Antagonists acting at multiple prostaglandin receptors for the treatment of inflammation

1. A compound of formula (I):

wherein:

A is selected from the group consisting of C 1 -C 3 alkylene and CO;

X is either CH or N, wherein:

when X is CH, R 3 is selected from the group consisting of:

and when X is N, R 3 is selected from the group consisting of:

W and Y are either C or N;

Z is either C or N, wherein:

when Z is C, R 1 is selected from the group consisting of C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, CH 2 OCH 3 , F, Cl, Br, halogen, OCF 3 , OCCl 3 , OCBr 3 and wherein C 1 -C 3 alkyl may be optionally substituted by hydroxyl, halogen, amine and functional amines,

and when Z is N, there is no R 1 substituent;

R 2 is selected from the group consisting of H, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, CH 2 OCH 3 , F, Cl, Br, halogen, and OCF 3 ;

R 4 and R 5 are independently selected from the group consisting of C 1 -C 3 alkyl and substituted C 1 -C 3 alkyl, and when R 3 is

R 4 and R 5 can be joined to form a C 3 -C 6 cycloalkyl;

Het is selected from the group consisting of:

wherein:

R 6 is selected from the group consisting of OH, OCH 3 , OCH(CH 3 ) 2 , and NHSO 2 R 8 ;

R 7 is selected from the group consisting of H, CH 3 , CH 2 CH 3 , OCH 3 , CH 2 OH, CH 2 OCH 3 , NH 2 , C 1 -C 3 alkylamino, and C 1 -C 3 dialkylamino;

R 8 is selected form the group consisting of C 1 -C 3 alkyl and substituted C 1 -C 3 alkyl; and,

R 9 is selected from the group consisting of O, OH, CH 3 , halogen and OCH 3 the dashed bond represents the presence of a single or double bond;

and wherein the compounds can be in the form of a tautomer, a racemate, an enantiomer, a diastereomer, or a pharmaceutically acceptable salt.

2. The compound of claim 1 , wherein A is C 1 -C 3 alkyl.

3. The compound of claim 1 , wherein A is CO.

4. The compound of claim 2 , wherein A is CH 2 .

5. The compound of claim 1 , wherein Z is C and X is N.

6. The compound of claim 5 , wherein R 3 is selected from group consisting of:

7. The compound of claim 6 , where R 1 is halogen.

8. The compound of claim 6 , wherein R 2 is H.

9. The compound of claim 1 , wherein Het is selected from the group consisting of:

10. The compound of claim 9 , wherein Het is:

11. The compound of claim 9 wherein Het is:

12. The compound of claim 1 wherein Z is C, R 1 is Cl or Br and R 7 is H or NCH 3 .

13. The compound of claim 12 wherein X is N, R 6 is OH and R 3 is

14. The compound of claim 13 selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1 selected from the group consisting of:

1-(5-Chloro-1-isobutyl-1H-indazol-7-ylmethyl)-1H-indazole-5-carboxylic acid;

1-(5-Bromo-1-isobutyl-1H-indazol-7-ylmethyl)-1H-indazole-5-carboxylic acid;

1-(5-Fluoro-1-isobutyl-1H-indazol-7-ylmethyl)-1H-indazole-5-carboxylic acid;

1-(1-Isobutyl-5-trifluoromethyl-1H-indazol-7-ylmethyl)-1H-indazole-5-carboxylic acid;

1-(1-Isobutyl-5-trifluoromethoxy-1H-indazol-7-ylmethyl)-1H-indazole-5-carboxylic acid;

1-(5-Bromo-1-isopropyl-1H-indazol-7-ylmethyl)-1H-indazole-5-carboxylic acid;

1-[5-Bromo-1-(2-ethyl-butyl)-1H-indazol-7-ylmethyl]-1H-indazole-5-carboxylic acid;

1-[5-Chloro-1-(2-propyl)-1H-indazol-7-ylmethyl]-1H-indazole-5-carboxylic acid;

1-(5-Chloro-1-isobutyl-1H-indazol-7-ylmethyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid;

1-(5-Chloro-1-isobutyl-1H-indazol-7-ylmethyl)-1H-benzoimidazole-5-carboxylic acid;

3-(5-Chloro-1-isobutyl-1H-indazol-7-ylmethyl)-3H-imidazo[4,5-b]pyridine-6-carboxylic acid;

1-(5-Chloro-1-isobutyl-1H-indazol-7-ylmethyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid;

1-(5-Bromo-1-isobutyl-1H-indazol-7-ylmethyl)-3-methyl-1H-indazole-5-carboxylic acid;

1-(5-Bromo-1-isobutyl-1H-indazol-7-ylmethyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic HCl salt;

1-(1-Isobutyl-5-trifluoromethyl-1H-indazol-7-ylmethyl)-1H-benzoimidazole-5-carboxylic acid;

1-(1-Isobutyl-5-trifluoromethoxy-1H-indazol-7-ylmethyl)-1H-benzoimidazole-5-carboxylic acid;

3-[(5-Chloro-1-isobutyl-indazol-7-yl)methyl]imidazo[1,5-a]pyridine-7-carb oxylic acid;

1-(5-Chloro-1-isobutyl-1H-indazol-7-ylmethyl)-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid;

3-Amino-1-[(5-chloro-1-isobutyl-indazol-7-yl)methyl]indazole-5-carboxylic acid;

1-[(5-Chloro-1-isobutyl-indazol-7-yl)methyl]-3-(methylamino)indazole-5-carboxylic acid;

or a pharmaceutically acceptable salt thereof.

16. A method of treating a patient suffering from a condition selected from the group consisting of inflammatory pain, neuropathic pain, visceral pain, and fibrosis, the method comprises administering to said patient an effective amount of a compound of claim 1 .

17. A pharmaceutical composition comprising a compound of claim 1 and one or more pharmaceutically acceptable excipients.