Therapeutic Compounds Based on Pyrazolopyridine

Abstract

The present invention provides compounds of formula (I): wherein all variables are as defined herein, pharmaceutical compositions containing the same, processes for preparing the same and their use as pharmaceutical agents.

1 . A compound of formula (I):  
     
       
         
         
             
             
         
       
       wherein;  
       p is 0, 1, 2, 3 or 4;  
       each R 1  is the same or different and is independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, Ay, Het, —OR 7 , —OAy, —OR 10 Ay, —OHet, —OR 10 Het, —C(O)R 9 , —C(O)Ay, —C(O)Het, —CO 2 R 9 , —C(O)NR 7 R 8 , —C(O)NR 7 Ay, —C(O)NHR 10 Ay, —C(O)NHR 10 Het, —C(S)NR 9 R 11 , —C(NH)NR 7 R 8 , —C(NH)NR 7 Ay, —S(O) n R 9 , —S(O) n Ay, —S(O) n Het, —S(O) 2 NR 7 R 8 , —S(O) 2 NR 7 Ay, —NR 7 R 8 , —NR 7 Ay, —NHHet, —NHR 10 Ay, —NHR 10 Het, —R 10 cycloalkyl, —R 10 Ay, —R 10 Het, —R 10 O—C(O)R 9 , —R 10 O—C(O)Ay, —R 10 O—C(O)Het, —R 10 O—S(O) n R 9 , —R 10 OR 9 , —R 10 C(O)R 9 , —R 10 CO 2 R 9 , —R 10 C(O)NR 9 R 11 , —R 10 C(O)NR 7 Ay, —R 10 C(O)NHR 10 Het, —R 10 C(S)NR 9 R 11 , —R 10 C(NH)NR 9 R 11 , —R 10 SO n R 9 , —R 10 SO 2 NR 9 R 11 , —R 10 SO 2 NHCOR 9 , —R 10 NR 7 R 8 , —R 10 NR 7 Ay, —R 10 NHC:(NH)NR 9 R 11  cyano, nitro and azido; or 
 two adjacent R 1  groups together with the atoms to which they are bonded form a C 5-6 cycloalkyl or a 5 or 6-membered heterocyclic ring containing 1 or 2 heteroatoms;  
 each R 7  and R 8  are the same or different and are independently selected from the group consisting of H, alkyl, alkenyl, cycloalkyl, cycloalkenyl, —C(O)R 9 , —CO 2 R 9 , —C(O)NR 9 R 11 , —C(S)NR 9 R 11 , —C(NH)NR 9 R 11 , —SO 2 R 10 , —SO 2 NR 9 R 11 , —R 10 cycloalkyl, —R 10 OR 9 , —R 10 C(O)R 9 , —R 10 CO 2 R 9 , —R 10 C(O)NR 9 R 11 , —R 10 C(S)NR 9 R 11 , —R 10 C(NH)NR 9 R 11 , —R 10 SO 2 R 10 , —R 10 SO 2 NR 9 R 11 , —R 10 SO 2 NHCOR 9 , —R 10 NR 9 R 11 , —R 10 NHCOR 9 , —R 10 NHSO 2 R 9  and —R 10 NHC(NH)NR 9 R 11 ;  
 each P 9  and R 11  are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, —R 10 cyoloalkyl, —R 10 OH, —R 10 (OR 10 ) w  where w is 1-10, and —R 10 NR 10 R 10 ;  
 each R 10  is the same or different and is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl;  
 Ay is aryl;  
 Het is a 5- or 6-membered heterocyclic or heteroaryl group;  
 
