Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta

Abstract

Compounds that inhibit PI3Kδ activity, including compounds that selectively inhibit PI3Kδ activity, are disclosed. Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3Kδ) activity, and methods of treating diseases, such as disorders of immunity and inflammation in which PI3Kδ plays a role in leukocyte function, using the compounds also are disclosed.

1 - 26 . (canceled) 
     
     
         27 . A compound, wherein the compound is 
       
         
           
           
               
               
           
         
         3-(2,6-difluoro-phenyl)-2-[1-(9H-purin-6-ylamino)-ethyl]-3H-quinazolin-4-one; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         28 . The compound according to  claim 27  wherein 3-(2,6-difluoro-phenyl)-2-[1-(9H-purin-6-ylamino)-ethyl]-3H-quinazolin-4-one or a pharmaceutically acceptable salt thereof is the S-enantiomer. 
     
     
         29 . A pharmaceutical composition comprising a compound according to  claim 27  and at least one pharmaceutically acceptable excipient. 
     
     
         30 . The pharmaceutical composition of  claim 29  wherein the compound 3-(2,6-difluoro-phenyl)-2-[1-(9H-purin-6-ylamino)-ethyl]-3H-quinazolin-4-one or a pharmaceutically acceptable salt thereof is the S-enantiomer. 
     
     
         31 . A method of treating a condition in a subject, wherein the condition is cancer, comprising administering to a subject in need thereof an effective amount of a compound, wherein the compound is 3-(2,6-difluoro-phenyl)-2-[1-(9H-purin-6-ylamino)-ethyl]-3H-quinazolin-4-one or a pharmaceutically acceptable salt thereof. 
     
     
         32 . The method according to  claim 31 , wherein the cancer is leukemia, lymphoma or multiple myeloma. 
     
     
         33 . The method according to  claim 31 , wherein the cancer is selected from the group consisting of Burkitt's lymphoma, Hodgkins' lymphoma, non-Hodgkins lymphoma, lymphocytic lymphoma, multiple myeloma, lymphocytic leukemia, and chronic myeloid leukemia. 
     
     
         34 . The method of  claim 31 , wherein the compound 3-(2,6-difluoro-phenyl)-2-[1-(9H-purin-6-ylamino)-ethyl]-3H-quinazolin-4-one or the pharmaceutically acceptable salt thereof is the S-enantiomer. 
     
     
         35 . The method of  claim 32 , wherein the compound 3-(2,6-difluoro-phenyl)-2-[1-(9H-purin-6-ylamino)-ethyl]-3H-quinazolin-4-one or the pharmaceutically acceptable salt thereof is the S-enantiomer. 
     
     
         36 . The method of  claim 33 , wherein the compound 3-(2,6-difluoro-phenyl)-2-[1-(9H-purin-6-ylamino)-ethyl]-3H-quinazolin-4-one or the pharmaceutically acceptable salt thereof is the S-enantiomer. 
     
     
         37 . A method of inhibiting a growth or a proliferation of cancer cells of hematopoietic origin comprising contacting the cancer cells with an effective amount of a compound according to  claim 27 . 
     
     
         38 . The method of  claim 37  where the cancer cells are related to or derived from B lymphocytes or B lymphocyte progenitors.