[1,2,4]triazolo[1,5-c]pyrimidine derivatives as hsp90 modulators

Abstract

The present invention relates to [1,2,4]triazolo[1,5-c]pyrimidine derivatives which inhibit the activity of Heat Shock Protein Hsp90. The compounds of the invention are therefore useful in treating proliferative diseases such as cancer and neurodegenerative diseases. The present invention also provides processes for preparing these compounds, methods of treating diseases and the pharmaceutical compositions comprising these compounds.

1 . A method for treating diseases caused by and/or associated with an altered HSP90 activity which comprises administering to a mammal in need thereof an effective amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         m is 0, 1 or 2; 
         X is phenyl, naphtyl, pyridine, furan or thiophene; 
         any R1, if present, is independently halogen, trifluoromethyl, cyano, nitro, CONHRa, ORa, NRbRc, NHCORa, NHSO 2 Ra, SO 2 Rd, COORe or an optionally substituted group selected from linear or branched C 1 -C 7  alkyl, C 2 -C 7  alkenyl, C 2 -C 7  alkynyl, C 3 -C 8 cycloalkyl, C 4 -C 8  cycloalkenyl and C 4 -C 8  heterocyclyl, 
         wherein
 Ra is hydrogen, trifluoromethyl or an optionally substituted group selected from linear or branched C 1 -C 7  alkyl, C 2 -C 7  alkenyl, C 2 -C 7  alkynyl, C 3 -C 8  cycloalkyl, C 4 -C 8  cycloalkenyl, C 4 -C 8  heterocyclyl, aryl and heteroaryl; 
 Rb and Rc, the same or different, are hydrogen or an optionally substituted group selected from linear or branched C 1 -C 7  alkyl, C 2 -C 7  alkenyl, C 2 -C 7  alkynyl, C 3 -C 8  cycloalkyl, C 4 -C 8  cycloalkenyl, C 4 -C 8  heterocyclyl, aryl and heteroaryl or Rb and Rc together with the nitrogen atom to which they are bonded form an optionally substituted heterocyclyl group comprising oxygen, sulfur or nitrogen atom, 
 Rd is an optionally substituted linear or branched C 1 -C 7  alky, 
 Re is hydrogen or an optionally substituted linear or branched C 1 -C 7  alky; 
 
         W is a substituted linear or branched C 1 -C 7  alkyl or an optionally substituted aryl or heteroaryl, optionally fused with C 3 -C 8 cycloalkyl or C 4 -C 8  heterocyclyl; 
         Z is CH 2 , CH(OR2) or CH(NHR3), 
         wherein
 R2 is hydrogen or an optionally substituted linear or branched C 1 -C 7  alky, 
 R3 is hydrogen or COR4, wherein R4 is O—C 1 -C 7  Alkyl, 
 
         and pharmaceutically acceptable salts thereof, 
         provided that 
         5-benzyl-[1,2,4]triazolo[1,5-c]quinazolin-2-ylamine is excluded. 
       
     
     
         2 . The method of  claim 1  wherein the mammal in need thereof is a human.