Use of isoQC inhibitors in the treatment and prevention of inflammatory diseases or conditions

1. A method of treatment of an inflammatory disease or condition comprising administering a therapeutically effective amount of an isoQC inhibitor to a subject in need thereof wherein:

(a) the inflammatory disease or condition is associated with a pyroglutamated peptide;

(b) the inflammatory disease or condition is selected from the group consisting of rheumatoid arthritis, atherosclerosis, restenosis, pancreatitis, and osteoporosis;

(c) the isoQC inhibitor comprises a compound of formula (I):

or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof;

(d) R 1 represents —C 3-8 carbocyclyl-heteroaryl, —C 2-6 alkenylheteroaryl, —C 1-6 alkylheteroaryl, or (CH 2 ) a CR 5 R 6 (CH 2 ) b heteroaryl with (1) a and b independently representing integers 0-5 provided that a+b=0-5 and (2) R 5 and R 6 being alkylene which, together with the carbon to which they are attached, form a C 3 -C 5 cycloalkyl group, or a bicyclic heteroaryl group, any of said heteroaryl groups being optionally substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, —C 1-6 thioalkyl, —SOC 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkoxy-, —O—C 3-8 cycloalkyl, C 3-8 cycloalkyl, —SO 2 C 3-8 cycloalkyl, —SOC 3-6 cycloalkyl, C 3-6 alkenyloxy-, C 3-6 alkynyloxy-, —C(O)C 1-6 alkyl, —C(O)OC 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-, nitro, halogen, cyano, hydroxyl, —C(O)OH, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl) and —C(O)NH(C 3-10 cycloalkyl) and any of said carbocyclyl groups being optionally substituted by one or more groups selected from C 1-4 alkyl, oxo, halogen and C 1-4 alkoxy;

(e) R 2 and R 3 are one of (i), (ii), (iii), (iv), or (v) defined as follows:

(i) R 2 represents C 1-8 alkyl, aryl, heteroaryl, carbocyclyl, heterocyclyl, —C 1-4 alkylaryl, —C 1-4 alkylheteroaryl, —C 1-4 alkylcarbocyclyl or —C 1-4 alkylheterocyclyl with (1) any of said aryl and heteroaryl groups optionally substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, —C 1-6 thioalkyl, —SOC 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkoxy, —O—C 3-8 cycloalkyl, C 3-8 cycloalkyl, —SO 2 C 3-8 cycloalkyl, —SOC 3-6 cycloalkyl, C 3-6 alkenyloxy-, C 3-6 alkynyloxy-, —C(O)C 1-6 alkyl, —C(O)OC 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-, nitro, halogen, cyano, hydroxyl, —C(O)OH, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl) and —C(O)NH(C 3-10 cycloalkyl); and (2) any of aforesaid carbocyclyl and heterocyclyl groups optionally substituted by one or more groups selected from C 1-4 alkyl, oxo, halogen and C 1-4 alkoxy; and

R 3 represents H, —C 1-4 alkyl or aryl with said aryl optionally substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, —C 1-6 thioalkyl, —SOC 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkoxy-, —O—C 3-8 cycloalkyl, C 3-8 cycloalkyl, —SO 2 C 3-8 cycloalkyl, —SOC 3-6 cycloalkyl, C 3-6 alkenyloxy-, C 3-6 alkynyloxy-, —C(O)C 1-6 alkyl, —C(O)OC 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-, nitro, halogen, cyano, hydroxyl, —C(O)OH, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl) and, —C(O)NH(C 3-10 cycloalkyl),

(ii) R 2 represents phenyl substituted by phenyl, phenyl substituted by a monocyclic heteroaryl group, phenyl substituted by benzyloxy, phenyl fused to carbocyclyl, phenyl fused to heterocyclyl, —C 1-4 alkyl(phenyl substituted by phenyl), —C 1-4 alkyl(phenyl substituted by a monocyclic heteroaryl group), —C 1-4 alkyl(phenyl substituted by benzyloxy), —C 1-4 alkyl(optionally substituted phenyl fused to optionally substituted carbocyclyl or —C 1-4 alkyl(optionally substituted phenyl fused to optionally substituted heterocyclyl), with (1) any of said phenyl, benzyloxy and heteroaryl groups optionally substituted by one or more groups selected from C 1-4 alkyl, halogen and C 1-4 alkoxy and (2) any of said carbocyclyl and heterocyclyl groups optionally substituted by one or more groups selected from C 1-4 alkyl, oxo, halogen and C 1-4 alkoxy; and

