Certain chemical entities, compositions and methods

Abstract

Chemical entities that modulate PI3 kinase activity, pharmaceutical compositions containing the chemical entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.

1 - 22 . (canceled) 
     
     
         23 . A compound of Formula I-1: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein
 B is alkyl or a moiety of Formula II: 
 
       
         
           
           
               
               
           
         
       
       wherein W c  is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl, and
 q is an integer of 0, 1, or 2; 
 X is absent or —(CH(R 9 )) z —, and z is an integer of 1, 2, 3, or 4; 
 Y is absent, —N(R 9 )—, or —N(R 9 )CH(R 9 )—; 
 wherein at least one of X and Y is present; 
 W d  is 
 
       
         
           
           
               
               
           
         
         R a′  is hydrogen, halo, or amino; 
         R 1  is hydrogen, —F, —Cl, —CN, —CH, isopropyl, —CF 3 , —OCH 3 , nitro, or phosphate; 
         R 2  is halo, hydroxy, cyano, nitro, or phosphate; 
         R 3  is aryl, heteroaryl, H, —CH 3 , —CF 3 , —Cl, or —F; 
         each R 9  is independently hydrogen, methyl, or ethyl; and 
         R 12  is hydrogen, alkyl, alkynyl, alkenyl, halo, aryl, heteroaryl, heterocycloalkyl, cycloalkyl, cyano, amino, carboxylic acid, alkoxycarbonyl, or amido. 
       
     
     
         24 . The compound of  claim 23 , wherein X is —CH 2 —, —CH(CH 2 CH 3 ), or —CH(CH 3 )—. 
     
     
         25 . The compound of  claim 23 , wherein Y is —NH—, —N(CH 3 )—, or —N(CH 2 CH 3 )—. 
     
     
         26 . The compound of  claim 23 , wherein X—Y is —CH(CH 2 CH 3 )—NH— or —CH(CH 3 )—NH—. 
     
     
         27 . The compound of  claim 23 , wherein R 3  is chloro. 
     
     
         28 . The compound of  claim 23 , wherein R 3  is methyl. 
     
     
         29 . The compound of  claim 23 , wherein R a′  is hydrogen. 
     
     
         30 . The compound of  claim 23 , wherein R 12  is hydrogen, halo, cyano, or amido. 
     
     
         31 . The compound of  claim 23 , wherein W d  is 
       
         
           
           
               
               
           
         
       
     
     
         32 . The compound of  claim 23 , wherein the compound is a compound of Formula IX-A2: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         33 . The compound of  claim 23 , wherein the compound is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         34 . The compound of  claim 23 , wherein W d  is 
       
         
           
           
               
               
           
         
       
     
     
         35 . The compound of  claim 23 , wherein the compound is a compound of Formula XI-A2: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         36 . The compound of  claim 23 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         37 . A compound, which is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         38 . A compound, which is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         39 . A pharmaceutical composition comprising a compound of  claim 23 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipient. 
     
     
         40 . A method of inhibiting a phosphatidyl inositol-3 kinase (PI13 kinase), comprising contacting the PI3 kinase with an effective amount of a compound of  claim 23 , or a pharmaceutically acceptable salt thereof. 
     
     
         41 . A method of inhibiting a phosphatidyl inositol-3 kinase (PI3 kinase), comprising contacting the PI3 kinase with an effective amount of a compound of  claim 37 , or a pharmaceutically acceptable salt thereof. 
     
     
         42 . A method of inhibiting a phosphatidyl inositol-3 kinase (PI3 kinase), comprising contacting the PI3 kinase with an effective amount of a compound of  claim 38 , or a pharmaceutically acceptable salt thereof.