Use of small molecule inhibitors targeting EYA tyrosine phosphatase

1. A method of treating a disease in an individual, comprising:

selecting or identifying an individual having a disease selected from the group consisting of proliferative retinopathy, retinopathy of prematurity, diabetic retinopathy, age related macular degeneration, retinal vasculitis, and exudative vitreoretinopathy;

administering to the individual an effective amount of a compound having the structure of Formula I:

or a pharmaceutically acceptable salt thereof,

wherein:

R 1 is selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, heterocyclyl, arylalkyl, heteroarylalkyl, heterocyclylalkyl, cycloalkyl, cycloalkenyl, (cyclolalkyl)alkyl, and amino, said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, heterocyclyl, arylalkyl, heteroarylalkyl, heterocyclylalkyl, cycloalkyl, cycloalkenyl, and (cyclolalkyl)alkyl are each optionally substituted with one or more R 1A ;

each R 1A is independently selected from the group consisting of hydroxy, halo, cyano, nitro, C 1-6 alkyl optionally substituted with up to 5 fluoro, C 1-6 alkoxy optionally substituted with up to 5 fluoro;

R 2 is selected from the group consisting of halo, hydroxy, and C 1-6 alkyl substituted with one or more hydroxy;

R 3 is selected from the group consisting of halo, hydroxy, and C 1-6 alkyl substituted with one or more hydroxy;

R 4 is halo;

R 5 and R 6 are each independently selected from the group consisting of H (hydrogen), halo, cyano, C 1-6 alkyl, aryl, heteroaryl, heterocyclyl, and amino, said C 1-6 alkyl, aryl, heteroaryl, and heterocyclyl each optionally substituted with one or more R 1A ;

X 1 is absent

X 2 is absent

Y 1 is O (oxygen);

each Z is CR 2A ; and

each R 2A is independently selected from the group consisting of H (hydrogen), halo, hydroxy, O-carbamyl, N-carbamyl, C-amido, S-sulfonamido, N-sulfonamido, C-carboxy, amino, aryl, heteroaryl, heterocyclyl, arylalkyl, heteroarylalkyl, heterocyclyl alkyl, cycloalkyl, cycloalkenyl, (cyclolalkyl)alkyl, C 1-6 alkyl substituted with one or more hydroxyl, and C 1-6 alkyl optionally substituted with up to 5 fluoro; and

with the proviso that the compound is not:

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

3. The method of claim 1 , wherein the compound of Formula I has the structure of Formula III:

or a pharmaceutically acceptable salt thereof,

wherein:

R 3 is halo or hydroxy;

R 2AA is H (hydrogen) or hydroxyl; and

R 2AB is H (hydrogen) or hydroxyl.

4. The method of claim 3 , wherein R 2AA is hydroxyl.

5. The method of claim 3 , wherein R 2AB is H (hydrogen).

6. The method of claim 1 , wherein R 1 is C 1-6 alkyl optionally substituted with one or more R 1A .

7. The method of claim 1 , wherein R 1 is ethyl.

8. The method of claim 1 , wherein R 2 is iodo or bromo.

9. The method of claim 1 , wherein R 4 is iodo or bromo.