Chemical entities and therapeutic uses thereof

Abstract

Certain chemical entities that modulate PI3 kinase activity, and chemical entities, pharmaceutical compositions, and methods of treatments of diseases and conditions associated with PB kinase activity are described.

1 . A compound of Formula I 
       
         
           
           
               
               
           
         
         and pharmaceutically acceptable salts thereof, wherein 
         W 1  is CR 6 , CHR 6 , NR 6 , or N; 
         W 2  is CR 7 , N, or NR 7 ; 
         W 3  is CR 2 , CHR 2 , N, or NR 2 ; 
         W 4  is CR 11  or N; 
         W 5  is C(O), CHR 3 , or CR 3 ; and no more than two adjacent ring atoms are N or NR 7 ; 
         R 1  is hydrogen, amino, alkyl, alkoxy, aryl, heteroaryl, or cyano; 
         R 2  is hydrogen, halo, amino, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl or X; 
         R 3  is hydrogen, amino, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or X; 
         R 4  is hydrogen and R 5  is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkoxycarbonyl, or acyl; or R 4  and R 5 , taken together with any intervening atoms, form a heteroaryl ring; 
         R 6  is hydrogen, halo, amino, alkoxy, lower alkyl, cyano, or X when W 1  is CR 6  or CHR 6 ; or R 6  is hydrogen or lower alkyl when W 1  is NR 6 ; 
         R 7  is hydrogen, halo, lower alkyl, or aryl when W 2  is CR 7 ; or R 7  is hydrogen, lower alkyl, or aryl when W 2  is NR 7 ; or R 7  and R 3 , taken together with any intervening atoms, form a cycloalkyl, heterocycloalkyl, or heteroaryl ring; 
         R 8  and R 9  are independently hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, or R 8  and R 9  taken together with any intervening atoms, form a heterocycloalkyl ring; 
         R 10  is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; 
         R 11  is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or X; or R 11  and R 5  taken together with any intervening atoms, form a heterocycloalkyl or heteroaryl ring; and 
         X is —C(O)NR 8 R 9 , —SO 2 NR 8 R 9 , —NHC(O)NR 8 R 9 , or —NR 8 C(O)R 10 . 
       
     
     
         2 .- 59 . (canceled)