Certain 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 - 41 . (canceled) 
     
     
         42 . A compound of Formula II: 
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof, wherein
 W 4  is CR 11  or N; 
 R 1  is hydrogen, amino, alkyl, alkoxy, aryl, heteroaryl, or cyano; 
 R 2  is hydrogen, halo, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; 
 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; and 
 R 11  is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or X. 
 
     
     
         43 . The compound of  claim 42  wherein W 4  is N. 
     
     
         44 . The compound of  claim 42  wherein R 1  is amino or alkyl. 
     
     
         45 . The compound of  claim 44  wherein R 1  is methyl or methyl substituted by one or more halo. 
     
     
         46 . The compound of  claim 44  wherein R 1  is methyl substituted by one or more fluoro. 
     
     
         47 . The compound of  claim 42  wherein R 2  is aryl, or heteroaryl. 
     
     
         48 . The compound of  claim 47  wherein when R 2  is aryl, it is substituted at the meta position or at both meta positions. 
     
     
         49 . The compound of  claim 47  wherein R 2  is bicyclic. 
     
     
         50 . The compound of  claim 42  wherein R 5  is alkyl, aryl, or heteroaryl. 
     
     
         51 . The compound of  claim 42  wherein the compound inhibits a protein kinase. 
     
     
         52 . The compound of  claim 42  wherein the compound inhibits a lipid kinase. 
     
     
         53 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of  claim 42 . 
     
     
         54 . The pharmaceutical composition of  claim 53  wherein the composition is formulated as a solid, semi-solid, liquid, or aerosol dosage form. 
     
     
         55 . A method of modulating the catalytic activity of a PI3 kinase comprising contacting said PI3 kinase with an effective amount of a compound of  claim 42 . 
     
     
         56 . A method of treating a condition or disorder mediated by PI3 kinase activity in a subject in need of such treatment comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of  claim 42 . 
     
     
         57 . The method of  claim 55  or  56  wherein the compound binds the p110α-affinity pocket of PI3 kinase. 
     
     
         58 . The method of  claim 56 , wherein said PI3 kinase related disorder is a cancer, bone disorder, inflammatory disease, immune disease, nervous system disease, metabolic disease, respiratory disease, or cardiac disease. 
     
     
         59 . The method of  claim 55  or  56  further comprising administering a second therapeutic agent.