R 3 represents H, —C 1-4 alkyl or aryl with said aryl optionally substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, —C 1-6 thioalkyl, —SOC 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkoxy-, —O—C 3-8 cycloalkyl, C 3-8 cycloalkyl, —SO 2 C 3-8 cycloalkyl, —SOC 3-6 cycloalkyl, C 3-6 alkenyloxy-, C 3-6 alkynyloxy-, —C(O)C 1-6 alkyl, —C(O)OC 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-, nitro, halogen, cyano, hydroxyl, —C(O)OH, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl) and, —C(O)NH(C 3-10 cycloalkyl),

(iii) R 2 and R 3 are joined to form a carbocyclyl ring which is optionally substituted by one or more C 1-2 alkyl groups,

(iv) R 2 and R 3 are joined to form a carbocyclyl ring which is fused to phenyl, with said carbocyclyl or phenyl optionally substituted by one or more groups selected from C 1-4 alkyl, halogen and C 1-4 alkoxy, and

(v) R 2 and R 3 are joined to form a carbocyclyl ring which is fused to monocyclic heteroaryl with said carbocyclyl or heteroaryl optionally substituted by one or more groups selected from C 1-4 alkyl, halogen and C 1-4 alkoxy;

(f) R 4 represents H, —C 1-8 alkyl, —C(O)C 1-6 alkyl or —NH 2 ;

(g) X represents O or S; and

(h) Y represents O or S.

2. The method according to claim 1 wherein the isoQC inhibitor is administered in combination with a further agent selected from the group consisting of anti-inflammatory agents, nootropic agents, neuroprotectants, antiparkinsonian drugs, amyloid protein deposition inhibitors, beta amyloid synthesis inhibitors, antidepressants, anxiolytic drugs, antipsychotic drugs and anti-multiple sclerosis drugs, inhibitors of the angiotensin converting enzyme (ACE), angiotensin II receptor blockers, diuretics; calcium channel blockers (CCB), beta-blockers, platelet aggregation inhibitors, cholesterol absorption modulators, HMG-Co-A reductase inhibitors, high density lipoprotein (HDL) increasing compounds, renin inhibitors, IL-6 inhibitors, antiinflammatory corticosteroids, antiproliferative agents, nitric oxide donors, inhibitors of extracellular matrix synthesis, growth factor or cytokine signal transduction inhibitors, MCP-1 antagonists and tyrosine kinase inhibitors.

3. The method according to claim 1 wherein the subject is a human.

4. The method according to claim 1 wherein R 1 represents a bicyclic heteroaryl group.

5. The method according to claim 1 wherein R 1 represents a benzene or pyridine ring fused to a 5-membered ring containing one or two nitrogen atoms.

6. The method according to claim 5 wherein the point of attachment is through a benzene or pyridine ring.

7. The method according to claim 1 wherein R 1 is:

imidazo[1,2-a]pyridine; or

benzo[c][1,25]thiadiazolyl.

8. The method according to claim 7 wherein R1 represents

9. The method according to claim 1 wherein R 1 represents —C 1-6 alkylheteroaryl.

10. The method according to claim 9 wherein the heteroaryl group of R 1 is a 5-membered ring containing 1 to 3 nitrogen atoms optionally substituted by one or more substituents selected from C 1-4 alkyl, C 1-4 alkoxy- and halogen.

11. The method according to claim 10 wherein the heteroaryl group is:

12. The method according to claim 1 wherein R 1 represents:

A represents

(i) an unbranched or branched C 1-6 alkylene chain;

(ii) a branched C 1-6 alkylene chain; or

(iii) (CH 2 ) a CR 5 R 6 (CH 2 ) b ; and

R 11 , R 12 and R 13 independently represent H or C 1-2 alkyl.

