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Sigma 1 receptor bound tricarbonyl cyclopentadiene ligand compound, and preparation method and application of ligand compound

A technology of tricarbonyl cyclopentadiene and ligand compounds, applied in the fields of radiopharmaceutical chemistry and clinical nuclear medicine, can solve the problems of less research on SPECT imaging agents, and achieve excellent biological properties, high radiochemical purity, high The effect of tagging rate

Inactive Publication Date: 2013-12-11
BEIJING NORMAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Currently, the F-18 marks the σ 1 There are many studies on receptor PET imaging agents, but less on technetium-99m-labeled SPECT imaging agents

Method used

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  • Sigma 1 receptor bound tricarbonyl cyclopentadiene ligand compound, and preparation method and application of ligand compound
  • Sigma 1 receptor bound tricarbonyl cyclopentadiene ligand compound, and preparation method and application of ligand compound
  • Sigma 1 receptor bound tricarbonyl cyclopentadiene ligand compound, and preparation method and application of ligand compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1 Combining σ 1 Synthesis of Tricarbonylcyclopentadiene Ligand Compound (Re-4-W) of Receptor

[0037]Dissolve 55.0 mg of Re-4-Br (4-bromobutyrylcyclopentadienetricarbonylrhenium) and 28.4 mg of 1-(3,4-methylenedioxybenzyl) piperidine in 2 mL of toluene and 2 mL of triethylamine To the solution, 9.1 mg of potassium iodide was added, stirred in the dark, and refluxed at 115° C. for 4 h. The solvent was spun off, and purified by a 200-300 mesh silica gel column, using ethyl acetate:petroleum ether:triethylamine=1:5:1 (volume ratio) as eluent to obtain 11.2mg of orange-red liquid (yield 15.7% ), the compound Re-4-W. The structure of the product was confirmed by nuclear magnetic resonance analysis and high-resolution mass spectrometry, the results: 1 H NMR (400MHz, CDCl 3 )δ: 6.83(s, 1H), 6.73(s, 2H), 5.97(t, J=2.1Hz, 2H), 5.93(s, 2H), 5.38(t, J=2.1Hz, 2H), 3.39( s, 2H), 2.60 (t, J = 6.9 Hz, 2H), 2.42-2.33 (m, 10H), 1.90-1.83 (m, 10H). 13 C NMR (100MHz, CDCl 3...

Embodiment 2

[0040] Example 2 Combining σ 1 Synthesis of Tricarbonylcyclopentadiene Ligand Compound (Re-6-W) of Receptor

[0041] Dissolve 66.3 mg of Re-6-Br (6-bromohexanoylcyclopentadienetricarbonylrhenium) and 57.0 mg of 1-(3,4-methylenedioxybenzyl) piperidine in 2 mL of toluene and 2 mL of triethylamine To the solution, 12.9 mg of potassium iodide was added, stirred in the dark, and refluxed at 115° C. for 4 h. The solvent was spun off, purified through a 200-300 mesh silica gel column, and ethyl acetate:petroleum ether:triethylamine=5:20:1 (volume ratio) was used as eluent to obtain 38.0 mg of orange-red liquid (yield 46.1%) ), the compound Re-6-W. The product was analyzed by nuclear magnetic resonance, the result: 1 H NMR (400MHz, CDCl 3 )δ: 6.85(s, 1H), 6.74(s, 2H), 5.98(t, J=2.2Hz, 2H), 5.94(s, 2H), 5.40(t, J=2.2Hz, 2H), 3.41( s, 2H), 2.59(t, J=7.3Hz, 2H), 2.46(s, 8H), 2.34(t, J=7.3Hz, 2H), 1.73-1.66(m, 2H), 1.56-1.48(m , 2H), 1.37-1.29 (m, 2H). 13 C NMR (100MHz, CDCl 3 )δ:...

Embodiment 3

[0045] Example 3 Technetium-99m labeled σ 1 Synthesis of Tricarbonylcyclopentadiene Ligand Compound (Tc-4-W) of Receptor

[0046] Include the following steps:

[0047] (1) Synthesis of the labeled precursor Fe-4-W: 300.0 mg of 4-bromobutyryl ferrocene and 56.2 mg of 1-(3,4-methylenedioxybenzyl)piperidine were dissolved in 4 mL of toluene and 4 mL of Add 19.7 mg of potassium iodide to the triethylamine solution, stir in the dark, and reflux at 115°C for 4 hours. The solvent was spun off, separated and purified through a 200-300 mesh silica gel column, and petroleum ether: triethylamine=10:1 (volume ratio) was used as the eluent to obtain 97.5 mg of an orange-red solid (yield 74.1%), namely the compound Fe -4-W. The structure of the product was confirmed by nuclear magnetic resonance analysis and mass spectrometry, the result: 1 H NMR (400MHz, CDCl 3 )δ: 6.84(s, 1H), 6.73(s, 2H), 5.93(s, 2H), 4.78(t, J=1.7Hz, 2H), 4.48(t, J=1.7Hz, 2H), 4.19( s, 5H), 3.41(s, 2H), 2.75(t, J=...

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Abstract

The invention relates to a sigma 1 receptor bound tricarbonyl cyclopentadiene ligand compound, and a preparation method and an application of the ligand compound. A structural general formula of the ligand compound is shown as (I) as shown in the specification, wherein n is equal to 3 or 5, and M is rhenium or technetium-99m. The tricarbonyl cyclopentadiene ligand compound has high affinity and moderate selectivity to a sigma 1 receptor, and is an initially found sigma 1 receptor ligand with nanomolar affinity. After labeled by technetium-99m, the ligand compound has a higher labeling rate, high radiochemical purity and excellent biological properties, is applicable to an SPECT (single photon emission computed tomography) tracer, breaks through the low brain uptake bottleneck of a 99 mTc labeled sigma 1 receptor tracer, and has wide clinical application prospects.

Description

technical field [0001] The invention relates to the technical fields of radiopharmaceutical chemistry and clinical nuclear medicine, in particular to a combination σ 1 A tricarbonylcyclopentadiene ligand compound for a receptor, a preparation method and application thereof. Background technique [0002] In the field of radiopharmaceutical chemistry and clinical nuclear medicine technology, the sigma (σ) receptor is a new type of receptor different from the opioid receptor, which is divided into sigma-1 (σ 1 ) and sigma-2(σ 2 ) of two subtypes. [0003] σ 1 The receptors are highly expressed in the brain and peripheral organs such as heart, spleen, kidney, liver, ovary, testis, placenta, etc. σ 1 Receptors are involved in the regulation of functions related to the central nervous system, endocrine system, behavior and immune system. σ 1 The receptor regulates various in vivo targets such as ion channels, G-protein-coupled receptors, lipid rafts, and other signaling pro...

Claims

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Application Information

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IPC IPC(8): C07F13/00A61K51/04A61K103/10
Inventor 贾红梅王霞李丹崔孟超刘伯里
Owner BEIJING NORMAL UNIVERSITY
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