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Compound for positron imaging, intermediate and preparation method thereof, and imaging agent containing compound

A technology of compounds and intermediates, applied in the field of new PET molecular probes and their preparation, can solve problems such as difficulty in functioning

Active Publication Date: 2018-12-14
XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, despite 18 F-FDG PET has been successfully applied in clinical tumor diagnosis, but 18 F-FDG PET imaging is difficult to play a role in further diagnosis and screening of patients with tumors caused by PIK3CA gene mutation, because the expression level of PI3K protein is not directly related to high glucose intake

Method used

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  • Compound for positron imaging, intermediate and preparation method thereof, and imaging agent containing compound
  • Compound for positron imaging, intermediate and preparation method thereof, and imaging agent containing compound
  • Compound for positron imaging, intermediate and preparation method thereof, and imaging agent containing compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0094] Example 1: 19 Preparation of F-BAR-3

[0095] In order to facilitate the study of the preparation method, first prepare the non-radioactive compound according to the following reaction formula.

[0096] Mix 0.5 g of BAR-1 (i.e. GDC-0941, Selleck, USA) with 1.5 g of TsO-PEG 3 -OTs (Bailingwei) was dissolved in 50 mL of acetonitrile, 0.5 g of potassium carbonate was added, and reacted at 70° C. for 1 to 3 days. After the reaction was completed, the solvent was concentrated and removed, and the residue was purified by silica gel column chromatography to obtain 0.4 g of the product as a light yellow oil with a yield of 82%. The resulting product was mass spectrometered (m / z (ESI+), calculated value 799.25, measured value 800.25, mass spectrometer Expression CMS, Advion), 1H-NMR (400MHzDRX NMR Spectrometer, Bruker Corporation, see figure 2 ) and HPLC (Shimadzu LC-20A, chromatographic column Phenomenon Luna C18 (2), 250mm 4.6mm, see figure 1, wherein, the two peaks at 19...

Embodiment 2

[0100] Example 2: 18 Synthesis of F-BAR-3

[0101] In this example, the automatic synthesis equipment (TRACELAB FX Fn) of GE Company of the United States was used to carry out a fully automated one-step rapid synthesis.

[0102] By cyclotron (GE, minitrace) bombardment 3mL18 oxygen-water (H 2 18 O) generate 18 F-HF500mCi. to contain 18 The target water of F-HF passes through the QMA column (Waters, Accell Plus QMA) to 18 f - Ions are retained on the QMA cartridge. Then with 1.5 mL of acetonitrile aqueous solution containing 3 mg of potassium carbonate and 15 mg of phase transfer catalyst K2.2.2 (Sigma-Aldrich) (acetonitrile to water volume ratio 2:1) 18 f - Elute from the QMA column and enter the reaction flask, heat and nitrogen until the solvent in the reaction flask is evaporated to obtain dry anhydrous K 18 F (~450mCi).

[0103] Add 1.0 mL of anhydrous DMSO solution containing 2 mg of BAR-2 prepared in Example 1 into the reaction flask, react at 80°C for 30 minu...

Embodiment 3

[0106] Embodiment 3: 18 F-BAR-3 with 11 Comparison of Biodistribution and Metabolism of C-BAR-1

[0107] Investigate the prepared by the embodiment of the present invention 2 by PET imaging 18 Biodistribution and metabolism of F-BAR-3 in normal Kunming mice (female, 4 weeks old, purchased from Beijing Huafukang Biotechnology Co., Ltd.) 11 C-BAR-1 served as a control.

[0108] 11 Preparation of C-BAR-1:

[0109] According to the reaction formula, the automatic synthesis equipment (TRACELAB FX) of GE Company of the United States was adopted. C Pro) for fully automated one-step rapid synthesis 11 C-BAR-1.

[0110]

[0111] 500mCi generated externally by cyclotron (GE MINItrace) 11 CO 2 . 500mCi 11 CO 2 Transfer into the reactor with 100mL / min H 2 Hybrid, generated online 11 CH 4 500mCi. Subsequent reaction with sublimated iodine (iodine furnace temperature 100°C, about 20g of iodine particles) at a high temperature of 720°C to generate methyl iodide ( 11 CH ...

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Abstract

The invention relates to a compound. The compound has a structure as shown in a formula I or a formula II which are described in the specification. In the formula I and the formula II, R is selected from the group consisting of C1-12 alkyl groups with at least one 18F substituent, -(CH2O)x-CH3, -(CH2CH2O)y-CH2CH3 and -(CH2CH2CH2O)z-CH2CH2CH3, wherein x is an integer in a range of 1 to 10; y is aninteger in a range of 1 to 5; and z is an integer in a range of 1 to 3. The invention also relates to an intermediate used for preparing the compound, a preparation method for the compound, and a positron imaging agent containing the compound. The compound provided by the invention is simple to prepare, has good stability and large radiation amount, and can specifically target a tumor region withan abnormally-activated PI3K pathway.

Description

technical field [0001] The present invention relates to the application fields of positron medicine and positron emission tomography (PET), in particular to a new type of PET molecular probe targeting PI3K / Akt / mTOR signaling pathway and its preparation method and application. Background technique [0002] The phosphatidylinositol-3-kinase (PI3K) signal transduction pathway plays an important role in the occurrence, development, treatment and prognosis of tumors, and it plays an important role in breast cancer, colorectal cancer, endometrial cancer, brain cancer, etc. Abnormal activation of this pathway has been found in many malignant tumors such as cancer, gastric cancer, and lung cancer (Bader, [0003] A.G., et al., Oncogenic PI3K deregulates transcription and translation. Nat Rev Cancer, 2005.5(12):p.921-9.). PI3K can activate and initiate signal transduction cascade reactions, and the most important downstream kinases are serine / threonine kinase (Protein kinase B, AKT)...

Claims

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Application Information

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IPC IPC(8): C07D495/04A61K51/04
CPCA61K51/0463C07D495/04
Inventor 兰晓莉盖永康包安瑞柳轻瑶韩娜
Owner XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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