Crystalline 6-(2-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-D]pyrimidin-1-yl)methyl)-3-(2-chlorobenzyl)-4-0X0-3,4-dihydroquinazolin-5-yl)-N,N-bis(2-methoxyethyl)hex-5-ynamide

Patent metadata

Field	Value
Publication number	US-9642799-B2
Application number	US-201314381289-A
Country	US
Kind code	B2
Filing date	Mar 13, 2013
Priority date	Mar 13, 2012
Publication date	May 9, 2017
Grant date	May 9, 2017

Abstract

There is provided inter alia 6-(2-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl) methyl)-3-(2-chlorobenzyl)-4-oxo-3,4-dihydroquinazolin-5-yl)-N,N-bis(2-methoxyethyl)hex-5-ynamide in the form of a solid crystalline hydrate and in solid crystalline anhydrous form. There are also provided dry powder pharmaceutical compositions for inhalation containing such solid crystalline forms.

First claim

The invention claimed is:

1. A crystalline form of a compound of formula (I)

wherein the crystalline form is a hydrate or is anhydrous.

2. The crystalline form of claim 1 , having an X-ray powder diffraction pattern comprising one, two, three or four peaks selected from peaks at 17.6°, 18.4°, 22.5° and 24.2° 2θ±0.2°.

3. The crystalline form of claim 1 , wherein the crystalline form is a hydrate.

4. The crystalline form of claim 3 , having an X-ray powder diffraction pattern comprising one, two, three, four, five, six or seven peaks selected from peaks at (±0.2) 9.6, 13.3, 13.9, 17.0, 18.9, 20.3, and 23.1 2 θ±0.2°.

5. The crystalline form of claim 1 , wherein the crystalline form is anhydrous.

6. The crystalline form of claim 5 , having an X-ray powder diffraction pattern comprising one, two, three, four, five, six or seven peaks selected from peaks at (±0.2°) 5.6, 7.9, 11.2, 12.3, 15.6, 17.6, 18.4, 21.4, and 24.2 ° 2θ(± 0 . 2 °).

7. A pharmaceutical composition comprising the crystalline form of claim 1 in admixture with one or more pharmaceutically acceptable diluents or carriers.

8. The pharmaceutical composition of claim 7 , further comprising a stabilizing agent selected from the group consisting of metal salts of stearic acid and metal salts of stearyl fumarate.

9. The pharmaceutical composition of claim 8 , wherein the stabilizing agent is magnesium stearate.

10. The pharmaceutical composition of claim 7 , wherein the pharmaceutically acceptable diluent or carrier comprises lactose.

11. The pharmaceutical composition of claim 7 , wherein the crystalline form is micronized.

12. An inhalation device comprising one or more doses of the pharmaceutical composition of claim 7 .

13. A method of inhibiting phosphoinositide-3 kinase activity in a subject comprising administering to the subject an effective amount of the crystalline form of claim 1 or the pharmaceutical composition of claim 7 .

14. A process for the preparation of the crystalline form of claim 3 comprising the step of crystallizing a compound of formula (I) from dichloromethane optionally in mixture with methanol.

15. A process for the preparation of the crystalline form of claim 5 comprising the step of crystallizing a compound of formula (I) from anhydrous 1-propanol.

16. The process of claim 15 , wherein the crystallization step comprises cooling from an elevated temperature.

17. A crystalline form of a compound of formula (I)

having the X-ray powder diffraction pattern as shown in FIG. 1 .

18. A crystalline form of a compound of formula (I)

having the X-ray powder diffraction pattern as shown in FIG. 2 .

Assignees

• Respivert Ltd
• Respivert Ltd

Inventors

• Broeckx Rudy Laurent Maria
• Filliers Walter Ferdinand Maria
• Nieste Patrick Hubert J
• Copmans Alex Herman
• Vanhoutte Filip Marcel
• Leys Carina

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title