Pyrimidineamines as angiogenesis modulators

1. A compound of Formula (I):

or a salt thereof:

wherein:

D is

X 1 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1- C 4 hydroxyalkyl;

X 2 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C(O)R 1 , or aralkyl;

X 3 is hydrogen or halogen;

X 4 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, heteroaralkyl, cyanoalkyl, —(CH 2 ) p C═CH(CH 2 ) t H, —(CH 2 ) p C≡C(CH 2 ) t H, or C 3 -C 7 cycloalkyl;

p is 1, 2, or 3;

t is 0 or 1;

W is C—R, wherein R is hydrogen, halogen, or cyano;

Q 1 is hydrogen, halogen, C 1 -C 2 haloalkyl, C 1 -C 2 alkyl, C 1 -C 2 alkoxy, or C 1 -C 2 haloalkoxy;

Q 2 is A 1 or A 2 ;

Q 3 is A 1 when Q 2 is A 2 and Q 3 is A 2 when Q 2 is A 1 ;

wherein

A 1 is hydrogen, halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —OR 1 , and

A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein

Z is CH 2 and m is 0, 1, 2, or 3, or

Z is NR 2 and m is 0 or 1, or

Z is oxygen and m is 0 or 1, or

Z is CH 2 NR 2 and m is 0 or 1;

Z 1 is S(O) 2 , S(O), or C(O); and

Z 2 is C 1 -C 4 alkyl, NR 3 R 4 , aryl, arylamino, aralkyl, aralkoxy, or heteroaryl,

R 1 is C 1 -C 4 alkyl;

R 2 , R 3 , and R 4 are each independently selected from hydrogen, C 1- C 4 alkyl, C 3- C 7 cycloalkyl, —S(O) 2 R 5 , and —C(O)R 5 ;

R 5 is C 1- C 4 alkyl, or C 3- C 7 cycloalkyl; and

when Z is oxygen then Z 1 is S(O) 2 and when D is

then X 2 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C(O)R 1 , or aralkyl.

2. A compound as claimed in claim 1 wherein D is

3. A compound as claimed in claim 1 wherein D is

4. A compound of claim 1 wherein D is

5. A compound of formula (II):

or a salt thereof:

wherein:

X 1 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1- C 4 hydroxyalkyl;

X 2 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C(O)R 1 , or aralkyl;

X 3 is hydrogen or halogen;

X 4 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, heteroaralkyl, cyanoalkyl, —(CH 2 ) p C═CH(CH 2 ) t H, —(CH 2 ) p C═C(CH 2 ) t H, or C 3 -C 7 cycloalkyl;

p is 1, 2, or 3;

t is 0 or 1;

W is C—R, wherein R is hydrogen, halogen, or cyano;

Q 1 is hydrogen, halogen, C 1 -C 2 haloalkyl, C 1 -C 2 alkyl, C 1 -C 2 alkoxy, or C 1 -C 2 haloalkoxy;

Q 2 is A 1 or A 2 ;

Q 3 is A 1 when Q 2 is A 2 and Q 3 is A 2 when Q 2 is A 1 ;

wherein

A 1 is hydrogen, halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —OR 1 , and

A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein

Z is CH 2 and m is 0, 1, 2, or 3, or

Z is NR 2 and m is 0 or 1, or

Z is oxygen and m is 0 or 1, or

Z is CH 2 NR 2 and m is 0 or 1;

Z 1 is S(O) 2 , S(O), or C(O); and

Z 2 is C 1- C 4 alkyl, NR 3 R 4 , aryl, arylamino, aralkyl, aralkoxy, or heteroaryl,

R 1 is C 1 -C 4 alkyl;

R 2 , R 3 , and R 4 are each independently selected from hydrogen, C 1- C 4 alkyl, C 3- C 7 cycloalkyl, —S(O) 2 R 5 , and —C(O)R 5 ;

R 5 is C 1- C 4 alkyl, or C 3- C 7 cycloalkyl; and

when Z is oxygen then Z 1 is S(O) 2 .

6. A compound of Formula (III):

or a salt thereof:

wherein:

X 1 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1- C 4 hydroxyalkyl;

X 2 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C(O)R 1 ;

X 3 is hydrogen or halogen;

X 4 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, heteroaralkyl, cyanoalkyl, —(CH 2 ) p C═CH(CH 2 ) t H, —(CH 2 ) p C≡C(CH 2 ) t H, or C 3 -C 7 cycloalkyl;

p is 1, 2, or 3;

t is 0 or 1;

W is C—R, wherein R is hydrogen, halogen, or cyano;

Q 1 is hydrogen, halogen, C 1 -C 2 haloalkyl, C 1 -C 2 alkyl, C 1 -C 2 alkoxy, or C 1 -C 2 haloalkoxy;

Q 2 is A 1 or A 2 ;

Q 3 is A 1 when Q 2 is A 2 and Q 3 is A 2 when Q 2 is A 1 ;

wherein

A 1 is hydrogen, halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —OR 1 , and

A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein

Z is CH 2 and m is 0, 1, 2, or 3, or

Z is NR 2 and m is 0 or 1, or

Z is oxygen and m is 0 or 1, or

Z is CH 2 NR 2 and m is 0 or 1;

Z 1 is S(O) 2 , S(O), or C(O); and

Z 2 is C 1- C 4 alkyl, NR 3 R 4 , aryl, arylamino, aralkyl, aralkoxy, or heteroaryl,

R 1 is C 1 -C 4 alkyl;

R 2 , R 3 , and R 4 are each independently selected from hydrogen, C 1- C 4 alkyl, C 3- C 7 cycloalkyl, —S(O) 2 R 5 , and —C(O)R 5 ;

R 5 is C 1- C 4 alkyl, or C 3- C 7 cycloalkyl; and

when Z is oxygen then Z 1 is S(O) 2 .

7. A compound of Formula (IV):

or a salt thereof:

wherein:

X 1 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C 1- C 4 hydroxyalkyl;

X 2 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, or C(O)R 1 , or aralkyl;

X 3 is hydrogen or halogen;

X 4 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, heteroaralkyl, cyanoalkyl, —(CH 2 ) p C═CH(CH 2 ) t H, —(CH 2 ) p C≡C(CH 2 ) t H, or C 3 -C 7 cycloalkyl;

p is 1, 2, or 3;

t is 0 or 1;

W is C—R, wherein R is hydrogen, halogen, or cyano;

Q 1 is hydrogen, halogen, C 1 -C 2 haloalkyl, C 1 -C 2 alkyl, C 1 -C 2 alkoxy, or C 1 -C 2 haloalkoxy;

Q 2 is A 1 or A 2 ;

Q 3 is A 1 when Q 2 is A 2 and Q 3 is A 2 when Q 2 is A 1 ;

wherein

A 1 is hydrogen, halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —OR 1 , and

A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein

Z is CH 2 and m is 0, 1, 2, or 3, or

Z is NR 2 and m is 0 or 1, or

Z is oxygen and m is 0 or 1, or

Z is CH 2 NR 2 and m is 0 or 1;

Z 1 is S(O) 2 , S(O), or C(O); and

Z 2 is C 1- C 4 alkyl, NR 3 R 4 , aryl, arylamino, aralkyl, aralkoxy, or heteroaryl,

R 1 is C 1 -C 4 alkyl;

R 2 , R 3 , and R 4 are each independently selected from hydrogen, C 1- C 4 alkyl, C 3- C 7 cycloalkyl, —S(O) 2 R 5 , and —C(O)R 5 ;

R 5 is C 1- C 4 alkyl, or C 3- C 7 cycloalkyl; and

when Z is oxygen then Z 1 is S(O) 2 .

8. A compound as claimed in claim 1 , wherein X 1 is hydrogen or C 1-4 alkyl.

9. A compound as claimed in claim 1 , wherein X 1 is methyl or ethyl.

10. A compound as claimed in claim 1 , wherein X 1 is methyl.

11. A compound as claimed in claim 1 , wherein X 2 is hydrogen or C 1-4 alkyl.

12. A compound as claimed in claim 1 , wherein X 2 is hydrogen or methyl.

13. A compound as claimed in claim 1 , wherein X 2 is hydrogen.

14. A compound as claimed in claim 1 , wherein X 2 is methyl.

15. A compound as claimed in claim 1 , wherein X 3 is halogen.

16. A compound as claimed in claim 1 , wherein X 3 is hydrogen.

17. A compound as claimed in claim 1 , wherein X 4 is hydrogen, C 1 -C 4 alkyl, cyanoalkyl, or —(CH 2 ) p C≡C(CH 2 ) t H.

