BI-Heteroaryl Substitute 1,4-Benzodiazepines And Uses Thereof For The Treatment Of Cancer

Abstract

The invention relates to new quinoline, pyridopyrazine, naphthyridine and quinazolinone derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
         including any tautomeric or stereochemically isomeric form thereof, wherein 
         n represents an integer equal to 1 or 2; 
         R 1  represents hydrogen, C 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkyl substituted with —C(═O)NHCH 3 , 
         or C 1-6 alkyl substituted with —S(═O) 2 —C 1-4 alkyl; 
         R 2a  represents hydrogen, fluoro or chloro; 
         R 2b  represents methoxy or hydroxyl; 
         R 2c  represents methoxy or hydroxyl; 
         R 3  represent hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, or C 1-2 alkyl substituted with C 3-6 cycloalkyl; 
         R 4  represents hydrogen, methyl or ethyl; 
         a pharmaceutically acceptable salt thereof or a solvate thereof. 
       
     
     
         2 - 5 . (canceled) 
     
     
         6 . The compound according to  claim 1 , wherein n represents an integer equal to 1. 
     
     
         7 . The compound according to  claim 1 , wherein R 1  represents hydrogen or C 1-6 alkyl. 
     
     
         8 . The compound according to  claim 7  wherein R 1  represents C 1-4 alkyl. 
     
     
         9 . The compound according to  claim 1 , wherein R 2a  represents hydrogen or fluoro. 
     
     
         10 . The compound according to  claim 9  wherein R 2a  represents fluoro. 
     
     
         11 . The compound according to  claim 1 , wherein R 2b  represents methoxy. 
     
     
         12 . The compound according to  claim 1 , wherein R 2c  represents methoxy. 
     
     
         13 . The compound according to  claim 1 , wherein R 3  represents C 1-6 alkyl. 
     
     
         14 . The compound according to  claim 1 , wherein R 4  represents hydrogen. 
     
     
         15 . The compound according to  claim 1  wherein the compound is selected from 
       
         
           
           
               
               
           
         
         a pharmaceutically acceptable salt thereof or a solvate thereof. 
       
     
     
         16 . A pharmaceutical composition comprising a compound as defined in  claim 1 . 
     
     
         17 - 22 . (canceled) 
     
     
         23 . A method for the prophylaxis or treatment of a disease state or condition mediated by a FGFR kinase, which method comprises administering to a subject in need thereof a compound as defined in any one of  claims 1 ,  6 ,  7 , or  15 . 
     
     
         24 . A method for the prophylaxis or treatment of cancer, which method comprises administering to a subject in need thereof a compound as defined in any one of  claims 1 ,  6 ,  7 , or  15 .