Fluorinated phosphine oxide compound and application thereof in positron emission imaging

A technology for positron emission and phosphine oxide substitution, which is applied in the direction of isotope introduction into organic compounds, compounds of Group 5/15 elements of the periodic table, luminescent materials, etc., which can solve the problems of high labeling reaction temperature, high radiochemical yield, and large molecular weight and other problems, to achieve high targeting, convenient post-processing, and low molecular weight

Active Publication Date: 2018-09-28
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In recent years, based on non-carbon atoms 18 F labeling methods are increasingly used in the preparation of PET probes. This type of labeling method has good selectivity, high radiochemical yields (RCYs), and can obtain high specific activity (Specific activity, SA) in vivo Metabolically stable radiotracers, however, such non-carbon 18 The F labeling method has the following disadvantages: 1) The labeling reaction temperature is high; 2) It needs to be labeled under strong acidity; 3) The molecular weight of the labeling precursor is large; 4) In vivo defluorination, etc.

Method used

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  • Fluorinated phosphine oxide compound and application thereof in positron emission imaging
  • Fluorinated phosphine oxide compound and application thereof in positron emission imaging
  • Fluorinated phosphine oxide compound and application thereof in positron emission imaging

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] This embodiment provides a positron emission imaging 18 The fluorinated phosphine oxide compound of F label, its preparation process and concrete steps are as follows:

[0078]

[0079] Tetrahydrofuran: Tetrahydrofuran DMF: N,N-Dimethylformamide

[0080] MeOH: methanol CsF: cesium fluoride

[0081] Pd / C: palladium carbon CuCl2: copper chloride

[0082] DCC: Dicyclohexylcarbodiimide 18 f - a.q.: accelerator shooting water

[0083] Synthetic steps of compound 1:

[0084] a: Take 7.5mmol of zinc powder in a dry reaction flask, add 5mL of tetrahydrofuran under the protection of argon. 1.2mmolI 2 After dissolving in 2 mL of tetrahydrofuran, add to the reaction flask. Then take 8mmol 2-bromoisobutyrate benzyl ester and dissolve it in 3mL tetrahydrofuran, then add it into the reaction flask. After the zinc powder has completely reacted, under an ice-water bath, dissolve 8 mmol of tert-butylphosphorus dichloride in 5 mL of tetrahydrofuran, slowly add it into the rea...

Embodiment 2

[0099]

[0100] Synthetic steps of compound 1:

[0101] a: Take 7.5mmol of zinc powder in a dry reaction flask, add 5mL of tetrahydrofuran under the protection of argon. 1.2mmolI 2 After dissolving in 2 mL of tetrahydrofuran, add to the reaction flask. Then take 8mmol 2-bromoisobutyrate benzyl ester and dissolve it in 3mL tetrahydrofuran, then add it into the reaction flask. After the zinc powder has completely reacted, under an ice-water bath, dissolve 8 mmol of tert-butylphosphorus dichloride in 5 mL of tetrahydrofuran, slowly add it into the reaction flask, and react overnight at room temperature. Recovery treatment: Add 20 mL of 0.1 mol / L dilute hydrochloric acid under ice-water bath, extract with ethyl acetate, spin dry and separate through column; Compound 1 is obtained.

[0102] Compound 1 NMR results: 1 H NMR (600MHz, CDCl 3 )δ1.14(d,9H,J=16.35Hz); 1.55(s,3H); 1.62(d,6H,J 1 =12.38Hz,J 2 =14.47Hz); 5.14(d,2H,J 1 =12.28Hz,J 2 = 12.28Hz); 6.51(d,1H,J=464.93Hz)...

Embodiment 3

[0110]

[0111] Synthetic steps of compound 8:

[0112] Take 2mmol of diethyl phosphite in a dry reaction bottle, add 3ml of tetrahydrofuran under the protection of argon, place it at -80°C for half an hour, add 6mmol of isopropylmagnesium bromide, and react at -80°C for 2 hours React at room temperature for 3 hours, add dilute hydrochloric acid to quench the reaction, extract with ethyl acetate, and finally spin dry and separate through the column.

[0113] Compound 8 NMR results: 1 H NMR (400MHz, CDCl 3 )δ1.24(d, 9H, J=39.46Hz); 2.03(d, 2H, J=32.51Hz); 6.33(d, 1H, J=431.69Hz). 31 P NMR (400MHz, CDCl 3 ) δ58.60(d,1P,J=464.53Hz).

[0114] Synthetic steps of compound 9:

[0115] 2mmol CsF and 2mmol CuCl 2 In the dried reaction flask, under the protection of argon, 1 mL of tetrahydrofuran was added. Subsequently, 1 mmol of product 1 was taken, dissolved in 1 mL of anhydrous tetrahydrofuran, added to the reaction flask, reacted at room temperature for 2 hours, spin-drie...

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Abstract

The invention relates to a fluorinated phosphine oxide compound used in the preparation of a positron emission imaging agent and a preparation method thereof, and has a structure shown in a formula I.For the first time, fluorinated phosphine oxide is used as an 18F-labeled auxiliary group, a positron nuclides probe is constructed by a 18F-19F isotope exchange strategy, a labeling method is mild in conditions, reactions can be directly conducted in an 18F-aqueous solution without blow-drying 18F-, and the compound has high radiochemical yield, easy purification, no need for high performance liquid chromatography separation and purification and broad application prospects in the field of positron drugs of preparing biomolecules such as heat sensitive and solvent sensitive peptides or proteins and the like.

Description

technical field [0001] The invention relates to a fluorinated phosphine oxide compound, in particular to the application of the compound in the preparation of positron emission imaging agents. Background technique [0002] Positron emission tomography (PET) 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] In recent years, based on non-carbon atoms 18 F labeling methods are increasingly used in the preparation of PET probes. This type of labeling method has good selectivity, high radiochemical yields (RCYs), and can obtain high specific activity (Specific activity...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/34C07B59/00C09K11/06A61K51/08A61K101/02
Inventor 李子婧洪华伟庄荣强杨鸿章刘欢欢
Owner XIAMEN UNIV
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