Triazole-substituted imidazo[1,2-a]pyrimidines as cGAS inhibitors

1. A compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof,

wherein

R 1 is hydrogen or a prodrug moiety;

R 2 is selected from the group consisting of hydrogen, halo, cyano, nitro, C 1-3 alkyl, halo (C 1-3 ) alkyl, halo (C 1-3 ) alkoxy, —S(O) R 7 , —SO 2 R 7 , —C(O) NR 7 R 8 , —NR 7 C(O) R 8 , —CO 2 R 7 , wherein C 1-3 alkyl, halo (C 1-3 ) alkyl, and halo (C 1-3 ) alkoxy is optionally substituted by hydroxyl or —NR 7 R 8 ;

R 3 is a 5- or 6-membered heteroaryl optionally substituted by C 1-3 alkyl, —C(O) R 8 or a prodrug moiety;

each R 4 , R 5 and R 6 is independently-L-Y;

each L is independently selected from a bond, —(CR a R b ) n —, —O—, —(CR a R b ) n O—, —O ( C R a R b ) n —, or —(CR a R b ) n O(CR a R b ) m —;

wherein each n or m is independently 1, 2 or 3;

each R a and R b is independently selected from hydrogen, halo and methyl;

each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-7 cycloalkyl, C 2-4 alkenyl, C 1-4 thioalkyl, C 1-6 hydroxyalkyl, C 1-4 cyanoalkyl, halo (C 1-4 ) alkyl, halo (C 2-4 ) alkenyl, —NR 9 R 10 , —C(O) NR 9 R 10 , —CO 2 R 10 , —C(O) R 10 , —SO 2 R 10 , —OSO 2 R 10 , —S(O) R 10 , —SO 2 NR 9 R 10 , —N(R 10 ) SO 2 R 10 , —CF 2 CH 2 OR 10 , phenyl, 5- or 6-membered heteroaryl, and 4- to 10-membered heterocycloalkyl ring containing one, two or three heteroatoms independently selected from N, O and S, wherein the C 3-7 cycloalkyl, phenyl, heteroaryl and heterocycloalkyl groups are optionally substituted with one, two or three substituents independently selected from halo, hydroxyl, —C(O) R 10 , oxo, C 1-4 alkyl, halo (C 1-4 ) alkyl and C 1-4 hydroxyalkyl; or

R 4 and R 5 taken together with the carbon atoms to which they are attached form a 5- to 8-membered monocyclic or bicyclic ring which optionally contains one or two heteroatoms independently selected from N, O and S, wherein the ring is optionally substituted with one, two or three substituents independently selected from halo, C 1-4 alkyl, oxo, —C(O) R 10 and —SO 2 R 10 ;

R 7 and R 8 are independently selected from hydrogen and C 1-4 alkyl;

R 9 is independently selected from the group consisting of hydrogen, C 1 -4 alkyl, —C(O) C 1-4 alkyl and halo (C 1-4 ) alkyl; and

R 10 is independently selected from hydrogen and C 1-6 alkyl; or

wherein R 9 and R 10 taken together with the nitrogen atom to which they are attached form a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O and S, wherein the heterocycloalkyl is optionally substituted with oxo;

wherein each prodrug moiety is independently selected from the group consisting of —CH(R c )O—P(O)(OR d ) (OR e ), —CH(R c )O—C(O)—C 1-6 alkylene-O—P(O)(OR d ) (OR e ), —CH(R c )O—C(O)—C 1-6 alkylene-P(O)(OR d ) (OR e ), —CH(R c )O—C(O)—C 1-6 alkylene-CO 2 H, —CH(R c )O—C(O) R d , —CH(R c )O—C(O)O—C 1-6 alkylene-CO 2 H, —CH(R c )O—C(O)—C 1-6 alkylene-NR d R e , —CH(R c )O—C(O)O—C 1-6 alkylene-NR d R e , —C(O) R d , —CH(R c )O—C(O)—C 1-6 alkylene-heterocycloalkyl, —CH(R c )O—C(O)—C 1-6 alkylene-heterocycloalkyl and —CR d R e —O—(C(O)—NR d -heteroarylene-CH 2 O—C(O)—CH 2 —NR d R e , wherein each heterocycloalkyl is 4- to 6-membered and contains one or two heteroatoms independently selected from N, O and S, and each heteroarylene is 5- or 6-membered and contains one or two heteroatoms independently selected from N, O and S;

wherein R c is independently selected from hydrogen and methyl; and

R d and R e are each independently hydrogen or C 1-6 alkyl.

2. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 , wherein R 3 is a 5-membered heteroaryl.

3. A compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof,

wherein

R 1 is hydrogen or a prodrug moiety;

R 2 is selected from the group consisting of hydrogen, halo, cyano, nitro, C 1-3 alkyl, halo (C 1-3 ) alkyl, halo (C 1-3 ) alkoxy, —S(O) R 7 , —SO 2 R 7 , —C(O) NR 7 R 8 , —NR 7 C(O) R 8 , —CO 2 R 7 , wherein C 1-3 alkyl, halo (C 1-3 ) alkyl, and halo (C 1-3 ) alkoxy is optionally substituted by hydroxyl or —NR 7 R 8 ;

R 3 is imidazolyl or pyrazolyl, where R 3 is optionally substituted by C 1-3 alkyl, —C(O) R 8 or a prodrug moiety;

each R 4 , R 5 and R 6 is independently-L-Y;

each L is independently selected from a bond, —(CR a R b ) n —, —O—, —(CR a R b ) n O—, —O ( C R a R b ) n —, or —(CR a R b ) n O(CR a R b ) m —;

wherein each n or m is independently 1, 2 or 3;

each R a and R b is independently selected from hydrogen or methyl;

each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-7 cycloalkyl, C 2-4 alkenyl, C 1-4 thioalkyl, C 1-6 hydroxyalkyl, C 1-4 cyanoalkyl, halo (C 1 -4) alkyl, halo (C 2-4 ) alkenyl, —NR 9 R 10 , —C(O) NR 9 R 10 , —CO 2 R 10 , —C(O) R 10 , —SO 2 R 10 , —OSO 2 R 10 , —S(O) R 10 , —SO 2 NR 9 R 10 , —N(R 10 ) SO 2 R 10 , —CF 2 CH 2 OR 10 , phenyl, 5- or 6-membered heteroaryl, and 4- to 10-membered heterocycloalkyl ring containing one, two or three heteroatoms independently selected from N, O and S, wherein the C 3-7 cycloalkyl, phenyl, heteroaryl and heterocycloalkyl groups are optionally substituted with one, two or three substituents independently selected from halo, hydroxyl, —C(O) R 10 , oxo, C 1-4 alkyl, halo (C 1-4 ) alkyl and C 1-4 hydroxyalkyl; or

R 4 and R 5 taken together with the carbon atoms to which they are attached form a 5- to 8-membered monocyclic or bicyclic ring which optionally contains one or two heteroatoms independently selected from N, O and S, wherein the ring is optionally substituted with one, two or three substituents independently selected from halo, C 1-4 alkyl, oxo, —C(O) R 10 and —SO 2 R 10 ;

R 7 and R 8 are independently selected from hydrogen and C 1-3 alkyl;

R 9 is independently selected from the group consisting of hydrogen, C 1-4 alkyl, —C(O) C 1-4 alkyl and halo (C 1-4 ) alkyl; and

R 10 is independently selected from hydrogen and C 1-6 alkyl; or

wherein R 9 and R 10 taken together with the nitrogen atom to which they are attached form a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O and S, wherein the heterocycloalkyl is optionally substituted with oxo;

