Selective protein tyrosine phosphatatase inhibitors

1. A compound of formula (I)

or a therapeutically acceptable salt, wherein

A is selected from the group consisting of

 wherein the dotted line is either absent or is a single bond;

B is selected from the group consisting of hydrogen, alkyl, aryl, arylalkyl,

D is selected from the group consisting of

wherein Z is selected from the group consisting of alkoxy, alkyl, amino, cyano, nitro, CO 2 P 1 , SO 3 H, PO(OH) 2 , CH 2 PO(OH) 2 , CHFPO(OH) 2 , CF 2 PO(OH) 2 , and C(═NH)NH 2 ;

wherein P 1 and P 2 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, cycloalkyl and (cycloalkyl)alkyl;

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, alkoxy, alkyl, aryl, arylalkyl, cyano, halo, haloalkoxy, haloalkyl, hydroxy, hydroxyalkyl, nitro, NR A R B , NR A R B C(O), NR A R B C(O)alkyl and NR A R B C(O)alkenyl, wherein R A and R B are independently selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, alkylsulfonyl, aryl, arylalkylcarbonyl, arylcarbonyl, arylsulfonyl and (R C R D N)carbonyl wherein R C and R D are independently selected from the group consisting of hydrogen, alkyl, aryl, and arylalkyl;

L is selected from the group consisting of —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —; —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p EC(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —; —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —; —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 (CH 2 ) q X 4 —; and —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p E(CH 2 ) q X 3 —, wherein each group is drawn with the left end attached to A and the right end attached to B;

m, n, p and q are independently between 0-4;

R 8 is selected from the group consisting of hydrogen, hydroxy, NR A R B and (NR A R B )alkyl;

R 9A and R 9B are independently selected from the group consisting of hydrogen, alkyl, hydroxyalkyl and R E R F Nalkyl, wherein R E and R F are independently selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl and alkanoyl, or R 9A and R 9B taken together are oxo;

R 10 is selected from the group consisting of hydrogen, alkyl, alkanoyl and alkoxycarbonyl;

R 11 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, cycloalkyl, and (cycloalkyl)alkyl;

E is selected from the group consisting of aryl and cycloalkyl;

X 1 , X 2 , X 3 , and X 4 are independently absent or are independently selected from the group consisting of NR G , O, S, S(O) and S(O) 2 , wherein R G is selected from the group consisting of hydrogen, alkyl, alkanoyl and alkoxycarbonyl; and

W 1 , W 2 , W 3 and W 4 are independently selected from the group consisting of CH, CH 2 , N, NH and O.

2. The compound according to claim 1 of formula (II)

or a therapeutically acceptable salt wherein A, B, L, P 1 , P 2 , R 1 , R 2 , and R 3 are defined in claim 1 .

3. The compound according to claim 2 , wherein A is selected from the group consisting of

R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, hydroxy, hydroxyalkyl, nitro, NR A R B , NR A R B C(O), NR A R B C(O)alkyl and NR A R B C(O)alkenyl;

R 10 is selected from the group consisting of hydrogen and alkyl; and

R 11 is independently selected from the group consisting of hydrogen, alkyl and arylalkyl.

4. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —.

5. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —; and

R 8 is NR A R B .

6. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ; and

R 9A and R 9B together are oxo.

7. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B ))X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo; and

X 2 is NR C .

8. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B ))X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ; and

B is aryl.

9. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B ))X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

B is aryl; and

A is

10. The compound according to claim 9 , which is

N-[5-({N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethylphenylalanyl}amino)pentanoyl]-L-tyrosine.

11. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B ))X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ; and

B is hydrogen.

12. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B ))X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

B is hydrogen; and

A is

13. The compound according to claim 12 , which is

N-[5-({N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethylphenylalanyl}amino)pentanoyl]-L-norleucine.

14. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p EC(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —.

15. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p EC(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —; and

R 8 is NR A R B .

16. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p EC(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ; and

R 9A and R 9B together are oxo.

17. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p EC(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo; and

X 2 is NR C .

18. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p EC(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ; and

B is hydrogen.

19. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 4 )C(R 9A )(R 9B )X 2 (CH 2 ) p EC(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

B is hydrogen; and

E is cycloalkyl.

20. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p EC(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

B is hydrogen;

E is cycloalkyl; and

A is

21. The compound according to claim 20 , which is N-{[4-({[N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-(2-hydroxyethyl)phenylalanyl]amino}methyl)cyclohexyl]carbonyl}-L-norleucine.

22. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B ))X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is S; and

B is alkyl.

23. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B ))X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is S;

B is alkyl; and

A is

24. The compound according to claim 23 , selected from the group consisting of

N-{5-[(N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethylphenylalanyl)amino]pentanoyl}-L-methionine;

methyl N-{5-[(N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethylphenylalanyl)amino]pentanoyl}-L-methioninate;

N-{5-[(N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethylphenylalanyl)amino]pentanoyl}-S-ethyl-L-homocysteine;

N-{5-[(N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-isopropylphenylalanyl)amino]pentanoyl}-L-methionine;

N-{5-[(N-acetyl-4-[(carboxycarbonyl)(2-carboxy-5-chlorophenyl)amino]-3-ethylphenylalanyl)amino]pentanoyl}-L-methionine; and

N-(5-{[N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-(2-hydroxyethyl)phenylalanyl]amino}pentanoyl)-L-methionine.

25. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B ))X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is S; and

B is aryl.

26. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B ))X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is S;

B is aryl; and

A is

27. The compound according to claim 26 , which is

N-{5-[(N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethylphenylalanyl)amino]pentanoyl}-S-benzyl-L-cysteine.

28. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B ))X 2 (CH 2 ) p C(O)N(R 10 )CH(CO 2 R 11 )(CH 2 ) q X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is S;

B is alkyl; and

A is

29. The compound according to claim 28 , which is

N-(5-{[3-(4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-1-naphthyl)-N-(methoxycarbonyl)alanyl]amino}pentanoyl)-L-methionine.

30. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —.

31. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —; and

R 8 is NR A R B .

32. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is NR A R B ; and

R 9A and R 9B together are oxo.

33. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo; and

is NR C .

34. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ; and

X 3 is O.

35. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R B )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is O; and

B is aryl.

36. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is O;

B is aryl; and

A is

37. The compound according to claim 36 , selected from the group consisting of

methyl 2-[4-({N-[(allyloxy)carbonyl]-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-L-phenylalanyl}amino)butoxy]-6-hydroxybenzoate;

methyl 2-{4-[(N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethylphenylalanyl)amino]butoxy}-6-hydroxybenzoate;

methyl 4-{4-[(N-acetyl-4-amino-3-ethylphenylalanyl)amino]butoxy}-2-hydroxy-1,1′-biphenyl-3-carboxylate;

2-[4-({N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethylphenylalanyl}amino)butoxy]-6-hydroxybenzoic acid;

methyl 6-{4-[(N-acetyl-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethylphenylalanyl)amino]butoxy}-3-bromo-2-hydroxybenzoate;

methyl 2-(4-{[4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-L-phenylalanyl]amino}butoxy)-6-hydroxy-4-pentylbenzoate;

methyl 2-(4-{[4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-L-phenylalanyl]amino}butoxy)-6-hydroxy-4-methoxybenzoate;

methyl 3-(4-{[4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-L-phenylalanyl]amino}butoxy)-5-hydroxy-1,1′-biphenyl-4-carboxylate;

methyl 2-(4-{[4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-L-phenylalanyl]amino}butoxy)-6-hydroxy-4-methylbenzoate;

methyl 2-(4-{[4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-L-phenylalanyl]amino}butoxy)-4-chloro-6-hydroxybenzoate;

methyl 2-(4-{[4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-L-phenylalanyl]amino}butoxy)-6-hydroxybenzoate;

4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-{4-[2-(aminocarbonyl)-3-hydroxyphenoxy]butyl}-N-(methoxycarbonyl)-L-phenylalaninamide;

methyl 3-(4-{[4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-L-phenylalanyl]amino}butoxy)-1-hydroxy-2-naphthoate;

4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(4-{3-hydroxy-2-[(methylamino)carbonyl]phenoxy}butyl)-N-(methoxycarbonyl)-L-phenylalaninamide;

4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(4-{2-[(ethylamino)carbonyl]-3-hydroxyphenoxy}butyl)-N-(methoxycarbonyl)-L-phenylalaninamide;

N-{4-[2-(acetylamino)-3-hydroxyphenoxy]butyl}-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(methoxycarbonyl)-L-phenylalaninamide; and

4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-N-(4-{2-[(dimethylamino)carbonyl]-3-hydroxyphenoxy}butyl)-N-(methoxycarbonyl)-L-phenylalaninamide.

38. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is O;

B is aryl; and

A is

39. The compound according to claim 38 , selected from the group consisting of

methyl 2-[(5-{[N-acetyl-3-(4-amino-1-naphthyl)-L-alanyl]amino}pentyl)oxy]-6-hydroxy-4-methylbenzoate; and

3-({5-[(N-acetyl-3-{4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-1-naphthyl}-L-alanyl)amino]pentyl}oxy)-2-naphthoic acid.

40. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —; and

R 8 is hydrogen.

41. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen; and

R 9A and R 9B together are oxo.

42. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen;

R 9A and R 9B together are oxo; and

X 2 is NR C .

43. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen;

R 9A and R 9B together are oxo;

X 2 is NR C ; and

X 3 is O.

44. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is O; and

B is aryl.

45. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is O; and

B is aryl; and

A is

46. The compound according to claim 45 , which is

methyl 2-(4-{[3-(4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-3-ethylphenyl)propanoyl]amino}butoxy)-6-hydroxybenzoate.

47. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is O;

B is aryl; and

A is

48. The compound according to claim 47 , which is

2-((carboxycarbonyl){4-[3-({4-[3-hydroxy-2-(methoxycarbonyl)phenoxy]butyl}amino)-3-oxopropyl]-[(carboxycarbonyl)(2-carboxyphenyl)amino]-1-naphthyl}amino)benzoic acid.

49. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen; and

R 9A is alkyl.

50. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen;

R 9A is alkyl; and

X 2 is NR C .

51. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen;

R 9A is alkyl;

X 2 is NR C ; and

X 3 is O.

52. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen;

R 9A is alkyl;

X 2 is NR C ;

X 3 is O; and

B is aryl.

53. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen;

R 9A is alkyl;

X 2 is NR C ;

X 3 is O;

B is aryl; and

A is

54. The compound according to claim 53 , which is

methyl 2-(4-{[3-(4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-1-naphthyl)-1-methylpropyl]amino}butoxy)-6-hydroxybenzoate.

55. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen; and

R 9A and R 9B are both hydrogen.

56. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen;

R 9A and R 9B are both hydrogen; and

X 2 is NR C .

57. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 ;

R 8 is hydrogen;

R 9A and R 9B are both hydrogen;

X 2 is NR C ; and

X 3 is O.

58. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen;

R 9A and R 9B are both hydrogen;

X 2 is NR C ;

X 3 is O; and

B is aryl.

59. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 —;

R 8 is hydrogen;

R 9A and R 9B are both hydrogen;

X 2 is NR C ;

X 3 is O;

B is aryl; and

A is

60. The compound according to claim 59 , which is methyl 2-(4-{[3-(4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-1-naphthyl)propyl]amino}butoxy)-6-hydroxybenzoate.

61. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 (CH 2 ) q X 4 —.

62. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R B )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 (CH 2 ) q X 4 —; and

R 8 is NR A R B .

63. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 (CH 2 ) q X 4 —;

R 8 is NR A R B ; and

R 9A and R 9B together are oxo.

64. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 (CH 2 ) q X 4 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo; and

X 2 is NR C .

65. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 (CH 2 ) q X 4 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ; and

X 3 is O.

66. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 (CH 2 ) q X 4 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is O; and

X 4 is O.

67. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 (CH 2 ) q X 4 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is O;

X 4 is O; and

B is aryl.

68. The compound according to claim 2 , wherein

L is —(CH 2 ) m X 1 (CH 2 ) n CH(R 8 )C(R 9A )(R 9B )X 2 (CH 2 ) p X 3 (CH 2 ) q X 4 —;

R 8 is NR A R B ;

R 9A and R 9B together are oxo;

X 2 is NR C ;

X 3 is O;

X 4 is O;

B is aryl; and

A is

69. The compound according to claim 68 , which is

methyl 2-{2-(2-({N-[(allyloxy)carbonyl]-4-[(carboxycarbonyl)(2-carboxyphenyl)amino)-L-phenylalanyl}amino)ethoxy]ethoxy}-6-hydroxybenzoate.

70. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable carrier.

71. A method of treating diabetes by selectively inhibiting protein tyrosine phosphatase 1B comprising administering a therapeutically effective amount of a compound of claim 1 .

72. A method of treating diabetes caused by overexpressed or altered protein tyrosine phosphatase 1B comprising administering a therapeutically effective amount of a compound of claim 1 .