Pyrazine compounds

Abstract

A compound of formula (I) wherein R 1 is phenyl substituted by one or more halogen atoms; R 2 is —NH 2 ; R 3 is —NH 2 or hydrogen; R 4 is —CXNR a R b , —CXNH—(CH 2 ) y —NR a R b ; wherein X is ═O or ═S; y is an integer zero, 1 or 2; R a and R b , which may be the same or different, are selected from hydrogen and C 1-4 alkyl or together with the nitrogen atom to which they are attached form a saturated 5- or 6-membered heterocycle containing one or two nitrogen heteroatoms, which heterocycle can be further substituted with one or more C 1-4 alkyl groups; and pharmaceutically acceptable derivatives thereof.

1 . A compound of formula (I)  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is phenyl substituted by one or more halogen atoms;  
 R 2  is —NH 2 ;  
 R 3  is —NH 2  or hydrogen;  
 R 4  is —CXNR a R b , —CXNH—(CH 2 ) y —NR a R b ;  
 wherein  
 X is ═O or ═S;  
 y is an integer zero, 1 or 2;  
 R a  and R b , which may be the same or different, are selected from hydrogen and C 1-4  alkyl, or together with the nitrogen atom to which they are attached, form a saturated 5- or 6-membered heterocycle containing one or two nitrogen heteroatoms, which heterocycle can be further substituted with one or more C 1-4  alkyl groups; and pharmaceutically acceptable derivatives thereof.  
 
     
     
         2 . A compound according to  claim 2  wherein R 1  is 2,3,5-trichlorophenyl.  
     
     
         3 . A compound according to  claim 1  or  claim 2  wherein R 3  is —NH 2 .  
     
     
         4 . A compound according to any of  claims 1  to  3  wherein R 4  is —CONH 2 .  
     
     
         5 . The compound according to any of  claims 1  to  4  which is 2,6-diamino-5-carboxamido-3-(2,3,5-trichlorophenyl)pyrazine.  
     
     
         6 . A compound according to any of  claims 1  to  5  for use in human or veterinary medicine.  
     
     
         7 . The use of a compound according to any one of  claims 1  to  5  in the manufacture of a medicament for use in the treatment of epilepsy, bipolar disorder or manic depression, unipolar depression, pain, functional bowel disorders, neurogenerative diseases, neuroprotection, neurodegeneration, tinnitus, or prevention or reducing dependence on, or preventing or reducing tolerance or reverse tolerance to, a dependence-inducing agent.  
     
     
         8 . A method of treating a human or animal subject suffering from, or susceptible to, epilepsy, bipolar disorder or manic depression, unipolar depression, pain, functional bowel disorders, neurogenerative diseases, neuroprotection, neurodegeneration, tinnitus, or prevention or reducing dependence on, or preventing or reducing tolerance or reverse tolerance to, a dependence-inducing agent, which method comprises administering to said subject a therapeutically effective amount of a compound according to any one of  claims 1  to  5 .  
     
     
         9 . A pharmaceutical composition comprising a compound according to any one of  claims 1  to  5  in admixture with one or more physiologically acceptable carriers or excipients.  
     
     
         10 . A process for preparing a compound of formula (I) and pharmaceutically acceptable derivatives thereof according to any of  claims 1  to  5  which comprises: 
 (A) interconversion of a compound of formula (I) into another compound of formula (I); or  
 (B) reacting a compound of formula (II)  
                     
 wherein R 4  is —CONH 2 , with a hydrolysing agent; or  
 (C) reacting a compound of formula (III)  
                     
 or a protected derivative thereof, wherein R 4  is C 1-4  alkyl, with palladium II acetate, bis(diphenylphosphino)ferrocene and an amine; or  
 (D) reacting a compound of formula (III)  
                     
 or a protected derivative thereof, with sodium cyanide and copper (I) cyanide;  
 and optionally converting compounds of formula (I) prepared by any one of processes (A) to (D) into pharmaceutically acceptable derivatives thereof.