EP2 receptor agonists
A compound of formula (I): or a salt, or chemically protected form thereof, wherein: R 5 is an optionally substituted phenyl; A is wherein Q is N; R 3 is selected from H, F, Cl and optionally substituted C 1-4 alkyl, C 1-4 alkoxy, C 5-7 aryl, and C 5-7 aryl-C 1-4 alkyl groups; R 4 is selected from H, F, Cl and optionally substituted C 1-4 alkyl, C 1-4 alkoxy, C 5-7 aryl, and C 5-7 aryl-C 1-4 alkyl groups; R 6 is selected from H, F, Cl, and optionally substituted C 1-4 alkyl, C 1-4 alkoxy, C 5-7 aryl, and C 5-7 aryl-C 1-4 alkyl groups; D is selected from: B is selected from the group consisting of: Where R N′ is selected from H and C 1-4 alkyl; where one of R P3 and R P4 is —C m -alkylene-R 2 and the other of R P3 and R P4 is H, m and n can be 0 or 1, and m+n=1 or 2; and additionally, when R P3 is —C m -alkylene-R 2 , m can also be 2 or 3, and m+n=1, 2, 3 or 4, and when R 2 is tetrazol-5-yl, m+n may be 0; or where one of R P3 and R P4 is —O—CH 2 —R 2 , and the other of R P3 and R P4 is H, n is 0; R N is H or optionally substituted C 1-4 alkyl; R 2 is either: (i) —CO 2 H; (ii) —CONH 2 ; (iii) —CH 2 —OH; or (iv) tetrazol-5-yl.
1. A compound of formula (I):
or a salt, or chemically protected form thereof, wherein:
R 5 is an optionally substituted phenyl;
A is:
wherein Q is N;
R 3 is selected from H, F, Cl and optionally substituted C 1-4 alkyl, C 1-4 alkoxy, C 5-7 aryl and C 5-7 aryl-C 1-4 alkyl groups;
R 4 is selected from H, F, Cl and optionally substituted C 1-4 alkyl, C 1-4 alkoxy, C 5-7 aryl and C 5-7 aryl-C 1-4 alkyl groups;
R 6 is selected from H, F, Cl and optionally substituted C 1-4 alkyl, C 1-4 alkoxy, C 5-7 aryl and C 5-7 aryl-C 1-4 alkyl groups;
D is selected from:
B is selected from the group consisting of:
where R N′ is selected from H and C 1-4 alkyl;
where one of R P3 and R P4 is —C m alkylene-R 2 and the other of R P3 and R P4 is H, m and n can be 0 or 1, and m+n=1 or 2; and additionally when R P3 is —C m alkylene-R 2 , m can also be 2 or 3, and m+n=1, 2, 3 or 4, and when R 2 is tetrazol-5-yl, m+n may be 0; or
where one of R P3 and R P4 is —O—CH 2 —R 2 , and the other of R P3 and R P4 is H, n is 0;
R N is H or optionally substituted C 1-4 alkyl;
R 2 is either:
(i) —CO 2 H (carboxy);
(ii) —CONH 2 ;
(iii) —CH 2 —OH (methoxy); or
(iv) tetrazol-5-yl.
2. The compound according to claim 1 , wherein R 5 is phenyl and is substituted by one or more substituents selected from: C 1-4 alkyl, C 1-4 alkoxy, C 5-6 aryl, halo, acyl, amino, alkoxylene.
3. A compound according to claim 1 , wherein either:
(i) R 3 , R 4 and R 6 are H; or
(ii) one of R 3 , R 4 and R 6 are Cl or F.
4. A compound according to claim 1 , wherein D is:
5. A compound according to claim 4 , wherein R N is H.
6. A compound according to claim 1 , wherein B is:
7. A compound according to claim 1 , wherein R 2 is carboxy or tetrazoly-5-yl.
8. A compound according to claim 7 , wherein R 2 is carboxy.
9. A compound according to claim 1 , wherein R P4 is H, and R P3 is —CH═CH—R 2 .
10. A compound according to claim 1 , wherein R P3 is —O—CH 2 —R 2 .
11. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.
