EP

1. A pharmaceutical composition comprising a compound of

formula (I):

or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or diluent, wherein:

R 2 is H or an optionally substituted C 1-4 alkyl group; Y is —(CH 2 ) n —X—, where n is 1 or 2 and X is O, S, S(═O), or S(═O) 2 ;

R 3 is an optionally substituted C 6 aryl group linked to a further optionally substituted C 6 aryl group, wherein if both C 6 aryl groups are benzene rings, there may be an oxygen bridge between the two rings, bound adjacent the link on both rings;

A is a single bond or a C 1-3 alkylene group; and

R 5 is either:

(i) carboxy;

(ii) a group of formula (II):

or

(iii) a group of formula (III):

wherein R is optionally substituted C 1-7 alkyl, C 5-20 aryl or NR N3 R N4 , where R N3 and R N4 are independently selected from

optionally substituted C 1-4 alkyl; or

(iv) tetrazol-5-yl.

2. A compound of formula (I):

or a salt, solvate or chemically protected form thereof,

wherein:

R 2 is H or an optionally substituted C 1-4 alkyl group;

Y is —(CH 2 ) n —X—, where n is 1 or 2 and X is O, S, S(═O), or S(═O) 2 ;

R 3 is an optionally substituted C 6 aryl group linked to a further optionally substituted C 6 aryl group, wherein if both C 6 aryl groups are benzene rings, there may be an oxygen bridge between the two rings, bound adjacent the link on both rings;

A is a single bond or a C 1-3 alkylene group; and

R 5 is either:

(i) carboxy;

(ii) a group of formula (II):

or

(iii) a group of formula (III):

wherein R is optionally substituted C 1-7 alkyl, C 5-20 aryl or NR N3 R N4 , where R N3 and R N4 are independently selected from optionally substituted C 1-4 alkyl; or

(iv) tetrazol-5-yl,

except that when R 2 is methyl, Y is —CH 2 —O— and R 5 is carboxy or C 1-7 alkyl ester thereof, then R 3 is not;

3. The compound according to claim 2 , wherein R 2 is selected from H, methyl, CF 3 or iso-propyl.

4. The compound according to claim 3 , wherein R 2 is methyl.

5. The compound according to claim 2 , wherein n is 1.

6. The compound according to claim 5 , wherein X is selected from O and S.

7. The compound according to claim 2 , wherein the C 6 aryl groups of R 3 are independently selected from those derived from benzene and heteroaryl groups, where the heteroatom or heteroatoms are nitrogen.

8. The compound according to claim 7 , wherein the C 6 aryl groups of R 3 are independently selected from those derived from benzene, pyridine and 1,3-pyrimidine.

9. The compound according to claim 2 , wherein A is a single bond.

10. The compound according to claim 2 , wherein A is a C 1-3 alkylene group.

11. The compound according to claim 2 , wherein R 5 is

either:

(i) a group of formula (II):

or

(ii) a group of formula (III):

12. The compound according to claim 11 , wherein R is selected from an optionally substituted C 5-20 aryl group, and an optionally substituted C 5-20 aryl-C 1-7 alkyl group.

13. A method of treating a primary headache disorder by antagonism of an EP4 receptor, which method comprises administering to a patient in need of said treating a pharmaceutical composition of claim 1 .

14. A method of treating a primary headache disorder by antagonism of an EP4 receptor, which method comprises administering to a patient in need of said treating a compound of claim 2 .

15. A method of treating a primary headache disorder by antagonism of an EP4 receptor, which method comprises administering to a patient in need of said treating a compound of claim 3 .

16. A method of treating a primary headache disorder by antagonism of an EP4 receptor, which method comprises administering to a patient in need of said treating a compound of claim 4 .

17. A method of treating a primary headache disorder by antagonism of an EP4 receptor, which method comprises administering to a patient in need of said treating a compound of claim 5 .

18. A method of treating a primary headache disorder by antagonism of an EP4 receptor, which method comprises administering to a patient in need of said treating a compound of claim 6 .

19. A method of treating a primary headache disorder by antagonism of an EP4 receptor, which method comprises administering to a patient in need of said treating a compound of claim 7 .

20. A method of treating a primary headache disorder by antagonism of an EP4 receptor, which method comprises administering to a patient in need of said treating a compound of claim 8 .

21. A method of treating a primary headache disorder by antagonism of an EP4 receptor, which method comprises administering to a patient in need of said treating a compound of claim 9 .

22. A method of treating a primary headache disorder by antagonism of an EP4 receptor, which method comprises administering to a patient in need of said treating a compound of claim 10 .

23. A method of treating a primary headache disorder by antagonism of an EP4 receptor, which method comprises administering to a patient in need of said treating a compound of claim 11 .

24. A method of treating a primary headache disorder by antagonism of an EP4 receptor, which method comprises administering to a patient in need of said treating a compound of claim 12 .

