and the result of compound of the present invention are as follows:

[0022] 1. In vitro experiment, determination of nitric oxide release

[0023]The polydatin-4'-nitroxybutyrate compound was made into 2.5mmol / L DMSO solution, and 1ml was mixed with 3.4mmol / L L-cysteine ​​or no L-cysteine ​​respectively. The PBS solution was diluted to 100ml, and the final concentration of the tested compound was 0.025mmol / L. After incubating the solution at 37°C, 8ml and 2ml of Griess reagent [4g p-sulfanilamide, 0.2g N-(1-naphthyl)ethylenediamine dihydrochloride, 10mL mass fraction were taken out at each time point. 85% phosphoric acid, dilute to 100ml with distilled water], mix at room temperature for 10min, and measure the absorbance at 540nm. The results are shown in Table 1.

[0024] Table 1 Comparison of NO release from polydatin-4'-nitroxybutyrate

[0025]

[0026] The results showed that the release amount of the target compound polydatin-...

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Abstract

The invention relates to the field of pharmaceutical chemistry and particularly provides a polydatin (PD) derivative containing a NO (nitric oxide) donor. A PD (3,4',5-trihydroxystilbene-3-beta-D-glucoside)4' hydroxyl group and a corresponding nitrate ester are subjected to chemical reaction so as to generate the NO donor type PD derivative which is in ester bond connection. After being absorbed into a lung tissue, the compound is subjected to biological transformation and ester bond breakage so that a bulk pharmaceutical chemical PD and the NO donor are dissociated, the NO donor can release NO slowly, and NO and PD can play roles of reducing pulmonary hypertension, relieving right ventricular hypertrophy, improving the pulmonary vascular endothelium function and resisting lipid peroxide cooperatively. The NO donor type PD derivative has an application in the aspect of preparing medicaments for preventing or treating pulmonary hypertension and high altitude pulmonary edema diseases caused by oxygen deficiency.

Description

technical field [0001] The present invention relates to the field of medicinal chemistry, in particular to a novel nitric oxide donor polydatin derivative, its preparation method and the medical application of the compound, especially as a method for preventing or treating hypoxia-induced pulmonary hypertension and high altitude pulmonary edema and its Drug use for related diseases. Background technique [0002] When people quickly enter the plateau (area above 3000m above sea level) from a low altitude area, it will sometimes cause a special type of disease to the human body—high altitude pulmonary edema (HAPE). HAPE is a common acute mountain sickness with a high mortality rate due to lung damage caused by high altitude hypoxia as the main clinical manifestation. According to statistics, the incidence rate of HAPE is about 0.4-2%, and some people who quickly go up to an altitude of 4500m, the incidence rate can reach 10%. HAPE has a sudden onset, rapid progress, and grea...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H15/203C07H1/00A61K31/7034A61P9/12A61P7/10
Inventor 王剑波王平安汤海峰韦华梅王萌拓小瑞
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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