12. The compound according to claim 1 wherein R5 is phenyl optionally substituted by one or more halo substituents.
13. A compound wherein the compound is:
{3-[(6-Phenyl-pyridine-2-carbonyl)-amino]-phenyl}-acetic acid;
6-Phenyl-pyridine-2-carboxylic acid [3-(1 H-tetrazol-5ylmethyl)-phenyl]-amide;
6-(4-Fluoro-phenyl)-pyridine-2-carboxylic acid [3-(1H-tetrazol-5ylmethyl)-phenyl]-amide;
6-(3-Fluoro-phenyl)-pyridine-2-carboxylic acid [3-(1H-tetrazol-5ylmethyl)-phenyl]-amide;
6-(4-chloro-phenyl)-pyridine-2-carboxylic acid [3-(1H-tetrazol-5ylmethyl)-phenyl]-amide;
3-(3-{[6-(3-Fluoro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-acrylic acid;
(3-{[6-(3-Fluoro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-acetic acid;
(3-{[6-(3-Chloro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-acetic acid;
3-(3-{[6-(3,5-Dichloro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-acrylic acid;
(3-{[6-(3,5-Dichloro-phenyl)-pyridine-2-carbonyl]-amino}-phenoxy)-acetic acid;
3-(3-{[6-(3,5-Dichloro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-propionic acid;
S-{[6-(3,5-Dichloro-phenyl)-pyridine-2-carbonyl]-amino}-1H-indole-2-carboxylic acid;
3-(3-{[6-(3-Chloro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-acrylic acid;
(3-{[6-(3-Chloro-phenyl)-pyridine-2-carbonyl]-amino}-phenoxy)-acetic acid;
(3-{[6-(4-Chloro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-acetic acid
3-(3-{[6-(4-Chloro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-acrylic acid;
(3-{[6-(4-Fluoro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-acetic acid
(3-{[6-(4-Chloro-phenyl)-pyridine-2-carbonyl]-amino}-phenoxy)-acetic acid;
3-(3-{[6-(4-Fluoro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-acrylic acid;
(3-{[6-(4-Fluoro-phenyl)-pyridine-2-carbonyl]-amino}-phenoxy)-acetic acid;
3-(3-{[6-(4-Fluoro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-propionic acid;
3-(3-{[6-(3-Fluoro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-propionic acid;
3-{3-[(6-Phenyl-pyridine-2-carbonyl)-amino]-phenyl}-propionic acid;
3-{3-[(6-Phenyl-pyridine-2-carbonyl)-amino]-phenyl}-propionic acid;
(3-{[6-(3-Fluoro-phenyl)-pyridine-2-carbonyl]-amino}-phenoxy)-acetic acid;
6-Phenyl-pyridine-2-carboxylic acid [3-(IH-tetrazol-5ylmethoxy)-phenyl]-amide;
6-Phenyl-pyridine-2-carboxylic acid {3-[2-(IH-tetrazol-5yl)-vinyl]-phenyl}-amide; or
3-{3-[(6-Phenyl-pyridine-2-carbonyl)-amino]-phenyl}-acrylic acid.
14. The compound of claim 13 wherein the compound is:
3-(3-{[6-(3-Fluoro-phenyl)-pyridine-2-carbonyl]-amino}-phenyl)-acrylic acid;
(3-{[6-(3,5-Dichloro-phenyl)-pyridine-2-carbonyl]-amino}-phenoxy)-acetic acid;
6-Phenyl-pyridine-2-carboxylic acid {3-[2-(IH-tetrazol-5yl)-vinyl]-phenyl}-amide; or
3-{3-[(6-Phenyl-pyridine-2-carbonyl)-amino]-phenyl}-acrylic acid.
15. The compound of claim 1 wherein D is (i) or (ii).