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P2X7 receptor imaging agent and preparation method thereof

An imaging agent and receptor technology, applied in the field of F-18-labeled P2X7 receptor imaging agent and its preparation, can solve the problem of poor specificity of positron imaging agents, prone to false positives or false negatives, and inability to distinguish significantly problems such as tumors and inflammation

Inactive Publication Date: 2019-03-01
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] In order to overcome the defects of the prior art positron imaging agents that have poor specificity, are prone to false positives or false negatives, and cannot significantly distinguish tumors from inflammation, a P2X7 receptor imaging agent with strong specificity and long half-life is provided, The inventors conducted systematic research and screening on P2X7 receptor antagonists, designed and synthesized a P2X7 receptor tracer molecule with a new structure, which can be used as a PET molecular probe as a P2X7 receptor imaging agent

Method used

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  • P2X7 receptor imaging agent and preparation method thereof
  • P2X7 receptor imaging agent and preparation method thereof
  • P2X7 receptor imaging agent and preparation method thereof

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Experimental program
Comparison scheme
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Embodiment 1

[0039] The synthesis of embodiment 1 precursor pre-PTTP

[0040]

[0041] Add TEA (i.e. Et 3 N) (499.88 mg, 4.94 mmol), the mixture was stirred at 20° C. for 0.5 h, and the reaction was detected by LCMS to generate the target product (pre-PTTP). Add H to the reaction mixture 2 The reaction was quenched with O (100 mL), extracted with DCM (50 mL×3). The organic phases were combined, dried, and concentrated to obtain a crude product, which was separated by column chromatography (DCM:MeOH=1:0~10:1), and a white solid was obtained, which was the compound product (510.00 mg) shown in Formula II. rate 44%. The hydrogen spectrum and mass spectrum data of the precursor pre-PTTP are as follows:

[0042] 1 H NMR: ES6134-17-P1A (CDCl 3 ,400MHz)δ8.89-8.85(dd,J 1 =4.8Hz,J 2 =13.6Hz,2H),7.96-7.92(m,1H),7.43-7.39(m,1H),7.30-7.27(m,1H),7.07-7.04(m,1H),5.17-5.02(m,1H ),4.60-4.46(m,1H),4.23-4.07(m,1H),3.60-3.56(m,1H),3.44-3.43(m,1H),3.41-3.21(m,1H).

[0043] MS(ESI):467.0([M+H] + ...

Embodiment 2

[0044] Compound of Example 2 18 Synthesis of F-PTTP

[0045]

[0046] Before the synthesis reaction, the reaction raw materials were divided into bottle A and bottle B to prepare respectively.

[0047] Bottle B: methyl chlorodifluoroacetate ClCF 2 CO 2 Me (6 μL, 57 μmol), tetramethylethylenediamine TMEDA (10 μL, 63 μmol), precursor pre-PTTP (7 mg), ultra-dry DMF (500 μL, ensure absolute anhydrous).

[0048] Bottle A: Add CuI (15 mg, 78 μmol) and a stirrer in advance, and then dissolve the [ 18 F]KF / K 222 MeCN solution was added to the bottle, under N 2 Heating under gas protection to remove the solvent, then adding ultra-dry MeCN, under N 2 The solvent was removed by heating under gas protection, and so repeated three times, the H in the system 2 Remove all O, then add the solution in bottle B to bottle A, and react at 150°C for 20 minutes.

[0049] The reaction system was cooled to room temperature, and a small amount of water was added to quench the reaction. The...

Embodiment 318

[0050] Example 3 18 In vitro stability test of F-PTTP

[0051] With embodiment 2 gained respectively 18 About 10 μCi of F-PTTP were respectively placed in 100 μL of 0.9% normal saline and 0.1% BSA, mixed thoroughly and stored at 37°C. Samples were taken at 1h, 2h, 4h and 6h, and their purity changes were checked on analytical HPLC. The results are shown in Table 1.

[0052] Table 1. Compounds 18 HPLC detection results of F-PTTP in normal saline and BSA

[0053]

[0054] The results showed that the compound 18 F-PTTP is very stable, with only a small amount of decomposition within 6 hours.

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Abstract

The invention discloses a F-18 tagged P2X7 receptor imaging agent which is a compound 18F-{(2-chloro-3-trifluorophenyl)(1-(pyrimidin-2-yl)-6,7-dihydro-1H-[1,2,3]triazolo[4,5-c]pyridin-5(4H)-yl)methanone shown as formula I. The P2X7 receptor imaging agent is suitable for identifying and diagnosing pulmonary inflammation and tumors.

Description

technical field [0001] The invention belongs to the field of radiodiagnostic drugs, in particular to an F-18-labeled P2X7 receptor imaging agent and a preparation method thereof. Background technique [0002] Nucleotide P2X receptors are adenosine triphosphate (ATP)-gated ion channels, and seven subtypes (P2X1-7) have been cloned in mammals. Among them, the P2X7 receptor is composed of 595 amino acids, including two transmembrane proteins including amino terminal (N terminal), carboxyl terminal (C terminal), intracellular domain and conserved extracellular loop, and its N terminal and C terminal are both in the cell Inside, a multimer consisting of three homologous isoforms is formed on the cell membrane. Its N-terminal sequence structure is highly conserved, while the C-terminal has no homology with other P2X receptor subtypes, which is a sign that distinguishes it from other subtypes of the family, and is also the molecular basis of its unique physiological functions. ...

Claims

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Application Information

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IPC IPC(8): C07D471/04C07B59/00A61K51/04A61K101/02
CPCA61K51/0459C07B59/002C07B2200/05C07D471/04
Inventor 程登峰林卿玉付哲荃石洪成
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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