Diagnosis and treatment radioactive glutamine derivative and method for preparing same

A technology for mixtures and compounds, applied in the preparation of carboxylic acid amides, in vivo radioactive preparations, radioactive carriers, etc., can solve the problems of long reaction time, easy to change the biological activity of glutamine, and many labeling steps.

Active Publication Date: 2019-02-22
CAPITAL UNIVERSITY OF MEDICAL SCIENCES +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Pc-3-loaded prostate cancer tumor pair 18 F-FPGLN has some uptake, but 18 F-FPGLN labeling steps are many, the reaction time is long, and the labeling site is easy to change the biological activity of glutamine
Glutamine SPECT imaging agent has not been reported

Method used

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  • Diagnosis and treatment radioactive glutamine derivative and method for preparing same
  • Diagnosis and treatment radioactive glutamine derivative and method for preparing same
  • Diagnosis and treatment radioactive glutamine derivative and method for preparing same

Examples

Experimental program
Comparison scheme
Effect test

example 1-41

[0630] Example 1-4.1: (4S)-2,5-diamino-4-fluoro-2-methyl-5-oxopentanoic acid, 2: (4R)-2,5-diamino-4-fluoro-2 -Methyl-5-oxopentanoic acid, 3: (4S)-2,5-diamino-4-fluoro-2-methyl-5-oxopentanoic acid, 4: (4R)-2,5- Diamino-4-fluoro-2-methyl-5-oxopentanoic acid

[0631]

[0632] The synthetic route is as follows:

[0633]

[0634]

[0635] (S)-tert-butyl 2-((diphenylmethylene)amino)propionate

[0636]

[0637] At room temperature, L-alanine tert-butyl ester hydrochloride (2g, 11mmol) was dissolved in 20mL of dichloromethane, and then benzophenone imine (2g, 11mmol) was added, and reacted for 2 hours at room temperature, The reaction produced a white precipitate. After adding 20mL H to the reaction solution 2 O, separate layers to obtain an organic phase, then back-extract the aqueous phase with 20 mL of dichloromethane, combine the organic phases, dry over anhydrous sodium sulfate, remove the dichloromethane, and obtain a colorless oily liquid (3 g, 89.2%) by column ...

example 5

[0696] (2S,4R)-2,5-Diamino-4-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)-5-oxo Valeric acid

[0697]

[0698] The reaction equation is as follows:

[0699]

[0700] 1-(tert-butyl)-5-methyl(tert-butoxycarbonyl)-L-glutamic acid

[0701]

[0702] Compound (S)-2-((tert-butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acid (5 g, 19.1 mmol) was dissolved in 20 mL of dichloromethane and 20 mL of cyclohexane, Then add tert-butyl 2,2,2-trichloroacetamidate (8.3g, 38.3mmol) and BF 3 ·Et 2O (0.2 mL, 1.9 mmol). React overnight at room temperature, then add solid NaHCO 3 (1.68g, 20mmol). Continue the reaction for 0.5h, then filter, remove the solvent, and obtain the product 1-(tert-butyl)-5-methyl(tert-butoxycarbonyl)-L-glutamic acid (5.76g, 95%) by column chromatography: HRMS calcd for C15H27NO6 317.1838; found, 318.1905 [M+H] + .

[0703] 1-(tert-butyl)-5-methyl(2S,4S)-2-((tert-butoxycarbonyl)amino)-4-(3-(trimethylsilyl)prop-2-yne- 1-yl) glutarate

[0704]

[0...

example 6

[0722] (2S,4S)-2,5-Diamino-4-(4-(2-fluoroethoxy)benzyl)-5-oxopentanoic acid

[0723]

[0724] The reaction equation is as follows:

[0725]

[0726] 5-(tert-butyl)1-methyl(2S,4S)-2-(4-(benzyloxy)benzyl)-4-((tert-butoxycarbonyl)amino)glutarate

[0727]

[0728] Compound 5-(tert-butyl) 1-methyl(2S, 4S)-2-(4-(benzyloxy)benzyl)-4-((tert-butoxycarbonyl) amino) glutarate ( 2g, 6.3mmol) was dissolved in 25mL THF, and then placed at -70°C, then LiHMDS (lithiumbis(trimethylsilyl)amide) (8.5mL, 1mol / L solution) was slowly added to the above solution, and added dropwise over 1h. After the dropwise addition, continue to react at this temperature for 2h. Then 1-benzyloxy-4-bromomethyl-benzene (8.69g, 31.5mmol) and 15mLTHF were added to the above reaction solution, and the reaction was continued at this temperature for 4h. The reaction was then quenched with 15 mL of HCl (1M) and extracted with ethyl acetate (20 x 3 mL). Dry over anhydrous sodium sulfate, remove the solvent, an...

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Abstract

The invention discloses a diagnosis and treatment radioactive glutamine derivative and a method for preparing the same, belongs to the field of glutamine derivative preparation, and relates to novel glutamine derivatives suitable to be labeled by <18>F, <123>I, <124>I, <125>I or <131>I, corresponding glutamine derivative bodies labeled by the <18>F, the <123>I, the <124>I, the <125>I or the <131>I, <19>F or <127>I fluorinated analogs of the glutamine derivative bodies, application of the <19>F or <127>I fluorinated analogs used as reference standards, methods for preparing compounds, compositions with the compounds, reagent kits with the compounds or the compositions, application of the compounds, the compositions or the reagent kits to positron emission tomography (PET) by means of positron emission tomography radiography or diagnostic imaging of single-photon emission computerized tomography (SPECT) or application of the <131>I to treating tumor.

Description

technical field [0001] The invention relates to the field of preparation of glutamine derivatives, and specifically provides a radioactive glutamine derivative for diagnosis and treatment and a preparation method thereof. suitable for use 18 F labeled novel glutamine derivatives and corresponding 18 Labeled precursors and intermediates of F, their 19 F Fluorinated intermediates and cold compounds and their use as reference standards, preparation 18 Method and preparation of F-labeled compounds 19 F. Methods of Fluorinated Analogs, Compositions Comprising Such Compounds, Kits Comprising Such Compounds or Analogs, and 18 F-labeled compounds are useful for uses such as tumor positron emission tomography positron emission tomography (PET) imaging single photon emission computed tomography (SPECT) imaging, or therapy. Background technique [0002] The imaging agent is to mark a certain substance, generally a necessary substance in the metabolism of biological life (such as g...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C237/06C07C231/08C07D249/04C07D213/61C07B59/00A61K31/44A61K31/4192A61K31/198A61P35/00A61K51/04A61K101/02
CPCA61K31/198A61K31/4192A61K31/44A61K51/04A61K51/0453A61K51/0455A61P35/00C07B59/001C07B59/002C07B2200/05C07B2200/07C07C231/08C07C237/06C07D213/61C07D249/04Y02P20/55
Inventor 吴泽辉黄勇吴仁博刘松
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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