13. The method according to claim 12 wherein R 1 represents

B represents a bond, —CH 2 —, —CH 2 —CH 2 —, —CH(Me)—, —CH(Me)-CH 2 — or —CH 2 —CH(Me)-; and

R 14 and R 15 independently represent H or C 1-2 alkyl.

14. The method according to claim 1 wherein R 2 represents:

aryl, heteroaryl, phenyl substituted by phenyl, or phenyl fused to heterocyclyl; or

R 2 and R 3 are joined to form a carbocyclyl ring which is fused to phenyl;

said aryl, heteroaryl, phenyl, heterocyclyl or carbocyclyl optionally being substituted.

15. The method according to claim 14 wherein R 2 represents phenyl substituted by phenyl, said phenyl groups optionally being substituted by one or more substitutents independently selected from halo, OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, and C 1-3 haloalkoxy.

16. The method according to claim 15 wherein R 2 is -biphenyl-4-yl.

17. The method according to claim 14 wherein R 2 represents phenyl optionally substituted by one, two or three substituents independently selected from halo, OH, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, and C 1-3 haloalkoxy.

18. The method according to claim 17 wherein R 2 is phenyl substituted by n-propyloxy.

19. The method according to claim 1 wherein R 3 represents H.

20. The method according to claim 1 wherein R 2 and R 3 are joined to form a carbocyclyl ring which is fused to phenyl.

21. The method according to claim 1 wherein R 4 represents H.

22. The method according to claim 1 wherein X represents O.

23. The method according to claim 1 wherein Y represents O.

24. The method according to claim 1 wherein formula (I) is represented by:

R 2 and R 3 are as defined in claim 1 .

25. The method according to claim 1 wherein the compound of formula (I) is selected from the group consisting of:

5-(benzo[c][1,2,5]thiadiazol-6-yl)-1-(1H-benzo[d]imidazol-5-yl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-phenylimidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(2-hydroxy-5-methylphenyl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(2-fluoro-5-trifluoromethyl)phenyl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(2-bromo-5-fluorophenyl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(4-propoxyphenyl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(4-chloro-3-trifluoromethyl)phenyl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(3-fluoro-4(trifluoromethyl)phenyl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(3-hydroxy-4-methoxyphenyl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(2-hydroxy-3-methoxyphenyl)imidazolidine-2,4-dione;

1-(1H-benzimidazol-5-yl)-5-(1,1′-biphenyl-4-yl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(3-chlorophenyl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(4-chlorophenyl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(2-chlorophenyl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(4-fluorophenyl)imidazolidine-2,4-dione;

1-(1H-benzo[d]imidazol-5-yl)-5-(2,3-dihydrobenzo[b][1,4]dioxin-7-yl)imidazolidine-2,4-dione;

1-(3-(1H-imidazol-1-yl)propyl)-5-phenylimidazolidine-2,4-dione;

1-(3-(1H-imidazol-1-yl)propyl)-5-(2-bromo-4-fluorophenyl)imidazolidine-2,4-dione;

1-(3-(1H-imidazol-1-yl)propyl)-5-(4-propoxyphenyl)imidazolidine-2,4-dione;

1-(3-(1H-imidazol-1-yl)propyl)-5-(3-fluoro-4-trifluoromethyl)phenyl)imidazolidine-2,4-dione;

1-[3-(1H-imidazol-1-yl)propyl]-5-(4-biphenyl)imidazolidine-2,4-dione;

1-(3-(1H-imidazol-1-yl)propyl)-5-(3-chlorophenyl)imidazolidine-2,4-dione;

1-(3-(1H-imidazol-1-yl)propyl)-5-(2-chlorophenyl)imidazolidine-2,4-dione;

1-(3-(5-methyl-1H-imidazol-1-yl)propyl)-5-phenylimidazolidine-2,4-dione;

5-(2-bromo-5-fluorophenyl)-1-(3-(5-methyl-1H-imidazol-1-yl)propyl)imidazolidine-2,4-dione;

1-(3-(5-methyl-1H-imidazol-1-yl)propyl)-5-(4-propoxyphenyl)imidazolidine-2,4-dione;

