Benzoxazole Kinase Inhibitors and Methods of Use

Abstract

The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating certain protein kinases such as mTor, tyrosine kinases, and/or lipid kinases such as PI3 kinase. Also provided in the present invention are methods of using these compositions to modulate activities of one or more of these kinases, especially for therapeutic applications.

1 .- 30 . (canceled) 
     
     
         31 . A method for treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         X 1  is N; 
         X 2  is N; 
         E 2  is —H or —CH 3 ; 
         R 1  is -L-C 1-10 alkyl, -L-C 3-8 cycloalkyl, or -L-heterocyclyl, each of which is optionally substituted by R 3 ; 
         L is a bond; 
         R 3  is OR 31 , —NR 31 R 32 , —C(O)R 31 , —C(O)OR 31 , or heterocyclyl; 
         W 2  is —NH— or —N(H)C(O)—; 
         k is 1; 
         R 2  is hydrogen or C 1-10 alkyl; and 
         R 31  and R 32  are independently H or C 1-10 alkyl. 
       
     
     
         32 . The method of  claim 31 , wherein R 1  is -L-C 1-10 alkyl. 
     
     
         33 . The method of  claim 31 , wherein W 2  is —NH—. 
     
     
         34 . The method of  claim 31 , wherein R 2  is H. 
     
     
         35 . The method of  claim 31 , wherein the compound is 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         36 . The method of  claim 31 , wherein the cancer is renal cancer. 
     
     
         37 . The method of  claim 36 , wherein the renal cancer is renal cell carcinoma. 
     
     
         38 . The method of  claim 31 , wherein the cancer is gynecological cancer. 
     
     
         39 . The method of  claim 31 , wherein the cancer is breast cancer. 
     
     
         40 . The method of  claim 35 , wherein the cancer is renal cancer. 
     
     
         41 . The method of  claim 40 , wherein the renal cancer is renal cell carcinoma. 
     
     
         42 . The method of  claim 35 , wherein the cancer is gynecological cancer. 
     
     
         43 . The method of  claim 35 , wherein the cancer is breast cancer.