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 0  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 10 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. 
     
     
         2 . A compound according to  claim 1  wherein:
 X is O; 
 Y is O; 
 R 1  and R 4  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 10 cycloalkyl-C 1 -C 10 alkyl, C 5 -C 8 cycloalkenyl, C 5 -C 8 cycloalkenyl-C 1 -C 10 alkyl, C 3 -C 10 heterocycloalkyl, C 3 -C 10 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 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 10 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, 
 where any carbon or heteroatom of R 1 , R 2 , R 3 , R 4 , 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 5 )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 as defined in  claim 1  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. 
     
     
         3 . A compound according to  claim 1  wherein:
 X is O; 
 Y is O; 
 R 1  and R 4  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 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 —OR 9 ; 
 R 3  is H or C 1 -C 4 alkyl;
 R 9  is H or a cation, or C 1 -C 10 alkyl which is unsubstituted or is substituted with one or more substituents independently selected from the group consisting of C 3 -C 6  cycloalkyl, heterocycloalkyl, aryl and heteroaryl, 
 where any carbon or heteroatom of R 1 , R 2 , R 3 , R 4 , 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, —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 5 )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 in  claim 1  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 10 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. 
     
     
         4 . A compound according to  claim 1  wherein:
 X is O; 
 Y is O; 
 R 1  and R 4  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 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 —OR 9 ; 
 R 3  is H;
 R 9  is H or a cation; 
 where any carbon or heteroatom of R 1 , R 2 , R 3 , R 4  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, —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 5 )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 in  claim 1  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 10 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. 
     
