Novel 18F labeled amino acid derivatives, preparation method and application thereof in tumor imaging

A technology for amino acids and derivatives, which is applied in the field of new 18F-labeled amino acid derivatives, can solve the problems of complex preparation and purification, and achieve the effects of simple operation, good biological activity and low cost

Inactive Publication Date: 2010-06-09
BEIJING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The preparation and purification of the compound of formula (A) as non-radioactive reference compound and the compound of formula (B) as labeling precursor are more complicated
F18-labeled 4-O-(fluoroalkyl)benzoyl amino acid compounds have not been reported so far

Method used

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  • Novel 18F labeled amino acid derivatives, preparation method and application thereof in tumor imaging
  • Novel 18F labeled amino acid derivatives, preparation method and application thereof in tumor imaging
  • Novel 18F labeled amino acid derivatives, preparation method and application thereof in tumor imaging

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Embodiment 1 formula C compound 4-(2-hydroxyethoxy) benzamide methyl acetate

[0069]

[0070] Amino acid methyl ester hydrochloride (3mmol) was dissolved in 20mL of dichloromethane, redistilled triethylamine (3mmol) was added in one go, stirred for 5min, and 4-(2-hydroxyethoxy)benzoic acid (2mmol) was added and HOBt (1-hydroxybenzotriazole) (2.2mmol), the reaction mixture was cooled to 0°C, and 5mL of DCC (2.2mmol) in dichloromethane was added dropwise. React overnight at room temperature, TLC shows that after the reaction is over, remove a large amount of white precipitate DCU by suction filtration, the organic phase is washed with water, saturated sodium bicarbonate aqueous solution, saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and the oil is obtained after spin-off solvent Object. Column chromatography, eluent (ethyl acetate: methanol 10: 1) to obtain a light yellow oil, add a small amount of ethyl acetate and petroleum ether m...

Embodiment 2

[0071] Example 2 Synthesis of 4-(2-p-toluenesulfonate ethoxy)benzamido amino acid methyl ester of compound of formula B.

[0072]

[0073] Dissolve the compound C (1 mmol) prepared above into 20 mL redistilled dichloromethane, add TEA (triethylamine) (1.5 mmol), cool in an ice bath to below 0°C, add DMAP (4-N, N-dichloromethane picoline) (0.2mmol) and p-toluenesulfonyl chloride (1.5mmol) of re-purification treatment, after continuing the low-temperature reaction for 30min, rising to room temperature and reacting overnight, TLC showed that the reaction was complete. After adding saturated aqueous sodium bicarbonate solution and fully stirring, the organic The layer was fully washed with saturated brine, dried over anhydrous sodium sulfate, and separated and purified by column chromatography.

Embodiment 3

[0074] Example 3 Synthesis of formula A compound 4-(2-fluoroethoxy)benzamido amino acid methyl ester.

[0075]

[0076] Dissolve 0.63 g of 2mmol tetrabutylammonium fluoride trihydrate into 1mL of re-evaporated dry acetonitrile, heat in a nitrogen atmosphere, and continuously feed nitrogen to evaporate the acetonitrile to dryness, then add 2mL of acetonitrile and repeat the above operation twice, and add 1mmol of the compound 10mL redistilled acetonitrile solution of B, the reaction mixture was refluxed for 6h under a nitrogen atmosphere, TLC showed that the reaction was complete, the acetonitrile was spinned off, column chromatography separation and purification can be obtained 19 F generation product, the yield is about 60%.

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Abstract

The invention discloses novel radioactive 18F labeled amino acid derivatives, which are used in research on tumor positron emission tomography (PET) imaging. The derivatives are characterized in that one end of the derivatives is provided with F substituted alkoxy benzoyl structure, and the other end of the derivatives is provided with alpha-amino acid structure; substituent R1 is positioned on an alpha site of carboxyl group and is hydrogen, methyl group, ethyl group, propyl group, isopropyl group, butyl group, methylthio-ethyl group, methyl acetate group or propionate carbomethoxy group; R2 is methoxy group; and n is a number between 1 and 5. The R1 is hydrogen, methyl group, ethyl group, propyl group, isopropyl group, butyl group, methylthio-ethyl group, methyl acetate group or propionate carbomethoxy group; the R2 is hydrogen; and the n is a number between 1 and 5. Compounds improve fat solubility. Different amino acid structures are introduced into the structure, and F in the structure is 19F and 18F. Compared with the prior art, the 18F labeled amino acid derivatives provided by the invention have better discrimination degree of biological distribution, the potential of being used as a tumor imaging agent (particularly a brain tumor imaging agent), as well as the characteristics of simple preparation and high labeling rate. The R1 is hydrogen, methyl group, ethyl group, propyl group, isopropyl group, butyl group, methylthio-ethyl group, methyl acetate group or propionate carbomethoxy group; the R2 is methoxy group; and the n is a number between 1 and 5. The R1 is hydrogen, methyl group, ethyl group, propyl group, isopropyl group, butyl group, methylthio-ethyl group, methyl acetate group or propionate carbomethoxy group; the R2 is hydrogen; and the n is a number between 1 and 5.

Description

technical field [0001] The present invention relates to a new class of 18 F-labeled amino acid derivatives, their preparation method and their application as molecular probes for positron emission tomography (PET) of tumors (especially brain tumors). Background technique [0002] Positron emission tomography (Positron emission tomography) PET imaging is currently the only technology that uses anatomical morphology to perform functional, metabolic and receptor imaging. It has high sensitivity and specificity, and can quantitatively and dynamically detect Observing the physiological and biochemical changes of drugs or metabolites in the human body from the molecular level has become the best means for diagnosing and guiding the treatment of tumors, cardiovascular diseases and neuropsychiatric diseases. [0003] 18 F has a longer half-life (t 1 / 2 =109.8min), through β + and EC decay, β + With an energy of 649keV, it has a lower radiation dose and a shorter range to the tis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C235/52C07C231/12A61K51/04A61K101/02
Inventor 齐传民贺勇张淑婷李桂霞刘航许荆立王潇汪铭
Owner BEIJING NORMAL UNIVERSITY
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