Azo compound for degrading tubulin as well as synthesis method and application of azo compound
What is Al technical title?
Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
A technology of tubulin and compounds, applied in the application field of medicine, can solve the problems such as the defects of acquired drug resistance of tubulin inhibitors
Pending Publication Date: 2022-04-15
ZHEJIANG MEDICAL COLLEGE
View PDF6 Cites 0 Cited by
Summary
Abstract
Description
Claims
Application Information
AI Technical Summary
This helps you quickly interpret patents by identifying the three key elements:
Problems solved by technology
Method used
Benefits of technology
Problems solved by technology
However, because it still exerts pharmacological effects by inhibiting tubulin, it needs a certain dose of binding and needs to occupy the active site o
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
Click on the blue label to locate the original text in one second.
Reading with bidirectional positioning of images and text.
Smart Image
Examples
Experimental program
Comparison scheme
Effect test
Embodiment 1
[0037] The synthesis of embodiment 1 Azo-H
[0038]
[0039] Select a 100ml three-necked flask, add a magnetic rotor, put a thermometer and a constant pressure dropping funnel on it, and place it on a magnetic stirrer. Weigh 1.83g (10mmol) of 3,4,5-trimethoxyaniline, add 5ml of 95% ethanol solution, cool to -10°C with -20°C glycerol, turn on the magnetic stirrer, stir and dissolve, the reaction solution is Bright yellow.
[0040] Measure 2ml of 37% concentrated hydrochloric acid and add it dropwise to the above reaction solution. During the dropwise addition, replace the cooling liquid regularly to ensure that the temperature of the reaction solution is lower than 0°C, and the reaction solution turns into a beige turbid liquid.
[0041] Weigh 1.39g (20mmol) of sodium nitrite, prepare 5ml of aqueous solution, and also place it in cooling liquid to cool. After the hydrochloric acid was added dropwise, the sodium nitrite solution was added dropwise, and the temperature was a...
Embodiment 2
[0045] Synthesis of Example 2 Azo-Me
[0046]
[0047] 0.55 g of Azo-H prepared in Example 1, 0.3 g of potassium carbonate and excess methyl iodide were added to 2 mL of DMF, and the reaction was stirred at room temperature 25° C. overnight. After the reaction was completed, water was added and extracted with ethyl acetate to obtain a brown-yellow solid. 1 H-NMR (CDCl 3 ,ppm):7.66(1H,dd,Ph),7.63(1H,d,Ph),7.23(2H,s,Ph),7.02(1H,d,CH),4.87(2H,f,CH2),3.97 (9H,s,3×OCH3),3.93(3H,s,OCH3).
Embodiment 3
[0048] The synthesis of embodiment 3 Azo-Pr
[0049]
[0050] According to the method described in Example 2, bromopropane was used instead of methyl iodide to obtain Azo-Pr. MS(ESI)m / z:[M+H] + =384.
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
Login to view more
Abstract
The invention discloses an azo compound for degrading tubulin as well as a synthesis method and application of the azo compound. According to the invention, azo small molecules with tubulin inhibition effect are used as raw materials, and further reaction is carried out to obtain the azo compound for degrading tubulin. The preparation method of the azo compound for degrading tubulin has the characteristics of low cost, simplicity in operation, mild conditions and the like. The azo compound for degrading the tubulin does not show pharmacological activity in a dark environment, but shows affinity to the tubulin under illumination of a specific wavelength due to the specific photoisomerization performance, and further promotes the tubulin to degrade, so that the effect of degrading the tubulin is achieved. The method can be applied to preparation of drugs for preventing or treating diseases caused by excessive growth of microtubulin.
Description
technical field [0001] The present invention relates to an azo compound, in particular to an azo compound (based on CRBN ligand) capable of degrading tubulin and its pharmaceutically available salt, its synthesis method and its role in selectively degrading tubulin application in medicine. Background technique [0002] Microtubules are dimers formed by α and β two types of tubulin, which are distributed in a network or bundle in the cell and participate in the formation of the cytoskeleton, maintenance of cell shape, cell contraction, and intracellular material transport and cell division. Therefore, by inhibiting the polymerization of tubulin into microtubules in the process of cell division, or inhibiting the depolymerization of microtubules into tubulin, mitosis will be unable to proceed or stagnate, and the interruption of cell mitosis process will have a greater impact on cells , so that its growth is inhibited, and finally induces the occurrence of apoptosis, so as t...
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
Application Date:The date an application was filed.
Publication Date:The date a patent or application was officially published.
First Publication Date:The earliest publication date of a patent with the same application number.
Issue Date:Publication date of the patent grant document.
PCT Entry Date:The Entry date of PCT National Phase.
Estimated Expiry Date:The statutory expiry date of a patent right according to the Patent Law, and it is the longest term of protection that the patent right can achieve without the termination of the patent right due to other reasons(Term extension factor has been taken into account ).
Invalid Date:Actual expiry date is based on effective date or publication date of legal transaction data of invalid patent.
Login to view more 
Login to view more