18F-labelled quinazolines irreversible EGFR (epidermal growth factor receptor) positive electron tracer agent, as well as preparation method and application thereof

A technology of positron tracers and quinazolines, which is applied in the fields of biochemical equipment and methods, radioactive carriers, and microbial measurement/inspection, to achieve the effects of overcoming the long synthesis time, facilitating the synthesis process, and simplifying the synthesis process

CN103656694AActive Publication Date: 2014-03-26HARBIN MEDICAL UNIVERSITY
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
Publication Date
2014-03-26

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Abstract

The invention discloses an 18F-labelled quinazolines irreversible EGFR (epidermal growth factor receptor) positive electron tracer agent, as well as a preparation method and application thereof. The 18F-labelled quinazolines irreversible EGFR positive electron tracer agent has a chemical structure represented by the formula II. The synthesized 18F-labelled small-molecular irreversible EGFR positive electron tracer agent has a clinical value for diagnosing and monitoring a treating effect and particularly plays an important role in pushing individual-based treatment. Furthermore, the invention further provides a one-step method for synthesizing the 18F-labelled small-molecular irreversible EGFR positive electron tracer agent. The method has the characteristics of multiple purposes, high yield, high efficiency, short synthesis time, low cost and the like and can meet a requirement on large-scale production.
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Description

[0001] Cross References to Related Applications

[0002] This application requires an application on January 5, 2013, the application number is 201310002893.9, and the title of the invention is "a 18 F-labeled quinazoline-based irreversible EGFR positron tracers and their preparation methods and applications” is the priority of the Chinese patent application, the description of which is incorporated herein by reference in its entirety. technical field

[0003] The present invention relates to a kind of fluorination substitution reaction synthesis 18 F-labeled small molecule aniline quinazoline EGFR positron tracer and its preparation method and application. The invention belongs to the field of chemical synthesis. Background technique

[0004] Positron nuclides produced by medical cyclotrons are currently used clinically 15 O. 13 N. 11 C. 18 F 18 F has a half-life of 110 minutes and has become the most clinically valued positron nuclide. 11 C due to the half-life of ...

Examples

Embodiment 1

[0077] Example 1: [ 18 F] Synthesis of FH411 (shown in formula II)

[0078]

[0079] [ 18 F] Synthetic steps of FH411:

[0080] 1. Precursor (N-[4-(3-Chloro-4-fluorophenylamino)-7-(Tso-PEG(4))quinazoline-6-yl]-4-(dimethylamino)-2(E)-butenamide; (2E)-N-[4-[(3-chloro-4-fluorophenyl)amino]-7-(p-toluenesulfonyl-polyethylene glycol 4)quinazolin-6-yl]-4-( Dimethylamino)-2-butenamide, shown in formula I), this compound is delivered to Jiangsu Huayi Co., Ltd. for synthesis;

[0081] 2. Will transmit from the medical cyclotron 18 F ions and water are passed to the receiving bottle (1-4Ci);

[0082] 3. will 18 F ions and water pass to the anion exchange column QMA;

[0083] 4. Using 0.15mL K 2 CO 3 (0.9mg) + 0.5mL acetonitrile was eluted from the QMA column 18 F ion and sent to the reaction bottle, 3mg precursor dissolved in 0.5mL DMSO or DMF mixture was added to the reaction bottle; under the protection of nitrogen or helium, heated at 65°C for 3.5 minutes, and heated at 9...

Embodiment 218

[0089] Example 2 [ 18 F] Application of FH411 (shown in formula II) in detecting the expression level of epidermal growth factor receptor