Xanthine derivative

A compound and pharmaceutical technology applied in the field of dipeptidyl peptidase IV inhibitors

Active Publication Date: 2014-01-15
CHENGDU EASTON BIOPHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the many side effects of these hypoglycemic drugs, it is particularly important to develop a new type of drug with low side effects and effective treatment of diabetes.

Method used

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Examples

Experimental program
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Effect test

Embodiment 1

[0029] 1-[(benzonitrile-2-yl)methyl]-3-[(benzonitrile-2-yl)methyl]-7-(2-butyn-1-yl)-8-[(R )-3-amino-piperidin-1-yl]-xanthine preparation

[0030]

[0031]

[0032] Preparation of the first step 7-(2-butyn-1-yl)-8-bromo-xanthine

[0033] Using a known method, 8-bromoxanthine (2.31g, 10mmol) was dissolved in N,N-dimethylformamide (20ml), and N,N-diisopropylethylamine (1.42g, 11mmol) was added . 1-Bromo-2-butyne (1.46g, 11mmol), reacted at room temperature for 6h, followed by thin-layer chromatography, which showed that the raw materials were completely consumed. Slowly add 200ml of water to the stirred reaction system, the off-white solid particles are separated out in the solution, after fully stirring for 30min, filter, wash with water, and dry to obtain compound 7-(2-butyn-1-yl)-8-bromo-xanthine 1a ( 2.1 g, yellow solid), yield: 74.2%.

[0034] MS m / z(ESI):283,285[M+1]

[0035] The second step 1-[(benzonitrile-2-yl)methyl]-3-[(benzonitrile-2-yl)methyl]-7-(2-butyn-1-...

Embodiment 2

[0046] 1-[(4-fluoro-benzonitrile-2-yl)methyl]-3-[(4-fluoro-benzonitrile-2-yl)methyl]-7-(2-butyne-1- Preparation of -8-[(R)-3-amino-piperidin-1-yl]-xanthine

[0047]

[0048]

[0049] The first step is the same as the first step in embodiment 1

[0050] The second step 1-[(4-fluoro-benzonitrile-2-yl)methyl]-3-[(4-fluoro-benzonitrile-2-yl)methyl]-7-(2-butyne Preparation of -1-yl)-8-bromo-xanthine

[0051] Using a known method, the compound 7-(2-butyn-1-yl)-8-bromo-xanthine 1a (283mg, 1mmol) was dissolved in N,N-methylformamide (5ml), and potassium hydroxide was added (140mg, 2.5mmol) was added with 2-cyano-5-fluorobenzyl bromide (535mg, 2.5mmol) while stirring, and reacted overnight at room temperature. TLC followed the reaction, showing that the raw materials were completely consumed, and slowly added 50ml of water, a light yellow solid precipitated out, stirred thoroughly for 30 minutes, filtered, washed with water, and dried to obtain compound 1-[(4-fluoro-benzonitri...

Embodiment 3

[0061] 1-[(3-fluoro-benzonitrile-2-yl)methyl]-3-[(3-fluoro-benzonitrile-2-yl)methyl]-7-(2-butyne-1- Preparation of -8-[(R)-3-amino-piperidin-1-yl]-xanthine

[0062]

[0063]

[0064] The first step is the same as the first step in embodiment 1

[0065] The second step 1-[(3-fluoro-benzonitrile-2-yl)methyl]-3-[(3-fluoro-benzonitrile-2-yl)methyl]-7-(2-butyne Preparation of -1-yl)-8-bromo-xanthine

[0066] Using a known method, the compound 7-(2-butyn-1-yl)-8-bromo-xanthine 1a (283mg, 1mmol) was dissolved in N,N-dimethylformamide (5ml), added with hydrogen Potassium (140mg, 2.5mmol) was added with 2-bromomethyl-3-fluorobenzocyanide (535mg, 2.5mmol) while stirring, and reacted overnight at room temperature. The reaction was tracked by thin-layer chromatography, which showed that the raw materials were completely consumed. Slowly add 50ml of water, a light yellow solid precipitates out, stir thoroughly for 30min, filter, wash with water, and dry to obtain the compound 1-[(...

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Abstract

The invention discloses a xanthine derivative and its pharmaceutically acceptable salt. In vitro DPP-IV activity inhibition tests, influence tests of normal mouse's glucose tolerance, and influence tests of spontaneous diabetic mouse's blood glucose confirm that the compound and its pharmaceutically acceptable salt show significant DPP-IV inhibitory activity, and can be used in preparation of drugs for treating dipeptidyl peptidase IV associated diseases.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a class of xanthine derivatives, a preparation method and the use of the derivatives as therapeutic drugs, especially dipeptidyl peptidase IV (DPP-IV) inhibitors. Background technique [0002] Diabetes mellitus is a metabolic disease of multiple etiologies characterized by chronic hyperglycemia accompanied by disturbances in carbohydrate, fat and protein metabolism due to defects in insulin secretion and / or action. Diabetes is also a very old disease, which is due to the relative or absolute lack of insulin in the human body, which causes the blood glucose concentration to rise, resulting in a large amount of sugar being excreted from the urine, accompanied by polydipsia, polyuria, polyphagia, weight loss, and dizziness , fatigue and other symptoms. [0003] In diabetes treatment, exercise therapy and diet therapy are two essential diabetes treatment methods. When these two t...

Claims

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Application Information

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IPC IPC(8): C07D473/04A61P3/10
CPCC07D473/04
Inventor 王颖向永哲岑国栋黄龙周宁
Owner CHENGDU EASTON BIOPHARM CO LTD
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