5-substituted phenyl-3-isoxazole carboxylic acid and ester compounds, compositions and preparation method thereof

A technology of ethyl isoxazolecarboxylate and isoxazolecarboxylate, which is applied in the field of medical technology, can solve the problem of not finding a preparation method for 5-substituted phenyl-3-isoxazolecarboxylate and its ester compound, etc., and achieves Effect of prevention of hyperuricemia and gout, simple and easy preparation method

Inactive Publication Date: 2009-11-18
SHENYANG PHARMA UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] No related reports on 5-substituted phenyl-3-isoxazole carboxylic acid and ester compounds, compositions and preparation methods thereof have been found in the prior art

Method used

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  • 5-substituted phenyl-3-isoxazole carboxylic acid and ester compounds, compositions and preparation method thereof
  • 5-substituted phenyl-3-isoxazole carboxylic acid and ester compounds, compositions and preparation method thereof
  • 5-substituted phenyl-3-isoxazole carboxylic acid and ester compounds, compositions and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Preparation of 5-(3-nitro-4-isobutoxy)phenyl-3-isoxazolecarboxylic acid

[0063] The title compound was prepared according to the method of the following scheme

[0064]

[0065] (1) Preparation of 3-nitro-4-hydroxyacetophenone

[0066] Dissolve p-hydroxyacetophenone (15.00g, 110.00mmol) in glacial acetic acid (40mL), stir at 45°C, slowly add concentrated nitric acid (10.5mL, 110.00mmol) dropwise, control the reaction temperature at 50°C-60°C, After dropping, continue to stir for 0.5h. The reaction solution was poured into a mixture of ice and water, a yellow solid precipitated out, filtered with suction, dried naturally at room temperature, and then recrystallized with absolute ethanol to obtain 10.50 g of yellow crystals, yield 52.6%, m.p.131.0-132.6°C.

[0067] (2) Preparation of 3-nitro-4-isobutoxyacetophenone

[0068] Add 3-nitro-4-hydroxyacetophenone (15.80 g, 87.30 mmol), anhydrous potassium carbonate (42.20 g, 306.00 mmol), DMF (150.0 mL), PEG-400 (4.0 mL)...

Embodiment 2

[0082] Preparation of 5-(3-nitro-4-benzyloxy)phenyl-3-isoxazolecarboxylic acid

[0083] The title compound was prepared according to the method of the following scheme

[0084]

[0085] (1) Preparation of 3-nitro-4-hydroxyacetophenone

[0086] Concrete operation refers to (1) in embodiment 1

[0087] (2) Preparation of 3-nitro-4-benzyloxyacetophenone

[0088] In a 250ml round bottom flask was added 3-nitro-4-hydroxyacetophenone (5.00g, 27.60mmol), anhydrous potassium carbonate (11.40g, 82.90mmol), potassium iodide (0.27g, 1.38mmol) and DMF (50mL ), after stirring at 65°C for 20min, benzyl chloride (6.4mL, 55.20mmol) was added, and the reaction was continued at this temperature for 3h. Then the reaction solution was poured into water (300mL), the solid was precipitated, and the crude product was obtained by suction filtration, which was recrystallized from ethyl acetate to obtain 5.00g of light yellow crystals, yield 66.8%, m.p.132.7-134.7°C.

[0089] (3) Preparation of ...

Embodiment 3

[0099] Preparation of 5-[3-nitro-4-(4-methyl)benzyloxy]phenyl-3-isoxazolecarboxylic acid

[0100] The title compound was prepared according to the method of the following scheme

[0101]

[0102] (1) Preparation of 3-nitro-4-hydroxyacetophenone

[0103] Concrete operation refers to (1) in embodiment 1

[0104] (2) Preparation of 3-nitro-4-(4-methyl)benzyloxyacetophenone

[0105] In a 250ml round bottom flask were added 3-nitro-4-hydroxyacetophenone (5.00g, 27.60mmol), anhydrous potassium carbonate (11.40g, 82.90mmol), potassium iodide (0.30g, 1.38mmol) and DMF (50mL ), after stirring at 65°C for 20min, 4-methylbenzyl chloride (7.80g, 55.20mmol) was added, and the reaction was continued at this temperature for 3h. Then the reaction liquid was poured into water (300mL), the solid was precipitated, and the crude product was obtained by suction filtration. Recrystallized from ethyl acetate to obtain 5.20g of yellow crystals, yield 66.0%, m.p.108.8-110.8°C.

[0106] 1 H-NMR...

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Abstract

The invention belongs to the technical field of medicaments, relates to 5-substituted phenyl-3-isoxazole carboxylic acid with xanthine oxidase inhibitory activity shown as in general expression I and ester compounds, tautomer, a pharmaceutical salt and a pharmaceutical solvate thereof and pharmaceutical compositions containing the components and a preparation method of the components, and also relates to application of the compounds and the compositions in preparing a medicament for treating hyperuricemia and gout (wherein R independently is substituted or unsubstituted linear and branched C1-C10 alkyl, C2-C10 alkenyl, C3-C7 naphthenic base, C3-C7 cycloalkenyl groups, an aromatic group, an aralkyl group, a heterocyclic group, heteroaryl, heterocyclic-alkyl, heteroarylalkyl, C3-C7 cycloalkyl-alkyl, aminoalkyl, primary alkyl aminoalkyl, dialkyl aminoalkyl, alkoxyl-alkyl, aryl-oxyalkyl, aralkoxy-alkyl and fully halogenated alkyl; R is a cyano-group, a nitro group, halogen and unsubstituted, monosubstituted or disubstituted aminocarbonyl; R is a hydrogen atom or ethyl; and A is an oxygen atom, a sulphur atom and a nitrogen atom).

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to 5-substituted phenyl-3-isoxazole carboxylic acid and ester compounds, compositions and preparation methods thereof, in particular to esters of 5-substituted phenyl-3-isoxazole carboxylic acid Compounds, derivatives, isomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable compositions containing them and their preparation methods, and the use of these compounds in medicine. Background technique [0002] Gout is a group of heterogeneous metabolic diseases caused by long-term purine metabolism disorder and / or decreased uric acid excretion. Gout is the second most common metabolic disease in humans after diabetes. The clinical features of gout are hyperuricemia, recurrent acute arthritis, tophi deposition, tophi chronic arthritis and joint deformities, chronic interstitial nephritis and nephrolithiasis caused by kidney involvement...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D261/18A61K31/42A61P19/06
Inventor 王绍杰晏菊芬陈家润
Owner SHENYANG PHARMA UNIVERSITY
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