     
         5 . A compound according to  claim 1  which is selected from:
 N-{[1-(4-chlorophenyl)-6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[1-{[2,4-bis(methyloxy)phenyl]methyl}-6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[1-(4-chlorophenyl)-6-hydroxy-4-oxo-3-(phenylmethyl)-2-thioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-({6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[6-hydroxy-2,4-dioxo-1-phenyl-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; and 
 N-[(1-(1,1-dimethylethyl)-3-{[4-(1,1-dimethylethyl)phenyl]methyl}-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 
       and/or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         6 . A compound according to  claim 1  which is selected from:
 N-{[6-Hydroxy-2,4-dioxo-3-(phenylmethyl)-1-(2-pyridinyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[6-Hydroxy-1-(2-nitrophenyl)-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[1-Cyclohexyl-6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[1-[(3-Cyanophenyl)methyl]-6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(6-Hydroxy-2,4-dioxo-3-(phenylmethyl)-1-{[4-(trifluoromethyl)phenyl]methyl}-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-{[1-[(3,4-Dichlorophenyl)methyl]-6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[6-Hydroxy-1-{[3-(methyloxy)phenyl]methyl}-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[1-[(2,6-Dichlorophenyl)methyl]-6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[6-Hydroxy-1-methyl-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[1-Cyclohexyl-3-(2-cyclopropylethyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(1,3-Dicyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-{[1-Hexyl-6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[1-Ethyl-6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[6-Hydroxy-2,4-dioxo-3-(phenylmethyl)-1-propyl-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[1-Butyl-6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[6-Hydroxy-2,4-dioxo-1-(2-phenylethyl)-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[3-{[4-(1,1-Dimethylethyl)phenyl]methyl}-6-hydroxy-1-(1-methylethyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(1-cyclohexyl-3-{[4-(1,1-dimethylethyl)phenyl]methyl}-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-{[6-Hydroxy-1,3-bis(1-methylethyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[3-[(2-Bromophenyl)methyl]-1-(1,1-dimethylethyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(1-(2,6-Dichlorophenyl)-3-{[4-(1,1-dimethylethyl)phenyl]methyl}-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-[(1-(2,4-dichlorophenyl)-3-{[4-(1,1-dimethylethyl)phenyl]methyl}-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-[(1-(2-Bromophenyl)-3-{[4-(1,1-dimethylethyl)phenyl]methyl}-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-[(1-(2-Biphenylyl)-3-{[4-(1,1-dimethylethyl)phenyl]methyl}-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-{[6-Hydroxy-2,4-dioxo-3-(phenylmethyl)-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[3-Cyclohexyl-6-hydroxy-2,4-dioxo-1-(tetrahydro-2H-pyran-4-yl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[3-{[4-(1,1-Dimethylethyl)phenyl]methyl}-6-hydroxy-2,4-dioxo-1-(2-thienyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-({1-Cyclohexyl-6-hydroxy-3-[3-(4-morpholinyl)propyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[3-{[4-(1,1-Dimethylethyl)phenyl]methyl}-6-hydroxy-2,4-dioxo-1-(3-pyridinyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-({1-Cyclohexyl-3-[(2-fluorophenyl)methyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-({3-[(2-Chlorophenyl)methyl]-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-({1-Cyclohexyl-6-hydroxy-2,4-dioxo-3-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)methyl]-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-({1-Cyclohexyl-3-[(2,4-dimethylphenyl)methyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-({1-Cyclohexyl-6-hydroxy-2,4-dioxo-3-[(2,4,6-trifluorophenyl)methyl]-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-[(1-Cyclohexyl-6-hydroxy-3-{[4-(1-methylethyl)phenyl]methyl}-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-({1-Cyclohexyl-3-[(2-ethylphenyl)methyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-({1-Cyclohexyl-3-[(4-ethylphenyl)methyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-({1-Cyclohexyl-6-hydroxy-2,4-dioxo-3-[(2,4,6-trimethylphenyl)methyl]-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[1-Cyclohexyl-3-(2-cyclohexylethyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(3-{[3,5-Bis(methyloxy)phenyl]methyl}-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-{[1-Cyclohexyl-6-hydroxy-3-(2-naphthalenylmethyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-({1-Cyclohexyl-6-hydroxy-3-[(4-methylphenyl)methyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[3-(4-Biphenylylmethyl)-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(3-{[4-(1,3-Benzoxazol-2-yl)phenyl]methyl}-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-({3-[2-(4-Biphenylyl)-2-oxoethyl]-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-[(1,3-Bis {[4-(1,1-dimethylethyl)phenyl]methyl}-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-{[1-Cyclohexyl-6-hydroxy-3-(4-methylcyclohexyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-({1-Cyclohexyl-3-[4-(1,1-dimethylethyl)cyclohexyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-[(1-Cyclohexyl-6-hydroxy-2,4-dioxo-3-phenyl-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-({1-Cyclohexyl-3-[4-(1,1-dimethylethyl)phenyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[1-Cyclohexyl-3-(cyclohexylmethyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(3-Cycloheptyl-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-[(3-Cyclohexyl-6-hydroxy-2,4-dioxo-1-tricyclo[3.3.1.1 3,7 ]dec-1-yl-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-({1-[(1R,2R,4S)-Bicyclo[2.2.1]hept-2-yl]-3-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[1-Cyclohexyl-6-hydroxy-3-(3-methylcyclohexyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(3-Cyclohexyl-1-cyclopropyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-[(1-Cyclobutyl-3-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-[(3-Cyclohexyl-1-cyclopentyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-{[6-Hydroxy-1,3-bis(3-methylbutyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(6-Hydroxy-1,3-bis {[2-(methyloxy)phenyl]methyl}-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-({1,3-Bis[(2-chlorophenyl)methyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-[(1,3-Dihexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-{[1-Cyclohexyl-6-hydroxy-3-(2-methylcyclohexyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[1-Cyclohexyl-6-hydroxy-3-(2-naphthalenyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(1-Cyclohexyl-3-hexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-[(1,3-Dicycloheptyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-[(1,3-Dicyclopentyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-{[1-Cyclohexyl-3-(2,3-dimethylcyclohexyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 4-[5-{[(Carboxymethyl)amino]carbonyl}-3-cyclohexyl-4-hydroxy-2,6-dioxo-3,6-dihydro-1(2H)-pyrimidinyl]cyclohexanecarboxylic acid; 
 N-{[1-Cyclohexyl-3-(4-ethylcyclohexyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 cis-4-[3-Cyclohexyl-5-({[2-(ethyloxy)-2-oxoethyl]amino}carbonyl)-4-hydroxy-2,6-dioxo-3,6-dihydro-1(2H)-pyrimidinyl]cyclohexanecarboxylic acid; 
 N-{[1-Cyclohexyl-6-hydroxy-3-(1-methylcyclohexyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 3-[5-{[(Carboxymethyl)amino]carbonyl}-3-cyclohexyl-4-hydroxy-2,6-dioxo-3,6-dihydro-1(2H)-pyrimidinyl]cyclohexanecarboxylic acid; 
 N-{[1-Cyclohexyl-6-hydroxy-2,4-dioxo-3-(2-oxo-2-phenylethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(1-Cyclohexyl-6-hydroxy-3-{2-[4-(methyloxy)phenyl]-2-oxoethyl}-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-({1-Cyclohexyl-6-hydroxy-3-[2-(4-methylphenyl)-2-oxoethyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[1-Cyclohexyl-3-(3,3-dimethyl-2-oxobutyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-({1-Cyclohexyl-3-[2-(4-fluorophenyl)-2-oxoethyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-({3-[2-(4-Cyanophenyl)-2-oxoethyl]-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-({3-[2-(1-Benzofuran-2-yl)-2-oxoethyl]-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[3-Cyclohexyl-6-hydroxy-1-(1-naphthalenyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[3-Cyclohexyl-1-(4,4-dimethylcyclohexyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-({1-Cyclohexyl-3-[(2,3-difluorophenyl)methyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 Ethyl N-[(1,3-dicyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonothioyl]glycinate; 
 N-[(1,3-Dicyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonothioyl]glycine; 
 6-[5-{[(Carboxymethyl)amino]carbonyl}-3-cyclohexyl-6-hydroxy-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]hexanoic acid; 
 6-[5-{[(Carboxymethyl)amino]carbonothioyl}-3-cyclohexyl-6-hydroxy-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]hexanoic acid; 
 N-({1-Cyclohexyl-3-[(3,4-dichlorophenyl)methyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-[(1-Cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-({3-Cyclohexyl-6-hydroxy-1-[trans-4-(methyloxy)cyclohexyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-({1-[1,1′-Bi(cyclohexyl)-4-yl]-3-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[6-Hydroxy-2,4-dioxo-1,3-bis(1-propylbutyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-({3-(2-Cyclopropylethyl)-6-hydroxy-1-[3-(methyloxy)phenyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[3-Cyclohexyl-6-hydroxy-2,4-dioxo-1-(4-phenylcyclohexyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-({1-Cyclohexyl-3-[(3,4-difluorophenyl)methyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-({3-(2-Cyclopropylethyl)-6-hydroxy-1-[4-(methyloxy)phenyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[3-(2-Cyclopropylethyl)-6-hydroxy-1-(3-nitrophenyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-({3-(2-Cyclopropylethyl)-6-hydroxy-2,4-dioxo-1-[4-(2-thienyl)phenyl]-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[1,3-Bis(1-ethylpropyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(6-Hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-[(1-Cyclohexyl-6-hydroxy-2,4-dioxo-3-{[4-(trifluoromethyl)phenyl]methyl}-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-[(1,3-Dibutyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-{[1,3-Bis(2-cyclopropylethyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[6-Hydroxy-1,3-bis(2-methylpropyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-({3-(2-Cyclopropylethyl)-6-hydroxy-1-[3-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-({3-(2-Cyclopropylethyl)-6-hydroxy-1-[4-(2-methyl-1,3-thiazol-4-yl)phenyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[3-Cyclohexyl-6-hydroxy-2,4-dioxo-1-(4-piperidinyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-({3-(2-Cyclopropylethyl)-1-[4-(2-furanyl)phenyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[1,3-Bis(1,1-dimethylpropyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[3-Cyclohexyl-6-hydroxy-2,4-dioxo-1-(3-piperidinyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[3-Cyclohexyl-6-hydroxy-2,4-dioxo-1-(1-{[(phenylmethyl)oxy]carbonyl}-3-piperidinyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-{[1-(1-Acetyl-3-piperidinyl)-3-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 N-[(1-Cyclohexyl-3-{[4-fluoro-2-(trifluoromethyl)phenyl]methyl}-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-({3-[(2-Bromophenyl)methyl]-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-({1-Cyclohexyl-3-[(2,6-dichlorophenyl)methyl]-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-[(3-{[2-Bromo-5-(methyloxy)phenyl]methyl}-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-[(3-{[2,4-Bis(trifluoromethyl)phenyl]methyl}-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-({3-[(2-Bromo-5-fluorophenyl)methyl]-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-[(3-{[2-Bromo-4-(1,1-dimethylethyl)phenyl]methyl}-1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycine; 
 N-({1-Cyclohexyl-6-hydroxy-3-[(2-methylphenyl)methyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl}carbonyl)glycine; 
 N-{[1-Cyclohexyl-3-(1,1-dimethylpropyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; and 
 N-{[1,3-Bis(2,6-dichlorophenyl)-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine; 
 
