Triazolo[4,5-d] pyramidine derivatives and their use as purine receptor antagonists

Abstract

Compounds of formula (I) that are capable of acting as purine receptor antagonists, pharmaceutical compositions including the compounds, and methods of making the compounds, are disclosed. The compounds and compositions can be used in treating or preventing disorders related to purine receptor hyperfunctioning.

1 - 19 . (canceled) 
     
     
         20 . A composition comprising:
 (i) a compound of formula:   
       
         
           
           
               
               
           
         
       
       and
 (ii) a base. 
 
     
     
         21 . The composition of  claim 20 , wherein the base is sodium hydride. 
     
     
         22 . The composition of  claim 20 , wherein the base is triethylamine. 
     
     
         23 . The composition of  claim 20 , wherein the base is N,N-diisopropylethylamine. 
     
     
         24 . The composition of  claim 20 , wherein the base is potassium carbonate. 
     
     
         25 . The composition of  claim 20 , wherein (i) is a compound of formula: 
       
         
           
           
               
               
           
         
       
     
     
         26 . A composition comprising:
 (i) a compound of formula:   
       
         
           
           
               
               
           
         
       
       and
 (ii) sodium hydride, triethylamine, N,N-diisopropylethylamine, or potassium carbonate. 
 
     
     
         27 . A method for forming a compound of formula (I): 
       
         
           
           
               
               
           
         
         comprising the step of reacting a compound of formula (A): 
       
       
         
           
           
               
               
           
         
         with a phenyl-boronic acid compound, a heteroaryl-boronic acid compound, a phenyl-trialkylstannane compound, a heteroaryl-trialkylstannane compound, a phenyl-zinc halide compound, or a heteroaryl-zinc halide compound, in the presence of a catalyst and a base, thereby forming the compound of formula (I); 
         wherein:
 R is —(CR a R b )—O—R 2 ; 
 R a  is H or alkyl; 
 R b  is H or alkyl; or R a  and R b  together with the atom to which they are attached form a 3 to 8 membered saturated or partially saturated hydrocarbon ring or form a 4 to 8 membered saturated or partially saturated heterocyclic ring comprising a ring member selected from the group consisting of O, N(R 3 ), and S; 
 R 1  is phenyl or heteroaryl, wherein the phenyl or the heteroaryl group is optionally substituted with alkyl, alkoxy, halo or —CN; 
 R 2  is H, alkyl, cycloalkyl or heterocycloalkyl, wherein the alkyl or cycloalkyl is optionally substituted with halo, alkoxy or heterocycloalkyl; and 
 R 3  is H or alkyl. 
 
       
     
     
         28 . The method of  claim 27 , wherein:
 heteroaryl is a 5 or 6 membered aromatic ring, comprising one or two ring members selected from the group consisting of N, N(R 4 ), S and O;   alkyl or alkyl of the alkoxy group is a linear or branched saturated hydrocarbon containing up to 10 carbon atoms;   heterocycloalkyl is a C-linked or N-linked 3 to 10 membered non-aromatic, monocyclic ring, wherein the heterocycloalkyl ring comprises 1, 2 or 3 ring members independently selected from the group consisting of N, N(R 4 ), S(O) q , and O;   R 4  is H or alkyl; and   q is 0, 1 or 2.   
     
     
         29 . The method of  claim 27 , comprising reacting the compound of formula (A) with the heteroaryl-boronic acid compound in the presence of the catalyst and the base. 
     
     
         30 . The method of  claim 29 , wherein the heteroaryl-boronic acid compound is 5-methylfuran-2-boronic acid. 
     
     
         31 . The method of  claim 27 , wherein R is 
       
         
           
           
               
               
           
         
       
     
     
         32 . The method of  claim 27 , wherein the base is an inorganic base. 
     
     
         33 . The method of  claim 27 , wherein the base is sodium carbonate or potassium carbonate. 
     
     
         34 . The method of  claim 27 , wherein the catalyst is a palladium catalyst. 
     
     
         35 . The method of  claim 27 , comprising reacting the compound of formula (A) with the heteroaryl-boronic acid compound in the presence of a palladium catalyst and an inorganic base. 
     
     
         36 . The method of  claim 35 , wherein the heteroaryl-boronic acid compound is 5-methylfuran-2-boronic acid, and wherein the inorganic base is sodium carbonate or potassium carbonate