Chemical compounds

1. A compound of formula (1)

wherein:

R 1 and R 2 each independently represent a C 1-6 alkyl, C 3-6 alkenyl, C 3-6 cycloalkylC 1-3 alkyl or C 3-6 cycloalkyl; each of which may be optionally substituted by 1 to 3 halogen atoms;

R 3 a group —CON(R 10 )YR 11 or —SO 2 N(R 10 )YR 11 ;

wherein Y is O, S or NR 12 wherein R 12 is hydrogen or C 1-6 alkyl;

and R 10 and R 11 are independently C 1-6 alkyl optionally substituted by halo, hydroxy, amino, C 1-6 alkylamino or di-(C 1-6 alkyl)amino;

Q is —CO— or —C(R 4 )(R 5 )— wherein R 4 is a hydrogen atom or C 1-4 alkyl and R 5 is a hydrogen atom or hydroxy group;

Ar is a 5- to 10-membered aromatic ring system wherein up to 4 ring atoms may be heteroatoms independently selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted by one or more substituents independently selected from C 1-4 alkyl optionally substituted by 1, 2 or 3 hydroxy groups, C 1-4 alkoxy, halogen, haloalkyl, dihaloalkyl, trihaloalkyl, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylthio, C 1-4 alkoxycarbonyl, C 2-4 alkanoyl, oxo, thioxo, nitro, cyano, —N(R 6 )R 7 and —(CH 2 )pN(R 8 )R 9 , hydroxy, C 1-4 alkylsulphonyl, C 1-4 alkylsulphinyl, carbamoyl, C 1-4 alkylcarbamoyl, di-(C 1-4 alkyl)carbamoyl, carboxy, or a 5 or 6 membered aromatic ring containing up to 4 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulphur;

p is 1 to 4;

R 6 and R 7 each independently represent a hydrogen atom, C 1-4 alkanoyl or C 1-4 alkyl, or together with the nitrogen atom to which they are attached form a 5- to 7-membered saturated heterocyclic ring;

R 8 and R 9 each independently represent a hydrogen atom, C 1-4 alkanoyl or C 1-4 alkyl, or together with the nitrogen atom to which they are attached form a 5- to 7-membered saturated heterocyclic ring;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 wherein R 2 is methyl or ethyl.

3. A compound according to claim 1 wherein R 1 is ethyl, n-propyl, 1-methylethyl, 2-methylpropyl, 2,2-dimethylpropyl, cyclopropylmethyl, trifluoromethyl 2,2,2-trifluoroethyl, 2-chloroethyl, 2-chloropropyl or 3,3,3-trifluoropropyl.

4. A compound according to claim 1 wherein Q is —CO— or —CH 2 —.

5. A compound according to claim 1 wherein R 10 is C 1-4 alkyl optionally substituted by hydroxy.

6. A compound according to claim 1 wherein R 11 is C 1-4 alkyl optionally substituted by hydroxy.

7. A compound according to claim 1 wherein Y is O.

8. A compound according to claim 1 wherein R 3 is —CON(Me)OMe, —CON(Et)OMe, —CON(OEt)Me, —CON(Et)OEt, —CON(CH 2 CH 2 OH)OEt, —CON(CH 2 CH 2 OH)Me, —CON(OCH 2 CH 2 OH)Me or —CON(OCH 2 CH 2 OH)Et.

9. A compound according to claim 1 wherein Ar contains at least 1 ring nitrogen.

10. A compound according to claim 1 wherein Ar contains at least 2 ring nitrogen.

11. A compound according to claim 1 wherein Ar is selected from the group consisting of imidazolyl, pyrazolyl, pyrrolyl, isoxazolyl, phenyl, quinolyl, indolyl, benzimidazolyl, indazolyl, benztriazolyl, 2,3-dihydrothiazolyl, 2,3-dihydrobenzoxazolyl, pyrrolo [2,3-b]pyridyl, imidazo [1,2-a]pyridyl, imidazo [4,5-b]pyridyl, 2,3-dihydrothiazolo[5,4-b]pyridyl, 2,3-dihydropyrazinyl, 2,3-dihydrobenzothiazolyl and 2,3-dihydrobenzimidazolyl, each ring system being optionally substituted according to claim 1 .

12. A compound according to claim 1 wherein Ar is substituted by 1, 2 or 3 substituents independently selected from C 1-4 alkyl optionally substituted by 1 or 2 hydroxy groups, C 1-4 alkoxy, halogen, trihaloalkyl, C 1-4 alkylthio, C 1-4 alkoxycarbonyl, C 2-4 alkanoyl, oxo, thioxo, cyano, —NHR 7 and —(CH 2 )pN(R 8 )R 9 wherein p is 1 or 2, hydroxy, C 1-4 alkylsulphonyl, carbamoyl, C 1-4 alkylcarbamoyl, di-(C 1-4 alkyl)carbamoyl, carboxy, and a 5 or 6 membered aromatic ring containing up to 4 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulphur.

