Salt of hydroxyl canthin-6-one derivative

Abstract

The invention relates to 4-methoxyl-5-hydroxyl canthin-6-one and a fumarate or a pharmaceutically acceptable solvate of a derivative thereof as well as an application thereof in preparation of a TNF-Alpha inhibitor medicine.

Description

field of invention

[0001] The invention relates to the field of medicinal chemistry, in particular, the invention relates to 4-methoxy-5-hydroxy fermidone organic acid salt and its pharmaceutical application. Background technique

[0002] For now, although there are many kinds of drugs used as TNF-α inhibitors, these drugs are likely to cause multiple and severe adverse reactions, and the therapeutic effects of the existing drugs are still not ideal. Some active compounds with TNF-α inhibition are described in the patent specification of China Invention Patent Granted Publication No. CN 101036646B. Contents of the invention

[0003] The present invention discloses some new compounds, preparation methods of these compounds, pharmaceutical compositions containing these compounds and pharmaceutical applications of these compounds and compositions.

[0004] These compounds exhibit good water solubility stability and solid form stability. Some of these compounds exhibit excep...

Examples

Embodiment 1

[0047] 4-Methoxy-5-hydroxyferramidone fumarate

[0048] Dissolve 2.66 g (0.01 mol) of the compound 4-methoxy-5-hydroxyfermidone and 1.17 g (0.01 mol) of fumaric acid in 80 ml of boiling ethanol. The hot solution is filtered through diatomaceous earth, then slowly cooled under gentle stirring, and left to stand for several hours in a temperature environment of 0-5°C to precipitate 4-methoxy-5-hydroxyferricone fumarate crystals , The crystals of 4-methoxy-5-hydroxyferricone fumarate were filtered off, washed with ethanol and dried under vacuum at 50°C to obtain 3.82 g of product.

Embodiment 2

[0050] 4-Methoxy-5-hydroxy ferricone fumarate

[0051] Stir 2.66 g of the compound 4-methoxy-5-hydroxyferramidone fumarate and 1.17 g of fumaric acid in 80 ml of refluxing ethanol until all the solids are dissolved. Add activated carbon, filter the hot solution through diatomaceous earth, and cool down to room temperature while stirring. Standing for several hours in the temperature environment of 0-5 ℃, 4-methoxy-5-hydroxy iron ketone fumarate crystals are precipitated, and 4-methoxy-5-hydroxy iron ketone fumarate is filtered out. The maleate salt crystals were washed with ethanol and dried under vacuum at 50°C, yielding 3.82 g of product.

field of invention

[0001] The invention relates to the field of medicinal chemistry, in particular, the invention relates to 4-methoxy-5-hydroxy fermidone organic acid salt and its pharmaceutical application. Background technique

[0002] For now, although there are many kinds of drugs used as TNF-α inhibitors, these drugs are likely to cause multiple and severe adverse reactions, and the therapeutic effects of the existing drugs are still not ideal. Some active compounds with TNF-α inhibition are described in the patent specification of China Invention Patent Granted Publication No. CN 101036646B. Contents of the invention

[0003] The present invention discloses some new compounds, preparation methods of these compounds, pharmaceutical compositions containing these compounds and pharmaceutical applications of these compounds and compositions.

[0004] These compounds exhibit good water solubility stability and solid form stability. Some of these compounds exhibit excep...

Examples

Embodiment 1

[0047] 4-Methoxy-5-hydroxyferramidone fumarate

[0048] Dissolve 2.66 g (0.01 mol) of the compound 4-methoxy-5-hydroxyfermidone and 1.17 g (0.01 mol) of fumaric acid in 80 ml of boiling ethanol. The hot solution is filtered through diatomaceous earth, then slowly cooled under gentle stirring, and left to stand for several hours in a temperature environment of 0-5°C to precipitate 4-methoxy-5-hydroxyferricone fumarate crystals , The crystals of 4-methoxy-5-hydroxyferricone fumarate were filtered off, washed with ethanol and dried under vacuum at 50°C to obtain 3.82 g of product.

Embodiment 2

[0050] 4-Methoxy-5-hydroxy ferricone fumarate

[0051] Stir 2.66 g of the compound 4-methoxy-5-hydroxyferramidone fumarate and 1.17 g of fumaric acid in 80 ml of refluxing ethanol until all the solids are dissolved. Add activated carbon, filter the hot solution through diatomaceous earth, and cool down to room temperature while stirring. Standing for several hours in the temperature environment of 0-5 ℃, 4-methoxy-5-hydroxy iron ketone fumarate crystals are precipitated, and 4-methoxy-5-hydroxy iron ketone fumarate is filtered out. The maleate salt crystals were washed with ethanol and dried under vacuum at 50°C, yielding 3.82 g of product.

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