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Fluorine-18-marked myocardial perfusion developing agent and preparation method and application thereof

A technology of labeling and pyridazinone, which is applied in the field of radiopharmaceutical chemistry and clinical nuclear medicine, and can solve the problems of long waiting time for imaging, poor stability of aqueous solution, complex synthetic route, etc.

Active Publication Date: 2012-02-01
BEIJING NORMAL UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above-mentioned imaging agents have some disadvantages, such as complex synthetic routes, poor stability in aqueous solution, too long waiting time for imaging, etc.

Method used

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  • Fluorine-18-marked myocardial perfusion developing agent and preparation method and application thereof
  • Fluorine-18-marked myocardial perfusion developing agent and preparation method and application thereof
  • Fluorine-18-marked myocardial perfusion developing agent and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1. Preparation of labeled compound 6

[0029] The synthetic route is as follows:

[0030]

[0031] (1) Synthesis of labeled precursor compound 4.

[0032] a. Synthesis of Compound 1

[0033]Add 1.392g of 2,6-dihydroxypyridine, 1.258g of 4,5-dichloropyridazinone, 3.256g of cesium carbonate and 10mL of anhydrous N,N-dimethylformamide into a 50mL eggplant-shaped bottle at 68°C Oil bath reaction 12h. The reaction solution was cooled to room temperature, diluted with 50 mL of ethyl acetate, and filtered with suction. The filtrate was transferred to a 100mL separatory funnel and washed 4 times with 50mL water respectively. The organic phase was dried over anhydrous magnesium sulfate, and after suction filtration, the filtrate was rotary distilled and purified through a 200-300 mesh silica gel column. The developing solvent was petroleum ether: ethyl acetate = 1:1. Compound 1 was finally obtained as a white solid. NMR spectrum: NMR spectrum: ( 1 HNMR, CDCl 3...

Embodiment 2

[0046] Example 2. Preparation of labeled compound 13

[0047]

[0048] (1) Synthesis of precursor compound 11:

[0049] a. Synthesis of Compound 8

[0050] Add 1.543g of compound 7, 1.258g of 4,5-dichloropyridazinone, 3.256g of cesium carbonate and 10mL of anhydrous N,N-dimethylformamide into a 50mL eggplant-shaped bottle, and react in an oil bath at 68°C for 12h. The reaction solution was cooled to room temperature, diluted with 50 mL of ethyl acetate, and filtered with suction. The filtrate was transferred to a 100mL separatory funnel and washed 4 times with 50mL water respectively. The organic phase was dried over anhydrous magnesium sulfate, and after suction filtration, the filtrate was rotary distilled, and purified through a 200-300 mesh silica gel column. The developing solvent was petroleum ether: ethyl acetate = 1:2. Compound 8 was finally obtained as a white solid. NMR spectrum: ( 1 HNMR, CDCl 3 )δ: 1.477(s, 9H, N(CH 3 ) 3 ), 2.801(t, 2H, CH 2 CH 2 OH),...

Embodiment 3

[0063] Example 3. Preparation of labeled compound 16

[0064]

[0065] (1) Synthesis of labeled precursor compound 14:

[0066] Add 0.125g of copper sulfate pentahydrate and 0.396g of sodium L-ascorbate into a 50mL flask, add 2mL of water under nitrogen protection, and stir for 15min. Dissolve 0.254 g of 1-ethoxy-2-propynyl p-toluenesulfonate in 1.5 mL of N,N-dimethylformamide and add to the reaction flask. 0.363 g of compound 10 was dissolved in 1.5 mL of N,N-dimethylformamide and added to the reaction flask. Stir at room temperature for 1 d under airtight conditions. Add 50 mL of dichloromethane. The solution was transferred to a 250 mL separatory funnel and washed with 50 mL saturated brine. The organic phase was dried with anhydrous magnesium sulfate, and after suction filtration, the filtrate was rotary distilled and purified through a 200-300 mesh silica gel column, and the developing solvent was petroleum ether: ethyl acetate = 1:7. Compound 14 was finally obtai...

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Abstract

The invention provides a fluorine-18-marked pyridazinone analogue. The general structural formula of the analogue is shown as a formula (A), wherein G is selected from S, O or NH; R1 is alkyl with 1-6 carbon atoms; R2 is halogen or halogenation alkyl; L is phenyl, cyclohexyl or a hexa-heterocycle radical containing heteroatoms; m is 1, 2, 3, 4, 5 or 6; n is an integer of 1-15; and M is methylene or ethoxy. A compound marking method is simple, and has high radiation chemistry yield, high stability, a high myocardium initial uptake value, high target to non-target ratio and low using cost. The pyridazinone analogue is applied to the technical fields of radiopharmaceutical chemistry and clinical nuclear medicine as a novel fluorine-18-marked myocardial perfusion developing agent.

Description

technical field [0001] The invention belongs to the technical fields of radiopharmaceutical chemistry and clinical nuclear medicine, and specifically relates to a class of fluorine-18 labeled pyridazinone analogues, a preparation method and application thereof. Background technique [0002] Coronary heart disease is one of the most serious diseases threatening human health. In my country, the morbidity and mortality of coronary heart disease are on the rise. The 2008 Statistical Bulletin on the Development of my country's Health Services shows that the death rate (1 / 100,000) of heart disease is about 130, which has become the second cause of death among urban and rural populations in my country, accounting for about 20% of the causes of death among Chinese residents. [0003] The use of myocardial perfusion imaging in non-invasive heart disease examinations began in the 1970s, and its great diagnostic value has been widely accepted around the world. It has become one of the...

Claims

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Application Information

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IPC IPC(8): C07D403/12A61K101/02C07D401/14C07D403/14A61K51/04
Inventor 张现忠牟甜甜赵祚全王学斌张俊波陆洁唐志刚方纬何作祥
Owner BEIJING NORMAL UNIVERSITY
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