Method for Treating Macular Degeneration

1 . A method for preventing, treating or ameliorating choroidal neovascularization in a patient, comprising administering to the patient an effective amount of a compound that modulates the patient's immune system, wherein the immune system has a type I immune responses and a type II immune responses, such that administering the compound to the patient increases the type I immune responses in the patient as compared to the type I immune responses in the patient prior to administering of the compound.

2 . The method of claim 1 , wherein the compound is selected from the group consisting of:

(a) a syk multikinase inhibitor;

(b) an hPGDS inhibitor; and

(c) a DP antagonist.

3 . The method of claim 2 , wherein the syk multikinase inhibitor is selected from the group consisting of phosphoric acid mono-{6-[5-fluoro-2-(3,4,5-trimethoxy-phenylamino)-pyrimidin-4-ylamino]-2,2-dimethyl-3-oxo-2,3-dihydro-pyrido[3,2-b][1,4]oxazin-4-ylmethyl}ester acetic acid salt

and 2-[4-(7-ethyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]-propan-2-ol

4 . The method of claim 2 , wherein the hPGDS inhibitor is selected from the group consisting of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid indol-1-ylamide

2-Pyridin-2-yl-pyrimidine-5-carboxylic acid 3-[5-(1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-benzylamide

and

4-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amide

5 . The method of claim 2 , wherein the DP antagonist is 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid phosphoric acid salt

6 . The method of claim 1 , wherein the compound modulates the activity of an immunocyte in the patient.

7 . The method of claim 6 , wherein the immunocyte comprises a natural killer cell (NK cell), a natural killer T cell (NKT cell), a mast cell, a dendritic cell, a granulocyte selected from the group consisting of an eosinophil, a basophil and neutrophil, or any combination thereof.

8 . The method of claim 1 , wherein the preventing, treating or ameliorating choroidal neovascularization also prevents, treats or ameliorates wet macular degeneration in the patient.

9 . The method of claim 1 , wherein the preventing, treating or ameliorating choroidal neovascularization also prevents, treats or ameliorates age-related macular degeneration in the patient.

10 . A method for treating, ameliorating or preventing macular degeneration in a patient, comprising administering to the patient an effective amount of a compound that modulates the patient's immune system, wherein the immune system has a type I immune responses and a type II immune responses, such that administering the compound to the patient increases the type I immune responses in the patient as compared to the type I immune responses in the patient prior to administering of the compound.

11 . The method of claim 10 , wherein the macular degeneration in the patient is age-related macular degeneration.

12 . The method of claim 10 , wherein the compound modulates the activity of an immunocyte in the patient.

13 . The method of claim 12 , wherein the immunocyte comprises a natural killer cell (NK cell), a natural killer T cell (NKT cell), a mast cell, a dendritic cell, a granulocyte selected from the group consisting of an eosinophil, a basophil and a neutrophil, or any combination thereof.

14 . The method of claim 10 , wherein the compound is selected from the group consisting of:

(a) a syk multikinase inhibitor;

(b) an hPGDS inhibitor; and

(c) a DP antagonist.

15 . The method of claim 14 , wherein the syk multikinase inhibitor is phosphoric acid mono-{6-[5-fluoro-2-(3,4,5-trimethoxy-phenylamino)-pyrimidin-4-ylamino]-2,2-dimethyl-3-oxo-2,3-dihydro-pyrido[3,2-b][1,4]oxazin-4-ylmethyl}ester acetic acid salt

16 . The method of claim 14 , wherein the hPGDS inhibitor is selected from the group consisting of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid indol-1-ylamide

2-Pyridin-2-yl-pyrimidine-5-carboxylic acid 3-[5-(1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-benzylamide

and

4-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amide

17 . The method of claim 14 , wherein the DP antagonist is 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid phosphoric acid salt

18 . A method for preventing, treating or ameliorating macular degeneration in a patient, comprising administering to the patient an effective amount of a compound that modulates the patient's immune system, wherein the immune system has a type I immune responses and a type II immune responses, such that administering the compound to the patient increases the type I immune responses in the patient as compared to the type I immune responses in the patient prior to administering of the compound.

19 . The method of claim 18 , wherein the macular degeneration in the patient is age-related macular degeneration.

20 . The method of claim 18 , wherein the administration of the compound also prevents, treats or ameliorates choroidal neovascularization in the patient.

21 . The method of claim 18 , wherein the compound modulates the activity of an immunocyte in the patient.

22 . The method of claim 21 , wherein the immunocyte comprises a natural killer cell (NK cell), a natural killer T cell (NKT cell), a mast cell, a dendritic cell, a granulocyte selected from the group consisting of an eosinophil, a basophil and a neutrophil, or any combination thereof.

23 . The method of claim 18 , wherein the compound is selected from the group consisting of:

(a) a syk multikinase inhibitor;

(b) an hPGDS inhibitor; and

(c) a DP antagonist.