wherein each prodrug moiety is independently selected from the group consisting of —CH(R c )O—P(O)(OR d ) (OR e ), —CH(R c )O—C(O)—C 1-6 alkylene-O—P(O)(OR d ) (OR e ), —CH(R c )O—C(O)—C 1-6 _alkylene-P(O)(OR d ) (OR e ), —CH(R c )O—C(O)—C 1-6 alkylene-CO 2 H, —CH(R c )O—C(O) R d , —CH(R c )O—C(O)O—C 1-6 alkylene-CO 2 H, —CH(R c )O—C(O)—C 1-6 alkylene-NR d R e , —CH(R c )O—C(O)O—C 1-6 alkylene-NR d R e , —C(O) R d , —CH(R c )O—C(O)—C 1-6 alkylene-heterocycloalkyl, —CH(R c )O—C(O)—C 1-6 alkylene-heterocycloalkyl and —CR d R e —O—(C(O)—NR d -heteroarylene-CH 2 O—C(O)—CH 2 —NR d R e , wherein each heterocycloalkyl is 4- to 6-membered and contains one or two heteroatoms independently selected from N, O and S, and each heteroarylene is 5- or 6-membered and contains one or two heteroatoms independently selected from N, O and S;

wherein R c is independently selected from hydrogen and methyl; and

R d and R e are each independently hydrogen or C 1-6 alkyl.

4. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 , wherein R a and R b are hydrogen.

5. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 , wherein each prodrug moiety is independently selected from the group consisting of —CH 2 O—P(O)(OR d ) (OR e ), —CH 2 O—C(O)—C 1-6 alkylene-O—P(O)(OR d ) (OR e ), —CH 2 O—C(O)—C 1-6 alkylene-P(O)(OR d ) (OR e ), —CH 2 O—C(O)—C 1-6 alkylene-CO 2 H, —CH 2 O—C(O)R d , —CH 2 O—C(O)O—C 1-6 alkylene-CO 2 H, —CH 2 O—C(O)—C 1-6 alkylene-NR d R e , —CH 2 O—C(O)O—C 1-6 alkylene-NR d R e , —C(O) R d , —CH 2 O—C(O)—C 1-6 alkylene-heterocycloalkyl, —CH 2 O—C(O)—C 1-6 alkylene-heterocycloalkyl and —CR d R e —O—(C(O)—NR d -heteroarylene-CH 2 O—C(O)—CH 2 —NR d R e ;

wherein R d and R e are each independently hydrogen or C 1-6 alkyl;

each heterocycloalkyl is 4- to 6-membered and contains one or two heteroatoms independently selected from N, O and S; and

each heteroarylene is 5- or 6-membered and contains one or two heteroatoms independently selected from N, O and S.

6. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 5 , wherein each prodrug moiety is independently selected from —CH 2 O—P(O)(OR d ) (OR e ), —CH 2 O—C(O)—C 1-6 alkylene-O—P(O)(OR d ) (OR e ), —CH 2 O—C(O)—C 1-6 alkylene-P(O)(OR d ) (OR e ), —CH 2 O—C(O)—C 1-6 alkylene-CO 2 H, —CH 2 O—C(O) R d , —CH 2 O—C(O)O—C 1-6 alkylene-CO 2 H, —CH 2 O—C(O)—C 1-6 alkylene-NR d R e , —CH 2 O—C(O)O—C 1-6 alkylene-NR d R e and —C(O) R d .

7. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 6 , wherein each prodrug moiety is independently selected from

8. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 , wherein each prodrug moiety is-CH 2 O—P(O)(OR d ) (OR e ).

9. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 8 , wherein each prodrug moiety is

10. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 , wherein R 3 is imidazolyl.

11. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 , wherein R 1 is a prodrug moiety selected from the group consisting of —CH(R c )O—P(O)(OR d ) (OR e ), —CH(R c )O—C(O)—C 1-6 alkylene-O—P(O)(OR d ) (OR e ), —CH(R c )O—C(O)—C 1-6 alkylene-P(O)(OR) (OR e ), —CH(R c )O—C(O)—C 1-6 alkylene-CO 2 H, —CH(R c )O—C(O) R d , —CH(R c )O—C(O)O—C 1-6 alkylene-CO 2 H, —CH(R c )O—C(O)—C 1-6 alkylene-NR d R e , —CH(R c )O—C(O)O—C 1-6 alkylene-NR d R e ;

wherein R c is independently selected from hydrogen and methyl;

R d and R e are each independently hydrogen or C 1-6 alkyl;

each heterocycloalkyl is 4- to 6-membered and contains one or two heteroatoms independently selected from N, O and S; and

each heteroarylene is 5- or 6-membered and contains one or two heteroatoms independently selected from N, O and S;

and R 3 is imidazolyl.

12. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 11 , wherein R 1 is

13. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 , wherein R 1 is hydrogen and R 3 is imidazolyl.

14. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 , wherein R 2 is selected from the group consisting of Br, cyano, —C(O) NH 2 , —CF 2 CH 2 NH 2 , —CF 2 CH 2 OH, —CH 2 F, —CHF 2 , —CF 3 , —CF 2 CF 3 , —CF 2 CH 3 , —CF 2 CHF 2 , —OCHF 2 and —S(O)CH 3 .

15. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 14 , wherein R 2 is-CF 3 .

16. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 , wherein each L is a bond.

17. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 16 , wherein each Y is independently selected from the group consisting of hydrogen, halo, cyano, C 1-4 alkyl, C 1-4 alkoxy, C 3-7 cycloalkyl, C 1-4 thioalkyl, C 1-6 hydroxyalkyl, C 1-4 cyanoalkyl, halo (C 1-4 ) alkyl, —NR 9 R 10 , —CO 2 R 10 , —C(O) R 10 , —CF 2 CH 2 OR 10 , and 4- to 10-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O and S where the heterocycloalkyl and C 3-7 cycloalkyl are optionally substituted with up to three substituents independently selected from halo, hydroxyl, —C(O) R 10 , oxo, C 1-4 alkyl, halo (C 1-4 ) alkyl and C 1-4 hydroxyalkyl; or

R 4 and R 5 taken together with the carbon atoms to which they are attached form a 5- to 8-membered monocyclic or bicyclic ring which optionally contains one or two heteroatoms independently selected from N, O and S, wherein the ring is optionally substituted with up to three substituents independently selected from halo, C 1-4 alkyl, oxo, —C(O) R 10 and —SO 2 R 10 .

18. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 , wherein each Y is independently selected from hydrogen, halogen, CO 2 R 10 and halo (C 1-4 ) alkyl.

19. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 , wherein R 6 is hydrogen.

20. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 , wherein R 4 and R 6 are hydrogen and R 5 is fluoro.

21. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof selected from the group consisting of:

5-[3-(1H-imidazol-4-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

5-[6-fluoro-3-(1H-imidazol-5-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

5-[3-(1H-imidazol-5-yl)-7-(trifluoromethyl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

5-[6-chloro-3-(1H-imidazol-4-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(difluoromethyl)-1H-1,2,4-triazole;

3-(difluoromethyl)-5-[6-fluoro-3-(1H-imidazol-4-yl) imidazo[1,2-a]pyrimidin-2-yl]-1H-1,2,4-triazole;

5-[7-chloro-3-(1H-imidazol-5-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

3-(difluoromethyl)-5-[7-(difluoromethyl)-3-(1H-imidazol-5-yl) imidazo[1,2-a]pyrimidin-2-yl]-1H-1,2,4-triazole;

5-[3-(1H-pyrazol-4-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

{4-oxo-4-[(4-{2-[3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]imidazo[1,2-a]pyrimidin-3-yl}-1H-imidazol-1-yl) methoxy]butoxy}phosphonic acid;

{4-oxo-4-[(5-{3-[1-({[4-(phosphonooxy) butanoyl]oxy}methyl)-1H-imidazol-4-yl]imidazo[1,2-a]pyrimidin-2-yl}-3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl) methoxy]butoxy}phosphonic acid;

({5-[6-fluoro-3-(1H-imidazol-5-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl}methoxy) phosphonic acid;

methyl 2-(3-bromo-1H-1,2,4-triazol-5-yl)-3-(1H-pyrazol-4-yl) imidazo[1,2-a]pyrimidine-7-carboxylate;

methyl 2-(3-bromo-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-4-yl) imidazo[1,2-a]pyrimidine-7-carboxylate;

3-bromo-5-[3-(1H-imidazol-4-yl) imidazo[1,2-a]pyrimidin-2-yl]-1H-1,2,4-triazole;

5-[6-fluoro-3-(1H-pyrazol-4-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

5-[6-chloro-3-(1H-imidazol-5-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

3-(difluoromethyl)-5-[3-(1H-imidazol-5-yl) imidazo[1,2-a]pyrimidin-2-yl]-1H-1,2,4-triazole;

