Inhibitors of human phosphatidylinositol 3-kinase delta

Abstract

Methods of inhibiting phosphotidylinositol 3-kinase delta isoform (PI3Kδ) activity, and methods of treating disease, such as disorders of immunity and inflammation, in which PI3Kδ plays a role in leukocyte function are disclosed. Preferably, the methods employ active agents that selectively inhibit PI3Kδ, while not significantly inhibiting activity of other PI3K isoforms. Compounds are provided that inhibit PI3Kδ activity, including compounds that selectively inhibit PI3Kδ activity. Methods of using PI3Kδ inhibitory compounds to inhibit cancer cell growth or proliferation are also provided. Accordingly, the invention provides methods of using PI3Kδ inhibitory compounds to inhibit PI3Kδ-mediated processes in vitro and in vivo.

1 . A method of disrupting leukocyte function comprising contacting leukocytes with a compound, or a pharmaceutically acceptable salt or solvate thereof, selected from the group consisting of: 
       
         
           
           
               
               
           
         
         in an amount sufficient to inhibit phosphatidylinositol 3-kinase delta activity in said leukocytes. 
       
     
     
         2 . (canceled) 
     
     
         3 . A method of inhibiting kinase activity of a phosphatidylinositol 3-kinase delta polypeptide comprising contacting the polypeptide with a compound, or a pharmaceutically acceptable salt or solvate thereof, selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         4 - 15 . (canceled) 
     
     
         16 . The method of  claim 1 , wherein the compound, or a pharmaceutically acceptable salt or solvate thereof, is: 
       
         
           
           
               
               
           
         
       
     
     
         17 . The method of  claim 1 , wherein the compound, or a pharmaceutically acceptable salt or solvate thereof, is: 
       
         
           
           
               
               
           
         
       
     
     
         18 . The method of  claim 3 , wherein the compound, or a pharmaceutically 
       acceptable salt or solvate thereof, is: 
       
         
           
           
               
               
           
         
       
     
     
         19 . The method of  claim 3 , wherein the compound, or a pharmaceutically acceptable salt or solvate thereof, is: