[18F] DPA-714 (N, N-diethyl-2-(2-(4-(2-[18]F-fluoroethyoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)aceamide) derivative and preparation and application methods thereof

A technology of DPA-714 and its derivatives, which is applied in the fields of organic chemistry methods, chemical instruments and methods, isotope introduction into organic compounds, etc. It can solve problems such as insufficient image display, high non-specific binding, and reduced image signal-to-noise ratio

Pending Publication Date: 2019-05-10
中国人民解放军东部战区总医院 +1
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  • Abstract
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Problems solved by technology

[0004] Invention purpose: to solve [ 18 F] DPA-714 imaging agent has problems such as low tumor uptake value, high non-specific binding, lower image signal-to-noise ratio, and unclear image display during the imaging process. [ 18 F] DPA-714 imaging agent is modified and transformed, increasing [ 18 F] the permeability of DPA-714 derivative imaging agent through the blood-brain barrier increases [ 18 F] The specific binding rate of the DPA-714 derivative imaging agent to the

Method used

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  • [18F] DPA-714 (N, N-diethyl-2-(2-(4-(2-[18]F-fluoroethyoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)aceamide) derivative and preparation and application methods thereof
  • [18F] DPA-714 (N, N-diethyl-2-(2-(4-(2-[18]F-fluoroethyoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)aceamide) derivative and preparation and application methods thereof
  • [18F] DPA-714 (N, N-diethyl-2-(2-(4-(2-[18]F-fluoroethyoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)aceamide) derivative and preparation and application methods thereof

Examples

Experimental program
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Example Embodiment

[0066] Example 1: One [ 18 F]DPA-714 derivative[ 18 F] Precursor synthesis of DPPEF imaging agent

[0067] The synthesis reaction formula of DPPEF precursor is as follows:

[0068]

[0069] Step 1-1. Add methyl paraben (9.615g, 63.2mmol, 1.0eq), anhydrous potassium carbonate (30.570g, 221mmol, 3.5eq), 150mL acetone and 2-bromopropane ( 11.660g, 94.8mmol, 1.5eq), sealed and reacted at 85°C for 72h, the reaction system was concentrated, and column chromatography was separated (PE:EA=20:1) to obtain 11.627g of colorless transparent liquid (substance 1), yield 94.7 %. 1 H-NMR (300MHz, CDCl3) δ 7.97 (2H, d, J = 9.0 Hz), 6.88 (2H, d, J = 8.9 Hz), 4.66-4.58 (1H, sep), 3.87 (3H, s), 1.35 (6H, d, J=6.0 Hz)); LC-MS: calculated for C11H14O3, 194.23; found[M+H]195.1.

[0070] Step 1-2. Add substance 1 [Compound 1] (11.627g, 59.86mmol, 1.0eq) and 60mL toluene into a 250mL three-necked flask, and add 60% sodium hydride (4.789g, 119.72) to the ice salt below 0°C. mmol, 2.0eq), after the addition...

Example Embodiment

[0076] Example 2: One [ 18 F]DPA-714 derivative[ 18 F] Precursor synthesis of DPAF imaging agent

[0077] The synthesis reaction formula of DPAF precursor is as follows:

[0078]

[0079] Step 2-1. Add methyl paraben (9.615g, 63.2mmol, 1.0eq), anhydrous potassium carbonate (30.570g, 221mmol, 3.5eq), 150mL acetone and 2-bromopropane ( 11.660g, 94.8mmol, 1.5eq), sealed and reacted at 85°C for 72h, the reaction system was concentrated, and column chromatography was separated (PE:EA=20:1) to obtain 11.627g of colorless transparent liquid (substance 1), yield 94.7 %. 1 H-NMR (300MHz, CDCl3) δ 7.97 (2H, d, J = 9.0 Hz), 6.88 (2H, d, J = 8.9 Hz), 4.66-4.58 (1H, sep), 3.87 (3H, s), 1.35 (6H, d, J=6.0 Hz)); LC-MS: calculated for C11H14O3, 194.23; found[M+H]195.1.

[0080] Step 2-2. Add substance 1 [Compound 1] (11.627g, 59.86mmol, 1.0eq) and 60mL of toluene into a 250mL three-necked flask, and add 60% sodium hydride (4.789g, 119.72) to the ice salt below 0°C. mmol, 2.0eq), after the additio...

Example Embodiment

[0086] Example 3: [ 18 F]DPA-714 derivative[ 18 F]DPDF imaging agent and [ 18 F] The precursor synthesis of DPUF imaging agent The synthesis reaction formula of DPDF precursor and DPUF precursor is as follows:

[0087]

[0088] Step 3-1. Add substance 10 [Compound 10] (2.88g, 8.7mmol, 1.0eq) and 50mL ethanol, 2,4-hexanedione (1.026g, 8.7mmol, 1.0eq) into a 500mL single-mouth bottle, and add After the temperature was raised to 90°C, the reaction was refluxed for 16-18h, and after concentration, column chromatography was separated (DCM:MeOH=150:1-80:1) to obtain substance 15[Compound 15] 1.317g, 1 H-NMR(CDCl 3 ) Meets, the yield is 37.0%; 1 H NMR (300MHz, CDCl3) δ 7.75 (2H, d, J = 8.7 Hz), 6.95 (2H, d,, J = 8.7 Hz), 6.49 (1H, s), 4.64-4.56 (1H, sep), 3.91 (2H, s), 3.50 (2H, q, J = 7.1 Hz), 3.40 (2H, q, J = 7.1 Hz), 3.19 (2H, q, J = 7.5 Hz), 2.55 (3H, s), 1.44 (3H, t, J = 7.5 Hz), 1.36-1.34 (6H, d, J = 6.1 Hz), 1.20 (3H, t, J = 7.1 Hz), 1.11 (3H, t, J = 7.1 Hz); LC-MS: calculated f...

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Abstract

The invention discloses a [18F] DPA-174 derivative. The [18F] DPA-174 derivative is prepared by modifying the benzene ring structure of or prolonging the carbon chain structure of a [18]F DPA-174 imaging agent. The invention also discloses preparation and application methods of the [18F] DPA-174 derivative. The [18F] DPA-174 derivative is simple in preparation, easy to implement, high in labellingyield and good in repeatability and can help in real time observe and in vivo monitor the status of intracerebral neuroinflammation of an animal model as well as the changes of the major organs and tissues of the animal model; the prepared imaging agents can achieve imaging effects on neuroinflammation; the [18F] DPAF imaging agent can achieve a high signal-to-noise ratio on neuroinflammation lesions to provide possibility for further monitoring and assessing the diagnosis and treatment effects on neuroinflammation..

Description

technical field [0001] The present invention relates to a class of 18 The F-labeled DPA-714 derivatives and their preparation method and application are mainly used for neuroinflammation state-specific imaging and belong to the field of medical diagnostic reagents. Background technique [0002] PET (Positron Tomography) utilizes nuclide labeling of positron emitters, such as some physiologically required compounds or metabolic substrates such as glucose, fatty acids, amino acids, receptor ligands, and water, etc. After being introduced into the body, positron scanning is applied In vivo radiological images obtained by machine. It has received extensive clinical attention for its ability to display the metabolic activity of organs or tissues and the function and distribution of receptors, also known as "in vivo biochemical imaging". It can be said that the emergence of PET has brought medical imaging technology to a new level, enabling non-invasive, dynamic and quantitative...

Claims

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Application Information

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IPC IPC(8): C07D487/04C07B59/00A61K51/04A61K101/02
Inventor 张龙江徐志红高峰孔祥杨桂芬桂媛
Owner 中国人民解放军东部战区总医院
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