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Novel crystal of osimertinib mesylate

A technology of enamide methanesulfonate and crystal, which is applied in the field of crystal form of pharmaceutical compounds, can solve the problems affecting the dissolution and release of pharmaceutical compositions, which is not conducive to improving the bioavailability and curative effect of drugs, and low solubility.

Inactive Publication Date: 2020-06-19
北京赛思源生物医药技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, crystal form D, crystal form E, and crystal form F are all hydrates, and their solubility is not high; in addition, in the case of alternatives, compared with their salt crystal forms, the three crystal forms are not conducive to improving the biological properties of drugs. Utilization and curative effect
[0004] Different crystal forms of drugs reflect that there may be significant differences in solubility and stability, which will affect the dissolution and release of pharmaceutical compositions in vitro, and then affect the bioavailability of drugs in vivo

Method used

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  • Novel crystal of osimertinib mesylate
  • Novel crystal of osimertinib mesylate
  • Novel crystal of osimertinib mesylate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Take 15g N-{2-{[2-(dimethylamino)ethyl]methylamino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl ) pyrimidin-2-yl] amino}phenyl}prop-2-enamide methanesulfonate is dispersed in 150ml of dichloromethane, then add 300ml of N,N-dimethylformamide (abbreviation: DMF) and water Mixed solution (DMF:H 2 O=7:3, v / v), rise to 50°C to dissolve; cool to room temperature to crystallize, collect the solid by filtration, and obtain the N-{2-{[2-(dimethylamino)ethyl] Methylamino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl}prop-2-enamide The new crystal of sulfonate, the X-ray diffraction pattern of gained product is as figure 1 shown.

Embodiment 2

[0054] Take 50g N-{2-{[2-(dimethylamino)ethyl]methylamino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl ) pyrimidin-2-yl] amino}phenyl}prop-2-enamide methanesulfonate is dispersed in 500ml chloroform, then add 700ml N,N-dimethylformamide (abbreviation: DMF) and water Mixed solution (DMF:H 2 O=7:3, v / v), rise to 50°C to dissolve; cool to room temperature to crystallize, collect the solid by filtration, and obtain the N-{2-{[2-(dimethylamino)ethyl] Methylamino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl}prop-2-enamide Sulfonate new crystals, the X-ray diffraction pattern of the product obtained is basically consistent with Example 1.

Embodiment 3

[0055] The prescription and preparation technology of embodiment 3 tablets:

[0056] The above-mentioned N-{2-{[2-(dimethylamino)ethyl]methylamino}-4-methoxy-5-{[4-(1-methoxy) Base-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl}prop-2-enamide methanesulfonate new crystals were formulated into tablets containing 80 mg each, and the results are shown in Table 7.

[0057] Table 7 Prescription situation

[0058]

[0059] Preparation process: Contains N-{2-{[2-(dimethylamino)ethyl]methylamino}-4-methoxy-5-{[4-(1-methyl-1H-indole-3 -yl)pyrimidin-2-yl]amino}phenyl}prop-2-enamide methanesulfonate new crystal tablet is made by combining the above-mentioned excipient with N-{2-{[2-(dimethyl Amino)ethyl]methylamino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl}propan- The new crystals of 2-enamide methanesulfonate were mixed uniformly by the method of equal increase, and pressed into tablets. The reference crystals were mixed and tableted in the same way. See Ta...

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Abstract

The invention discloses a crystal of osimertinib mesylate. The crystal at least comprises the following characteristic peaks and relative strength as described in the specification in an X-ray powderdiffraction pattern determined by Cu-Ka rays. The obtained new crystal has good physical stability and chemical stability, the preparation method is simple and convenient, and commercial production isfacilitated. In addition, the invention also provides a preparation method and a pharmaceutical composition of the novel crystal.

Description

technical field [0001] The present invention relates to a crystal form of a pharmaceutical compound, in particular to said N-{2-{[2-(dimethylamino)ethyl]methylamino}-4-methoxy-5-{[4-(1- Methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl}prop-2-enamide methanesulfonate crystal form and its preparation method and pharmaceutical composition. Background technique [0002] Osimertinib mesylate (English name: Osimertinib Mesylate), code name: AZD9291, its chemical name is N-{2-{[2-(dimethylamino)ethyl]methylamino}-4-methoxy -5-{[4-(1-Methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl}prop-2-enamide methanesulfonate, developed by AstraZeneca The third-generation oral epidermal growth factor receptor inhibitor (EGFR-TKI), was approved by the U.S. Food and Drug Administration (FDA) on November 10, 2015 as a metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non- Therapeutic drug for small cell lung cancer (NSCLC), trade name: Tagrisso. The targeted preparation ...

Claims

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Application Information

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IPC IPC(8): C07D403/04A61P35/00A61K31/506
CPCA61P35/00C07B2200/13C07D403/04
Inventor 赵紫岭王守亮
Owner 北京赛思源生物医药技术有限公司