2-fluoro-aniline quinazoline tumour positron imaging agents as well as preparation method and application thereof

A technology for substituting aniline quinazoline and aniline quinazoline, which is applied in the fields of organic chemistry and radioactive carriers, can solve the problems of false positive, false negative, and inability to distinguish inflammation and tumor, etc., and achieves the goal of simple labeling method and automatic production Effect

Active Publication Date: 2015-05-06
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

18F-Fluorodeoxyglucose (18FDG) is the main positron drug currently used in PET examination. 18FDG is used as a As a kind of tumor metabolism drug, it has played a huge role in the diagnosis and differential diagnosis of malignant tumors. However, as a relatively non-specific imaging agent, 18FDG, if inflammation and tumor cannot be distinguished, many The report is false positive or false negative, and the diagnosis and research of tumors still need to develop novel and more specific imaging agents

Method used

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  • 2-fluoro-aniline quinazoline tumour positron imaging agents as well as preparation method and application thereof
  • 2-fluoro-aniline quinazoline tumour positron imaging agents as well as preparation method and application thereof
  • 2-fluoro-aniline quinazoline tumour positron imaging agents as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1 2- 18 Radiochemical Synthesis of F-6,7-Dimethoxyquinazoline-4-aniline

[0033] see figure 1 , using a cyclotron to apply bombardment 18 O water, through 18 O(p n) 18 F nuclear reaction produces 100mCi 18 F ions, which will be accelerator-produced 18 F is captured by the QMA column;

[0034] ⑴ Use 1mL solution (12.5 mg K 222 Add 2.5mg K 2 CO 3 Dissolved in 0.1mL water and 0.9mL acetonitrile mixed solution) will 18 F is rinsed into the reaction tube;

[0035] (2) Dry the solution in the reaction tube at 116°C with nitrogen;

[0036] (3) Add 2 mL of dry acetonitrile in No. 2 bottle to the reaction tube, and blow dry at 116°C with nitrogen;

[0037] (4) Add 5 mg of 2-chloro-6,7-dimethoxyquinazoline-4-aniline precursor and 0.8 mL of dry DMSO in bottle No. 3 to the reaction tube, and react at 140 ° C for 10 min;

[0038]⑸ Add 30mL of water from No. 5 bottle to the reaction tube three times, pass the mixed liquid through the C-18 column between the V7 an...

Embodiment 2

[0040] Example 2 2- 18 Radiochemical Synthesis of F-6,7-Dimethoxyquinazoline-4-aniline

[0041] Applied Cyclotron Applied Bombardment 18 O water, through 18 O(p n) 18 F nuclear reaction produces 100mCi 18 F ions, which will be accelerator-produced 18 F is captured by the QMA column;

[0042] ⑴ Use 1mL solution (12.5 mg K 222 Add 2.5mg K 2 CO 3 Dissolved in 0.1mL water and 0.9mL acetonitrile mixed solution) will 18 F is rinsed into the reaction tube;

[0043] (2) Dry the solution in the reaction tube at 116°C with nitrogen;

[0044] (3) Add 2 mL of dry acetonitrile in No. 2 bottle to the reaction tube, and blow dry at 116°C with nitrogen;

[0045] (4) Add 5 mg of 2-bromo-6,7-dimethoxyquinazoline-4-N-tert-butylcarbonyl-aniline and 0.8 mL of dry DMF in bottle No. 3 to the reaction tube, and react at 140 °C for 10 min;

[0046] ⑸Add 2mL hydrochloric acid solution in No. 6 bottle to the reaction tube and hydrolyze for 15min

[0047] ⑹Add 30mL water to the No. 5 bottle ...

Embodiment 3

[0049] Example 3 2- 18 Quality control of F-6,7-dimethoxyquinazoline-4-aniline

[0050] See HPLC chromatogram figure 2 , 3. The quality control conditions are 50% acetonitrile aqueous solution, C-18 (4.5mm×250mm) column, ultraviolet 254nm and radioactive detector. The results show that the standard product has the same ultraviolet absorption and radioactive absorption. It is the same substance, and the synthesis time is 45min. , uncorrected synthetic yield 20–30%, radiochemical purity >98%. The spectrum of the standard product is: ESI-MS(m / z,%):300([M+H] + ,100), 1 H NMR(CDCl3,400MHz): 7.69(2H,d, J =7.93,4-position benzene ring 2’-H,6’-H); 7.45(1H,br.s,-NH); 7.42 (2H,dd, J 1 =7.53Hz, J 2 =8.32Hz, 4-position benzene ring 3’-H,5’-H); 7.20 (1H,dd, J 1 =7.14Hz, J 2 =6.34Hz,4-position benzene ring 4’-H); 7.15(1H,s,8-H); 7.04(1H,s,5-H); 4.00 (6H,s,2-OCH 3 ).

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Abstract

The invention provides a 2-fluoro-aniline quinazoline compound labelled by F-18, wherein 18 F is produced by a circular accelerator via 18O(pn)18F nuclear reaction and automatically synthesised by a radioactive synthesis module, and can also be produced by the existing domestic F-18 multifunctional synthesis device after process reformation. The 2-fluoro-aniline quinazoline compound provided by the invention is of an aniline quinazoline structure substituted by 2-bit positron nuclide fluorine-18, and can be modified on 6-bit, 7-bit and benzene ring connected with an amino group. The invention provides novel tumour positron imaging agents, wherein compared with 18F-fluoro-deoxyglucose (18FDG), the imaging agents are specific, and capable of identifying the tumours highly expressed by an epidermal growth factor receptor (EGFR). The preparation method is reasonable in design, simple in labelling method, capable of realizing automatic production, and suitable for application. The structural general formula of the 2-fluoro-aniline quinazoline compound is defined in the specification.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to an aniline quinazoline compound, in particular to an F-18-labeled 2-fluoroaniline quinazoline compound and a preparation method thereof, as well as preparation of tumor positron emission tomography (PET) imaging application in agents. Background technique [0002] As the most advanced medical imaging technology at present, PET can realize high-resolution imaging of cell metabolism and function, and conduct non-invasive, three-dimensional and dynamic research on the physiological and biochemical processes of the human body at the molecular level. PET is used in tumors, including tumors. Diagnosis, identification of benign and malignant tumors, early diagnosis and identification of malignant tumor staging, typing, recurrence, and metastasis, selection of treatment options, monitoring of chemotherapy effects, observation of tumor changes, and detection of prognosis. PET examination is differe...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/95C07D491/056A61K51/04A61K101/02
Inventor 刘振锋董孟杰王国林张倩晋建文赵葵
Owner ZHEJIANG UNIV
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