Inhibitors of the fibroblast growth factor receptor

Abstract

Described herein are inhibitors of FGFR, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions to inhibit the activity of tyrosine kinases.

1 - 7 . (canceled) 
     
     
         8 . A compound of Formula II, or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein Warhead is a moiety capable of forming a covalent bond with a nucleophile;
 W is C or N; 
 Z is CH or N; 
 Y is CH or N—R 4  where R 4  is H or C 1-6  alkyl; 
 R 1  is H or C 1-6  alkyl; 
 each of R 2  and R 3  is, independently, halo, cyano, optionally substituted C 1-6  alkoxy, hydroxy, amino, amido, optionally substituted alkyl urea, optionally substituted C 1-6  alkyl, optionally substituted C 1-6  heterocyclyl; 
 n is 0-4; 
 and p is 0-2. 
 
     
     
         9 . The compound of  claim 8 , wherein R 2  is halo or methoxy. 
     
     
         10 . The compound of  claim 8 , wherein n is 4. 
     
     
         11 . The compound of  claim 8 , wherein Y is N—R 4 , where R 4  is methyl 
     
     
         12 . The compound of  claim 8 , wherein R 1  is methyl. 
     
     
         13 . A compound of Formula III, or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein Warhead is a moiety capable of forming a covalent bond with a nucleophile;
 R 1  is H or optionally substituted C 1-6  alkyl, including dialkylaminoalkyl; 
 each of R 2  and R 3  is, independently, halo, cyano, optionally substituted C 1-6  alkoxy, hydroxy, amino, amido, optionally substituted alkyl urea, optionally substituted C 1-6  alkyl, optionally substituted C 1-6  heterocyclyl; 
 n is 0-4; and p is 0-2. 
 
     
     
         14 . The compound of  claim 13 , wherein each R 2  is, independently, halo or methoxy. 
     
     
         15 . The compound of  claim 14 , wherein n is 2. 
     
     
         16 . The compound of  claim 14 , wherein n is 4. 
     
     
         17 . The compound of  claim 13 , wherein R 1  is methyl. 
     
     
         18 . The compound of  claim 13 , wherein R 1  is diethylaminobutyl. 
     
     
         19 . A compound of Formula IV, or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein Warhead is a moiety capable of forming a covalent bond with a nucleophile;
 R 1  is H or optionally substituted C 1-6  alkyl; 
 each of R 2  and R 3  is, independently, halo, cyano, optionally substituted C 1-6  alkoxy, hydroxy, amino, amido, optionally substituted alkyl urea, optionally substituted C 1-6  alkyl, optionally substituted C 1-6  heterocyclyl; 
 n is 0-4; and p is 0-2. 
 
     
     
         20 . The compound of  claim 19 , wherein R 2  is halo or methoxy. 
     
     
         21 . The compound of  claim 19 , wherein n is 2. 
     
     
         22 . The compound of  claim 19 , wherein n is 4. 
     
     
         23 . The compound of  claim 19 , wherein R 1  is methyl. 
     
     
         24 - 80 . (canceled)