25. A compound of formula (I):

or a salt, solvate and chemically protected form thereof, wherein:

R 2 is selected from H, methyl, CF 3 or iso-propyl;

Y is —CH 2 —X— and X is O or S;

R 3 is an optionally substituted C 6 aryl group linked to a further optionally substituted C 6 aryl group and wherein the said C 6 aryl groups are independently selected from those derived from benzene and heteroaryl groups, where the heteroatom or heteroatoms are nitrogen and wherein if both C 6 aryl groups are benzene rings, there may be an oxygen bridge between the two rings, bound adjacent the link on both rings;

A is a single bond or a C 1-3 alkylene group; and

R 5 is either:

(i) carboxy;

(ii) a group of formula (II):

or

(iii) a group of formula (III):

wherein R is optionally substituted C 1-7 alkyl, C 5-20 aryl or NR N3 R N4 , where R N3 and R N4 are independently selected from optionally substituted C 1-4 alkyl; or

(iv) tetrazol-5-yl,

Wherein the substitution on the C 6 aryls of R 3 is selected from the group consisting of —CH 3 , —CF 3 —CH 2 OH, —OMe-OCF 3 —OEt-OCHF 2 —SMe, —NMe 2 , F, Cl, —CN, —O—CH2-O— and —C(═O)Me

except that when R 2 is methyl, Y is —CH 2 —O— and R 5 is carboxy or C 1-7 alkyl ester thereof, then R 3 is not:

26. A compound of formula (I):

or a salt, solvate and chemically protected form thereof, wherein:

R 2 is methyl

Y is —(CH) n —X— wherein n is 1 or 2 and X is O or S;

R 3 is an optionally substituted C 6 aryl group linked to a further optionally substituted C 6 aryl group and wherein the said C 6 aryl groups are independently selected from those derived from benzene, pyridine and 1,3-pyrimidine and wherein if both C 6 aryl groups are benzene rings, there may be an oxygen bridge between the two rings, bound adjacent the link on both rings;

A is a single bond or a C 1-3 alkylene group; and

R 5 is either:

(i) a group of formula (II):

or

(ii) a group of formula (III):

wherein R is optionally substituted C 5-20 aryl group or an optionally substituted C 5-20 aryl-C 1-7 alkyl group

Wherein the substitution on the C 6 aryls of R 3 is selected from the group consisting of —CH 3 , —CF 3 —CH 2 OH, —OMe-OCF 3 —OEt-OCHF 2 —SMe, —NMe 2 , F, Cl, —CN, —O—CH2-O— and —C(═O)Me, and

wherein the C 5-20 aryl group and C 5-20 aryl-C 1-7 alkyl groups of R are optionally substituted by C 1-4 alkyl.

27. A compound of formula (I):

or a salt, solvate and chemically protected form thereof, wherein:

R 2 is methyl;

Y is —CH 2 —X— and X is O or S;

R 3 is an optionally substituted C 6 aryl group linked to a further optionally substituted C 6 aryl group wherein one of the said C 6 aryl groups is derived from benzene and the other from pyridine or 1,3-pyrimidine;

A is a single bond or a C 1-3 alkylene group; and

R 5 is either:

(i) a group of formula (II):

or

(ii) a group of formula (III):

wherein R is optionally substituted C 5-20 aryl group, and an optionally substituted C 5-20 aryl-C 1-7 alkyl group

Wherein the substitution on the C 6 aryls of R 3 is selected from the group consisting of —CH 3 , —CF 3 —CH 2 OH, —OMe-OCF 3 —OEt-OCHF 2 —SMe, —NMe 2 , F, Cl, —CN, —O—CH2-O— and —C(═O)Me, and

wherein the C 5-20 aryl group and C 5-20 aryl-C 1-7 alkyl groups of R are optionally substituted by C 1-4 alkyl.

28. A compound of formula (I):

or a salt, solvate and chemically protected form thereof, wherein:

R 2 methyl;

Y is —CH 2 —O—;

R 3 is an optionally substituted C 6 aryl group linked to a substituted C 6 aryl group wherein one of the said C 6 aryl groups is derived from benzene and the other from pyridine and wherein only the ring not bound to Y is substituted;

A is a single bond or a C 1-3 alkylene group; and

R 5 is a group of formula (II):

Wherein the substitution on the C 6 aryls of R 3 is selected from the group consisting of —CH 3 , —CF 3 —CH 2 OH, —OMe-OCF 3 —OEt-OCHF 2 —SMe, —NMe 2 , F, Cl, —CN, —O—CH2-O— and —C(═O)Me, and

wherein the C 5-20 aryl group and C 5-20 aryl-C 1-7 alkyl groups of R are optionally substituted by C 1-4 alkyl.

29. A compound of formula (I):

or a salt, solvate and chemically protected form thereof, wherein:

R 2 methyl;

Y is —CH 2 —X— where X is O or S;

R 3 is an optionally substituted C 6 aryl group linked to a further optionally substituted C 6 aryl group wherein one of the said C 6 aryl groups is derived from benzene and the other from pyridine the pyridine derived group being furthest from the furan core and wherein only the ring not bound to Y is substituted;

A is a single bond; and

R 5 is a group of formula (II):

Wherein the substitution on the substituted C 6 aryl of R 3 is selected from the group consisting of —CH 3 , —CF 3 —CH 2 OH, —OMe-OCF 3 —OEt-OCHF 2 —SMe, —NMe 2 , F, Cl, —CN, —O—CH2-O— and —C(═O)Me, and

wherein the C 5-20 aryl group and C 5-20 aryl-C 1-7 alkyl groups of R are optionally substituted by C 1-4 alkyl.

30. A compound of formula (I):

or a salt, solvate and chemically protected form thereof, wherein:

R 2 methyl;

Y is —CH 2 —O—;

R 3 is an optionally substituted C 6 aryl group linked to a further optionally substituted C 6 aryl group wherein one of the said C 6 aryl groups is derived from benzene and the other from pyridine and wherein only the ring not bound to Y is substituted;

A is a single bond; and

R 5 is a group of formula (II):

Wherein the substitution on the substituted C 6 aryl of R 3 is selected from the group consisting of —CH 3 , —CF 3 —CH 2 OH, —OMe-OCF 3 —OEt-OCHF 2 —SMe, —NMe 2 , F, Cl, —CN, —O—CH2-O— and —C(═O)Me, and

wherein the C 5-20 aryl group and C 5-20 aryl-C 1-7 alkyl groups of R are optionally substituted by C 1-4 alkyl.