       and/or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         7 . A pharmaceutical composition which comprises a compound as described in  claim 1  and one or more of pharmaceutically acceptable carriers, diluents and excipients. 
     
     
         8 . A method of treating anemia in a mammal in need thereof which comprises administering to such mammal a therapeutically effective amount of a compound as described in of  claim 1 . 
     
     
         9 . The method of  claim 8  wherein the mammal is a human. 
     
     
         10 . A method of inhibiting HIF prolyl hydroxylases in a mammal in need thereof which comprises administering to such mammal a therapeutically effective amount of a compound as described in  claim 1 . 
     
     
         11 . The method of  claim 10  wherein the mammal is a human. 
     
     
         12 . A method of treating Ischemia in a mammal in need thereof which comprises administering to such mammal a therapeutically effective amount of a compound as described in  claim 1 . 
     
     
         13 . The method of  claim 12  wherein the mammal is a human. 
     
     
         14 . A method of treating myocardial infarction in a mammal in need thereof which comprises administering to such mammal a therapeutically effective amount of a compound as described in  claim 1 . 
     
     
         15 . The method of  claim 14  wherein the mammal is a human. 
     
     
         16 . A method of treating diseases of the hematopoietic system, in a mammal in need thereof, which comprises: administering to such mammal a therapeutically effective amount of
 a) a compound as described in  claim 1 ; and   b) EPO or a derivative thereof.   
     
     
         17 . A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and an effective amount of a compound as described in  claim 1  which process comprises bringing the compound as described in  claim 1  into association with a pharmaceutically acceptable carrier or diluent. 
     
     
         18 . A process for preparing a compound of 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 10 cycloalkyl-C 1 -C 10 alkyl, C 5 -C 8 cycloalkenyl, C 5 -C 8 cycloalkenyl-C 1 -C 10 alkyl, C 3 -C 10 heterocycloalkyl, C 3 -C 10 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 10 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, —CO(C 1 -C 4 alkyl), —CO(C 3 -C 6 cycloalkyl), —CO(C 3 -C 6 heterocycloalkyl), —CO(aryl), —CO(heteroaryl) and —SO 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 10 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, —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 5 )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, —CO(C 1 -C 4 alkyl), —CO(aryl), —CO(heteroaryl), —CO(C 3 -C 6 cycloalkyl), —CO(C 3 -C 6 heterocycloalkyl), —SO 2 (C 1 -C 4 alkyl), C 3 -C 8 cycloalkyl, C 3 -C 10 heterocycloalkyl, C 6 -C 14 aryl, aryl-C 1 -C 10 alkyl, heteroaryl and heteroaryl-C 1 -C 10 alkyl; 
 comprising treating a compound of formula A: 
 
 
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 4  are the same as for those groups in formula (I) with glycine and an appropriate base in an appropriate solvent under conventional thermal conditions or by microwave irradiation, to form the compound of formula (I). 
     
     
         19 . A process for preparing a compound of 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, —CO(C 1 -C 4 alkyl), —CO(C 3 -C 6 cycloalkyl), —CO(C 3 -C 6 heterocycloalkyl), —CO(aryl), —CO(heteroaryl) and —SO 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 0  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 1 , —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 5 )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, —CO(C 1 -C 4 alkyl), —CO(aryl), —CO(heteroaryl), —CO(C 3 -C 6 cycloalkyl), —CO(C 3 -C 6 heterocycloalkyl), —SO 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; 
 comprising treating a compound of formula B: 
 
 
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 4  are the same as for those groups in formula (I) with an alkali, in an appropriate solvent at a suitable temperature to form the compound of formula (I).