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Benzothiadiazine compound, application thereof and positron drug of AMPAR

A technology of benzothiadiazines and compounds, applied in the field of positron emission tomography tomography, can solve the problems of poor specificity and low brain volume

Active Publication Date: 2020-02-21
JINAN UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the positron drugs of AMPAR are mainly divided into two types: antagonist and agonist, but the positron drugs of AMPAR generally have the problems of low brain crossing volume and poor specificity

Method used

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  • Benzothiadiazine compound, application thereof and positron drug of AMPAR
  • Benzothiadiazine compound, application thereof and positron drug of AMPAR
  • Benzothiadiazine compound, application thereof and positron drug of AMPAR

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preparation example Construction

[0072] The preparation method of the above-mentioned marked benzothiadiazine compound has high yield, simple and convenient operation, good repeatability, and automatic production; and the marked benzothiadiazine compound synthesized by the above-mentioned preparation method The radioactive specific activity of the thiadiazines compound is high, which meets the quality standard of positron drugs for injection.

[0073] Application of the above-mentioned labeled benzothiadiazine compounds in the preparation of AMPAR positron medicines.

[0074] One embodiment of the present invention also provides a positron medicine of AMPAR, including the above-mentioned labeled benzothiadiazine compound.

[0075] The positron drugs of the above-mentioned AMPARs include labeled benzothiadiazines, which have good specificity to AMPARs, can quickly pass through the blood-brain barrier of rats, and can realize AMPAR imaging in the brains of living rats. Drugs related to neurological diseases an...

Embodiment 1

[0080] Synthesis of Compound P1

[0081] The synthetic route is as follows:

[0082]

[0083] The specific steps are:

[0084] (1) 5-Bromo-2-fluoroaniline (10g, 52.63mmol) was dissolved in HCl (12N, 80mL), cooled to 0°C, and 24mL NaNO was added 2 (3.6g, 52.63mmol) in water to give a diazotized mixture. Take another SO 2 (24mL) was dissolved in water (160mL), cooled to 10°C, then Cu(I)Cl (2g, 21.05mmol) was added in batches, and reacted at 10°C for 1 hour to obtain a reaction solution. The diazotization mixture was added to the reaction solution at 0°C, stirred at 0°C for 30 minutes, and then heated to room temperature to react for 1 hour. Then the reacted mixture was poured into ice water, filtered, and the obtained solid was dried under reduced pressure to obtain 5 g of compound 2 (yield 34%). Compound 2 is a brown solid powder.

[0085] (2) Compound 2 (400 mg, 1.46 mmol) obtained in step (1) was added into ammonium hydroxide (4.0 mL), dissolved in tetrahydrofuran, a...

Embodiment 2

[0095] [ 11 C] Synthesis of JPC827

[0096] The synthetic route is as follows:

[0097]

[0098] The specific steps are:

[0099] (1)[ 11 C]CH 3 Preparation of I: [ 11 C]CH 3 I is the application of medical cyclotron, in GE's automated synthesis module reaction generation. Through the synthesis module software GE TRACERlab FX MeI, set the program and call the method. 30 minutes before production, the liquid nitrogen tank is filled with liquid nitrogen to ensure airtightness, and the program is run until the program appears to receive the Activity command. After the accelerator transfers the activity, click the command to automatically cycle and generate [ 11 C]CH 3 I stand by.

[0100] (2) will [ 11 C]CH 3 I reacts with the compound P1 synthesized in Example 1 to generate 11 C] JPC827, the schematic diagram of the synthesis device is figure 1 . specifically:

[0101] Compound P1 (1.5 mg) was dissolved in anhydrous N,N-dimethylformamide (DMF) solution (300 μL...

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Abstract

The invention relates to a benzothiadiazine compound, application thereof and a positron drug of AMPAR (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor). The structure of the benzothiadiazine compound is shown as the specification, wherein R is selected from one of Br, Cl, F, I and the groups shown as the specification. A marked benzothiadiazine compound prepared by taking the above benzothiadiazine compound as a precursor has high standard uptake value and high specificity to AMPAR.

Description

technical field [0001] The invention relates to the technical field of positron electron computed tomography, in particular to a benzothiadiazine compound and its application, and a positron medicine of AMPAR. Background technique [0002] α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, AMPAR) as a central nervous system disease A biomarker (biomarker) plays an important role in information transmission. AMPAR is a glutamate-gated ion channel mainly expressed on the postsynaptic membrane. After AMPAR is activated by glutamate released by the presynaptic membrane, it can mediate the transmission of fast excitatory synapses in the nervous system; the dynamic expression of AMPAR in the postsynaptic membrane is associated with the increase in the duration of nerve cell potential ((Long- term potentiation (LTP), long-term depression (Long-term depression, LTD) induction and maintenance. [0003] In ...

Claims

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Application Information

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IPC IPC(8): C07D285/24C07F5/02C07F7/18A61K51/04A61P25/14A61P25/16A61P25/28A61P25/08A61K101/00
CPCC07D285/24C07F5/025C07F7/1804A61K51/0465A61P25/14A61P25/16A61P25/28A61P25/08C07B2200/05
Inventor 王璐陈家辉车超叶伟健龚建贤张伟滨徐浩
Owner JINAN UNIVERSITY
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