13. A compound according to claim 1 which is:

6-[(4,5-dichloro-2-methyl-1H-imidazol-1-yl)methyl]-1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-(4-quinolinylmethyl)thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-6-(1H-indol-3-ylmethyl)-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-6-(1H-indol-3-ylcarbonyl)-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

6-[(4,5-dichloro-2-methyl-1H-imidazol-1-yl)methyl]-1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(1-methylethyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-6-(1H-indazol-3-ylmethyl)-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

6-[(4,5-dichloro-2-methyl-1H-imidazol-1-yl)methyl]-1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-2,4-dioxo-1-propyl-thieno[2,3-d]pyrimidine-5-carboxamide;

1-(2,2-dimethylpropyl)-1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-2,4-dioxo-6-(quinolin-4-ylmethyl)-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-6-[[2-(1-methylethyl)-1H-imidazol-1-yl]methyl]-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-6-[[2-(methylthio)-1H-imidazol-1-yl]methyl]-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

6-[(2-chloro-1H-imidazol-1-yl)methyl]-1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-6-[2-(methylthio)-1H-benzimidazol-1-yl]-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-(2-hydroxyethyl)-N-methoxy-3-methyl-1-(2-methylpropyl)-6-[[2-(methylthio)-1H-imidazol-1-yl]methyl]-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-6-[[2-(methylamino)-1H-benzimidazol-1-yl]methyl]-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[(2-propyl-1H-benzimidazol-1-yl)methyl]-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[(2,3-dihydro-3-methyl-2-oxo-1H-benzimidazol-1-yl)methyl]-thieno[2,3-d]pyrimidine-5-carboxamide;

6-[(2,3-dihydro-2-oxo-benzothiazol-3-yl)methyl]-1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

6-[(1-acetyl-1H-indol-3-yl)methyl]-1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-6-[(2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

6-[(3-chloroquinolin-4-yl)methyl]-1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

N-methoxy-N,3-dimethyl-2,4-dioxo-1-propyl-6-(quinolin-4-ylmethyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxamide;

1-ethyl-N-methoxy-N,3-dimethyl-2,4-dioxo-6-(quinolin-4-ylmethyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxamide;

1-(cyclopropylmethyl)-N-methoxy-N,3-dimethyl-2,4-dioxo-6-(quinolin-4-ylmethyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-6-[(2-methyl-1H-indol-3-yl)methyl]-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-6-[2-methyl-1H-indol-3-ylmethyl]-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide;

N-methoxy-N,3-dimethyl-2,4-dioxo-1-propyl-6-(quinolin-4-ylmethyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxamide;

1-ethyl-N-methoxy-N,3-dimethyl-2,4-dioxo-6-(quinolin-4-ylmethyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxamide;

1-(cyclopropylmethyl)-N-methoxy-N,3-dimethyl-2,4-dioxo-6-(quinolin-4-ylmethyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxamide;

6-[4,5-dichloro-2-(hydroxymethyl)-1H-imidazol-1-ylmethyl]-1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-6-[2-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl]-2,4-dioxo-1-propyl-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(1-methylethyl)-6-[2-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl]-2,4-dioxo-thieno[2,3-d]pryimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[2-(trifluoromethyl)phenylmethyl]thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-(benzyl)thieno[2,3-d]pyrimidine-5-carboxamide;

methyl 4-[1,2,3,4-tetrahydro-5-[(N-methoxy-N-methylamino)carbonyl]-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidin-6-yl](hydroxy)methyl]-1-methyl-1H-pyrrole-2-carboxylate;

methyl 1-methyl-4-[1,2,3,4-tetrahydro-5-[(methoxymethylamino)carbonyl]-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidin-6-ylmethyl]-1H-pyrrole-2-carboxylate;

methyl 2,5-dimethyl-4-[1,2,3,4-tetrahydro-5-[(N-methoxy-N-methyl amino)carbonyl]-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidin-6-ylmethyl]-1H-pyrrole-3-carboxylate;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[2-oxo-3(2H-benzoxazolylmethyl]-thieno[2,3-d]pyrimidine-5-carboxamide;

1,2,3,4-tetrahydro-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[(2,4,5-trichloro-1H-imidazol-1-yl)methyl]-thieno[2,3-d]pyrimidine-5-carboxamide;

6-[4,5-dichloro-2-methyl-1H-imidazol-1-ylmethyl]-N-(2-hydroxyethyl)-1-isobutyl-N-methoxy-3-methyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxamide;

6-[4,5-dichloro-2-methyl-1H-imidazol-1-ylmethyl]-N-(2-hydroxyethoxy)-1-isobutyl-N,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carboxamide; and

6-[4,5-dichloro-2-methyl-1H-imidazol-1-ylmethyl]-N-ethyl-1,2,3,4-tetrahydro-N-methoxy-3-methyl-1-(2-methylpropyl)-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxamide;

or a pharmaceutically-acceptable salt thereof.

14. A process for the preparation of a compound of the formula (1) as defined in claim 1 , or a compound of the formula (1) as defined in claim 1 wherein at least 1 functional group is protected, using one of the following processes:

a) when R 3 is of the formula —CON(R 10 )Y(R 11 ), reacting a compound of the formula (10):

 with a compound of the formula HN(R 10 )Y(R 11 );

b) when R 1 is of the formula —SO 2 N(R 10 )Y(R 11 ), reacting a compound of the formula (11):

 with a compound of the formula HN(R 10 )Y(R 11 );

c) when Q is methylene, reacting a compound of the formula (12):

 with a compound of the formula Ar;

d) when Q is methylene, reducing a compound of the formula (13):

e) reacting a compound of the formula (14):

 with a compound of the formula L′-R 10 ; or

f) converting one compound of the formula (1) into another compound of the formula (1);

wherein L and L′ are leaving groups, X is —CO— or —SO 2 — and R 1 , R 2 , R 3 , R 10 , Q and Ar are as hereinabove defined and any functional groups are optionally protected;

and optionally after a), b), c), d), e) or f), converting the compound of the formula (1) into a further compound of formula (1) and/or forming a pharmaceutically-acceptable salt thereof.

15. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable adjuvant, diluent or carrier.