Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Crystalline form of androgen receptor inhibitor and preparation method thereof

A technology of crystallization and interplanar spacing, applied in organic chemistry, drug combination, antineoplastic drugs, etc., can solve problems such as easy agglomeration, poor product stability, difficult filtration, etc., and achieve repeatable and controllable production process and stable crystal form Good performance and stable production process

Inactive Publication Date: 2017-03-22
JIANGSU HENGRUI MEDICINE CO LTD
View PDF1 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Generally speaking, amorphous drug products have no regular crystal structure and often have other defects, such as poor product stability, fine crystallization, difficult filtration, easy agglomeration, poor fluidity, etc.

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
  • Crystalline form of androgen receptor inhibitor and preparation method thereof
  • Crystalline form of androgen receptor inhibitor and preparation method thereof
  • Crystalline form of androgen receptor inhibitor and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Take (1.0g, 2.09mmol) the compound represented by formula (I) (prepared according to the method provided by WO2014036897A1) into a 25ml single-necked bottle, add 5.0ml of methanol, heat to reflux to dissolve, continue to reflux for 10min, cool, stir and crystallize, pump Filter and dry to obtain 516mg of solid, the yield is 51.6%. The X-ray diffraction spectrum figure of this crystalline sample is shown in figure 1 . The crystallization at about 4.63 (19.06), 7.37 (11.99), 9.25 (9.55), 10.91 (8.11), 11.48 (7.70), 12.40 (7.13), 13.05 (6.78), 13.73 (6.45), 15.03 (5.89), 16.04 (5.52), 16.96(5.22), 17.87(4.96), 19.03(4.66), 19.45(4.56), 20.59(4.31), 21.87(4.06), 22.50(3.95), 23.11(3.85), 23.53(3.78), 23.96 (3.71), 25.43(3.50), 27.00(3.30), 27.60(3.23), 29.77(3.00) have characteristic peaks. See the DSC spectrum figure 2 , with a sharp melting endothermic peak at 119°C, this crystal form is defined as II crystal form.

Embodiment 2

[0037]Take (1.0g, 2.09mmol) the compound shown in formula (I) (prepared according to Example 1) in a 25ml single-necked bottle, add 5.0ml of ethanol, heat to reflux to dissolve, continue to reflux for 10min, cool, stir and crystallize, and suction filter , and dried to obtain 633 mg of solid, with a yield of 63.3%. Its X-diffraction and DSC patterns are researched and compared, and it is determined that the product is in the II crystal form.

Embodiment 3

[0039] Repeat all the operations of WO2014036897A1 Example 44, (R)-4-(3-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzene Base)-4,4-dimethyl-5-keto-2-thioimidazolin-1-yl)-2-(trifluoromethyl)benzonitrile (2.2g, 4.20mmol) was dissolved in 100mL acetic acid, Add 50mL of water, raise the temperature to 70°C and stir for 1h. The reaction solution is concentrated under reduced pressure to remove acetic acid, 100mL of water and 100mL of ethyl acetate are added, and the layers are separated. The organic phase is washed with saturated sodium bicarbonate solution and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and purified by silica gel chromatography to obtain crystals of Compound I (1.1 g, 55.0%). The X-ray diffraction and DSC spectra of the crystalline sample were studied and compared, and it was confirmed that it was not the II crystal form, and it was defined as the III crystal form here.

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

No PUM Login to View More

Abstract

The invention relates to a crystalline form of an androgen receptor inhibitor and a preparation method thereof, in particular to a type II crystal of (S)-4-(3-(4-(2,3-hydroxypropoxy)phenyl)-4,4-dimethyl-5-carbonyl-2-trifluoromethyl-1-yl)-2-(trifluoromethyl)benzonitrile (a compound shown as a formula (I)) and a preparation method thereof. The method comprises the following steps: 1) adding the compound shown as the formula (I) of any crystalline form or an amorphous form into a proper amount of organic solvent, and crystalizing after dissolved clarification, wherein the solvent is selected from methanol or ethanol; 2) filtering the crystal, washing and drying. The type II crystal of the compound shown as the formula (II) has the advantages of excellent chemical stability and crystalline form stability, and the used crystal solvent has low toxicity and low residue, and can be better applied to clinical therapy. The formula is shown in the description.

Description

technical field [0001] The invention relates to a crystalline form of an androgen receptor inhibitor and a preparation method thereof. Specifically the present invention relates to (S)-4-(3-(4-(2,3-dihydroxypropoxy)phenyl)-4,4-dimethyl-5-carbonyl-2-thioimidazoline Novel crystalline forms of -1-yl)-2-(trifluoromethyl)benzonitrile and processes for their preparation. Background technique [0002] Prostate cancer (PCa) is a malignant tumor occurring in male prostate tissue, which is the result of abnormal and disordered growth of prostate acinar cells. The differentiation and growth of normal prostate epithelial cells and the development of prostate cancer depend on androgen, and androgen is mainly synthesized in the testis, accounting for about 80-90%. Synthetic androgen enters the cell and binds to the androgen receptor (AR), causing heat shock protein (HSP) to dissociate from AR and allowing AR to enter the nucleus, activating multiple downstream genes, including prostate-...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D233/86A61K31/4166A61P35/00
Inventor 武乖利张全良边林卢韵
Owner JIANGSU HENGRUI MEDICINE CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com