A kind of coumarin compound targeting β-amyloid protein and its preparation and application
A technology of amyloid and coumarin, applied in the direction of isotope introduction of organic compounds, heterocyclic compound isotope introduction, preparations for in vivo tests, etc., can solve the problem of no drug available, and achieve the effect of simple preparation method
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Embodiment 1
[0031] Compound A(R 1 for CH 3; 2 for C 2 h 4 ) preparation of coumarin compound
[0032] Take K 222 (10-12mg) and potassium carbonate (1-2mg) in acetonitrile solution enriched [ 18 F]F - The QMA column (2mCi) was collected into the reaction bottle, and the reaction bottle was placed at 90°C, blown dry by blowing nitrogen gas (1mL / min), then added anhydrous acetonitrile solvent and evaporated to dryness, repeated three times, and added 0.6mL anhydrous DMF . Add 0.3mL containing 2mg of precursor compound B (R 1 for CH 3 ; 2 for C 2 h 4 ) in anhydrous DMF solution, sealed reaction at 120°C for 30min, and cooled to room temperature after the reaction.
[0033] Add 5mL of pure water to the reaction product and pass through a sep-pak C18 column in advance, and then use a semi-preparative C18 column for separation and purification, such as figure 1 As shown, the peak at t=8.1min is unreacted 18 f - The characteristic peak at t=25.5min is the product peak. Collect the...
Embodiment 2
[0042] Embodiment 2 PET imaging
[0043] prepared by the above method 18 F-labeled coumarin compound A for micro-PET imaging
[0044] AD model mice and normal control mice were injected into the tail vein prepared by the above method 18 F-labeled coumarin compound A, after isoflurane inhalation anesthesia, use a heating module to keep its body temperature at about 37°C, use R4micro-PET to scan dynamically for 2 hours, and divide the data into frames after the end of data collection (the first half hour, 2 minutes / frame; 10 minutes / frame), using the OSEM3D method for image reconstruction, using Inveon Research Workplace 2.2 (IRW, Siemens) software to manually select each region of interest (ROI) in the brain region, and calculate the SUV. Its image is shown in Figure 3. It can be seen from the figure that the pairing in the brain of AD model rats 18 F-labeled coumarin compound A was significantly concentrated, compared with no concentration in normal mice.
[0045] Example...
Embodiment 3
[0057] A method for preparing a coumarin compound targeting β-amyloid, comprising the following steps:
[0058] 1. What will be obtained contains 18 f - H 2 18 O solution was enriched by QMA column 18 f - , use the solution containing phase transfer catalyst, potassium salt to wash the QMA column to obtain phase transfer catalyst, potassium salt and 18 f - The mixed solution, said containing phase transfer catalyst, potassium salt and 18 f - The ratio of the amount of substance of each component in the mixture is: phase transfer catalyst: potassium salt=7.5:1, 18 f - The activity is 2Ci. in 18 f - From bombardment of H with a cyclotron 2 18 O target income.
[0059] 2. In an organic solvent (anhydrous tetrahydrofuran), under the protection of an inert gas (nitrogen), the phase-transfer catalyst K 222 , potassium carbonate and 18 f - H 2 18The O solution was subjected to nucleophilic substitution reaction with compound B at a reaction temperature of 120° C. ...
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