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Crystal form of bazedoxifene L-lactate

A bazedoxifene and lactate technology, applied in the field of medicinal chemistry, can solve problems such as poor stability, and achieve the effects of good stability, improved water solubility, and avoidance of crystallization

Inactive Publication Date: 2018-06-29
FUJIAN INST OF MICROBIOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The water solubility of crystal form D is similar to that of B. When the temperature is lower than 30°C, the solubility of B and D is close. When the temperature is higher than 30°C, the solubility of D is slightly higher than that of B; C is amorphous and has poor stability, so it is not suitable for preparation.

Method used

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  • Crystal form of bazedoxifene L-lactate
  • Crystal form of bazedoxifene L-lactate
  • Crystal form of bazedoxifene L-lactate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Dissolve 0.25g of L-lactic acid in 5mL of absolute ethanol at room temperature, heat in a 50ml reaction flask in a water bath at 60°C for 15min, add 1.00g of bazedoxifene and heat in a water bath at 60°C for another 20min, cool naturally, and refrigerate at 5°C After standing for 10 h, after crystallization, suction filtration and drying gave 0.79 g of white crystals with a yield of 66.4%. Characterize the crystal, its MP: 160-171°C, the X-ray powder diffraction pattern exhibited by this crystal form contains peaks with the following spacing values: 9.38 Å, 12.12 Å, 12.32 Å, 12.44 Å, 15.22 Å, 16.34 Å , 16.84 Å, 18.00 Å, 18.36 Å, 18.66 Å, 18.94 Å, 19.40 Å, 21.66 Å. IR: ν3396.32, ν2929.69, ν2961.31, ν2869.35, ν1611.51, ν1509.95, ν1246.44, ν1214.77, ν842.77, ν819.94. 1 HNMR: (500 MHz, CDCl 3 )δ 7.20-7.13 (m, 2H), 7.09-7.03 (d, 1H), 6.90-6.84 (m, 2H), 6.82-6.78 (m, 1H), 6.77-6.71 (m, 4H), 6.61-6.55 (dd, 1H), 5.12-5.08(s, 1H), 4.80-4.75(s, 2H), 4.30-4.25(s, 1H), 3.98-3.9...

Embodiment 2

[0024] Dissolve 0.25g of L-lactic acid in 5ml of isopropanol at room temperature, heat in a 50ml reaction flask in a water bath at 60°C for 15min, add 1.08g of bazedoxifene and heat in a water bath at 60°C for 20min, cool naturally, and refrigerate at 5°C After standing for 10 hours, the crystals were precipitated, filtered by suction, and dried to obtain 0.56 g of white crystals, with a yield of 47.1%. The characterization results are consistent with Example 1.

Embodiment 3

[0026] Dissolve 0.30 g of L-lactic acid in 8 ml of absolute ethanol at room temperature, heat in a 50 ml reaction flask in a water bath at 60°C for 15 minutes, add 1.01 g of bazedoxifene and heat in a water bath at 60°C for 20 minutes, cool naturally, and refrigerate at 5°C After standing for 10 hours, the crystals were precipitated, filtered by suction, and dried to obtain 0.59 g of white crystals, with a yield of 49.7%.

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Abstract

The invention discloses a crystal form of bazedoxifene L-lactate. An X-ray powder diffraction pattern displayed by the crystal form has peaks of the following spacing values: 21.66 angstroms, 19.40 angstroms, 18.94 angstroms, 18.66 angstroms, 18.36 angstroms, 18.00 angstroms, 16.84 angstroms, 16.34 angstroms, 15.22 angstroms, 12.44 angstroms, 12.32 angstroms, 12.12 angstroms, and 9.38 angstroms. According to the crystal form of the bazedoxifene L-lactate, disclosed by the invention, the water solubility is much higher than that of various crystal forms (A, B, C and D) of bazedoxifene acetate;crude drugs for preparing tablets do not need to be micronized and the crystal form has good stability; the risk of crystal form transformation does not occur in a medicine preparation process.

Description

technical field [0001] The present invention relates to the field of medicinal chemistry. More specifically, the present invention relates to 1-{4-[2-(cycloheximino-1-)ethoxy]benzyl}-2-(4-hydroxyphenyl)-3-methyl-1 H - Crystalline form of indole-5-ol lactate (bazedoxifene L-lactate). Background technique [0002] Bazedoxifene acetate (bazedoxifene), which belongs to a class of drugs called selective estrogen receptor modulators (SERMs), has been approved by the US Food and Drug Administration (FDA) for combined estrogen (CE) + bazedoxifene Treat menopausal-related vasomotor symptoms and delay bone aging, reduce the risk of vertebral fractures in postmenopausal women, and prevent osteoporosis. In recent years, the curative effect of bazedoxifene acetate has gradually expanded to blood lipids, cardiovascular, breast, female reproductive system and other fields. According to literature reports, bazedoxifene acetate has crystal forms A, B, D and amorphous C. Form A is a metas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/12
CPCC07B2200/13C07D209/12
Inventor 林燕琴赵学清成佳威陈忠郑向阳范琳沈博惠董媛侦
Owner FUJIAN INST OF MICROBIOLOGY
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