Furopyridine and furopyrimidine derivatives for the treatment of hyper-proliferative disorders

Abstract

This invention relates to a compound of Formula I wherein Y is CH or N; Ar 1 is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each selected independently from (C 1 -C 3 )alkoxy, halo, OH, CF 3 , CN, NO 2 and (C 1 -C 3 )alkyl, said alkyl being optionally substituted with CF 3 ; Ar 2 is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each independently selected from halo, OH, CN, NO 2 , CF 3 , (C 1 -C 6 )alkoxy, NR 1 R 1 , S(O) 2 R 2 , C(O)R 3 , and (C 1 -C 6 )alkyl optionally substituted with R 4 , and its use in treating hyper-proliferative disorder.

1 . A compound of Formula I 
     
       
         
         
             
             
         
       
     
     wherein
 Y is N; 
 Ar 1  is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each selected independently from (C 1 -C 3 )alkoxy, halo, OH, CF 3 , CN, NO 2  and (C 1 -C 3 )alkyl, said alkyl being optionally substituted with CF 3 ; 
 Ar 2  is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each independently selected from halo, OH, CN, NO 2 , CF 3 , (C 1 -C 6 )alkoxy, NR 1 R 1 , S(O) 2 R 2 , C(O)R 3 , and (C 1 -C 6 )alkyl optionally substituted with R 4 ; 
 R 1  is selected from H, S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl where said alkyl is optionally substituted with NR 5 R 5 , and (C 1 -C 3 )alkyl where said alkyl is optionally substituted with 1 or 2 substituents each selected independently from OH and (C 1 -C 3 )alkoxy,
 with the proviso that in any NR 1 R 1  group when one R 1  is S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl then the other R 1  must be other than S(O) 2 N [(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl; 
 
 R 2  is selected from (C 1 -C 3 )alkyl, pyrrolidinyl, and
 NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH; 
 
 R 3  is selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, morpholinyl, pyrrolidinyl, piperidinyl, and NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH, (C 1 -C 3 )alkoxy
 or N[(C 1 -C 3 )alkyl] 2 ; 
 
 R 4  is selected from OH, CN, CF 3 , (C 1 -C 3 )alkoxy, C(O)NR 5 R 5 , NR 5 R 5 , and piperidinyl; and 
 R 5  is selected from H, (C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl, S(O) 2 (C 1 -C 3 )alkyl and piperidinyl,
 with the proviso that in any NR 5 R 5  group when one R 5  is C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl, then the other R 5  must be other than C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl; 
 
 
     or a pharmaceutically acceptable salt thereof. 
   
   
       2 - 11 . (canceled) 
   
   
       12 . A compound of claim  11  wherein Ar 1  is optionally substituted phenyl. 
   
   
       13 . A compound of claim  11  wherein Ar 1  is optionally substituted pyridyl. 
   
   
       14 . A compound of claim  11  wherein Ar 2  is optionally substituted phenyl. 
   
   
       15 . A compound of claim  11  wherein Ar 2  is optionally substituted pyridyl. 
   
   
       16 . A compound of  claim 12  wherein Ar 2  is optionally substituted pyridyl. 
   
   
       17 . A compound of  claim 12  wherein Ar 2  is optionally substituted phenyl. 
   
   
       18 . A compound of  claim 13  wherein Ar 2  is optionally substituted phenyl. 
   
   
       19 . A compound of  claim 13  wherein Ar 2  is optionally substituted pyridyl. 
   
   
       20 . A compound of claim  11  wherein Ar 1  and Ar 2  are each substituted phenyl. 
   
   
       21 . A compound of claim  11  wherein Ar 1  is phenyl substituted with at least 1 substituent selected from (C 1 -C 3 )alkoxy, halo, OH, CF 3 , CN, or (C 1 -C 3 )alkyl, said alkyl being optionally substituted with CF 3 ; 
   
   
       22 . A compound of claim  11  wherein Ar 2  is substituted with at least 1 substituent selected from halo, OH, CN, NO 2 , CF 3 , (C 1 -C 6 )alkoxy, NR 1 R 1 , S(O) 2 R 2 , C(O)R 3 , and (C 1 -C 6 )alkyl substituted with R 4 ; 
   
   
       23 . A pharmaceutical composition comprising a compound of Formula I 
     
       
         
