N4-phenyl-quinazoline-4-amine derivatives and related compounds as ErbB type I receptor tyrosine kinase inhibitors for the treatment of hyperproliferative diseases
This invention provides compounds of Formula I wherein B, G, A, E, R 1 , R 2 , R 3 , m and n are as defined herein, which are useful as type I receptor tyrosine kinase inhibitors, and methods of use thereof in the treatment of hyperproliferative disorders in mammals.
1. A pharmaceutical composition comprising a compound having the Formula:
or a pharmaceutically acceptable salt thereof;
and a pharmaceutically acceptable diluent or carrier.
2. The pharmaceutical composition of claim 1 , wherein the compound has the Formula:
or a pharmaceutically acceptable salt thereof.
3. The pharmaceutical composition of claim 1 , wherein the compound has the Formula:
or a pharmaceutically acceptable salt thereof.
4. The composition of claim 1 , wherein an anti-tumor agent is administered in combination.
5. The composition of claim 4 , wherein the anti-tumor agent is an anti-metabolite.
6. The composition of claim 5 , wherein the anti-metabolite is 5-fluorouracil.
7. The composition of claim 4 , wherein the anti-tumor agent is an antimitotic agent.
8. The composition of claim 7 , wherein the antimitotic agent is selected from the group consisting of taxol and taxotere.
9. The composition of claim 4 , wherein the anti-tumor agent is an inhibitor of growth factor function.
10. The composition of claim 9 , wherein the inhibitor of growth factor function is trastuzumab.
11. The composition of claim 4 , wherein the anti-tumor agent is an antiangiogenic agent.
12. The composition of claim 11 , wherein the antiangiogenic agent is bevacizumab.
13. A method of treating a cancer that over-expresses HER2 in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound having the Formula:
or a pharmaceutically acceptable salt thereof; wherein the cancer is breast cancer.
14. The method of claim 13 , wherein the compound has the Formula:
or a pharmaceutically acceptable salt thereof.
15. The method of claim 13 , wherein the compound has the Formula:
or a pharmaceutically acceptable salt thereof.
16. The method of claim 13 , wherein the compound has the Formula:
17. The method of claim 13 , wherein the compound has the Formula:
18. The method of claim 13 , wherein an anti-tumor agent is administered in combination.
19. The method of claim 18 , wherein the anti-tumor agent is an anti-metabolite.
20. The method of claim 19 , wherein the anti-metabolite is 5-fluorouracil.
21. The method of claim 18 , wherein the anti-tumor agent is an antimitotic agent.
22. The method of claim 21 , wherein the antimitotic agent is selected from the group consisting of taxol and taxotere.
23. The method of claim 18 , wherein the anti-tumor agent is an inhibitor of growth factor function.
24. The method of claim 23 , wherein the inhibitor of growth factor function is trastuzumab.
25. The method of claim 18 , wherein the anti-tumor agent is an antiangiogenic agent.
26. The method of claim 25 , wherein the antiangiogenic agent is bevacizumab.
27. The pharmaceutical composition of claim 1 , wherein the compound has the Formula:
28. The pharmaceutical composition of claim 1 , wherein the compound has the Formula: