MEK inhibitors useful in the treatment of diseases

1. A compound of Formula (I)

wherein

R 1 is H or F;

R 2 is Br or I;

R 4 is H, F, Cl, or Br;

represents a double or single bond;

X and Y are independently selected from

H,

OH,

OR 3 , or

NH 2 ,

provided that when represents a double bond, X and Y are H;

Z is H, F, or OR 3 ;

wherein R 3 is C 1 -C 6 alkyl; and

A and A′ are independently H, or C 1 -C 6 alkyl;

or

A and A′, together with the C atom to which they are attached, form a cyclopropyl, cyclobutyl or cyclopentyl ring;

or a pharmaceutically acceptable salt, solvate or tautomer thereof.

2. A compound of Formula (Ia)

wherein

R 1 is H or F;

R 2 is Br or I;

R 4 is H, F, Cl, or Br;

and

Z is H, F, OR 3 , wherein R 3 is C 1 -C 6 alkyl;

or a pharmaceutically acceptable salt, solvate, or tautomer thereof.

3. A compound of claim 2 wherein

R 1 is H or F;

R 2 is Br or I;

R 4 is H, F, Cl, or Br, and

Z is H, F, or OMe;

or a pharmaceutically acceptable salt, solvate or tautomer thereof.

4. A compound of Formula (Ic):

wherein

R 1 is H or F;

R 2 is Br or I;

R 4 is H, F, Cl, or Br;

Z is H, F, or R 3 ,

or a pharmaceutically acceptable salt, solvate or tautomer thereof.

5. A compound selected from

6. A compound selected from

7. A method of treating arthritis in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound of Formula (I), or a pharmaceutically acceptable salt, solvate, or tautomer thereof.

8. A method of treating cancer, comprising administering to a subject in need thereof an effective amount of a compound of Formula (I), wherein the cancer is selected from the group consisting of colon cancer, liver cancer, melanoma, and non-small cell lung cancer.

9. A pharmaceutical composition comprising an effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt, solvate, or tautomer thereof.

10. A method of inhibiting a MEK enzyme, comprising contacting the enzyme with an effective inhibitory amount of a compound of Formula (I).