Tetrahydropyrrolopyrimidinediones and their use in therapy

1. A compound of formula (I):

wherein

A is selected from the group consisting of aryl and heteroaryl;

D is selected from the group consisting of oxygen and sulphur;

R 1 , R 2 , and R 3 are independently each selected from the group consisting of hydrogen, halogen, nitro, cyano, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, hydroxyl, C 1 -C 6 -alkoxy and C 2 -C 6 -alkenyloxy, wherein C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy can be further substituted with one to three identical or different radicals selected from the group consisting of halogen, hydroxy and C 1 -C 4 -alkoxy;

R 5 is hydrogen;

R and R 4 each independently represent a radical of formula —[X] m —[Alk 1 ] p -[Q] n -[Alk 2 ] q —[X 1 ] k —Z wherein

k, m, n, p and q are independently selected from 0 and 1;

Alk 1 and Alk 2 each independently represent an optionally substituted C 1 -C 6 alkylene or C 2 -C 6 alkenylene radical which may optionally contain an ether (—O—), thioether (—S—) or amino (—NR A —) link;

Q represents (i) a divalent radical selected from the group consisting of —O—, —S—, —S(═O)—, —S(═O) 2 —, —S + (R A )—, —N(R A )—, —N + (R A )(R B )—, —C(═O)—, —C(═O)O—, —OC(═O)—, —C(═O)NR A —, —NR A C(═O)—, —S(O 2 )NR A —, —NR A S(O 2 )—, —NR A C(═O)NR B —, —NR A C(═NR A )NR B —, —C(═NR D )NR E —, and —NR E C(═NR D )—, wherein R A , R B , R D and R E are independently, selected from the group consisting of hydrogen, C 1 -C 6 alkyl and C 3 -C 6 cycloalkyl, or R A and R B, or R D and R E taken together with the nitrogen to which they are attached form a monocyclic heterocyclic ring of 5 to 7 ring atoms which may contain a further heteroatom selected from N, O and S, or (ii) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 3-6 ring members;

X represents a divalent radical selected from the group consisting of —(C═O)—, —S(O 2 )—, —C(═O)O—, —(C═O)NR A — and —S(O 2 )NR A —, wherein

X 1 is selected from the group consisting of —O—, —S— and —NH; and

Z is hydrogen or an optionally substituted mono- or bicyclic carbocyclic or heterocyclic radical having 3-6 ring members; or a pharmaceutically acceptable salt thereof.

2. The compound as claimed in claim 1 wherein A is selected from the group consisting of phenyl, pyridyl and pyrimidinyl.

3. The compound as claimed in claim 1 wherein one of R 1 and R 2 is selected from the group consisting of methyl, —C≡CH and cyano.

4. The compound as claimed in claim 1 wherein —AR 1 R 2 is selected from the group consisting of 4-cyanophenyl and 4-ethynylphenyl.

5. The compound as claimed in claim 1 wherein D is O.

6. The compound as claimed in claim 1 wherein R 3 is selected from the group consisting of H, CF 3 , F, Cl and Br.

7. The compound as claimed in claim 1 wherein R 4 and/or R is a radical of formula —[X] m —[Alk 1 ] p -[Q] n -[Alk 2 ] q —[X 1 ] k —Z wherein m is 0; k, p, n and q are each 1; Q is —N(R A ) or —N + (R A )(R B )—; and R A , R B Alk 1 , Alk 2 , X 1 and Z are as defined in claim 1 .

8. The compound as claimed in claim 7 wherein X 1 is —O—.

9. The compound as claimed in claim 1 wherein one of R and R 4 is hydrogen.

10. The compound as claimed in claim 1 wherein R or R 4 is selected from the group consisting of C 1 -C 6 -alkyl, formyl, aminocarbonyl, mono- or di-C 1 -C 4 -alkylaminocarbonyl, C 3 -C 8 -cycloalkylcarbonyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, N—(C 1 -C 4 -alkylsulfonyl)-aminocarbonyl, N—(C 1 -C 4 -alkylsulfonyl)-N—(C 1 -C 4 -alkyl)-aminocarbonyl, heteroaryl, heterocycloalkyl, heteroarylcarbonyl and heterocycloalkylcarbonyl; wherein C 1 -C 6 -alkyl, mono- and di-C 1 -C 4 -alkylaminocarbonyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, heteroaryl and heterocycloalkyl can be substituted with one to three identical or different radicals selected from the group consisting of aryl, heteroaryl, hydroxyl, C 1 -C 4 -alkoxy, hydroxycarbonyl, C 1 -C 6 -alkoxycarbonyl, aminocarbonyl, mono and di-C 1 -C 4 -alkylaminocarbonyl, amino, mono- and di-C 1 -C 4 -alkylamino C 1 -C 4 -alkylcarbonylamino, cyano, N-(mono- and di-C 1 -C 4 -alkylamino-C 1 -C 4 -alkyl)-aminocarbonyl, N—(C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl)-aminocarbonyl and halogen.

11. The compound as claimed in claim 1 wherein R and/or R 4 represents a group of Formula (VIIIA), (VIIIB) or (VIIIC):

wherein R 4A is hydrogen or C 1 -C 6 -alkyl, and s is 1 or 2.

12. The compound as claimed in claim 1 wherein R and/or R 4 represents a group of Formula (IX)

wherein

R 4B is hydrogen or C 1 -C 6 -alkyl;

R 4C , R 4D , R 4E are each C 1 -C 6 -alkyl, and the nitrogen to which they are attached is quaternary and carries a positive charge; and additionally any two of R 4C , R 4D , R 4E may be joined to form a ring, optionally containing a second heteroatom selected from oxygen or nitrogen; or

one of R 4C , R 4D , R 4E is a lone pair and the other groups are as defined above, and the nitrogen to which they are attached is tertiary; and

v1 and v2 are each independently 0-5.

13. The compound as claimed in claim 1 wherein R and/or R 4 represents a group selected from the following:

wherein

R 4B is hydrogen or C 1 -C 6 -alkyl;

R 4C , R 4D , R 4E are each C 1 -C 6 -alkyl, and the nitrogen to which they are attached is quaternary and carries a positive charge; and additionally any two of R 4C , R 4D , R 4E may be joined to form a ring, optionally containing a second heteroatom selected from oxygen or nitrogen;

one of R 4C , R 4D , R 4E is a lone pair and the other groups are as defined above, and the nitrogen to which they are attached is tertiary;

R 4F and R 4I are independently hydrogen or C 1 -C 6 -alkyl;

R 4G and R 4H are independently hydrogen or C 1 -C 6 -alkyl, or R 4G and R 4H taken together with the nitrogen to which they are attached form a monocyclic heterocyclic ring of 5 to 7 ring atoms which may contain a further heteroatom selected from N, O and S; and

v1 and v2 are each independently 0-5.

14. A compound of claim 1 , wherein the compound is a pharmaceutically acceptable salt.