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Synthesis method of ferrioxamine succinimide activated ester and application thereof

A technology of ferrioxamine succinimide and oxalamine succinimide, which is applied in the field of radiopharmaceutical labeling, can solve the problems of complex and time-consuming, poor water solubility of Df-Bz-NCS, and the inability to easily measure the radiochemical purity, and achieve The effect of low cost, good stability in vivo, and good application prospects

Pending Publication Date: 2020-07-14
NANJING PET TRACER
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, both bifunctional coupling agents have certain disadvantages
and (with 89 Zr labeling as an example), Df-Bz-NCS has poor water solubility and is difficult to distinguish by thin layer chromatography (TLC) 89 Zr-labeled drug molecules and impurities 89 Zr-Df-Bz-NCS, which cannot be easily determined 89 Radiochemical purity of Zr-labeled products without complicated and time-consuming HPLC methods

Method used

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  • Synthesis method of ferrioxamine succinimide activated ester and application thereof
  • Synthesis method of ferrioxamine succinimide activated ester and application thereof
  • Synthesis method of ferrioxamine succinimide activated ester and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] 1) Synthesis of compound Ⅱ-a

[0049]

[0050] Add deferoxamine methanesulfonate DFO (500mg, 0.761mmol) and succinic anhydride (760mg, 7.59mmol) into pyridine (7.5mL), shake to dissolve, and stir overnight at 25°C.

[0051] The reaction solution was added to a sodium hydroxide (125 mL, 0.06 mol / L) solution, and allowed to stand overnight at 25° C., and the pH was detected to be 7.5. Hydrochloric acid (18.5 mL, 6 mol / L) was added to the reaction solution, the pH was detected to be 2, and a white precipitate was formed. Place in a refrigerator at 4°C for 2 hours, centrifuge, wash with 0.01mol / L HCl (150mL), and dry to obtain 417mg of compound II-a as a white powder with a yield of 83%.

[0052] MS Spectrum: M / Z[M-H] - = 659.4.

[0053] 2) Synthesis of Compound Ⅰ-a

[0054]

[0055] FeCl 3 ·6H 2 O (17.6mg, 0.0697mmol) was dissolved in acetonitrile (1.3mL), compound II-a (20mg, 0.0303mmol) and acetonitrile (5mL) were added, shaken to dissolve, and the solution w...

Embodiment 2

[0076] The succinic anhydride used in the preparation of compound II-a in Example 1 was replaced by glutaric anhydride and adipic anhydride, respectively, to prepare the corresponding activated ester of ferrioxamine succinimide.

[0077] MS Spectrum: M / Z[M+Na] + They are 847.36 and 861.39 respectively.

Embodiment 3

[0079] The NHS of compound I-a prepared in Example 1 was replaced by DSC, 1-hydroxy-2,5-dioxo-3-pyrrolidine carboxylic acid, sodium salt of N-hydroxysuccinimide sulfonate, respectively, to prepare the corresponding Activated ester of ferrioxamine succinimide.

[0080] MS Spectrum: M / Z[M+Na] + They are 833.37, 877.43, 913.36 respectively.

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Abstract

The invention belongs to the technical field of radiopharmaceutical labeling, and particularly relates to a synthesis method of ferrioxamine succinimide activated ester and an application of saflufenacil succinimide activated ester in preparation of radiopharmaceutical. According to the invention, deferoxamine (DFO) is used as a raw material to synthesize the ferrioxamine succinimide activated ester. The activated ester can be subjected to an amide condensation reaction with drug molecules with primary amino groups under a mild condition to generate an iron oxadiazon conjugate, and then ferricions are removed by a metal chelating agent through a competitive reaction to obtain a deferoxamine conjugate. The invention also relates to the use of the radiolabeled deferoxamine conjugate as an imaging agent and a therapeutic agent, by using medical radionuclides (such as 89Zr, 68Ga, 67Ga, 177Lu, 111In, 90Y) to efficiently label the deferoxamine conjugate, the generated labeled drug can be used for living PET imaging, SPECT imaging or radiotherapy.

Description

technical field [0001] The invention belongs to the technical field of radiopharmaceutical labeling, in particular to a synthesis method of ferrioxamine succinimide activated ester and its application in the preparation of radiolabeled medicines. Background technique [0002] Malignant tumors seriously endanger the health of the people. Many cancers have no obvious clinical symptoms in the early stage, and nuclear medicine PET and SPECT imaging with high sensitivity and specificity can be used for monitoring and diagnosis of early tumors and other diseases. The tumor immune imaging and treatment technology developed in recent years uses radionuclide-labeled tumor-specific targeting antibody drugs for non-invasive PET and SPECT imaging, or radiotherapy, which has high clinical potential. Some important medical radionuclides are ions with a trivalent or higher valence state, such as 68 Ga 3+ , 67 Ga 3+ , 177 Lu 3+ , 90 Y 3+ , 89 Zr 4+ , 111 In 3+ Wait. Labeling o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/46A61K39/395A61K47/54A61K51/04A61P35/00A61K103/00A61K103/30
CPCC07D207/46A61K39/395A61K47/547A61K51/0472A61P35/00A61K2300/00
Inventor 李世红蔡飞王正罗志刚
Owner NANJING PET TRACER
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