24 . The method of claim 23 , wherein the syk multikinase inhibitor is phosphoric acid mono-{6-[5-fluoro-2-(3,4,5-trimethoxy-phenylamino)-pyrimidin-4-ylamino]-2,2-dimethyl-3-oxo-2,3-dihydro-pyrido[3,2-b][1,4]oxazin-4-ylmethyl}ester acetic acid salt

25 . The method of claim 23 , wherein the hPGDS inhibitor is selected from the group consisting of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid indol-1-ylamide

2-Pyridin-2-yl-pyrimidine-5-carboxylic acid 3-[5-(1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-benzylamide

and

4-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amide

26 . The method of claim 23 , wherein the DP antagonist is 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid phosphoric acid salt

27 . A method of treating, preventing or ameliorating macular degeneration in a patient having an immune system which has a type I immune responses and a type II immune responses, the method comprising administering to the patient an effective amount of a compound that modulates the activity of an immunocyte in the patient, wherein the immunocyte that comprises a natural killer cell (NK cell), a natural killer T cell (NKT cell), a mast cell, a dendritic cell, a granulocyte selected from the group consisting of an eosinophil, a basophil and a neutrophil, or any combination thereof, which increases the type I immune responses in the patient relative to the type I immune responses in the patient prior to administering the compound, and the increase in the type I responses treats, ameliorates or prevents choroidal neovascularization in the patient.

28 . The method of claim 27 , wherein the macular degeneration is age-related macular degeneration.

29 . The method of claim 27 , wherein the compound is selected from the group consisting of:

(a) a syk multikinase inhibitor;

(b) an hPGDS inhibitor; and

(c) a DP antagonist.

30 . The method of claim 29 , wherein the syk multikinase inhibitor is selected from the group consisting of:

phosphoric acid mono-{6-[5-fluoro-2-(3,4,5-trimethoxy-phenylamino)-pyrimidin-4-ylamino]-2,2-dimethyl-3-oxo-2,3-dihydro-pyrido[3,2-b][1,4]oxazin-4-ylmethyl}ester Acetic Acid Salt acetic acid salt; and

2-[4-(7-ethyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]-propan-2-ol.

31 . The method of claim 29 , wherein the hPGDS inhibitor is selected from the group consisting of:

2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid indol-1-ylamide;

2-Pyridin-2-yl-pyrimidine-5-carboxylic acid 3-[5-(1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-benzylamide; and

4-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amide.

32 . The method of claim 29 , wherein the DP antagonist is 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid phosphoric acid salt.

33 . A method of preventing, treating or ameliorating wet macular degeneration in a patient having an immune system which has a type I immune responses and a type II immune responses, the method comprising administering to the patient an effective amount of a compound that modulates the activity of an immunocyte in the patient, wherein the immunocyte comprises a natural killer cell (NK cell), a natural killer T cell (NKT cell), a mast cell, a dendritic cell, a granulocyte selected from the group consisting of an eosinophil, a basophil and a neutrophil, or any combination thereof, so that the type I immune responses in the patient are increased relative to the type I immune responses prior to administering the compound, and the increase in the type I responses treats, ameliorates or prevents choroidal neovascularization in the patient, wherein the compound is selected from the group consisting of:

(a) phosphoric acid mono-{6-[5-fluoro-2-(3,4,5-trimethoxy-phenylamino)-pyrimidin-4-ylamino]-2,2-dimethyl-3-oxo-2,3-dihydro-pyrido[3,2-b][1,4]oxazin-4-ylmethyl}ester acetic acid salt;

(b) 2-[4-(7-ethyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]-propan-2-ol;

(c) 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid indol-1-ylamide;

(d) 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid phosphoric acid salt;

(e) 2-Pyridin-2-yl-pyrimidine-5-carboxylic acid 3-[5-(1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-benzylamide; and

(f) 4-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amide.

34 . A method of preventing, treating or ameliorating macular degeneration in a patient having an immune system which has a type I immune responses and a type II immune responses, the method comprising administering to the patient an effective amount of a compound that modulates the activity of an immunocyte in the patient, wherein the immunocyte comprises a natural killer cell (NK cell), a natural killer T cell (NKT cell), a mast cell, a dendritic cell, a granulocyte selected from the group consisting of an eosinophil, a basophil and a neutrophil, or any combination thereof, so that the type I immune responses in the patient are increased relative to the type I immune responses prior to administering the compound, and the increase in the type I responses treats, ameliorates or prevents choroidal neovascularization in the patient, wherein the compound is selected from the group consisting of:

(a) phosphoric acid mono-{6-[5-fluoro-2-(3,4,5-trimethoxy-phenylamino)-pyrimidin-4-ylamino]-2,2-dimethyl-3-oxo-2,3-dihydro-pyrido[3,2-b][1,4]oxazin-4-ylmethyl}ester acetic acid salt;

(b) 2-[4-(7-ethyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenyl]-propan-2-ol;

(c) 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid indol-1-ylamide;

(d) 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid phosphoric acid salt;

(e) 2-Pyridin-2-yl-pyrimidine-5-carboxylic acid 3-[5-(1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-benzylamide; and

(f) 4-Methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amide.