Pyrimidineamines as angiogenesis modulators

1. A compound of formula (II):

or a salt thereof,

wherein:

X 1 is methyl or ethyl;

X 2 is hydrogen or methyl;

X 3 is hydrogen;

X 4 is hydrogen, methyl, or ethyl;

W is N;

Q 1 is hydrogen, chlorine, or methoxy;

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, 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 , and

Z 2 is C 1 -C 4 alkyl or NR 3 R 4 ; and

R 2 , R 3 , and R 4 are each independently selected from hydrogen and C 1 -C 4 alkyl.

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

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

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

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

6. 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.

7. 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.

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

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

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

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

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

13. 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; Z 1 is S(O) 2 ; and Z 2 is C 1 -C 4 alkyl.

14. 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 ) 4 Z 2 ), wherein Z is CH 2 and m is 0, 1, 2, or 3; Z 1 is S(O) 2 ; and Z 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.

15. A compound as claimed in claim 1 selected from the group consisting of:

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

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

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

N-[2-methyl-5-({4-[methyl(3-methyl-1H-indazol-6-yl)amino]-1,3,5-triazin-2-yl}amino)phenyl]methanesulfonamide;

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

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

5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]-1,3,5-triazin-2-yl}amino)-2-methylbenzenesulfonamide;

or a salt thereof.

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

17. The pharmaceutical composition of claim 16 , further comprising at least one additional agent that is an anti-neoplastic agent.

18. The pharmaceutical composition of claim 16 , further comprising an additional agent that inhibits angiogenesis.

19. A method of treating a disorder in a mammal, said disorder being characterized by inappropriate angiogenesis, wherein said disorder is selected from the group consisting of colon cancer and breast cancer, comprising administering to said mammal a therapeutically effective amount of a compound as claimed in claim 1 .

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