Check patentability & draft patents in minutes with Patsnap Eureka AI!

Solid state form of enzalutamide, preparation method and use thereof

A technology of enzalutamide and amorphous state, which is applied in the field of medicinal chemical crystallization to achieve the effects of high solubility, good storage stability and low hygroscopicity

Active Publication Date: 2017-04-26
倪云
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Therefore, there are certain defects in the known solid-state forms of enzalutamide, and it is necessary to develop new solid-state forms of enzalutamide with more superior properties

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Solid state form of enzalutamide, preparation method and use thereof
  • Solid state form of enzalutamide, preparation method and use thereof
  • Solid state form of enzalutamide, preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] Enzalutamide was synthesized according to the synthetic method of Patent Document US7709517 Example 56, specifically:

[0113] N-methyl-2-fluoro-4-(1,1-dimethyl-cyanomethyl)aminobenzamide (3g, 13mmol) and 4-isothiocyanato-2-trifluoromethylbenzene Formonitrile (5.8g, 26mmol) was added to 100mL DMF, heated to 100°C for 11 hours under microwave irradiation, cooled to 50°C, added 2000mL of methanol and 500mL of 1N hydrochloric acid, then heated to reflux for 1.5 hours, cooled to room temperature, poured into In 5000mL of cold water, extracted with 5000mL of ethyl acetate, the organic phase was dried by adding magnesium sulfate, filtered, the filtrate was concentrated, and the obtained residue was subjected to column chromatography (developing solvent: methylene chloride: acetone = 95: 5) to obtain 1.5 g of Enza Lutamine is a white solid, molar yield: 25%.

[0114] 1 H-NMR (300MHz, DMSO-d6): 1.61(s, 6H), 3.07(d, 3H, J=4.1Hz), 6.71(m, 1H), 7.15(dd, 1H, J=11.7Hz), 7.24 (dd,...

Embodiment 2

[0121] Take 100 mg of enzalutamide prepared in Example 1 and put it into a 30 mL single-necked flask, add 10 mL of dichloromethane, ultrasonicate at 40 KHz for 30 seconds to ensure that it is completely dissolved, then place it on a rotary evaporator, spin dry at 40 ° C, and remove the solvent The rate is about 15 ml / min, resulting in amorphous enzalutamide.

[0122] XRPD patterns such as Image 6 As shown, it appears to be amorphous without any sharp diffraction peaks. .

[0123] DSC spectrum such as Figure 7 As shown, it is amorphous, with a glass transition temperature of 46°C and a crystal transition at 137°C. After detection, crystal form I was formed after crystallization.

[0124] TGA spectrum such as Figure 8 shown.

[0125] IR spectrum such as Figure 9 shown.

[0126] Raman spectrum such as Figure 10 shown.

Embodiment 3

[0128]Take 10 mg of enzalutamide prepared in Example 1 and put it into a 30 mL single-necked flask, add 10 mL of dichloromethane, ultrasonicate at 40KHz for 20 seconds to ensure that it is completely dissolved, then place it on a rotary evaporator, spin dry at 40°C, and remove the solvent The rate is about 5 ml / min, resulting in amorphous enzalutamide.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Temperatureaaaaaaaaaa
Melting pointaaaaaaaaaa
Login to View More

Abstract

The present invention relates to new solid state forms of enzalutamide having one or more improved properties compared to the prior art, such as good solubility, dissolution rate, good stability properties, favorable processing and handling characteristics, suitable for solid dosage forms, etc. The present invention also relates to the preparation method of the new solid form of enzalutamide, its pharmaceutical composition and its use in the preparation of medicines for treating metastatic castration-resistant prostate cancer and other diseases.

Description

technical field [0001] The invention relates to the technical field of medicinal chemical crystallization. In particular, it relates to a new solid state form of enzalutamide, as well as processes for the preparation of said new solid state form, pharmaceutical compositions and uses thereof. Background technique [0002] The chemical name of enzalutamide is 4-{3-[4-cyano-3-(trifluoromethyl)phenyl]5,5-dimethyl-4-oxo-2-thioimidazolidine- 1-yl}-2fluoro-N-methylbenzamide, the English name is Enzalutamide, also known as MDV-3100, molecular formula C 21 h 16 f 4 N 4 o 2 S, the chemical structural formula is as follows: [0003] [0004] Enzalutamide is an androgen receptor antagonist developed jointly by Medivation and Astellas Pharma. On August 31, 2012, it was approved by the US Food and Drug Administration (FDA) for the treatment of advanced (metastatic) castration-resistant prostate cancer that has spread or recurred, even if the patient has previously received docet...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K31/4166A61K9/00A61K9/20A61K9/48A61K9/08A61K9/10A61P35/00
CPCC07B2200/13C07D233/86A61P35/00
Inventor 沈涛盛晓霞盛晓红
Owner 倪云
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com