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Preparation method for tritium or deuterium labeled mequindox

A technology of acemequine and deuterium labeling, applied in the direction of organic chemistry, etc., can solve the problems of not meeting the requirements of drug tracer research, no public reports or patents, and inability to explain drug metabolism characteristics, etc., so that the reaction conditions are easy to grasp, The effect of high specific activity and suitable synthesis conditions

Active Publication Date: 2013-12-04
HUAZHONG AGRI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although this method successfully marked the synthesized 14 C-labeled quinocetones have obvious defects: for example, the method will 14 C is marked on the side chain of the parent ring of quinoxaline. In animal metabolism studies, if the degradation reaction occurs, the side chain will leave the parent ring, which cannot explain the metabolic characteristics of the overall drug.
[0006] 1) 14 The cost of C-labeled synthesis is high, and it is difficult to find suitable starting materials in China
[0007] 2) The radiolabeled sites are unreasonable and do not meet the requirements of tracer studies of such drugs in animals
[0008] 3) No published reports or patents
[0009] 4) The synthetic route is long, the operation steps are complicated, and the conditions are harsh

Method used

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  • Preparation method for tritium or deuterium labeled mequindox

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1 Synthesis of Tritiated Methoquine

[0043] Take 20 mg of 4-bromo-2-nitroaniline, 5 mg of palladium / carbon (Pd / C) catalyst with a mass ratio of 10%, 4 mg of sodium hydroxide, and 1 ml of ethanol are added to a 25 ml reaction bottle in turn, and sealed to the glass tritiation reaction On the device, vacuumize, pass tritium (or deuterium) gas, the pressure in the reaction bottle reaches 200mmHg, the reaction temperature is 10°C, stir the reaction for 45min, stop stirring, freeze with liquid nitrogen, recover the tritium gas, let it melt, and collect the catalyst by suction filtration. Preparative chromatographic separation gives [ 3 H]-o-nitroaniline. Yield 67.2%.

[0044] Put into the 3ml reaction bottle [ 3 H]-o-nitroaniline 15 mg, isopropanol 100 μl, sodium hydroxide 6 mg. Slowly drop 100 μl of sodium hypochlorite solution with an effective chlorine molar ratio of 5% under stirring, react at 10°C for 2 hours, let stand for 1 hour, filter with suction, wash...

Embodiment 2

[0046] Example 2 Synthesis of Tritiated Methoquine

[0047] Take 25 mg of 4-iodo-2-nitroaniline, 5 mg of Pd / C catalyst with a mass ratio of 10%, 4 mg of sodium hydroxide, and 1 ml of ethanol are sequentially added to a 25 ml reaction bottle, sealed and connected to the tritiation reaction device, and vacuumized. Pass tritium (or deuterium) gas, the pressure in the reaction bottle reaches 200mmHg, the reaction temperature is 10°C, stir the reaction for 5 minutes, stop the stirring, freeze with liquid nitrogen, recover the tritium gas, let it melt, and collect the catalyst by suction filtration. Preparative chromatographic separation gives [ 3 H]-o-nitroaniline. Yield 68.4%.

[0048] Put into the 3ml reaction bottle [ 3 H]-o-nitroaniline 15 mg, isopropanol 100 μl, sodium hydroxide 6 mg. Slowly drop 100 μl of sodium hypochlorite solution with an effective chlorine molar ratio of 5% under stirring, react at 10°C for 2 hours, let stand for 1 hour, filter with suction, wash the ...

Embodiment 3

[0050] Example 3 Synthesis of Tritiated Methoquine

[0051] The operating method of this embodiment is the same as that of Example 1 respectively, the debromination reaction catalyst is respectively Raney nickel, mass ratio is 10% palladium / carbon (Pd / C) catalyst, palladium chloride, and the acid acceptor is respectively sodium acetate , Potassium carbonate, the results are basically the same.

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Abstract

The invention belongs to the technical field of veterinary drug preparation, and particularly relates to a preparation method for a tritium and deuterium labeled veterinary drug mequindox. The method comprises the following steps: adopting a trace synthesis method to allow tritium gas or deuterium gas and 4-bromine-2-nitroaniline or 4-iodine-2-nitroaniline to be subjected to dehalogenation reaction under the action of a catalyst and an acid acceptor, and meanwhile, introducing tritium gas or deuterium gas alternatively to generate 4-3H-2-nitroaniline or 4-2H-2-nitroaniline; performing the oxidation reaction and the Beirut reaction to prepare the C-6 tritium labeled or deuterium labeled mequindox, wherein the obtained product is clear in labeling point, high in specific activity (12.63 Ci / mmol), high in radiochemical purity (more than 98 percent) and high in chemical purity (more than 99.5 percent). The prepared tritium labeled mequindox provides a material foundation for the research of absorption, distribution, metabolism and residue elimination rules of the mequindox in an animal body; the prepared deuterium labeled mequindox can serve as an internal standard substance for the quantitative analysis of a mequindox trace amount.

Description

technical field [0001] The invention belongs to the technical field of veterinary drug preparation, and in particular relates to a preparation method of tritium- or deuterium-labeled acemequine. The present invention uses radioactive isotope tritium or stable isotope deuterium to carry out isotope labeling on the C6 position on the quinoxaline ring of a kind of veterinary drug Mequindox, so as to prepare tritium-labeled or deuterium-labeled Mequindox. This tritium-labeled acemethaquine can be used to trace the absorption, distribution, metabolism and excretion of acemethaquine in animals, and the deuterium-labeled acemethaquine can be used as an internal standard substance for the detection of trace amounts of acemethaquine. Background technique [0002] Acetylmethaquine (Mequindox) has another name called dysentery net, and its chemical name is 3-methyl-2-acetylquinoxaline-1,4-dioxide. National Class I new veterinary drug independently developed in the 1980s. Clinical app...

Claims

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Application Information

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IPC IPC(8): C07D241/52
Inventor 袁宗辉潘源虎黄玲利尹伏军王玉莲陶燕飞陈冬梅刘振利彭大鹏戴梦红谢书宇
Owner HUAZHONG AGRI UNIV
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