Imidazo-Pyridine Derivatives For Use In The Treatment of Herpes Viral Infection

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 or 2; 
         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 , —OHet, —C(O)R 9 , —C(O)Het, —CO 2 R 9 , —C(O)NR 7 R 8 , —C(NH)NR 7 R 8 , —S(O) n R 9 , —S(O) 2 NR 7 R 8 , —NR 7 R 8 , —NR 7 Ay, —NHHet, —R 10 cycloalkyl, —R 10 Het, —R 10 OR 9 , —R 10 SO 2 NHCOR 9 , —R 10 NR 7 R 8 , 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 5- or 6-membered heterocyclic group 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(NH)NR 9 R 11 , —SO 2 R 10 , —SO 2 NR 9 R 11 , —R 10 cycloalkyl, —R 10 OR 9  and —R 10 NR 19 R 11 ; 
 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 H, alkyl and cycloalkyl; 
         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 , —C(O)R 7 , —CO 2 R 7 —SO 2 NHR 9 , —NR 7 R 8 , —NHHet and —NHR 10 Het; 
         q and q′ are the same or different and are each independently selected from the group consisting of 0, 1, 2 and 3; and 
         each R 5  and R 5′  are the same or different and are 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 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) 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)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 2 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 5  or R 5′  groups together with the atoms to which they are bonded form a C 5-6  cycloalkyl or aryl; 
 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The compound according to  claim 1  wherein p is 1 or 2. 
     
     
         3 . 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 11 —C(O)R 9 , —C(O)Het, —CO 2 R 9 , —S(O) n R 9 , —S(O) 2 NR 7 R 8 , —NR 7 R 8 , —NR 7 Ay, —NHHet, —R 10 cycloalkyl, —R 10 Het, —R 10 OR 9 , —R 10 NR 7 R 8 , cyano, nitro and azido. 
     
     
         4 . The compound according to  claim 1  wherein each R 1  is the same or different and is independently selected form the group consisting of halo, alkyl, Het, —OR 7 , —S(O) n R 9 , —NR 7 R 8  and —NHHet. 
     
     
         5 . The compound according to  claim 1  wherein R 2  is H or alkyl. 
     
     
         6 . The compound according to  claim 1  wherein R 2  is H. 
     
     
         7 - 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  and —NR 7 R 8 . 
     
     
         10 . The compound according to  claim 1  wherein R 3  and R 4  are each independently H or alkyl. 
     
     
         11 . The compound according to  claim 1  wherein q and q′ are the same or different and are each independently selected from the group consisting of 0, 1 and 2. 
     
     
         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, Ay, Het, —OR 7 , —OAy, —CO 2 R 9 , —C(O)NR 7 R 8 , —S(O) 2 NR 7 R 8 , —NR 7 R 8 , —NR 7 Ay, —NHR 10 Ay, cyano, nitro and azido. 
     
     
         13 . 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. 
     
     
         14 . 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, Ay, Het, —OR 7 , —OAy, —C(O)Ay, —C(O)Het, —CO 2 R 9 , —C(O)NR 7 R 8 , —S(O) 2 NR 7 R 8 , —NR 7 R 8 , cyano, nitro and azido. 
     
     
         15 . 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 , —C(O)Ay, —C(O)Het and —NR 7 R 8 . 
     
     
         16 . (canceled) 
     
     
         17 . A pharmaceutical composition comprising a compound according to  claim 1 . 
     
     
         18 . The pharmaceutical composition according to  claim 17  further comprising a pharmaceutically acceptable carrier or diluent. 
     
     
         19 . The pharmaceutical composition according to  claim 17 , further comprising an antiviral agent selected from the group consisting of aciclovir and valaciclovir. 
     
     
         20 . A method for the treatment of a herpes viral infection selected from herpes simplex virus 1 and herpes simplex virus 2 in an animal, said method comprising administering to the animal a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         21 . (canceled) 
     
     
         22 . A method for the treatment of a condition or disease associated with a herpes viral infection selected from herpes simplex virus 1 and herpes simplex virus 2 in an animal, comprising administering to the animal a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         23 - 25 . (canceled) 
     
     
         26 . A process for preparing the compound according to  claim 1 ,
 said process comprising reacting a compound of formula (XV):   
       
         
           
           
               
               
           
         
         wherein X 1  is halo; 
         with a compound of formula (XVI): 
       
       
         
           
           
               
               
           
         
         wherein M 2  is —B(OH) 2 , —B(ORa) 2 , —B(Ra) 2 , —Sn(Ra) 3 , Zn-halide, ZnRa or Mg-halide where Ra is alkyl or cycloalkyl and halide is halo. 
       
     
     
         27 - 34 . (canceled)