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

Idelalisib crystal form A and preparation method thereof

A crystal form and powder technology, applied in the field of medicinal chemistry, can solve the problems of unfavorable absorption, poor solubility, poor solubility, etc., and achieve the effects of good solubility, short production cycle and stable quality

Active Publication Date: 2017-04-19
SHANGHAI ACEBRIGHT PHARMA CO LTD
View PDF6 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In the WO2005113556 international patent application, Idelalisib and its preparation method were disclosed. Later studies showed that the solvate of Idelalisib with 0.4 molecules of ethanol (referred to as crystal form I in the WO2015014315 international patent application) was obtained by using the preparation method. The following defects: the weight change is about 0.95% in the range of 20-80% relative humidity, has certain hygroscopicity, and poor stability (see the background technology part in WO2015014315 for details)
And studies have shown that: Idelalisib's crystal form I, crystal form IV, crystal form V, crystal form VI, crystal form VII, crystal form VIII, crystal form IX and crystal form X are all easy to transform into crystal form II; crystal form I and The other crystal forms mentioned in this invention (including crystal form VI and crystal form IX) all transform into crystal form III during the competitive reaction; while crystal form II and crystal form III are both anhydrous substances with poor solubility, which is not conducive to human body absorb
[0006] It can be seen from the above-mentioned prior art that there are various crystal forms of Idelalisib, and some crystal forms have good stability but poor solubility, while some crystal forms have good solubility but poor stability. Crystal form with good stability, suitable for industrial preparation of preparations and meeting various performance requirements of preparations

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
  • Idelalisib crystal form A and preparation method thereof
  • Idelalisib crystal form A and preparation method thereof
  • Idelalisib crystal form A and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Embodiment 1: Preparation of Idelalisib Form A

Embodiment 11

[0061] At 30°C, dissolve 1g of Idelalisib raw material (regardless of its form) in 30mL of acetone to obtain a clear solution; at 30°C, slowly add anti-solvent water to the above solution until initial turbidity (about 100mL) ; Insulated and stirred to crystallize for 2 hours, cooled to room temperature; filtered and dried to obtain 0.85 g of crystals; the yield was 85%, and the HPLC purity was 99.58%.

[0062] figure 1 is the XRD spectrum of the obtained crystal, by figure 1 It can be seen that under powder X-ray diffraction, the crystal has Characteristic peaks with relative intensities greater than 50%; 8.5±0.2°, 10.7±0.2°, 13.6±0.2°, 14.6±0.2°, 15.0±0.2°, 15.8±0.2°, 16.8±0.2°, 17.1±0.2° in 2θ °, 19.9±0.2°, 20.2±0.2°, 22.9±0.2°, 23.6±0.2°, 23.7±0.2°, 24.3±0.2°, 26.3±0.2° have characteristic peaks with relative intensities greater than 30%.

[0063] figure 2 For the DSC spectrum of the obtained crystal, by figure 2 It can be seen that the crystal has a solvent endot...

Embodiment 12

[0067] At 65°C, dissolve 1g of Idelalisib raw material (regardless of its form) in 20mL of acetonitrile to obtain a clear solution; at 50°C, slowly add anti-solvent water to the above solution until initial turbidity (about 110mL) ; Insulated and stirred to crystallize for 2 hours, cooled to room temperature; filtered and dried to obtain 0.90 g of crystals; the yield was 90%, and the HPLC purity was 99.70%.

[0068] After determination and analysis, the obtained crystals have figure 1 Shown XRD spectrogram feature and figure 2 The DSC spectral features shown and image 3 The characteristics of the TGA spectrum shown in this example illustrate that the crystal obtained in this example is also Idelalisib crystal form A of the present invention.

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
concentrationaaaaaaaaaa
concentrationaaaaaaaaaa
wavelengthaaaaaaaaaa
Login to View More

Abstract

The present invention discloses an Idelalisib crystal form A and a preparation method thereof. According to the present invention, the Idelalisib crystal form A is a single molecule hydrate, and has the characteristic peak having a relative intensity of more than 50% at a 2[theta] angle of 8.5+ / -0.2 DEG, 10.7+ / -0.2 DEG, 13.6+ / -0.2 DEG, 15.8+ / -0.2 DEG, 20.2+ / -0.2 DEG, 23.7+ / -0.2 DEG and 24.3+ / -0.2 DEG under powder X-ray diffraction; the preparation method comprises: dissolving an Idelalisib raw material in a suitable solvent to obtain a clarified solution, adding an antisolvent to the obtained solution in a dropwise manner until the turbidity initially appears, carrying out thermal insulation stirring to crystallize, cooling to a room temperature, filtering, and drying to prepare the Idelalisib crystal form A; and the Idelalisib crystal form A has advantages of excellent solubility, excellent thermal stability, excellent high-humidity stability and excellent pressure stability, and can be used as the pharmaceutically active ingredient of the preparation.

Description

technical field [0001] The invention relates to an Idelalisib crystal form A and a preparation method thereof, belonging to the technical field of medicinal chemistry. Background technique [0002] Idelalisib, its chemical name is: (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one, commercial Name: Zydelig, molecular formula: C 22 h 18 FN 7 O, molecular weight: 415.42, CAS number: 870281-82-6, chemical structural formula: The drug is a phosphatidylinositol 3-kinase δ inhibitor (referred to as PI3Kδ inhibitor) developed by Gilead, which is used for chronic lymphocytic leukemia, indolent non-Hodgkin's lymphoma, mantle cell lymphoma, diffuse large The treatment of B-cell lymphoma, Hodgkin's lymphoma, multiple myeloma, acute myeloid leukemia and hematological malignancies was approved by the FDA on July 23, 2014. The dosage form is tablet (100mg and 150mg). [0003] In the WO2005113556 international patent application, Idelalisib and its preparati...

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): C07D473/34
CPCC07B2200/13C07D473/34
Inventor 安晓霞申淑匣
Owner SHANGHAI ACEBRIGHT PHARMA 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