Oxazolidin-2-one-pyrimidine derivatives and the use thereof as phosphatidylinositol-3-kinase inhibitors

Abstract

The present invention relates to oxazolidin-2-one substituted pyrimidine compounds that act as PI3K (phosphatidylinositol-3-kinase) inhibitors, as well as pharmaceutical compositions thereof, methods for their manufacture and uses for the treatment of conditions, diseases and disorders dependent on PI3K.

What is claimed is: 
     
         1 . A compound of the formula (I) and/or a pharmaceutically acceptable salt and/or solvate thereof, 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  is methyl, ethyl or hydroxymethyl; 
         R 2  is phenyl, which is unsubstituted or substituted in meta and/or para positions by 1 or 2 substituents independently selected from D, F or methoxy for the meta position and from D, F, methoxy, C 1 -C 5 -alkoxy, hydroxy-C 2 -C 4 -alkoxy or C 1 -C 2 -alkoxy-C 2 -C 4 -alkoxy for the para position, or 
         pyridyl, which is unsubstituted or substituted in meta and/or para positions by 1 or 2 substituents independently selected from D, F or methoxy for the meta position and from D, F, methoxy, C 1 -C 5 -alkoxy, hydroxy-C 2 -C 4 -alkoxy or C 1 -C 2 -alkoxy-C 2 -C 4 -alkoxy for the para position, or 
         a 5 membered monocyclic heteroaryl, containing 2 to 3 heteroatoms selected from N, O or S, which is unsubstituted or substituted by 1 to 2 substituents independently selected from D or F; and 
         R 3  is H or methyl. 
       
     
     
         2 . A compound according to  claim 1 , of formula (Ib) 
       
         
           
           
               
               
           
         
       
     
     
         3 . A compound according to  claim 1 , wherein
 R 2  is phenyl, which is unsubstituted or substituted in meta and/or para positions by 1 or 2 substituents independently selected from D, F or methoxy for the meta position and from D, F, methoxy, C 1 -C 5 -alkoxy, hydroxy-C 2 -C 4 -alkoxy or C 1 -C 2 -alkoxy-C 2 -C 4 -alkoxy for the para position.   
     
     
         4 . A compound according to  claim 1 , wherein
 R 2  is pyridyl, which is unsubstituted or substituted in meta and/or para positions by 1 or 2 substituents independently selected from D, F or methoxy for the meta position and from D, F, methoxy, C 1 -C 5 -alkoxy, hydroxy-C 2 -C 4 -alkoxy or C 1 -C 2 -alkoxy-C 2 -C 4 -alkoxy for the para position.   
     
     
         5 . A compound according to  claim 1 , wherein
 R 2  is a 5 membered monocyclic heteroaryl, containing 2 to 3 heteroatoms selected from N, O or S, which is unsubstituted or substituted by 1 to 2 substituents independently selected from D or F.   
     
     
         6 . A compound according to  claim 1 , wherein
 R 1  is methyl.   
     
     
         7 . A compound according to  claim 1 , wherein
 R 1  is ethyl.   
     
     
         8 . A compound according to  claim 1 , wherein
 R 1  is hydroxymethyl.   
     
     
         9 . A compound, or a pharmaceutically acceptable salt thereof, according to  claim 1  which is selected from the examples described herein. 
     
     
         10 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers. 
     
     
         11 . A combination comprising a therapeutically effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, and one or more therapeutically active co-agents. 
     
     
         12 . A method of treating a subject comprising administering to the subject a therapeutically effective amount of the compound, or a pharmaceutically acceptable salt thereof, according to  claim 1 . 
     
     
         13 . The method of treating keloids, actinic keratosis or Cutaneous squamous cell carcinoma in a subject comprising administering to the subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof according to  claim 1 .