CRYSTALLINE Pl3 KINASE INHIBITORS

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-di hydroquinazolin-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.

1 .- 19 . (canceled) 
     
     
         20 . A method of treating a condition selected from COPD, asthma, cystic fibrosis, sarcoidosis, idiopathic pulmonary fibrosis, cachexia, and lung cancer, said method comprising administering to a subject an effective amount of a compound of formula (I) in crystalline form, 
       
         
           
           
               
               
           
         
         wherein the crystalline form is a hydrate or is anhydrous. 
       
     
     
         21 . The method of  claim 20 , wherein the condition is COPD. 
     
     
         22 . The method of  claim 21 , wherein the condition is chronic bronchitis and emphysema. 
     
     
         23 . The method of  claim 20 , wherein the condition is asthma. 
     
     
         24 . The method of  claim 23 , wherein the condition is paediatric asthma. 
     
     
         25 . The method of  claim 20 , wherein the condition is lung cancer. 
     
     
         26 . The method of  claim 25 , wherein the condition is non-small cell lung carcinoma. 
     
     
         27 . The method of  claim 20 , wherein the crystalline form is a hydrate. 
     
     
         28 . The method of  claim 20 , wherein the crystalline form has an X-ray powder diffraction pattern comprising one, two, three or four peaks selected from peaks at (±0.2) 17.6, 18.4, 22.5 and 24.2° 2θ±0.2°. 
     
     
         29 . The method of  claim 20 , wherein the crystalline form is formulated with one or more pharmaceutically acceptable diluents or carriers in a pharmaceutical composition. 
     
     
         30 . The method of  claim 29 , wherein the one or more pharmaceutically acceptable diluents or carriers comprise lactose. 
     
     
         31 . The method of  claim 30 , wherein the lactose is lactose monohydrate. 
     
     
         32 . The method of  claim 20 , wherein the crystalline form is further formulated with a stabilizing agent selected from the group consisting of metal salts of stearic acid and metal salts of stearyl fumarate in the pharmaceutical composition. 
     
     
         33 . The method of  claim 32 , wherein the stabilizing agent is magnesium stearate. 
     
     
         34 . The method of  claim 29 , wherein the crystalline form is micronized.