Pyrazolo[1,5-a]pyridine derivatives and methods of their use

Abstract

The invention is directed to pyrazolo[1,5-a]pyridine derivatives and their use as AXL and c-MET kinase inhibitors.

What is claimed: 
     
         1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H; halo; —C 1-6 alkyl; —C 1-6 alkoxy; optionally substituted pyridyl; optionally substituted pyrimidinyl; optionally substituted pyrazinyl; optionally substituted pyrazolyl; optionally substituted imidazolyl; optionally substituted isoxazolyl; optionally substituted oxazolyl; optionally substituted thiazolyl; optionally substituted isothiazolyl; optionally substituted morpholinyl; optionally substituted piperazinyl, optionally substituted piperidinyl; optionally substituted tetrahydropyranyl; optionally substituted pyrrolidinyl; tetrahydrothiopyranyl 1,1-dioxide; thiomorpholinyl 1,1-dioxide; pyrrolidinyl-one; piperidinyl-one; optionally substituted —NH-aryl; optionally substituted —NH-pyridyl; optionally substituted —NH-pyrimidinyl; —C(O)NHC 1-6 alkyl; —C(O)N(C 1-6 alkyl) 2 ; —NHS(O) 2 C 1-6 alkyl; —N(C 1-6 alkyl)S(O) 2 C 1-6 alkyl; —NHC(O)C 1-6 alkyl; —NC 1-6 alkylC(O)C 1-6 alkyl; —NHC(O)OC 1-6 alkyl; —NC 1-6 alkylC(O)OC 1-6 alkyl; —NHC(O)NHC 1-6 alkyl; —NC 1-6 alkylC(O)N(C 1-6 alkyl) 2 ; optionally substituted —NHC(O)-piperazinyl; or optionally substituted —NC 1-6 alkylC(O)-piperazinyl; 
         each R 2  is independently H, halo, —C 1-6 alkyl, —C 1-6 alkoxy, —OH, —O-alkaryl, or trihaloalkyl; 
         R 3  is H or halo; 
         A is CR 2  or N; 
         B is CR 2  or N; 
         Q is —S(O) 2 aryl optionally substituted with halo or C 1-6 alkyl; pyridyl optionally substituted with halo or —C(O)NHphenyl; pyrimidinyl; pyrazinyl; 
         —C(O)—NHC(O)-alkaryl optionally substituted with halo or C 1-6 alkyl; 
         —C(S)—NHC(O)-alkaryl optionally substituted with halo or C 1-6 alkyl; 
         —C(O)-alkaryl optionally substituted with halo or C 1-6 alkyl; —C(O)NH-aryl optionally substituted with halo, C 1-6 alkyl or C 1-6 alkoxy; —C(O)—O-aryl optionally substituted with halo, C 1-6 alkyl or C 1-6 alkoxy; or 
       
       
         
           
           
               
               
           
         
         wherein X is CR 6 , wherein R 6  is H or C 1-6 alkyl; or N;
 R 4  is H; C 1-6 alkoxy; halo; —OC 1-6 alkylene-O—C 1-6 alkyl; —NHC 1-6 alkyl; or —N(C 1-6 alkyl) 2 ; 
 R 5  is aryl optionally substituted with halo or C 1-6 alkyl; or alkaryl optionally substituted with halo or C 1-6 alkyl; 
 
         or 
       
       
         
           
           
               
               
           
         
         wherein Y is C or N;
 R 7  is H or C 1-6 alkyl; 
 R 8  is H; C 1-6 alkylene-O—C 1-6 alkyl; C 1-6 alkyl; C 1-6 alkylene-O—C 1-6 alkaryl; C 1-6 alkylene-OH; 
 R 9  is H, C 1-6 alkyl; or halo; 
 
         or 
       
       
         
           
           
               
               
           
         
         wherein
 R 10  is H; halo; or C 1-6 alkyl; 
 
         or 
       
       
         
           
           
               
               
           
         
         wherein
 R 11  is H or C 1-6 alkyl; 
 R 12  is H; C 1-6 alkyl; or aryl optionally substituted with halo 
 R 13  is H; C 1-6 alkyl; or trihaloC 1-6 alkyl; 
 
         or 
       
       
         
           
           
               
               
           
         
         wherein
 R 14  is H; C 1-6 alkyl; or halo; 
 
         or a pharmaceutically acceptable salt thereof.