1-[3-(5-methyl-1H-imidazol-1-yl)propyl]-5-(4-phenylphenyl)imidazolidine-2,4-dione;

5-(3-chlorophenyl)-1-(3-(5-methyl-1H-imidazol-1-yl)propyl)imidazolidine-2,4-dione;

1-(3-(4-methyl-1H-imidazol-1-yl)propyl)-5-phenylimidazolidine-2,4-dione;

1-[3-(4-methyl-1H-imidazol-1-yl)propyl]-5-(4-biphenyl)imidazolidine-2,4-dione;

5-(3-chlorophenyl)-1-(3-(4-methyl-1H-imidazol-1-yl)propyl)imidazolidine-2,4-dione;

3-(1H-benzimidazol-5-yl)-1′,3′-dihydro-2H,5H-spiro[imidazolidine-4,2′-indene]-2,5-dione;

5-(benzo[c][1,2,5]thiadiazol-6-yl)-1-(1H-benzo[d]imidazol-5-yl)-2-thioxoimidazolidin-4-one;

1-(1H-benzo[d]imidazol-5-yl)-5-phenyl-2-thioxoimidazolidin-4-one;

1-(1H-benzimidazol-5-yl)-5-(1,1′-biphenyl-4-yl)-2-thioxoimidazolidin-4-one;

1-(1H-benzo[d]imidazol-5-yl)-5-(3-hydroxy-4-methoxyphenyl)-2-thioxoimidazolidin-4-one;

1-(1H-benzo[d]imidazol-5-yl)-5-phenyl-4-thioxoimidazolidin-2-one;

1-(1H-benzimidazol-5-yl)-5-(1,1′-biphenyl-4-yl)-4-thioxoimidazolidin-2-one;

3-(1H-benzimidazol-5-yl)-5-thioxo-1′,3′-dihydro-2H-spiro[imidazolidine-4,2′-inden]-2-one;

1-(1H-benzo[d]imidazol-5-yl)-5-(4-chlorophenyl)-4-thioxoimidazolidin-2-one;

1-(1H-benzo[d]imidazol-5-yl)-5-(2,3,4-trifluorophenyl)-4-thioxoimidazolidin-2-one;

1-(1H-benzo[d]imidazol-6-yl)-5-(4-bromo-2-fluorophenyl)-4-thioxoimidazolidin-2-one;

1-(1H-benzo[d]imidazol-5-yl)-5-(2,3-difluoro-4-methylphenyl)-4-thioxoimidazolidin-2-one;

1-(1H-benzo[d]imidazol-5-yl)-5-(4-chloro-3-methylphenyl)-4-thioxoimidazolidin-2-one;

1-(1H-benzo[d]imidazol-5-yl)-3-methyl-5-phenylimida4zolidine-2,4-dione; and

1-(H-imidazo[1,2-a]pyridin-7-yl)-5-phenylimidazolidine-2,4-dione; or

a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof.

26. The method according to claim 1 wherein the compound of formula (I) is 1-(1H-benzo[d]imidazol-5-yl)-5-(4-propoxyphenyl)imidazolidine-2,4-dione, having a structure of:

a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof.

27. The method according to claim 1 wherein the isoQC inhibitor inhibits an activity of:

a polypeptide comprising SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59 or SEQ ID NO: 60; or

a polypeptide encoded by a nucleic acid comprising SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55 or SEQ ID NO: 56.

28. The method according to claim 1 wherein the isoQC inhibitor inhibits an activity of:

a polypeptide comprising SEQ ID NO: 11 or SEQ ID NO: 12; or

a polypeptide encoded by a nucleic acid comprising SEQ ID NO: 2 or SEQ ID NO: 3.

29. The method according to claim 1 wherein the isoQC inhibitor inhibits an activity of:

a polypeptide comprising SEQ ID NO: 11; or

a polypeptide encoded by a nucleic acid comprising SEQ ID NO: 2.

30. A method according to claim 1 wherein the isoQC inhibitor inhibits an activity of:

a polypeptide comprising SEQ ID NO: 12; or

a polypeptide encoded by a nucleic acid comprising SEQ ID NO: 3.

31. The method according to claim 1 wherein the isoQC inhibitor is formulated as a pharmaceutical composition comprising one or more pharmaceutically acceptable diluents or carriers.

