Therapeutic Compounds

Abstract

The present invention provides compounds of formula (I); pharmaceutical compositions containing the same, processes for preparing the same and their use as pharmaceutical agents.

1 . A compound of formula (I):  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1  is selected from the group consisting of halo, —NR 7 R 5 , Ay, —NR 7 Ay, Het, —NHR 10 Het, —NHHet and —NHR 10 Ay; 
 each R 7  and R 8  are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, cycloalkenyl, —R 10 cycloalkyl, —R 10 OR 9 , —NR 9 R 11 , —R 10 NR 9 R 11 , —R 10 C(O)R 9 , —C(O)R 9 , —C(O)R 10 Ay, —C(O)R 10 Het, —CO 2 R 9 , —R 10 CO 2 R 9 , —C(O)NR 9 R 11 , —R 10 C(O)NR 9 R 11 , —R 10 C(O)Ay, —R 10 C(O)Het, —C(S)NR 9 R 11 , —R 10 C(S)NR 9 R 11 , —R 10 NHC(NH)NR 9 R 11 , —R 10 NHC(O)R 10 Het, —R 10 NHC(O)R 10 CO 2 R 9 , —R 10 NHC(NCO 2 R 9 )NHCO 2 R 9 , —R 10 NHC(O)NHSO 2 R 9 , —R 10 NHC(O)NHSO 2 Ay, —R 10 NHC(O)NHSO 2 Het, —R 10 C(NH)NR 9 R 11 —C(NH)NR 9 R 11 , —SO 2 NR 9 R 11 , R 10 SO 2 NR 9 R 11 , —R 10 NHSO 2 R 9 , —SO 2 R 10 , —R 10 SO 2 R 10 , —R 10 NHCOR 9 , —R 10 SO 2 NHCOR 9 , —R 10 NHP(O)(OR 9 ) 2 , —R 10 OP(O)(OR 9 ) 2  and —R 10 OP(O)(OR 10 Ay) 2 ;  
 each R 9  and R 11  are the same or different and are independently selected from the group consisting of H, alkyl, cycloalkyl, —R 10 cycloalkyl, —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, cycloalkyl, alkenyl, cycloalkenyl and alkynyl;  
 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, cycloalkyl, alkenyl, cycloalkenyl, —NR 7 R 8 , —OR 7 , —OAy, —S(O) n R 9 , —S(O) n Ay, —R 10 NR 7 R 8 , —R 10 NR 7 Ay, Ay, Het, —NHHet, —NHR 10 Het, —OHet and —OR 10 Het;  
 
 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, cycloalkyl, alkenyl, Ay, —OR 7 , —OAy, —R 10 OR 7 , —R 10 OAy, —NR 7 R 8 , —NR 7 Ay, —R 10 NR 7 R 8 , —R 10 NR 7 Ay, —C(O)R 7 , —C(O)Ay, —CO 2 R 7 , —CO 2 Ay, —SO 2 NHR 9 , Het, —NHHet and —NHR 10 Het;  
 q is 0, 1, 2, 3, 4 or 5; and  
 each R 5  is the same or different and is independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, —R 10 cycloalkyl, Ay, —NHR 10 Ay, Het, —NHHet, —NHR 10 Het, —OR 7 , —OAy, —OHet, —R 10 OR 9 , —NR 7 R 8 , —NR 7 Ay, —R 10 NR 7 R 8 , —R 10 NR 7 Ay, —R 10 C(O)R 9 , —C(O)R 9 , —CO 2 R 9 , —R 10 CO 2 R 9 , —C(O)NR 7 R 8 , —C(O)Ay, —C(O)NR 7 Ay, —C(O)Het, —C(O)NHR 10 Het-R 10 C(O)NR 9 R 11 , —C(S)NR 9 R 11 , —R 10 C(S)NR 9 R 11 , —R 10 NHC(NH)NR 9 R 11 , —C(NH)NR 7 R 8 , —C(NH)NR 7 Ay, —R 10 C(NH)NR 9 R 11 , —S(O) 2 NR 7 R 8 , —S(O) 2 NR 7 Ay, —R 10 SO 2 NHCOR 9 , —R 10 SO 2 NR 9 R 11 , —R 10 SO 2 R 9 , —S(O) n R 9 , cyano, nitro and azido; or 
 two adjacent R 5  groups together with the atoms to which they are bonded form a C 5-6  cycloalkyl or aryl;  
 
 wherein when q is 1 and R 5  is in the para position, R 5  is not halo; and  
 wherein when Y is CH, R 3  is not —NR 7 Ay;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         2 . The compound according to  claim 1  wherein R 1  is selected from the group consisting of —NR 7 R 8 , Ay, —NR 7 Ay, Het, —NHR 10 Het, —NHHet and —NHR 10 Ay.  
     
     
         3 . The compound according to  claim 1  wherein R 1  is selected from the group consisting of —NR 7 R 8  and Het.  
     
     
         4 . The compound according to  claim 1  wherein R 2  is selected from the group consisting of —NR 7 R 8 , —OR 7 , —OAy, —S(O) n R 9 , —S(O) n Ay, —R 10 NR 7 R 8 , —R 10 NR 7 Ay, Ay, Het, —NHR 10 Het, —NHHet, —OHet and —OR 10 Het.  
     
     
         5 . The compound according to  claim 1  wherein R 2  is selected from the group consisting of —NR 7 R 8  and Het.  
     
     
         6 - 7 . (canceled)  
     
     
         8 . 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, —OR 7 , —R 10 OR 7 , —NR 7 R 8 , —R 10 NR 7 R 8 , —CO 2 R 7  and Ay.  
     
     
         9 . The compound according to  claim 1  wherein R 3  and R 4  are each H.  
     
     
         10 . The compound according to  claim 1  wherein q is 0 or 1.  
     
     
         11 . The compound according to  claim 1  wherein each R 5  is the same or different and is independently selected from the group consisting of halo, alkyl, alkenyl, —OR 7   1 —CO 2 R 9 , —NR 7 R 8 , —C(O)NR 7 R 8 , Ay, —NHR 10 Ay, Het, —S(O) 2 NR 7 R 8 , cyano, nitro and azido.  
     
     
         12 . The compound according to  claim 1 , wherein each R 5  is the same or different and is independently selected from the group consisting of halo, alkyl, —OR 7 , NR 7 R 8  and cyano.  
     
     
         13 . (canceled)  
     
     
         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 . The pharmaceutical composition according to  claim 14  further comprising an antiviral agent selected from the group consisting of aciclovir and valaciclovir.  
     
     
         17 . A method for the treatment of a herpes viral infection selected from HSV-1 and HSV-2 in an animal, said method comprising administering to the animal a therapeutically effective amount of a compound according to  claim 1 .  
     
     
         18 . (canceled)  
     
     
         19 . A method for the treatment of a condition or disease associated with a herpes viral infection selected from HSV-1 and HSV-2 in an animal, comprising administering to the animal a therapeutically effective amount of a compound according to  claim 1 .  
     
     
         20 - 22 . (canceled)  
     
     
         23 . A process for preparing the compound according to  claim 1 , said process comprising reacting a compound of formula (XXII):  
       
         
           
           
               
               
           
         
         wherein X 1  is chloro, bromo or iodo,  
         with a compound of formula XXIV;  
         
           
             
             
                 
                 
             
           
         
         wherein M 2  is selected from the group consisting of −B(OH) 2 , —B(ORa) 2 , —B(Ra) 2 , —Sn(Ra) 3 , Zn-halide, ZnRa, and Mg-halide where Ra is alkyl or cycloalkyl and halide is halo.  
       
     
     
         24 - 32 . (canceled)