Medicinal salts of saxagliptin and preparation methods of medicinal salts

A technology of medicinal salt and maleate, which is applied in the field of pharmacy, can solve the problems of complex preparation process, difficulty in realizing industrial production, and difficulty in quality control

Inactive Publication Date: 2011-06-08
廖国超
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] Because the conventional oral preparations of saxagliptin hydrochloride are difficult to achieve industrial production, the quality is diffic

Method used

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  • Medicinal salts of saxagliptin and preparation methods of medicinal salts
  • Medicinal salts of saxagliptin and preparation methods of medicinal salts
  • Medicinal salts of saxagliptin and preparation methods of medicinal salts

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0081] Example 1 Preparation of saxagliptin mesylate

[0082] Dissolve saxagliptin (0.50g, 1.59mmol) in 8ml ethanol solution, stir, heat to 40℃, slowly add 2ml ethanol containing methanesulfonic acid (0.15g, 1.59mmol), cool to room temperature after adding, Add 16 ml of ether, continue stirring for 1 hour, cool to 0°C and stir overnight, filter, and vacuum-dry the filter cake at 30°C to obtain 0.43 g of light yellow powdery solid with a yield of 66.2%.

[0083] 1 HNMR(CD 3 OD), δ (ppm): 0.94 (m, 1H), 1.10 (m, 1H), 1.52-1.88 (m, 12H), 2.02 (m, 1H), 2.27 (s, 2H), 2.34 (m, 1H) ), 2.60 (m, 1H), 2.89 (s, 3H), 3.93 (m, 1H), 4.28 (s, 1H), 5.20 (m, 1H).

[0084] ESI-MS m / z: 316.2[M+H] + .

[0085] Elemental Analysis (C 19 H 29 N 3 O 5 S·H 2 O): Test value (%): C, 53.02; H, 7.35; N, 9.63 (calculated value (%): C, 53.13; H, 7.27; N, 9.78).

Example Embodiment

[0086] Example 2 Preparation of saxagliptin maleate (1:1)

[0087] Dissolve saxagliptin (3.50g, 11.1mmol) in 25ml ethyl acetate solution, stir, heat to 45°C, slowly add maleic acid (1.29g, 11.1mmol) in batches, and stir for 10 minutes after the addition. The temperature was lowered to room temperature, 25ml of cyclohexane was slowly added, after stirring for 1 hour, the temperature was lowered to 0°C and stirred overnight, filtered, and the filter cake was vacuum dried at 30°C to obtain 3.46g of white powdery solid with a yield of 72.2%.

[0088] 1 HNMR(CD 3 OD), δ (ppm): 0.95 (m, 1H), 1.12 (m, 1H), 1.54-1.88 (m, 12H), 2.01 (m, 1H), 2.27 (s, 2H), 2.34 (m, 1H) ), 2.61 (m, 1H), 3.93 (m, 1H), 4.28 (s, 1H), 5.19 (m, 1H), 6.28 (s, 2H).

[0089] ESI-MS m / z: 316.2[M+H] + .

[0090] Elemental Analysis (C 22 H 29 N 3 O 6 ): Test value (%): C, 61.09; H, 6.81; N, 9.48 (calculated value (%): C, 61.24; H, 6.77; N, 9.74).

Example Embodiment

[0091] Example 3 Preparation of saxagliptin maleate (2:1)

[0092] Dissolve saxagliptin (0.50g, 1.59mmol) in 5ml ethyl acetate solution, stir, heat to 45°C, slowly add maleic acid (0.09g, 0.78mmol) in batches, and stir for 10 minutes after the addition. The temperature was lowered to room temperature, 5ml of cyclohexane was slowly added, and after stirring for 1 hour, the temperature was lowered to 0°C and stirred overnight, filtered, and the filter cake was vacuum dried at 30°C to obtain 0.38 g of white powdery solid with a yield of 64.4%.

[0093] 1 HNMR(CD 3 OD), δ (ppm): 0.95 (m, 2H), 1.10 (m, 2H), 1.52-1.86 (m, 24H), 2.00 (m, 2H), 2.28 (s, 4H), 2.34 (m, 2H) ), 2.61 (m, 2H), 3.93 (m, 2H), 4.28 (s, 2H), 5.19 (m, 2H), 6.30 (s, 2H).

[0094] ESI-MS m / z: 316.2[M+H] + .

[0095] Elemental Analysis (C 40 H 54 N 6 O 8 ): Test value (%): C, 64.47; H, 7.35; N, 11.09 (calculated value (%): C, 64.32; H, 7.29; N, 11.25).

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Abstract

The invention provides medicinal salts of saxagliptin, and particularly relates to mesylate, meleate, malate, succinate and citrate as well as preparation methods of the medicinal salts. The medicinal salts have the advantage of good stability, and are not easy to degrade. Preparations with controllable quality and low cost, which are suitable for industrial production, are prepared from the medicinal salts and pharmaceutically acceptable carriers through a conventional preparation technology. The medicinal salts can be used for treating and/or preventing diabetes mellitus.

Description

1. Technical field [0001] The invention belongs to the field of pharmacy, and more specifically relates to a new pharmaceutically acceptable salt of dipeptidyl-peptidase-IV (DPP-IV) inhibitor saxagliptin, a preparation method thereof and an application in treating diabetes. 2. Background technology [0002] Diabetes is a multi-cause metabolic disease that seriously endangers health. About 5% of people in the world suffer from this chronic life-long disease. Disability and high mortality rate seriously affect the physical and mental health of patients. With the change of people's lifestyle and the acceleration of the aging process in our country, the prevalence of diabetes is rising rapidly. Its incidence has risen from 0.67% in 1979 to 5.6% in recent years, and the total number of patients exceeds 70 million. After cardiovascular and cerebrovascular diseases and tumors, another important chronic disease that seriously endangers people's health brings a heavy burden to indiv...

Claims

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Application Information

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IPC IPC(8): C07D209/52A61K31/403A61P3/10
Inventor 廖国超曲昌海谢寅省
Owner 廖国超
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