Substituted indazole derivatives active as kinase inhibitors

Abstract

Substituted indazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a deregulated protein kinase activity, like cancer.

1 .- 20 . (canceled) 
     
     
         21 . A compound of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         Ar is aryl selected from phenyl, pyrazolyl and pyridyl, which aryl is optionally substituted with one or more substituents independently selected from halogen, nitro, COR4, OR7, NR5R6, NHSO 2 R10, R8R9N—C 1 -C 6  alkyl, a straight or branched C 1 -C 6  alkyl optionally substituted by a heterocyclyl, in its turn optionally substituted by a straight or branched C 1 -C 6  alkyl or an heterocyclylalkyl, or a heterocyclyl optionally substituted by a straight or branched C 1 -C 6  alkyl, in its turn optionally substituted by a heterocyclyl or a C 1 -C 6  alkoxycarbonyl, or a C 1 -C 6  dialkylamino 
         R4 is hydrogen, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, NR5R6, OR7, SR7, R8R9N—C 1 -C 6  alkyl, R80-C 1 -C 6  alkyl, an optionally further substituted straight or branched C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, heterocyclyl, aryl or heteroaryl; 
         R5 and R6 are independently hydrogen, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, R8R9N—C 2 -C 6  alkyl, R80-C 2 -C 6  alkyl, an optionally further substituted straight or branched C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, heterocyclyl, aryl or heteroaryl; or R5 and R6, taken together with the nitrogen atom to which they are bonded, form an optionally substituted heterocyclyl group; 
         R7 is hydrogen, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, SOR10, SO 2 R10, R8R9N—C 2 -C 6  alkyl, R80-C 2 -C 6  alkyl, an optionally further substituted straight or branched C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, heterocyclyl, aryl or heteroaryl; 
         R8 and R9 are independently hydrogen, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, an optionally further substituted straight or branched C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, heterocyclyl, aryl or heteroaryl; or 
         R8 and R9, taken together with the nitrogen atom to which they are bonded, may form an optionally substituted heterocyclyl group; and 
         R10 is hydrogen, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, an optionally further substituted straight or branched C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, heterocyclyl, aryl, or heteroaryl; 
         R is aryl selected from phenyl and pyridyl, which aryl is optionally substituted with halogen or straight or branched C 1 -C 6  alkyl; and 
         R1, R2 and R3 are hydrogen. 
       
     
     
         22 . The compound according to  claim 21  wherein Ar is group of formula: 
       
         
           
           
               
               
           
         
         R is aryl substituted with one or more halogen; 
         Ra is hydrogen, halogen, nitro, NHCOR4 or NR5R6; and 
         Rb is hydrogen, nitro, NR5R6, OR7, or R8R9N—C 1 -C 6  alkyl. 
       
     
     
         23 . The compound according to  claim 21 , wherein R is phenyl substituted with one or more fluoro. 
     
     
         24 . The compound according to  claim 21 , wherein:
 Ar is group of.   
       
         
           
           
               
               
           
         
       
     
     
         25 . The compound according to  claim 22 , wherein R is phenyl substituted with one or more fluoro. 
     
     
         26 . The compound according to  claim 21 , wherein Ra and Rb are each independently NR5R6. 
     
     
         27 . The compound according to  claim 22 , wherein Ra and Rb are each independently NR5R6. 
     
     
         28 . The compound according to  claim 23 , wherein Ra and Rb are each independently NR5R6. 
     
     
         29 . The compound according to  claim 25 , wherein Ra is NR5R6, wherein R5 is hydrogen and R6 is heterocyclyl. 
     
     
         30 . The compound according to  claim 25 , wherein Rb is NR5R6, wherein R5 and R6, taken together with the nitrogen atom to which they are bonded, form an optionally substituted heterocyclyl group, or a pharmaceutically acceptable salt thereof. 
     
     
         31 . The compound according to  claim 21 , wherein:
 R is phenyl substituted with one or more fluoro;   Ar is group of formula   
       
         
           
           
               
               
           
         
       
       and
 Ra and Rb are each independently NR5R6. 
 
     
     
         32 . The compound according to  claim 31 , wherein:
 Ra is NR5R6, wherein R5 is hydrogen and R6 is heterocyclyl; and   Rb is NR5R6, wherein R5 and R6, taken together with the nitrogen atom to which they are bonded, form an optionally substituted heterocyclyl group.   
     
     
         33 . The compound according to  claim 21 , wherein R is difluorophenyl. 
     
     
         34 . The compound according to  claim 31 , wherein R is difluorophenyl. 
     
     
         35 . The compound according to  claim 21 , wherein:
 R is phenyl substituted with one or more fluoro;   Ar is group of formula   
       
         
           
           
               
               
           
         
       
       and
 Ra and Rb are independently NR5R6. 
 
     
     
         36 . The compound according to  claim 35 , wherein:
 Ra is NR5R6, wherein R5 is hydrogen and R6 is heterocyclyl; and   Rb is NR5R6, wherein R5 and R6, taken together with the nitrogen atom to which they are bonded, form an optionally substituted heterocyclyl group.   
     
     
         37 . A compound according to  claim 35 , wherein R is difluorophenyl, or a pharmaceutically acceptable salt thereof. 
     
     
         38 . A compound according to  claim 36 , wherein R is difluorophenyl, or a pharmaceutically acceptable salt thereof.