5-[3-(1H-imidazol-5-yl)-6-(trifluoromethyl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

5-[6-bromo-3-(1H-imidazol-5-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

3-(difluoromethyl)-5-[3-(1H-imidazol-5-yl)-7-(trifluoromethyl) imidazo[1,2-a]pyrimidin-2-yl]-1H-1,2,4-triazole;

3-bromo-5-[3-(1H-imidazol-5-yl)-7-(trifluoromethyl) imidazo[1,2-a]pyrimidin-2-yl]-1H-1,2,4-triazole;

5-[3-(1H-pyrazol-4-yl)-7-(trifluoromethyl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

5-[7-(difluoromethyl)-3-(1H-imidazol-5-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

5-[3-(1H-imidazol-5-yl)-7-(trifluoromethyl) imidazo[1,2-a]pyrimidin-2-yl]-1H-1,2,4-triazole;

5-[3-(1H-imidazol-5-yl)-7-(trifluoromethyl) imidazo[1,2-a]pyrimidin-2-yl]-3-methyl-1H-1,2,4-triazole;

methyl 3-(1H-imidazol-4-yl)-2-[3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]imidazo[1,2-a]pyrimidine-7-carboxylate;

3-(1H-imidazol-4-yl)-2-[3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl]imidazo[1,2-a]pyrimidine-7-carboxylic acid;

3-(difluoromethoxy)-5-[3-(1H-imidazol-5-yl) imidazo[1,2-a]pyrimidin-2-yl]-1H-1,2,4-triazole;

5-[6-(difluoromethyl)-3-(1H-imidazol-4-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

5-[6-fluoro-3-(1H-imidazol-5-yl)-7-(trifluoromethyl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

5-[6-chloro-3-(1H-imidazol-5-yl)-7-(trifluoromethyl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

5-[3-(2-methyl-1H-imidazol-4-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole;

5-[3-(1-methyl-1H-pyrazol-4-yl) imidazo[1,2-a]pyrimidin-2-yl]-3-(trifluoromethyl)-1H-1,2,4-triazole; and

3-bromo-5-[6-fluoro-3-(1H-imidazol-4-yl) imidazo[1,2-a]pyrimidin-2-yl]-1H-1,2,4-triazole.

22. A compound according to claim 1 , which is

or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof.

23. A compound according to claim 1 , which is

wherein R 1 is a prodrug moiety selected from the group consisting of —CH(R c )O—P(O)(OR d ) (OR e ), —CH(R c )O—C(O)—C 1-6 alkylene-O—P(O)(OR d ) (OR e ), —CH(R c )O—C(O)—C 1-6 alkylene-P(O)(OR d ) (OR e ), —CH(R c )O—C(O)—C 1-6 alkylene-CO 2 H, —CH(R c )O—C(O) R d , —CH(R c )O—C(O)O—C 1-6 alkylene-CO 2 H, —CH(R c )O—C(O)—C 1-6 alkylene-NR d R e , —CH(R c )O—C(O)O—C 1-6 alkylene-NR d R e , —C(O) R d , —CH(R c )O—C(O)—C 1-6 alkylene-heterocycloalkyl, —CH(R c )O—C(O)—C 1-6 alkylene-heterocycloalkyl and —CR d R e —O—(C(O)—NR d -heteroarylene-CH 2 O—C(O)—CH 2 —NR d R e ;

wherein R c is independently selected from hydrogen and methyl;

R d and R e are each independently hydrogen or C 1-6 alkyl;

each heterocycloalkyl is 4- to 6-membered and contains one or two heteroatoms independently selected from N, O and S; and

each heteroarylene is 5- or 6-membered and contains one or two heteroatoms independently selected from N, O and S;

or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof.

24. A compound according to claim 23 , which is

or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof.

25. A pharmaceutical composition comprising (a) a compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 1 ; and (b) a pharmaceutically acceptable excipient.

26. The compound according to claim 22 , which is

or a tautomer thereof.

27. The compound according to claim 22 , which is

or a tautomer thereof.

28. A compound according to claim 24 , which is

or a tautomer thereof.