32. The method according to claim 1 wherein the isoQC inhibitor is formulated as a pharmaceutical composition comprising one or more pharmaceutically acceptable diluents or carriers.

33. A method of diagnosing an inflammatory disease or condition comprising:

collecting a sample from a subject suspected to be afflicted with said disease or condition;

contacting said sample with an isoQC inhibitor; and

determining whether or not said subject is afflicted by said disease or condition;

wherein,

(a) the inflammatory disease or condition is selected from the group consisting of rheumatoid arthritis, atherosclerosis, restenosis, pancreatitis, and osteoporosis;

(b) the isoQC inhibitor comprises a compound of formula (I):

or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof;

(d) R 1 represents —C 3-8 carbocyclyl-heteroaryl, —C 2-6 alkenylheteroaryl, —C 1-6 alkylheteroaryl, or (CH 2 ) a CR 5 R 6 (CH 2 ) b heteroaryl with (1) a and b independently representing integers 0-5 provided that a+b=0-5 and (2) R 5 and R 6 being alkylene which, together with the carbon to which they are attached, form a C 3 -C 5 cycloalkyl group, or a bicyclic heteroaryl group, any of said heteroaryl groups being optionally substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, —C 1-6 thioalkyl, —SOC 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkoxy-, —O—C 3-8 cycloalkyl, C 3-8 cycloalkyl, —SO 2 C 3-8 cycloalkyl, —SOC 3-6 cycloalkyl, C 3-6 alkenyloxy-, C 3-6 alkynyloxy-, —C(O)C 1-6 alkyl, —C(O)OC 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-, nitro, halogen, cyano, hydroxyl, —C(O)OH, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl) and —C(O)NH(C 3-10 cycloalkyl) and any of said carbocyclyl groups being optionally substituted by one or more groups selected from C 1-4 alkyl, oxo, halogen and C 1-4 alkoxy;

(e) R 2 and R 3 are one of (i), (ii), (iii), (iv), or (v) defined as follows:

(i) R 2 represents C 1-8 alkyl, aryl, heteroaryl, carbocyclyl, heterocyclyl, —C 1-4 alkylaryl, —C 1-4 alkylheteroaryl, —C 1-4 alkylcarbocyclyl or —C 1-4 alkylheterocyclyl with (1) any of said aryl and heteroaryl groups optionally substituted by one or more groups selected from C 1-6 alkyl, C 2-8 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, —C 1-6 thioalkyl, —SOC 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkoxy, —O—C 3-8 cycloalkyl, C 3-8 cycloalkyl, —SO 2 C 3-8 cycloalkyl, —SOC 3-6 cycloalkyl, C 3-6 alkenyloxy-, C 3-6 alkynyloxy-, —C(O)C 1-6 alkyl, —C(O)OC 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-, nitro, halogen, cyano, hydroxyl, —C(O)OH, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl) and —C(O)NH(C 3-10 cycloalkyl); and (2) any of aforesaid carbocyclyl and heterocyclyl groups optionally substituted by one or more groups selected from C 1-4 alkyl, oxo, halogen an C 1-4 alkoxy; and

R 3 represents H, —C 1-4 alkyl or aryl with said aryl optionally substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, —C 1-6 thioalkyl, —SOC 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkoxy-, —O—C 3-8 cycloalkyl, C 3-6 cycloalkyl, —SO 2 C 3-8 cycloalkyl, —SOC 3-6 cycloalkyl, C 3-6 alkenyloxy-, C 3-6 alkynyloxy-, —C(O)C 1-6 alkyl, —C(O)OC 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-, nitro, halogen, cyano, hydroxyl, —C(O)OH, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl) and, —C(O)NH(C 3-10 cycloalkyl),