18. A compound as claimed in claim 1 , wherein X 4 is hydrogen, methyl, ethyl, isopropyl, cyanomethyl, or —(CH 2 ) p C≡C(CH 2 ) t H, wherein p is 1 and t is 0.

19. A compound as claimed in claim 1 , wherein X 4 is methyl.

20. A compound as claimed in claim 1 , wherein X 1 is methyl or ethyl, X 2 is hydrogen or methyl, X 3 is hydrogen or halogen, and X 4 is hydrogen, methyl, ethyl, isopropyl, cyanomethyl, or —(CH 2 ) p C≡C(CH 2 ) t H, wherein p is 1 and t is 0.

21. A compound as claimed in claim 1 , wherein X 1 is methyl, X 2 is hydrogen, X 3 is hydrogen, and X 4 is methyl.

22. A compound as claimed in claim 1 , wherein X 1 is methyl, X 2 is methyl, X 3 is hydrogen, and X 4 is methyl.

23. A compound as claimed in claim 1 , wherein D is:

and X 1 is methyl, X 2 is hydrogen, X 3 is hydrogen, and X 4 is methyl.

24. A compound as claimed in claim 1 , wherein D is

and X 1 is methyl, X 2 is methyl, X 3 is hydrogen, and X 4 is methyl.

25. A compound as claimed in claim 1 , wherein W is C—R wherein R is H, F, Cl, or CN.

26. A compound as claimed in claim 1 , wherein W is C—F, or C—H.

27. A compound as claimed in claim 1 , wherein Q 1 is hydrogen, halogen, C 1- C 2 alkyl or C 1- C 2 alkoxy.

28. A compound as claimed in claim 1 , wherein Q 1 is hydrogen.

29. A compound as claimed in claim 1 , wherein Q 1 is chlorine.

30. A compound as claimed in claim 1 , wherein Q 1 is methyl.

31. A compound as claimed in claim 1 , wherein Q 1 is methoxy.

32. A compound as claimed in claim 1 , wherein Q 2 is A 1 and Q 3 is A 2 .

33. A compound as claimed in claim 1 , wherein Q 2 is A 2 and Q 3 is A 1 .

34. A compound as claimed in claim 1 , wherein Q 2 is A 2 and Q 3 is A 1 , wherein A 1 is hydrogen, halogen, or C 1- C 3 haloalkyl and A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3, or Z is NR 2 and m is 0 or 1, or Z is CH 2 NR 2 and m is 0 or 1; Z 1 is S(O) 2 , S(O), or C(O); and Z 2 is C 1- C 4 alkyl or NR 3 R 4 and wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen or C 1- C 4 alkyl.

35. A compound as claimed in claim 1 , wherein Q 2 is A 2 and Q 3 is A 1 , wherein A 1 is hydrogen or chlorine and A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3, or Z 1 is S(O) 2 ; and Z 2 is C 1- C 4 alkyl.

36. A compound as claimed in claim 1 , wherein Q 2 is A 1 and Q 3 is A 2 , wherein A 1 is hydrogen, halogen, or C 1- C 3 alkyl and A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3, or Z is NR 2 and m is 0 or 1, or Z is CH 2 NR 2 and m is 0 or 1; Z is S(O) 2 , S(O), or C(O); and Z 2 is C 1- C 4 alkyl or NR 3 R 4 , and wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen or C 1- C 4 alkyl.

37. A compound as claimed in claim 1 , wherein Q 2 is A 1 and Q 3 is A 2 , wherein A 1 is hydrogen, methyl, or chlorine and A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3; Z 1 is S(O) 2 ; and Z 2 is C 1- C 4 alkyl or NR 3 R 4 , wherein R 3 and R 4 are each independently selected from hydrogen or C 1- C 4 alkyl.