         
             
             
         
       
     
     wherein
 Y is N; 
 Ar 1  is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each selected independently from (C 1 -C 3 )alkoxy, halo, OH, CF 3 , CN, NO 2  and (C 1 -C 3 )alkyl, said alkyl being optionally substituted with CF 3 ; 
 Ar 2  is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each independently selected from halo, OH, CN, NO 2 , CF 3 , (C 1 -C 6 )alkoxy, NR 1 R 1 , S(O) 2 R 2 , C(O)R 3 , and (C 1 -C 6 )alkyl optionally substituted with R 4 ; 
 R 1  is selected from H, S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl where said alkyl is optionally substituted with NR 5 R 5 , and (C 1 -C 3 )alkyl where said alkyl is optionally substituted with 1 or 2 substituents each selected independently from OH and (C 1 -C 3 )alkoxy,
 with the proviso that in any NR 1 R 1  group when one R 1  is S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl then the other R 1  must be other than S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl; 
 
 R 2  is selected from (C 1 -C 3 )alkyl, pyrrolidinyl, and
 NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH;
 R 3  is selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, morpholinyl, pyrrolidinyl, piperidinyl, and 
 NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH, (C 1 -C 3 )alkoxy
 or N[(C 1 -C 3 )alkyl] 2 ; 
 
 
 
 R 4  is selected from OH, CN, CF 3 , (C 1 -C 3 )alkoxy, C(O)NR 5 R 5 , NR 5 R 5 , and piperidinyl; and 
 R 5  is selected from H, (C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl, S(O) 2 (C 1 -C 3 )alkyl and piperidinyl, with the proviso that in any NR 5 R 5  group when one R 5  is C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl, then the other R 5  must be other than C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl; and 
 
     or a pharmaceutically acceptable salt thereof, 
     and a pharmaceutically acceptable carrier. 
   
   
       24 . A method of treating a hyper-proliferative comprising the administration to a patient in need thereof of an effective amount of a compound of Formula 
     
       
         
         
             
             
         
       
     
     wherein
 Y is N; 
 Ar 1  is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each selected independently from (C 1 -C 3 )alkoxy, halo, OH, CF 3 , CN, NO 2  and (C 1 -C 3 )alkyl, said alkyl being optionally substituted with CF 3 ; 
 Ar 2  is phenyl or pyridyl each optionally substituted with 1 or 2 substituents each independently selected from halo, OH, CN, NO 2 , CF 3 , (C 1 -C 6 )alkoxy, NR 1 R 1 , S(O) 2 R 2 , C(O)R 3 , and (C 1 -C 6 )alkyl optionally substituted with R 4 ; 
 R 1  is selected from H, S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl,
 C(O)(C 1 -C 3 )alkyl where said alkyl is optionally substituted with NR 5 R 5 , and (C 1 -C 3 )alkyl where said alkyl is optionally substituted with 1 or 2 substituents each selected independently from OH and (C 1 -C 3 )alkoxy, 
 with the proviso that in any NRIR 1  group when one R 1  is S(O) 2 N[(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl then the other R 1  must be other than S(O) 2 N [(C 1 -C 3 )alkyl] 2 , S(O) 2 NH(C 1 -C 3 )alkyl or C(O)(C 1 -C 3 )alkyl; 
 
 R 2  is selected from (C 1 -C 3 )alkyl, pyrrolidinyl, and NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH; 
 R 3  is selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, morpholinyl, pyrrolidinyl, piperidinyl, and NH(C 1 -C 3 )alkyl where said alkyl is optionally substituted with OH, (C 1 -C 3 )alkoxy or N[(C 1 -C 3 )alkyl] 2 ; 
 R 4  is selected from OH, CN, CF 3 , (C 1 -C 3 )alkoxy, C(O)NR 5 R 5 , NR 5 R 5 , and piperidinyl; and 
 R 5  is selected from H, (C 1 -C 3 )alkyl, C(O)(C 1 -C 3 )alkyl, S(O) 2 (C 1 -C 3 )alkyl and piperidinyl, with the proviso that in any NR 5 R 5  group when one R 5  is C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl, then the other R 5  must be other than C(O)(C 1 -C 3 )alkyl or S(O) 2 (C 1 -C 3 )alkyl; 
 
     or a pharmaceutically acceptable salt thereof.