(ii) R 2 represents phenyl substituted by phenyl, phenyl substituted by a monocyclic heteroaryl group, phenyl substituted by benzyloxy, phenyl fused to carbocyclyl, phenyl fused to heterocyclyl, —C 1-4 alkyl(phenyl substituted by phenyl), —C 1-4 alkyl(phenyl substituted by a monocyclic heteroaryl group), —C 1-4 alkyl(phenyl substituted by benzyloxy), —C 1-4 alkyl(optionally substituted phenyl fused to optionally substituted carbocyclyl or —C 1-4 alkyl(optionally substituted phenyl fused to optionally substituted heterocyclyl), with (1) any of said phenyl, benzyloxy and heteroaryl groups optionally substituted by one or more groups selected from C 1-4 alkyl, halogen and C 1-4 alkoxy and (2) any of said carbocyclyl and heterocyclyl groups optionally substituted by one or more groups selected from C 1-4 alkyl, oxo, halogen and C 1-4 alkoxy; and

R 3 represents H, —C 1-4 alkyl or aryl with said aryl optionally substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, —C 1-6 thioalkyl, —SOC 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkoxy-, —O—C 3-8 cycloalkyl, C 3-8 cycloalkyl, —SO 2 C 3-8 cycloalkyl, —SOC 3-6 cycloalkyl, C 3-6 alkenyloxy-, C 3-6 alkynyloxy-, —C(O)C 1-6 alkyl, —C(O)OC 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-, nitro, halogen, cyano, hydroxyl, —C(O)OH, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl) and, —C(O)NH(C 3-10 cycloalkyl),

(iii) R 2 and R 3 are joined to form a carbocyclyl ring which is optionally substituted by one or more C 1-2 alkyl groups,

(iv) R 2 and R 3 are joined to form a carbocyclyl ring which is fused to phenyl, with said carbocyclyl or phenyl optionally substituted by one or more groups selected from C 1-4 alkyl, halogen and C 1-4 alkoxy, and

(v) R 2 and R 3 are joined to form a carbocyclyl ring which is fused to monocyclic heteroaryl with said carbocyclyl or heteroaryl optionally substituted by one or more groups selected from C 1-4 alkyl, halogen and C 1-4 alkoxy;

(f) R 4 represents H, —C 1-8 alkyl, —C(O)C 1-6 alkyl or —NH 2 ;

(g) X represents O or S; and

(h) Y represents O or S.

34. The method according to claim 33 wherein said compound of formula (I) is (1-(1H-benzo[d]imidazol-5-yl)-5-(4-propoxyphenyl)imidazolidine-2,4-dione.

35. The method according to claim 33 wherein the subject is a human.

36. A method according to claim 33 wherein said sample is a blood sample, a serum sample, a sample of cerebrospinal liquor or a urine sample.

37. A method of prevention of an inflammatory disease or condition comprising administering a therapeutically effective amount of an isoQC inhibitor to a subject in need thereof wherein:

(a) the inflammatory disease or condition is selected from the group consisting of rheumatoid arthritis, atherosclerosis, restenosis, pancreatitis, and osteoporosis;

(b) the isoQC inhibitor comprises a compound of formula (I):

or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof;

(d) R 1 represents —C 3-8 carbocyclyl-heteroaryl, —C 2-6 alkenylheteroaryl, —C 1-6 alkylheteroaryl, or (CH 2 ) a CR 5 R 6 (CH 2 ) b heteroaryl with (1) a and b independently representing integers 0-5 provided that a+b=0-5 and (2) R 5 and R 6 being alkylene which, together with the carbon to which they are attached, form a C 3 -C 5 cycloalkyl group, or a bicyclic heteroaryl group, any of said heteroaryl groups being optionally substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, —C 1-6 thioalkyl, —SOC 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkoxy-, —O—C 3-8 cycloalkyl, C 3-8 cycloalkyl, —SO 2 C 3-8 cycloalkyl, —SOC 3-6 cycloalkyl, C 3-6 alkenyloxy-, C 3-6 alkynyloxy-, —C(O)C 1-6 alkyl, —C(O)OC 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-, nitro, halogen, cyano, hydroxyl, —C(O)OH, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl) and —C(O)NH(C 3-10 cycloalkyl) and any of said carbocyclyl groups being optionally substituted by one or more groups selected from C 1-4 alkyl, oxo, halogen and C 1-4 alkoxy;

(e) R 2 and R 3 are one of (i), (ii), (iii), (iv), or (v) defined as follows:

(i) R 2 represents C 1-8 alkyl, aryl, heteroaryl, carbocyclyl, heterocyclyl, —C 1-4 alkylaryl, —C 1-4 alkylheteroaryl, —C 1-4 alkylcarbocyclyl or —C 1-4 alkylheterocyclyl with (1) any of said aryl and heteroaryl groups optionally substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, —C 1-6 thioalkyl, —SOC 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkoxy-, —O—C 3-8 cycloalkyl, C 3-8 cycloalkyl, —SO 2 C 3-8 cycloalkyl, —SOC 3-6 cycloalkyl, C 3-6 alkenyloxy-, C 3-6 alkynyloxy-, —C(O)C 1-6 alkyl, —C(O)OC 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-, nitro, halogen, cyano, hydroxyl, —C(O)OH, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl) and —C(O)NH(C 3-10 cycloalkyl); and (2) any of aforesaid carbocyclyl and heterocyclyl groups optionally substituted by one or more groups selected from C 1-4 alkyl, oxo, halogen and C 1-4 alkoxy; and

R 3 represents H, —C 1-4 alkyl or aryl with said aryl optionally substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, —C 1-6 thioalkyl, —SOC 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkoxy-, —O—C 3-8 cycloalkyl, C 3-8 cycloalkyl, —SO 2 C 3-8 cycloalkyl, —SOC 3-6 cycloalkyl, C 3-6 alkenyloxy-, C 3-6 alkynyloxy-, —C(O)C 1-6 alkyl, —C(O)OC 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-, nitro, halogen, cyano, hydroxyl, —C(O)OH, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl) and, —C(O)NH(C 3-10 cycloalkyl),

(ii) R 2 represents phenyl substituted by phenyl, phenyl substituted by a monocyclic heteroaryl group, phenyl substituted by benzyloxy, phenyl fused to carbocyclyl, phenyl fused to heterocyclyl, —C 1-4 alkyl(phenyl substituted by phenyl), —C 1-4 alkyl(phenyl substituted by a monocyclic heteroaryl group), —C 1-4 alkyl(phenyl substituted by benzyloxy), —C 1-4 alkyl(optionally substituted phenyl fused to optionally substituted carbocyclyl or —C 1-4 alkyl(optionally substituted phenyl fused to optionally substituted heterocyclyl) with (1) any of said phenyl, benzyloxy and heteroaryl groups optionally substituted by one or more groups selected from C 1-4 alkyl, halogen and C 1-4 alkoxy and (2) any of said carbocyclyl and heterocyclyl groups optionally substituted by one or more groups selected from C 1-4 alkyl, oxo, halogen and C 1-4 alkoxy; and

R 3 represents H, —C 1-4 alkyl or aryl with said aryl optionally substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, —C 1-6 thioalkyl, —SOC 1-4 alkyl, —SO 2 C 1-4 alkyl, C 1-6 alkoxy-, —O—C 3-8 cycloalkyl, C 3-8 cycloalkyl, —SO 2 C 3-8 cycloalkyl, —SOC 3-6 cycloalkyl, C 3-6 alkenyloxy-, C 3-6 alkynyloxy-, —C(O)C 1-6 alkyl, —C(O)OC 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl-, nitro, halogen, cyano, hydroxyl, —C(O)OH, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)N(C 1-4 alkyl)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl) and, —C(O)NH(C 3-10 cycloalkyl),

(iii) R 2 and R 3 are joined to form a carbocyclyl ring which is optionally substituted by one or more C 1-2 alkyl groups,

(iv) R 2 and R 3 are joined to form a carbocyclyl ring which is fused to phenyl, with said carbocyclyl or phenyl optionally substituted by one or more groups selected from C 1-4 alkyl, halogen and C 1-4 alkoxy, and

(v) R 2 and R 3 are joined to form a carbocyclyl ring which is fused to monocyclic heteroaryl with said carbocyclyl or heteroaryl optionally substituted by one or more groups selected from C 1-4 alkyl, halogen and C 1-4 alkoxy;

(f) R 4 represents H, —C 1-8 alkyl, —C(O)C 1-6 alkyl or —NH 2 ;

(g) X represents O or S; and

(h) Y represents O or S.