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[*F] fluoraro-marked purine compound, its production and use

A compound and fluorine-labeled technology, which is applied in the field of purine nucleoside compounds, can solve the problems of difficult preparation, difficult to repeat experiments, difficult to purchase, etc., and achieve the effect of simple process and high product purity

Active Publication Date: 2009-07-01
SHANGHAI ATOM KEXING PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, the raw material compound of formula 3 used in the first step of the above synthetic route is not a conventional reagent, and is not easy to buy, and because the boiling point of trimethylamine (TMA) is relatively low (2 ~ 3 ° C), it is generally necessary to add samples and react under low temperature condensation , the synthesis conditions are relatively harsh, and the reaction time is as long as 5 days; in the second step, according to the literature method, there are many side reaction products at 80 ° C, and the experiment is difficult to repeat
[0007] It can be seen that the preparation of the compound of formula 1 as a non-radioactive reference compound and the compound of formula 4 as a labeling precursor is difficult, so it affects the preparation of the radiolabeled compound of the compound of formula 1 and its application research, especially F-18 labeling 2-Amino-6-[ 18 F] Fluoro-9-(4-hydroxyl-3-hydroxymethylbutyl)purine has not been reported so far

Method used

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  • [*F] fluoraro-marked purine compound, its production and use
  • [*F] fluoraro-marked purine compound, its production and use
  • [*F] fluoraro-marked purine compound, its production and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Synthesis of formula 3 compound 2-amino-6-chloro-9-(4-hydroxyl-3-hydroxymethylbutyl)purine

[0039] Get formula 2 compound (358mg, 1mmol), be dissolved in 12ml THF, add 10ml K 2 CO 3 (150mg, 1mmol) mixed solution of methanol and water (MeOH / H 2 (2 volume ratio = 1:1), placed at 0°C to stir the reaction, followed by TLC (developer: 10% ethanol / dichloromethane, volume ratio = 1:9) until the reaction of the raw materials was basically complete. The reaction was stopped, and the reaction solvent was removed by rotary evaporation to obtain a light yellow solid, which was washed with 25 ml of ethanol and dissolved with a small amount of THF. Separation through silica gel column (10% ethanol / dichloromethane, volume ratio = 1:9 as eluent), collect R f The value was 0.36 components, the solvent was removed by rotary evaporation, and vacuum-dried to obtain the compound of formula 3 as a white solid with a yield of 78.4%.

Embodiment 2～3

[0040] The synthesis of embodiment 2~3 formula 3 compounds

[0041] The reaction temperatures were 15° C. and 20° C., and the remainder was the same as in Example 1 to obtain the compound of formula 3 as a white solid with yields of 70.8% and 64.5%, respectively.

Embodiment 4

[0042] Embodiment 4 The synthesis of formula 4 compound nucleoside ammonium chloride salt

[0043] The compound of formula 3 (813mg, 3mmol) was dissolved in 40ml of a mixed solvent (THF / DMF volume ratio = 3:1) and placed in an ice-water bath at 0°C under nitrogen protection. Take 9ml trimethylamine ethanol solution and add it to the above system dropwise, and stir to react. The reaction was slowly raised to room temperature and reacted overnight, a white solid was formed. TLC tracking (developing solvent: 10% methanol / dichloromethane, volume ratio = 1:9) reacted until the reaction of the raw materials was basically complete. Stop the reaction, filter, wash with anhydrous ether (10ml×2), and dry under vacuum to obtain the compound of formula 4 as a white solid with a yield of 90.5%.

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Abstract

The invention discloses a [18F]fluorine-labeled purine compound, which is 2-amino-6-[18F]fluoro-9-(4-hydroxyl-3-hydroxymethylbutyl ) Purine. The invention also discloses a preparation method of the above-mentioned [18F] fluorine-labeled purine compound and its application as a molecular probe for positron electron tomography (PET) of reporter gene HSV1-tk.

Description

technical field [0001] The present invention relates to a [ 18 F] Fluorine-labeled purine nucleosides, especially 2-amino-6-[ 18 F] fluoro-9-(4-hydroxyl-3-hydroxymethylbutyl) purine and its radiochemical preparation method, and its use as reporter gene HSV1-tk (herpes simplex virus 1-thymidine kinase gene) Application of molecular probes in positron emission tomography (PET). Background technique [0002] In recent years, with the in-depth research on the synthesis and biological evaluation of purine nucleosides and their analogs, it has been found that these compounds have anti-tumor and anti-viral activities clinically. Through structural modification of nucleoside analogs, a series of nucleoside analogs with obvious antiviral activity have been produced, which has become an important part of antiviral drug research. At the same time, many compounds have physiological activity due to the fluorine atom, and when it is introduced into the compound, its physical and chemic...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D473/40A61K51/04A61K101/02
Inventor 张岚蔡汉成尹端沚汪勇先
Owner SHANGHAI ATOM KEXING PHARMA
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