Heterocyclic compounds and uses thereof

Abstract

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

1 - 36 . (canceled) 
     
     
         37 . A method for selectively inhibiting at least one mutant of EGFR as compared to WT EGFR, in a biological sample or in a patient, comprising contacting the biological sample with, or administering to the patient, a compound of formula I-a 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 n is 0, 1, or 2; 
 m is 0, 1, or 2, wherein m and n are not simultaneously 0; 
 W is —NH—; 
 R 1  is —OR; 
 each R is independently C 1-4  alkyl or C 1-4  fluoroalkyl; 
 R 2  is —CF 3 , Cl, or Br; and 
 G is —O—. 
 
     
     
         38 . The method according to  claim 37 , wherein said method is sparing for WT EGFR. 
     
     
         39 . The method according to  claim 37 , wherein the at least one mutant is T790M. 
     
     
         40 . The method according to  claim 38 , wherein the at least one mutant is T790M. 
     
     
         41 . The method according to  claim 37 , wherein the at least one mutant of EGFR is an activating mutant. 
     
     
         42 . The method according to  claim 39 , wherein the at least one activating mutant of EGFR is a deletion mutant. 
     
     
         43 . The method according to  claim 41 , wherein the at least one activating mutant of EGFR is a point mutation. 
     
     
         44 . The method according to  claim 42 , wherein the at least one activating mutant is delE746-A750. 
     
     
         45 . The method according to  claim 43 , wherein the at least one activating mutant is L858R. 
     
     
         46 . The method according to  claim 43 , wherein the at least one activating mutant is G719S. 
     
     
         47 . The method according to  claim 37 , wherein the compound selectively inhibits at least one activating mutant and T790M. 
     
     
         48 . The method according to  claim 47 , wherein the at least one activating mutant of EGFR is a deletion mutant. 
     
     
         49 . The method according to  claim 47 , wherein the at least one mutant of EGFR is a point mutation. 
     
     
         50 . The method according to  claim 48 , wherein the at least one activating mutant is delE746-A750. 
     
     
         51 . The method according to  claim 49 , wherein the at least one activating mutant is L858R. 
     
     
         52 . The method according to  claim 49 , wherein the at least one activating mutant is G719S. 
     
     
         53 . (canceled) 
     
     
         54 . A method for treating a mutant EGFR-mediated disorder or condition in a patient, comprising administering to the patient a compound of formula I-a: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 n is 0, 1, or 2; 
 m is 0, 1, or 2, wherein m and n are not simultaneously 0; 
 W is —NH—; 
 R 1  is —OR; 
 each R is independently C 1-4  alkyl or C 1-4  fluoroalkyl; 
 R 2  is —CF 3 , Cl, or Br; and 
 G is —O—. 
 
     
     
         55 . The method according to  claim 54 , wherein the disorder or condition is a cancer. 
     
     
         56 . The method according to  claim 55 , wherein the cancer is non-small cell lung cancer. 
     
     
         57 - 62 . (canceled) 
     
     
         63 . The method according to  claim 37 , wherein the compound is of formula II: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         64 . The compound according to  claim 63 , wherein R 2  is —CF 3 . 
     
     
         65 . The compound according to  claim 63 , wherein R 2  is Cl. 
     
     
         66 . The compound according to  claim 63 , wherein the compound is selected from: selected from: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.