38. A compound as claimed in claim 1 , wherein X 1 is hydrogen or C 1-4 alkyl; X 2 is hydrogen or C 1-4 alkyl; X 3 is hydrogen or halogen; and X 4 is hydrogen, C 1 -C 4 alkyl, cyanoalkyl, or —(CH 2 ) p C≡C(CH 2 ) t H; W is C—R wherein R is H, F, Cl, or CN; Q 1 is hydrogen, halogen, C 1- C 2 alkyl or C 1- C 2 alkoxy; and Q 2 is A 2 and Q 3 is A 1 , wherein A 1 is hydrogen, halogen, or C 1- C 3 haloalkyl and A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3, or Z is NR 2 and m is 0 or 1, or Z is CH 2 NR 2 and m is 0 or 1; Z 1 is S(O) 2 or C(O); and Z 2 is C 1- C 4 alkyl or NR 3 R 4 and wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen or C 1- C 4 alkyl.

39. A compound as claimed in claim 1 , wherein X 1 is hydrogen or C 1-4 alkyl; X 2 is hydrogen or C 1-4 alkyl; X 3 is hydrogen or halogen; and X 4 is hydrogen, C 1 -C 4 alkyl, cyanoalkyl, or —(CH 2 ) p C≡C(CH 2 ) t H; W is C—R wherein R is H, F, Cl, or CN; Q 1 is hydrogen, halogen, C 1- C 2 alkyl or C 1- C 2 alkoxy; and Q 2 is A 1 and Q 3 is A 2 , wherein A 1 is hydrogen, halogen, or C 1- C 3 haloalkyl and A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3, or Z is NR 2 and m is 0 or 1, or Z is CH 2 NR 2 and m is 0 or 1; Z 1 is S(O) 2 , S(O), or C(O); and Z 2 is C 1- C 4 alkyl or NR 3 R 4 , and wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen or C 1- C 4 alkyl.

40. A compound as claimed in claim 1 , wherein X 1 is methyl or ethyl; X 2 is hydrogen or methyl; X 3 is hydrogen; and X 4 is hydrogen, methyl, ethyl, isopropyl, cyanomethyl, or —(CH 2 ) p C≡C(CH 2 ) t H, wherein p is 1 and t is 0; W is C—H or C—F; Q 1 is hydrogen, chlorine, methyl, or methoxy; Q 2 is A 1 and Q 3 is A 2 , wherein A 1 is hydrogen, methyl, or chlorine and A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3, or Z is NR 2 and m is 0 or 1, or Z is CH 2 NR 2 and m is 0 or 1; Z 1 is S(O) 2 , S(O), or C(O); and Z 2 is C 1- C 4 alkyl or NR 3 R 4 , and wherein R 2 , R 3 , and R 4 are each independently selected from H or C 1- C 4 alkyl.

41. A compound as claimed in claim 1 , wherein X 1 is methyl; X 2 is hydrogen; X 3 is hydrogen; and X 4 is methyl; W is C—H; Q 1 is hydrogen, chlorine, methyl, or methoxy; Q 2 is A 1 and Q 3 is A 2 , wherein A 1 is hydrogen, methyl, or chlorine and A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3, or Z is NR 2 and m is 0 or 1, or Z is CH 2 NR 2 and m is 0 or 1; Z 1 is S(O) 2 , S(O), or C(O); and Z 2 is C 1- C 4 alkyl or NR 3 R 4 , and wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen or C 1- C 4 alkyl.

42. A compound as claimed in claim 1 , wherein X 1 is methyl; X 2 is methyl; X 3 is hydrogen; and X 4 is methyl; W is C—H; Q 1 is hydrogen, chlorine, methyl, or methoxy; Q 2 is A 1 and Q 3 is A 2 , wherein A 1 is hydrogen, methyl, or chlorine and A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3, or Z is NR 2 and m is 0 or 1, or Z is CH 2 NR 2 and m is 0 or 1; Z 1 is S(O) 2 , S(O), or C(O); and Z 2 is C 1- C 4 alkyl or NR 3 R 4 , and wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen or C 1- C 4 alkyl.

43. A compound as claimed in claim 1 , wherein X 1 is methyl; X 2 is hydrogen; X 3 is hydrogen; and X 4 is methyl; W is C—F; Q 1 is hydrogen, chlorine, or methoxy; Q 2 is A 1 and Q 3 is A 2 1 , wherein A 1 is hydrogen, methyl, or chlorine and A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3, or Z is NR 2 and m is 0 or 1, or Z is CH 2 NR 2 and m is 0 or 1; Z 1 is S(O) 2 , S(O), or C(O); and Z 2 is C 1- C 4 alkyl or NR 3 R 4 , and wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen or C 1- C 4 alkyl.