       R 2  is selected from the group consisting of halo, alkyl, alkenyl, cycloalkyl, cycloalkenyl, Ay, Het, —OR 7 , —OAy, —OHet, —OR 10 Het, —S(O) n R 9 , —S(O) n Ay, —S(O) n NR 7 R 8 , —S(O) n Het, —NR 7 R 8 , —NHHet, —NHR 10 Ay, —NHR 10 Het, —R 10 NR 7 R 8  and —R 10 NR 7 Ay;  
       n is 0, 1 or 2;  
       Y is CH;  
       R 3  and R 4  are the same or different and are each independently selected from the group consisting of H, halo, alkyl, alkenyl, cycloalkyl, Ay, Het, —OR 7 , —OAy, —C(O)R 7 , —C(O)Ay, —CO 2 R 7 , —CO 2 AY, —SO 2 NHR 9 , —NR 7 R 8 , —NR 7 Ay, —NHHet, —NHR 10 Het, —R 10 cycloalkyl, —R 10 OR 7 , —R 10 OAy, —R 10 NR 7 R 8  and —R 10 NR 7 Ay,  
       R 5  is the selected from the group consisting of H, halo, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —OR 7 , —OAy, —OHet, —OR 10 Ay, —OR 10 Het, —C(O)R 9 , —C(O)Ay, —C(O)Het, —CO 2 R 9 , —C(O)NR 7 R 8 , —C(O)NR 7 Ay, —C(O)NHR 10 Het, —CH(OR 9 ) 2 , —CH(OR 9 )—R 10 , —CH(OR 9 )-Ay. —C(S)NR 9 R 11 , —C(NH)NR 7 R 8 , —C(NH)NR 7 Ay, —S(O) n R 9 , —S(O) 2 NR 7 R 8 , —S(O) Z NR 7 Ay, —NR 7 R 8 , —NR 7 Ay, —NHHet, —NHR 10 Ay, —NHR 10 Het, —R 10 cycloalkyl, —R 10 Ay, —R 10 Het, —R 10 OR 9 , —R 10 C(O)R 9 , —R 10 C(O)Ay, —R 10 C(O)Het, —R 10 CO 2 R 9 , —R 10 C(O)NR 9 R 11 , —R 10 C(O)NR 7 Ay, —R 10 C(O)NHR 10 Het, —R 10 CH(OR 9 )—R 10 ; —R 10 CH(OR 9 )-Ay, —R 10 C(S)NR 9 R 11 , —R 10 C(NH)NR 9 R 11 , —R 10 SO n R 9 , —R 10 SO 2 NR 9 R 11 , —R 10 SO 2 NHCOR 9 , —R 10 NR 7 R 8 , —R 10 NR 7 Ay, —R 10 NHC(NH)NR 9 R 11 , cyano, nitro and azido; or  
       wherein when Y is CH, R 9 ; is not —NR 7 Ay;  
       or a pharmaceutically acceptable salt thereof.  
     
   
   
       2 . The compound according to  claim 1  wherein each R 1  is the same or different and is independently selected from the group consisting of halo, alkyl, cycloalkyl, Ay, Het, —OR 7 , —C(O)R 9 , —C(O)Het, —CO 2 R 9 , —C(O)NR 7 R 8 , —C(O)NR 7 Ay, —C(O)NHR 10 Het, —S(O) n R 9 , —S(O) 2 NR 7 R 8 , —S(O) 2 NR 7 Ay, —NR 7 R 8 , —NR 7 Ay, —NHHet, —NHR 10 Ay, —NHR 10 Het, —R 10 cycloalkyl, —R 10 Het, —R 10 OR 9 , —R 10 C(O)NR 7 Ay, —R 10 SO 2 NHCOR 9 , —R 10 NR 7 R 8 , —R 10 NR 7 Ay, cyano, nitro and azido.  
   
   
       3 . (canceled)  
   
   
       4 . The compound according to  claim 1  wherein p is 0 or 1.  
   
   
       5 . The compound according to  claim 1  wherein R 2  is selected from the group consisting of halo, alkenyl, cycloalkyl, cycloalkenyl, Ay, Het, —OR 7   1 , —OAy, —OHet, —OR 10 Het, —S(O) n R 9   1 , —NR 7 R 8 , —NHHet, —NHR 1 Het, —R 10 NR 7 R 8  and —R 10 NR 7 Ay  
   
   
       6 - 8 . (canceled)  
   
   
       9 . The compound according to  claim 1  wherein R 3  and R 4  are the same or different and are each independently selected from the group consisting of H, halo, alkyl, Ay, —OR 7 , —CO 2 R 7 , —NR 7 R 8 , —R 10 OR 7  and —R 10 NR 7 R 8 .  
   
   
       10 . (canceled)  
   
   
       11 . The compound according to  claim 1  wherein R 5  is selected from the group consisting of halo, alkyl, cycloalkyl, —OR 7 , —C(O)R 9 , —C(O)Ay, —C(O)Het, —CH(OR 9 )—R 10 , —CH(OR 9 )-Ay, —S(O) n R 9 , —S(O) 2 NR 7 R 8 , —NR 7 R 8 , —NR 7 Ay, —R 10 cycloalkyl, —R 10 Ay, —R 10 Het, —R 10 OR 9   1 , —R 10 C(O)R 9 , —R 10 SO 2 NR 9 R 11  and —R 10 NR 7 R 8 .  
   
   
       12 . (canceled)  
   
   
       13 . A compound selected from the group consisting of: 
 3-(2-Fluoropyridin-4-yl)-2-propylpyrazolo[1,5-a]pyridine;    N-Cyclopentyl-4-(2-propylpyrazolo[1,5-a]pyridin-3-yl)pyridin-2-amine;    7-Chloro-3-(2-fluoropyridin-4-yl)-2-propylpyrazolo[1,5-a]pyridine;    N-Cyclopentyl-3-[2-(cyclopentylamino)pyridin-4-yl]-2-propylpyrazolo[1,5-a]pyridin-7-amine;    or a pharmaceutically acceptable salt thereof.    
   
   
       14 . A pharmaceutical composition comprising a compound according to  claim 1 .  
   
   
       15 . The pharmaceutical composition according to  claim 14  further comprising a pharmaceutically acceptable carrier or diluent.  
   
   
       16 - 28 . (canceled)