Prolyl Hydroxylase Inhibitors

Abstract

The invention described herein relates to certain pyrimidinetrione N-substituted glycine derivatives of formula (I)which are antagonists of HIF prolyl hydroxylases and are useful for treating diseases benefiting from the inhibition of this enzyme, anemia being one example.

What is claimed is: 
     
         1 . A compound according to formula (I): 
       
         
           
           
               
               
           
         
         wherein:
 R 1  and R 4  are each independently selected from the group consisting of hydrogen, —NR 5 R 6 , C 1- C 10 alkyl, C 2- C 10 alkenyl, C 2- C 10 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl-C 1- C 10 alkyl, C 5 -C 8 cycloalkenyl, C 5 -C 8 cycloalkenyl-C 1- C 10 alkyl, C 3 -C 8 heterocycloalkyl, C 3 -C 8 heterocycloalkyl-C 1- C 10 alkyl, aryl, aryl-C 1- C 10 alkyl, heteroaryl and heteroaryl-C 1- C 10 alkyl; 
 R 2  is —NR 7 R 8  or —OR 9 ; 
 R 3  is H or C 1- C 4 alkyl;
 where R 5  and R 6  are each independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl-C 1- C 10 alkyl, C 3 -C 8 heterocycloalkyl, C 3 -C 8 heterocycloalkyl-C 1- C 10 alkyl, aryl, aryl-C 1- C 10 alkyl, heteroaryl, heteroaryl-C 1- C 10 alkyl, —C(O)C 1 -C 4 alkyl, —C(O)C 3 -C 6 cycloalkyl, —C(O)C 3 -C 6 heterocycloalkyl, —C(O)aryl, —C(O)heteroaryl and —S(O) 2 C 1 -C 4 alkyl, or, when R 5  and R 6  are attached to the same nitrogen, R 5  and R 6  taken together with the nitrogen to which they are attached form a 5- or 6- or 7-membered saturated ring optionally containing one other heteroatom selected from oxygen, nitrogen and sulphur, 
 R 7  and R 8  are each independently selected from the group consisting of hydrogen, C 1- C 10 alkyl, C 2- C 10 alkenyl, C 2- C 10 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 heterocycloalkyl, aryl and heteroaryl, and 
 R 9  is H or a cation, or C 1- C 10 alkyl which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of C 3 -C 6 cycloalkyl, heterocycloalkyl, aryl and heteroaryl; 
 
 X is O or S; and 
 Y is O or S;
 where any carbon or heteroatom of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9  is unsubstituted or is substituted with one or more substituents independently selected from C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halogen, —OR 10 , —NR 5 R 6 , oxo, cyano, nitro, —C(O)R 10 , —C(O)OR 10 , —SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —NR 5 R 6 , —CONR 5 R 6 , —N(R 5 )C(O)R 10 , —N(R 5 )C(O)OR 10 , —OC(O)NR 5 R 6 , —N(R 5 )C(O)NR 5 R 6 , —SO 2 NR 5 R 6 , —N(R)SO 2 R 10 , C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 heterocycloalkyl, aryl, C 1 -C 6 alkyl-aryl, heteroaryl and C 1 -C 6 alkyl-heteroaryl, wherein R 5  and R 6  are the same as defined above and R 10  is selected from hydrogen, C 1- C 10 alkyl, C 2- C 10 alkenyl, C 2- C 10 alkynyl, —C(O)C 1 -C 4 alkyl, —C(O)aryl, —C(O)heteroaryl, —C(O)C 3 -C 6 cycloalkyl, —C(O)C 3 -C 6 heterocycloalkyl, —S(O) 2 C 1 -C 4 alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 heterocycloalkyl, C 6 -C 14 aryl, aryl-C 1- C 10 alkyl, heteroaryl and heteroaryl-C 1- C 10 alkyl; 
 
 
         and/or a pharmaceutically acceptable salt or solvate thereof.