4,6-dimethyl-oxazolo[5,4-d]pyrimidine-5,7(4H,6H)-dione derivative acting on FGF receptor
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 kind of dimethyl, 4-d technology, applied in the field of medicinal chemistry
Active Publication Date: 2014-06-25
WENZHOU MEDICAL UNIV
View PDF4 Cites 1 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
We collected the crystal structures of FGFR-1 tyrosine kinases that have been reported so far. Through computer simulation analysis, we found that the current FGFR-1 inhibitors all have large conjugated structures, and the ATP binding site in the inhibitory active region is only A small part of the FGFR-1 protein pocket is located on the left side of the entire pocket cavity, while there is a large unused space on the right side of the ATP pocket
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.
[0048] 1.2.11 Preparation of 3-dimethyl-5-nitrosopyrimidine-2,4,6(1H,3H,5H)-trione (2)
[0049] Add 5g of 1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (1) into a mixture of 140ml of acetic acid and water (acetic acid: water = 1:1), at 75°C Heating at low temperature for 30min until the reaction mixture is homogeneous, lowering the temperature to 50°C, adding NaNO in batches 2 4.0g, after the addition, cooled to room temperature and stirred for 1h to obtain a precipitate, which was filtered, washed with water, suction filtered, and dried to obtain 1,3-dimethyl-5-nitrosopyrimidine-2,4,6 ( 1H, 3H, 5H)-triketone (2), yield: 90%.
[0050] 1.2.2 Preparation of 1,3-dimethyl-5-amino...
Embodiment 2
[0067] Example 2 compound antitumor activity
[0068] MTT is a yellow compound that accepts hydrogen ions. It can act on the respiratory chain in the mitochondria of living cells. The succinate dehydrogenase in the mitochondria of living cells reduces it to produce a water-insoluble blue-purple crystalline formazan. And deposited in cells, and dead cells do not have this function. DMSO can dissolve formazan in cells, and use an enzyme-linked immunosorbent assay to measure its light absorption value at a specific wavelength. Within a certain range of cell numbers, the amount of formazan formed is proportional to the number of cells, so it can indirectly reflect the number of living cells. quantity.
[0069] 2.1 Experimental process
[0070] 2.1.1 Cell culture
[0071] A549 cells, B16F10 cells, and H460 cells were incubated at 37°C in 5% CO 2 Under these conditions, the cells were respectively subcultured with RPMI1640 medium containing 10% fetal bovine serum, and the cells ...
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 a 4,6-dimethyl-oxazolo[5,4-d]pyrimidine-5,7(4H,6H)-dione derivative acting on a fibroblast growth factor (FGF) receptor. A target compound is prepared by implementing nitrosation on 1,3-dimethyl pyrimidine-2,4,6(1H,3H,5H)-trione which serves as a starting material through NaNO2, reducing the material through Na2S2O4, implementing a Schiff alkali reaction with aromatic aldehyde, and finally cyclizing through SOCl2. The 4,6-dimethyl-oxazolo[5,4-d]pyrimidine-5,7(4H,6H)-dione derivative disclosed by the invention has a certain inhibiting function on experimental cells and shows a certain antitumor activity. For an H460 cell, IC50 values of compounds N5a, N5g and N5k are less than that of a positive control drug; for a B16F10 cell, IC50 values of compounds N5f, N5h and N5i are less than IC50 value of the positive control drug; for an A549 cell, IC50 value of the positive control is relatively high, and IC50 values of compounds N5f, N5g, N5h and N5l are less than IC50 value of the positive control drug.
Description
technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a derivative of 4,6-dimethyl-oxazolo[5,4-d]pyrimidine-5,7(4H,6H)-dione acting on FGF receptors things. Background technique [0002] Malignant tumor is a common and frequently-occurring disease that seriously threatens human health. The mortality rate caused by malignant tumor is second only to cardiovascular and cerebrovascular diseases. At present, although there are many kinds of treatment methods, chemotherapy is still the main method. Although traditional antitumor drugs have strong effects, they lack selectivity and have relatively high toxicity and side effects, which limit their clinical application. Therefore, people have always hoped to develop drugs based on the transmission mechanism of tumor signals. [0003] Protein kinases are phosphotransferases that play key roles in regulating metabolism, gene expression, cell growth, cell division, and cell diffe...
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.