Preparation of fluorine-18 labeled targeted P2X7 receptor molecular probe and PET imaging application of fluorine-18 labeled targeted P2X7 receptor molecular probe in animal model

A technology of P2X7 and receptor molecules, applied in the field of nuclear medicine and imaging, can solve the problems of low yield, poor repeatability, no imaging research, etc., and achieve the effect of good specific binding ability

Pending Publication Date: 2022-03-25
THE FIFTH AFFILIATED HOSPITAL SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, patent CN 113307758 A reports [ 18 F] Synthetic method of GSK1482160, but the yield is very low and the reproducibility is poor, and there is no imaging study at the animal level

Method used

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  • Preparation of fluorine-18 labeled targeted P2X7 receptor molecular probe and PET imaging application of fluorine-18 labeled targeted P2X7 receptor molecular probe in animal model
  • Preparation of fluorine-18 labeled targeted P2X7 receptor molecular probe and PET imaging application of fluorine-18 labeled targeted P2X7 receptor molecular probe in animal model
  • Preparation of fluorine-18 labeled targeted P2X7 receptor molecular probe and PET imaging application of fluorine-18 labeled targeted P2X7 receptor molecular probe in animal model

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] This example discloses a medical radioactive isotope-labeled P2X7 receptor targeting probe precursor, the structural formula of which is shown in Compound 1-1:

[0067]

[0068] (compound 1-1)

[0069]

[0070] The preparation method of the compound 1-1 is:

[0071] The compound (2-chloro-3-(trifluoromethyl)phenyl)formamide (500 mg, 2.39 mmol) and 8 mL of boron tribromide (1 M in CH 2 Cl 2 ), reacted at room temperature under nitrogen protection for one hour, then heated to reflux for two hours, monitored with gas chromatography-mass spectrometry after the reaction was completed, and separated and purified by column chromatography to obtain compound (3-(bromodifluoromethyl) -2-Chlorophenyl)methanamine (538 mg, 2 mmol). Then (3-(bromodifluoromethyl)-2-chlorophenyl)methanamine (500 mg, 1.86 mmol), (S)-1-methyl-5-oxopyrrolidine-3 -Carboxylic acid (266 mg, 1.86 mmol), 2-(7-azabenzotriazole)- N,N,N',N' - Tetramethyluronium hexafluorophosphate (HATU) (848 mg, 2.23...

Embodiment 2

[0081] This example discloses a medical radioactive isotope-labeled P2X7 receptor targeting probe precursor, the structural formula of which is shown in compound 1-2:

[0082]

[0083] (compound 1-2)

[0084]

[0085] The preparation method of the compound 1-2 is:

[0086] The compound (2-chloro-3-(trifluoromethyl)phenyl)formamide (750 mg, 3.59 mmol) and 12 mL of boron tribromide (1 M in CH 2 Cl 2 ), reacted at room temperature under nitrogen protection for one hour, then heated to reflux for two hours, monitored with gas chromatography-mass spectrometry after the reaction was completed, and separated and purified by column chromatography to obtain compound (3-(bromodifluoromethyl) -2-Chlorophenyl)methanamine (807 mg, 3 mmol). Then (3-(bromodifluoromethyl)-2-chlorophenyl)methanamine (807 mg, 3 mmol), (S)-1-methyl-5-oxopyrrolidine-2 -Carboxylic acid (430 mg, 3 mmol), 2-(7-azabenzotriazole)- N,N,N',N' - Tetramethyluronium hexafluorophosphate (HATU) (1.369 g, 3.6 mmol...

Embodiment 3

[0096] This example discloses a medical radioactive isotope-labeled P2X7 receptor targeting probe precursor, the structural formula of which is shown in Compound 1-3:

[0097]

[0098] (Compounds 1-3)

[0099]

[0100] The preparation method of the compound 1-3 is:

[0101] 2,4,6-Trimethylphenylboronic acid (285 mg, 1.7 mmol) was dissolved in dichloromethane (5 mL). The solution was cooled to 0°C and BF was added 3 •Et 2 O (225 µL, 1.8 mmol), and the mixture was stirred for 5 min. Then (2-iodo-3-(trifluoromethyl)phenyl)formamide (512 mg.1.7 mmol) was added dropwise as a solution in dichloromethane (3 mL). The mixture was slowly warmed to room temperature and stirred for 3.5 hours. By adding saturated NaBF 4 (aqueous solution, 3 mL) to quench the reaction. After stirring vigorously for 4 h, the aqueous layer was extracted with dichloromethane (2 x 50 mL). The combined organic layers were in Na 2 SO 4 Dry over, filter, and concentrate in vacuo. The residue was p...

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PUM

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Abstract

The invention relates to improvement of radiopharmaceutical yield and application of the radiopharmaceutical yield to the field of nuclear medicine and imaging, in particular to a medical radioisotope labeled P2X7 receptor targeting probe precursor, a targeting probe thereof and application of the targeting probe to diagnosis of neurodegenerative diseases. The structural formulas of the targeting probe are shown as a formula (III) and a formula (IV), wherein R4 and R6 are any one of a hydrogen atom, < 18 > FCH2CH2-and < 18 > FCH2CH2CH2-; r5 is any one of a fluorine atom, a chlorine atom, a bromine atom, an iodine atom and < 18 > F; x is any one of halogen atoms.

Description

technical field [0001] The invention relates to improving the yield of radiopharmaceuticals and applying them to the fields of nuclear medicine and imaging, specifically a medical radioisotope-labeled P2X7 receptor targeting probe precursor and its targeting probe and its application in the diagnosis of neurodegenerative diseases Applications. Background technique [0002] Brain disorders affect 1 billion people worldwide. Neurodegenerative diseases are the most common form of brain disease, and because they are age-related, as the global population lives longer, this will seriously affect the longevity and quality of life of the elderly. Currently available medications can only partially relieve symptoms. Studies have found that the overexpression of P2X7R is closely related to neuroinflammation. P2X7R is a gated ion channel of adenosine triphosphate, which plays an important role in various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease; ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/28C07D207/277A61K51/04
CPCC07D207/277C07D207/28A61K51/0446C07B2200/05
Inventor 金红军黄国龙丘益帆毕蕾李志军刘浩杨帅
Owner THE FIFTH AFFILIATED HOSPITAL SUN YAT SEN UNIV
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