44. A compound as claimed in claim 1 , wherein D is:

and X 1 is methyl; X 2 is hydrogen; X 3 is hydrogen; and X 4 is methyl; W is C—H; Q 1 is hydrogen, methyl, chlorine, or methoxy; Q 2 is A 1 and Q 3 is A 2 , wherein A 1 is hydrogen, methyl, or chlorine and A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3, or Z is NR 2 and m is 0 or 1, or Z is CH 2 NR 2 and m is 0 or 1; Z 1 is S(O) 2 , S(O), or C(O); and Z 2 is C 1- C 4 alkyl or NR 3 R 4 , and wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen or C 1- C 4 alkyl.

45. A compound as claimed in claim 1 , wherein D is

and X 1 is methyl; X 2 is methyl; X 3 is hydrogen; and X 4 is methyl; W is C—H; Q 1 is hydrogen, chlorine, methyl, or methoxy; Q 2 is A 1 and Q 3 is A 2 , wherein A 1 is hydrogen, methyl, or chlorine and A 2 is the group defined by -(Z) m -(Z 1 )-(Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3, or Z is NR 2 and m is 0 or 1, or Z is CH 2 NR 2 and m is 0 or 1; Z 1 is S(O) 2 , S(O), or C(O); and Z 2 is C 1- C 4 alkyl or NR 3 R 4 , and wherein R 2 , R 3 , and R 4 are each independently selected from hydrogen or C 1- C 4 alkyl.

46. A compound selected from the group consisting of:

N 2 -[5-(ethylsulfonyl)-2-methoxyphenyl]-5-fluoro-N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

3-({5-fluoro-4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)-4-methoxy-N-methylbenzenesulfonamide;

5-fluoro-N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-N 2 -{3-[(methylsulfonyl)methyl]phenyl}-2,4-pyrimidinediamine;

3-({5-fluoro-4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)-N-isopropylbenzenesulfonamide;

5-fluoro-N 2 -[5-(isopropylsulfonyl)-2-methoxyphenyl]-N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

N-[5-({5-fluoro-4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)-2-methylphenyl]methanesulfonamide;

5-fluoro-N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-N 2 -[4-(methylsulfonyl)phenyl]-2,4-pyrimidinediamine;

N 4 -(3-ethyl-1H-indazol-6-yl)-5-fluoro-N 4 -methyl-N 2 (-methyl-N 2 -{3-[(methylsulfonyl)methyl]phenyl}-2,4-pyrimidinediamine;

4-({5-fluoro-4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

N 4 -ethyl-5-fluoro-N 2 -[2-methoxy-5-(methylsulfonyl)phenyl]-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

[4-({5-fluoro-4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)phenyl]-N-methylmethanesulfonamide;

5-fluoro-N 2 -{3-[(isopropylsulfonyl)methyl]phenyl}-N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

3-({5-fluoro-4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)-4-methoxybenzamide;

4-({5-fluoro-4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)-3-methoxybenzenesulfonamide;

3-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

N 2 -[5-(ethylsulfonyl)-2-methoxyphenyl]-N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-N 2 -{3-[(methylsulfonyl)methyl]phenyl}-2,4-pyrimidinediamine;

N-isopropyl-3-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

N-cyclopropyl-3-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

N 4 -ethyl-N 2 -[5-(ethylsulfonyl)-2-methoxyphenyl]-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

N-[3-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)phenyl]methanesulfonamide;

N 2 -{3-[(isopropylsulfonyl)methyl]phenyl}-N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

N 2 -{4-[(isopropylsulfonyl)methyl]phenyl}-N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

N 2 -[5-(isobutylsulfonyl)-2-methoxyphenyl]-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

N-[3-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)phenyl]acetamide;

N-[3-({4-[ethyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)phenyl]acetamide;

N 2 -(2-methoxy-5-{[(5-methyl-3-isoxazolyly)methyl]sulfonyl}phenyl)-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

4-methoxy-3-({4-[(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

N 2 -[5-(isopropylsulfonyl)-2-methoxyphenyl]-N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

N 2 -[5-(ethylsulfonyl)-2-methoxyphenyl]-N 4 -isopropyl-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

N 4 -(1H-indazol-6-yl)-N 4 -methyl-N 2 -{3-[(methylsulfonyl)methyl]phenyl}-2,4-pyrimidinediamine;

