2-((4-amino-3-(3-fluoro-5-hydroxyphenyl)-1h-pyrazolo[3,4-d]pyrimidin-1 -yl)methyl)-3-(2-(trifluoro-met hyl)benzyl)quinazolin-4(3h)-one derivatives and their use as phosphoinositide 3-kinase inhibitors

Abstract

The present invention relates inter alia to a compound of formula (I) and to compositions comprising the same and to the use of the compounds and to compositions of the compounds in treatment, for example in the treatment of inflammatory diseases, in particular respiratory inflammatory disease. The invention also extends to methods of making the said compounds.

1 - 17 . (canceled) 
     
     
         18 . A dry powder pharmaceutical formulation for inhalation comprising a compound of formula (I): 
       
         
           
           
               
               
           
         
         that is 2-((4-Amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-5-(3-(2-(2-methoxyethoxy)ethoxy)prop-1-yn-1- yl)-3-(2-(trifluoromethyl)benzyl)quinazolin-4(3H)-one, or a pharmaceutically acceptable salt thereof, including all stereoisomers, tautomers and isotopic derivatives thereof; and 
         lactose. 
       
     
     
         19 . A dry powder pharmaceutical formulation acccording to  claim 18  wherein the compound of formula (I) is in its free base form. 
     
     
         20 . A dry powder pharmaceutical formulation acccording to  claim 18  wherein the compound of formula (I) is micronized. 
     
     
         21 . A dry powder pharmaceutical formulation acccording to  claim 18  wherein compound of formula (I) is in finely divided form and has a D 50  of 1-5 μm. 
     
     
         22 . A dry powder pharmaceutical formulation acccording to  claim 18  wherein the lactose is alpha-lactose monohydrate. 
     
     
         23 . A dry powder pharmaceutical formulation acccording to  claim 18  further comprising magnesium stearate. 
     
     
         24 . A dry powder pharmaceutical formulation acccording to  claim 18  further comprising a second or further active ingredient selected from corticosteroids, beta agonists, xanthenes, muscarinic antagonists and p38 MAP kinase inhibitors. 
     
     
         25 . A method of treating an inflammatory condition of the lungs which comprises administering to a subject in need thereof an effective amount of a dry powder pharmaceutical formulation acccording to  claim 18 . 
     
     
         26 . A method according to  claim 25  wherein the inflammatory condition of the lungs is selected from chronic obstructive pulmonary disease and asthma. 
     
     
         27 . A method according to  claim 25  wherein the compound of formula (I) is in its free base form. 
     
     
         28 . A method according to  claim 25  wherein the lactose is alpha-lactose monohydrate. 
     
     
         29 . A method according to  claim 25  further comprising magnesium stearate. 
     
     
         30 . A method according to  claim 25  further comprising a second or further active ingredient selected from corticosteroids, beta agonists, xanthenes, muscarinic antagonists and p38 MAP kinase inhibitors. 
     
     
         31 . An inhalation device comprising the dry powder pharmaceutical formulation according to  claim 18 . 
     
     
         32 . An inhalation device acccording to  claim 31  wherein the compound of formula (I) is in its free base form. 
     
     
         33 . An inhalation device acccording to  claim 31  wherein the compound of formula (I) is micronized. 
     
     
         34 . An inhalation device acccording to  claim 31  wherein compound of formula (I) is in finely divided form and has a D 50  of 1-5 μm. 
     
     
         35 . An inhalation device acccording to  claim 31  wherein the lactose is alpha-lactose monohydrate. 
     
     
         36 . An inhalation device acccording to  claim 31  further comprising magnesium stearate. 
     
     
         37 . An inhalation device acccording to  claim 31  further comprising a second or further active ingredient selected from corticosteroids, beta agonists, xanthenes, muscarinic antagonists and p38 MAP kinase inhibitors.