Preparation method of tritium or deuterium-labeled cyadox

A technology of deuterium-labeled and cyadoxine, which is applied in the field of preparation of tritium or deuterium-labeled cyadoxine, can solve the problems of long synthetic route, harsh conditions, complicated operation steps, etc., achieve high radiochemical purity and chemical purity, and label position Clear, chemically pure effect

Inactive Publication Date: 2009-09-23
HUAZHONG AGRI UNIV
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Problems solved by technology

so the method will 14 C is labeled on the side chain of the parent ring of quinoxaline. In animal tracking studies, once the side chain is decomposed from the parent ring, it cannot explain the metabolic properties of the overall drug.
In 2005, Li Jianyong et al. (Li Jianyong, Zhou Xuzheng, Li Jinshan, Zhao Rongcai, Miao Xiaolou, Zhang Jiyu, Zhang Ping. Studies on the Metabolic Kinetics of Tritiated Quinocetone in Chickens. Journal of Toxicology, 2005, 19(3): 273.) Studies on the metabolic kinetics of tritiated quinocetone in chickens, but no report on its tritiated synthesis
[0005] 1) 14 The cost of C-labeled synthesis is high, and suitable starting materials cannot be found in China
[0006] 2) The location of the mark is unreasonable and does not meet the requirements for traceability of such drugs in animals
[0007] 3) No published reports or patents
[0008] 4) The synthetic route is long, the operation steps are complicated, and the conditions are harsh
[0009] In view of the fact that there is no radioactive or stable isotope labeling synthesis method for quinoxaline compounds suitable for animal tracer studies so far, and there is no radioactive or stable isotope labeling synthesis method for cyadoxone. , but also suitable for the isotope synthesis method of quinoxaline drug tracer research, in order to carry out isotope tracer research on it

Method used

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  • Preparation method of tritium or deuterium-labeled cyadox
  • Preparation method of tritium or deuterium-labeled cyadox

Examples

Experimental program
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Effect test

example 1

[0047] 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 were added in turn in a 25 ml reaction bottle, and sealed to a glass tritiation reaction device On, vacuumize, pass tritium 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%.

[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 product twice with water, and dry naturally to obtain light yellow crystal...

example 2

[0052] 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 were successively added to a 25 ml reaction bottle, sealed and connected to the tritiation reaction device, vacuumed, and ventilated Tritium gas, the pressure in the reaction bottle reaches 200mmHg, the reaction temperature is 10°C, the reaction is stirred for 5 minutes, the stirring is stopped, the liquid nitrogen is frozen, the tritium gas is recovered, left to melt, and the catalyst is collected by suction filtration. Preparative chromatographic separation gives [ 3 H]-o-nitroaniline. Yield 68.4%.

[0053] 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 product twice with water, and dry to obtain ...

Embodiment 3

[0057] Operation method is identical with example 1 respectively, and debromination reaction catalyst is palladium / carbon (Pd / C) catalyzer, palladium chloride that respectively Raney nickel, mass ratio are 10% respectively, and when acid acceptor is respectively sodium acetate, salt of wormwood, its The result is also basically the same.

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Abstract

The invention relates to a preparation method of a feed drug additive cyadox by tritium or deuterium labeling. The preparation method comprises the following steps: dehalogenating 4-bro-2-nitroaniline or 4-iodo-2-nitroaniline to exchange with tritium or deuterium in tritium gas or deuterium gas in the presence of a catalyst and an acid receptor to produce 4-[3]H-2-nitroaniline or 4-[2]H-2-nitroaniline; and preparing the tritium or deuterium-labeled cyadox by microsynthesis after an oxidation reaction, a Beirut reaction and a hydrazone forming reaction so as to obtain the tritium-labeled cyadox with high specific activity (12.63Ci / mmol), high radiochemical purity (above 98%) and high chemical purity (above 99.5%) or the deuterium-labeled cyadox with high chemical purity (above 99.5%). The method provides a material basis for systematic development of rules of absorption, distribution and metabolism of the cyadox in animals. The prepared 4-[3]H-2-nitroaniline or 4-[2]H-2-nitroaniline can be taken as a starting material for synthesizing all tritium or deuterium-labeled quinoxaline drugs without other substituents at the sixth place of a quinoxaline ring and is an important substance for synthesizing the tritium or deuterium-labeled drugs.

Description

technical field [0001] The invention relates to a preparation method of tritium or deuterium labeled cycadol. This method uses radioactive isotope tritium or stable isotope deuterium, on the quinoxaline ring of a kind of feed drug additive drug Cyadox (Cyadox) positioning mark preparation, so that tracing the absorption of cyadox in animal body, distribution, metabolism and Excretion status. Background technique [0002] Isotope tracer test is an important means of scientific research, which plays a powerful role in promoting various fields of life science research. Isotope tracer tests can be used to study various issues of substance metabolism, such as metabolic pathways, transformation speeds, positions of metabolites in the body, and quantitative determination of important metabolites such as hormones and vitamins. The radioisotope tracer method is used in the field of medicine to study the distribution, metabolism and excretion of drugs in the body. The chemical and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D241/52A61K51/00A23K1/16A61K101/00A23K20/137
Inventor 袁宗辉斯琴朝克图黄玲利王玉莲陶燕飞陈冬梅刘振利彭大鹏戴梦红刘振果邱荣超刘志亮
Owner HUAZHONG AGRI UNIV
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