N 4 -(1,3-dimethyl-1H-indazol-6-yl)-N 4 -methyl-N 2 -{3-[(methylsulfonyl)methyl]phenyl}-2,4-pyrimidinediamine;

N 4 -(2,3-dimethyl-2H-indazol-6-yl)-N 4 -methyl-N 2 -{3-[(methylsulfonyl)methyl]phenyl}-2,4-pyrimidinediamine;

N 4 -(2,3-dimethyl-2H-indazol-6-yl)-N 2 -[5-(ethylsulfonyl)-2-methoxyphenyl]-N 4 -methyl-2,4-pyrimidinediamine;

1-[4-methoxy-3-({4-[(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)phenyl]-1-propanone;

4-methoxy-N-[3-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)phenyl]benzenesulfonamide;

4-methoxy-N-methyl-3-({4-[(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

[(3-methyl-1H-indazol-6-yl)(2-{4-[(methylsulfonyl)methyl]anilino}-4-pyrimidinyl)amino]acetonitrile;

[{2-[5-(ethylsulfonyl)-2-methoxyanilino]-4-pyrimidinyl}(3-methyl-1H-indazol-6-yl)amino]acetonitrile;

[(3-methyl-1H-indazol-6-yl)(2-{3-[(methylsulfonyl)methyl]anilino}-4-pyrimidinyl)amino]acetonitrile;

4-methoxy-N-methyl-3-({4-[methyl (3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

4-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzamide;

3-methoxy-4-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

N 4 -ethynyl-N 4 -(3-methyl-1H-indazol-6-yl)-N 2 -{3-[(methylsulfonyl)methyl]phenyl}-2,4-pyrimidinediamine;

3-({4-[(3-methyl-1H-indazol-6-yl)(2-propynyl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

4-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-N 2 -[3-(methylsulfonyl)phenyl]-2,4-pyrimidinediamine;

4-methoxy-3-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

N 2 -[5-(ethylsulfonyl)-2-methoxyphenyl]-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

3-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzamide;

N 2 -[4-(ethylsulfonyl)phenyl]-N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

N-[4-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzyl]ethanesulfonamide;

N-[3-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzyl]methanesulfonamide;

2-chloro-5-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

2-chloro-4-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

4-chloro-3-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

3-methyl-4-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

2-methyl-5-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

4-methyl-3-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-2-pyrimidinyl}amino)benzenesulfonamide;

N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-N 2 -[3-(methylsulfinyl)phenyl]-2,4-pyrimidinediamine;

N 2 -[2-fluoro-5-(methylsulfonyl)phenyl]-N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

N 2 -[2-methoxy-5-(methylsulfonyl)phenyl]-N 4 -methyl-N 4 -(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine;

3-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)benzenesulfonamide;

2-[4-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)phenyl]ethanesulfonamide;

3-({4-[[3-(hydroxymethyl)-2-methyl-2H-indazol-6-yl](methyl)amino]pyrimidin-2-yl}amino)benzenesulfonamide;

3-({4-[(1,2-dimethyl-1H-benzimidazol-5-yl)(methyl)amino]pyrimidin-2-yl}amino)benzenesulfonamide,

3-({4-[(2-benzyl-1-methyl-1H-benzimidazol-5-yl)(methyl)amino]pyrimidin-2-yl}amino)benzenesulfonamide;

3-({4-[(2-ethyl-3-methyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)benzenesulfonamide; and

3-({4-[[2-(3-chlorobenzyl)-3-methyl-2H-indazol-6-yl](methyl)amino]pyrimidin-2-yl}amino)benzenesulfonamide;

or a salt thereof.

47. A pharmaceutical composition, comprising: a therapeutically effective amount of a compound as claimed in claim 1 , or a salt thereof and one or more of pharmaceutically acceptable carriers, diluents and excipients.

48. The pharmaceutical composition of claim 47 , further comprising at least one additional anti-neoplastic agent.

49. The pharmaceutical composition of claim 47 , further comprising an additional agent which inhibits angiogenesis.

50. A method of treating a disorder in a mammal, said disorder being characterized by inappropriate angiogenesis, wherein the disorder is a proliferative retinopathy, comprising: administering to said mammal a therapeutically effective amount of a compound as claimed in claim 1 , or a salt thereof.