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Novel 18F labeled aromatic amino acids, preparation method and application thereof in tumor imaging

A labeling method and amino acid technology are applied in the preparation of carboxylic acid amides, chemical instruments and methods, preparation of organic compounds, etc., which can solve the problems of complicated preparation and purification, and achieve the effects of simple operation method, huge development potential and high labeling rate.

Active Publication Date: 2010-06-09
BEIJING SHENLANHAI BIO PHARM TECH
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  • 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-(2-fluoroalkyl)benzamides have not been reported so far

Method used

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  • Novel 18F labeled aromatic amino acids, preparation method and application thereof in tumor imaging
  • Novel 18F labeled aromatic amino acids, preparation method and application thereof in tumor imaging
  • Novel 18F labeled aromatic amino acids, preparation method and application thereof in tumor imaging

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Embodiment 1 Formula C compound 2-(4-(2-hydroxyethoxy) benzamido) methyl phenylpropionate

[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-hydroxyalkoxy)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 petr...

Embodiment 3

[0074] Example 3 Synthesis of the compound of formula A, methyl 2-(4-(2-fluoroethoxy)benzamido)phenylpropionate.

[0075]

[0076] Dissolve 0.63 g of 2mmol tetrabutylammonium fluoride trihydrate into 1mL of re-evaporated dry acetonitrile, heat in a nitrogen atmosphere, 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, after the reaction mixture was refluxed for 6h under nitrogen atmosphere, TLC showed that after the reaction was complete, the acetonitrile was rotated off, and column chromatography could be obtained 19 F generation product, the yield is about 60%.

Embodiment 4

[0077] Example 4 Radiosynthesis of formula (A) 4-(2-fluoroalkoxy)benzamido amino acid methyl ester.

[0078] Take 100 μL [ 18 F]F - A solution containing K is added to 222 (10-15 mg) and potassium carbonate (3 mg) in a reaction flask, immerse the reaction flask in an oil bath at 80°C--140°C, add 500 μL of acetonitrile and azeotropically remove water under nitrogen. Add the precursor solution dissolved in 0.5mL DMF, and seal the reaction for 20min. Cool to room temperature after the reaction. The radiochemical yield is 20%--40%, and the radiochemical purity is >99%.

[0079] Raw materials in this preparation method: acetonitrile, N, N-dimethylamide, and Kriyptofix222 were purchased from Fluka Chemical Reagent Company. Triethylamine was purchased from Beijing Chemical Plant. [ 18 F]F - Provided by partner hospital units.

[0080] The physical and chemical properties and spectral data of final product of the present invention and main intermediate are as follows:

[008...

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Abstract

The invention discloses novel radioactive 18F labeled aromatic amino acids, which is characterized in that one end of the acids 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 phenyl group, benzyl group or 3-indole methyl group; R2 is methoxyl group; and n is a number between 1 and 5. The substituent R1 is positioned on an alpha site of carboxyl group and is phenyl group, benzyl group or 3-indole methyl group; the R2 is methoxyl group; 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. The substituent R1 is positioned on an alpha site of carboxyl group and is phenyl group, benzyl group or 3-indole methyl group; the R2 is methoxyl group; and the n is a number between 1 and 5. The substituent R1 is positioned on an alpha site of carboxyl group and is phenyl group, benzyl group or 3-indole methyl group; the R2 is methoxyl group; and the n is a number between 1 and 5. 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.

Description

technical field [0001] The present invention relates to a new class of 18 F-labeled aromatic amino acid, its preparation method and its application as a positron emission tomography (PET) molecular probe for 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 tissue. It i...

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 齐传民张淑婷贺勇李桂霞刘航许荆立王潇汪铭
Owner BEIJING SHENLANHAI BIO PHARM TECH
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