INHIBITORS OF INTEGRIN VLA-4

1 . A complex of formula I, its stereoisomer or pharmaceutically acceptable salt:

wherein:

W is a group that is A, B, or C:

R 1 is hydrogen, alkyl or alkoxy;

R 2 is a bond, hydrogen or alkyl;

R 3 , R 4 and R 5 are independently hydrogen, iodine, alkyl, alkoxy, hydroxyl, amino, aminoalkyl, dialkylamino, or carboxyl;

X is a bond, C═O, O═C—O, or CH 2 ;

Y is a bond, CH 2 , or O;

m is an integer ranging from 1 to 6;

n is an integer ranging from 0 to 6;

Metal represents a metallic moiety comprising a radionuclide; and

Chelate represents a chelating moiety that coordinates with said radionuclide to form the complex.

2 . The complex of claim 1 , wherein said radionuclide is technetium, rhenium, yttrium, indium, gallium, gadolinium, or copper.

3 . The complex of claim 1 , wherein said Chelate is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), diethylenetriaminepentaacetic acid (DTPA), pyridylmethylene amine (PDA), quinolinemethylene amine, isoquinoline amine, pyridine-2-ylmethylamino acetic acid (PAMA), isoquinolin-3-ylmethylamino acetic acid, thiazol-2-ylmethyl amine, thiazol-2-ylmethylamino acetic acid, N-methylimidazole(methylene)amine, N-methylimidazole(methylene)amino acetic acid NOTA, Hynic, MAG3, N 2 S 2 , MAMA, or DADT.

4 . The complex of claim 1 , wherein said Metal-Chelate moiety is D, E, F, G, H, or J:

wherein:

R 8 is selected from the group consisting of O, H, OH, alkoxy, or O-alkyl;

R 9 is a pharmaceutically acceptable 5 or 6-member heterocyclic ring;

R 10 and R 11 are each independently hydrogen, alkyl, or substituted alkyl;

R 12 is selected from the group consisting of aryl, alkyl, or heterocycle; and

R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 are independently hydrogen or methyl.

5 . The complex of claim 1 which has the structure of I-a:

6 . The complex of claim 1 which has the structure of I-b:

7 . The complex of claim 1 which has the structure of I-c:

8 . The complex of claim 1 which has the structure of I-d:

9 . The complex of claim 1 which has the structure of formula I-e:

10 . The complex of claim 1 which has the structure of formula I-f:

11 . A method of imaging tissue of a mammal which expresses VLA-4 comprising administering to said mammal an effective amount of a complex of formula I, its stereoisomer or pharmaceutical salt:

wherein:

W is a group that is A, B, or C:

R 1 is hydrogen, alkyl or alkoxy;

R 2 is a bond, hydrogen or alkyl;

R 3 , R 4 and R 5 are independently hydrogen, iodine, alkyl, alkoxy, hydroxyl, amino, aminoalkyl, dialkylamino, or carboxyl;

X is a bond, C═O, O═C—O, or CH 2 ;

Y is a bond, CH 2 , or O;

m is an integer ranging from 1 to 6;

n is an integer ranging from 0 to 6;

Metal represents a metallic moiety comprising a radionuclide; and

Chelate represents a chelating moiety that coordinates with said radionuclide to form the complex.

12 . The method of claim 11 , wherein said radionuclide is technetium, rhenium, yttrium, indium, gallium, gadolinium, or copper.

13 . The method of claim 11 , wherein said Chelate is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), diethylenetriaminepentaacetic acid (DTPA), pyridylmethylene amine (PDA), quinolinemethylene amine, isoquinoline amine, pyridine-2-ylmethylamino acetic acid (PAMA), isoquinolin-3-ylmethylamino acetic acid, thiazol-2-ylmethyl amine, thiazol-2-ylmethylamino acetic acid, N-methylimidazole(methylene)amine, N-methylimidazole(methylene)amino acetic acid NOTA, Hynic, MAG3, N 2 S 2 , MAMA, or DADT.

14 . The method of claim 11 , wherein said Metal-Chelate moiety is D, E, F, G, H, or J:

wherein:

R 8 is selected from the group consisting of O, H, OH, alkoxy, or O-alkyl;

R 9 is a pharmaceutically acceptable 5 or 6-member heterocyclic ring;

R 10 and R 11 are each independently hydrogen, alkyl, or substituted alkyl;

R 12 is selected from the group consisting of aryl, alkyl, or heterocycle; and

R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 are independently hydrogen or methyl.

15 . The method of claim 11 in which said complex is:

16 . A method of treating a mammal suffering a disease which is characterized by overexpression of VLA-4, the method comprising administering to said mammal a therapeutically effective amount of a complex of formula I, its stereoisomer or pharmaceutical salt:

wherein:

W is a group that is A, B, or C:

R 1 is hydrogen, alkyl or alkoxy;

R 2 is a bond, hydrogen or alkyl;

R 3 , R 4 and R 5 are independently hydrogen, iodine, alkyl, alkoxy, hydroxyl, amino, aminoalkyl, dialkylamino, or carboxyl;

X is a bond, C═O, O═C—O, or CH 2 ;

Y is a bond, CH 2 , or O;

m is an integer ranging from 1 to 6;

n is an integer ranging from 0 to 6;

Metal represents a metallic moiety comprising a radionuclide; and

Chelate represents a chelating moiety that coordinates with said radionuclide to form the complex.

17 . The method of claim 16 , wherein said radionuclide is technetium, rhenium, yttrium, indium, gallium, gadolinium, or copper.

18 . The method of claim 16 , wherein said Chelate is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), diethylenetriaminepentaacetic acid (DTPA), pyridylmethylene amine (PDA), quinolinemethylene amine, isoquinoline amine, pyridine-2-ylmethylamino acetic acid (PAMA), isoquinolin-3-ylmethylamino acetic acid, thiazol-2-ylmethyl amine, thiazol-2-ylmethylamino acetic acid, N-methylimidazole(methylene)amine, N-methylimidazole(methylene)amino acetic acid NOTA, Hynic, MAG3, N 2 S 2 , MAMA, or DADT.

19 . The method of claim 16 in which said Metal-Chelate moiety is D, E, F, G, H, or J:

wherein:

R 8 is selected from the group consisting of O, H, OH, alkoxy, or O-alkyl;

R 9 is a pharmaceutically acceptable 5 or 6-member heterocyclic ring;

R 10 and R 11 are each independently hydrogen, alkyl, or substituted alkyl;

R 12 is selected from the group consisting of aryl, alkyl, or heterocycle; and

R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 are independently hydrogen or methyl.

20 . The method of claim 16 in which said complex is:

21 . A kit comprising a complex of formula I, its stereoisomer or pharmaceutical salt:

wherein:

W is a group that is A, B, or C:

R 1 is hydrogen, alkyl or alkoxy;

R 2 is a bond, hydrogen or alkyl;

R 3 , R 4 and R 5 are independently hydrogen, iodine, alkyl, alkoxy, hydroxyl, amino, aminoalkyl, dialkylamino, or carboxyl;

X is a bond, C═O, O═C—O, or CH 2 ;

Y is a bond, CH 2 , or O;

m is an integer ranging from 1 to 6;

n is an integer ranging from 0 to 6;

Metal represents a metallic moiety comprising a radionuclide;

Chelate represents a chelating moiety that coordinates with said radionuclide to form the complex; and

a pharmaceutically acceptable carrier.