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Claims for Patent: 7,125,875

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Claims for Patent: 7,125,875

Title:Cyclic protein tyrosine kinase inhibitors
Abstract:Novel cyclic compounds and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic and oncologic disorders.
Inventor(s): Das; Jagabandhu (Mercerville, NJ), Padmanabha; Ramesh (Hamden, CT), Chen; Ping (Belle Mead, NJ), Norris; Derek J. (Trenton, NJ), Doweyko; Arthur M. P. (Long Valley, NJ), Barrish; Joel C. (Richboro, PA), Wityak; John (Robbinsville, NJ), Lombardo; Louis J. (Belle Mead, NJ), Lee; Francis Y. F. (Yardley, PA)
Assignee: Bristol-Myers Squibb Company (Princeton, NJ)
Application Number:10/395,503
Patent Claims: 1. A method for the treatment of a cancer comprising administering to a subject in need thereof an effective amount of the compound of formula III or a salt thereof: ##STR00626## wherein: each R.sub.1, R.sub.3 and R.sub.4 is, independently, a heterocyclic group or an aryl group, optionally substituted with one or more substituents; and R.sub.2 is hydrogen or alkyl; wherein the cancer is chronic myelogenous leukemia (CML), gastrointestinal stromal tumor (GIST), small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), ovarian cancer, melanoma, mastocytosis, germ cell tumors, acute myelogenous leukemia (AML), pediatric sarcomas, breast cancer, colorectal cancer, pancreatic cancer, or prostate cancer.

2. A method for the treatment of a cancer comprising administering to a subject in need thereof an effective amount of a compound of formula IV: ##STR00627## wherein the cancer is chronic myelogenous leukemia (CML), gastrointestinal stromal tumor (GIST), small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), ovarian cancer, melanoma, mastocytosis, germ cell tumors, acute myelogenous leukemia (AML), pediatric sarcomas, breast cancer, colorectal cancer, pancreatic cancer, or prostate cancer.

3. A method for the treatment of a cancer comprising administering to a subject in need thereof an effective amount of a therapeutic agent and an effective amount of a compound of formula III: ##STR00628## wherein: each R.sub.1, R.sub.3 and R.sub.4 is, independently, a heterocyclic group or an aryl group, optionally substituted with one or more substituents; and R.sub.2 is hydrogen or alkyl; wherein the cancer is chronic myelogenous leukemia (CML), gastrointestinal stromal tumor (GIST), small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), ovarian cancer, melanoma, mastocytosis, germ cell tumors, acute myelogenous leukemia (AML), pediatric sarcomas, breast cancer, colorectal cancer, pancreatic cancer, or prostate cancer.

4. The method of claim 3 wherein the therapeutic agent is administered following administration of the compound of formula III.

5. The method of claim 3 wherein the therapeutic agent is administered prior to administration of the compound of formula III.

6. The method of claim 3 wherein the therapeutic agent is administered simultaneously with administration of the compound of formula III.

7. The method of claim 3 wherein the compound of formula III is the compound of formula IV: ##STR00629##

8. The method of claim 6 wherein the compound of formula III is the compound of formula IV: ##STR00630##

9. The method of claim 1 wherein the cancer is resistant to treatment by STI-571.

10. The method of claim 2 wherein the cancer is resistant to treatment by STI-571.

11. A method for the oral treatment of cancer comprising administering to a subject in need thereof an effective amount of the compound of formula IV or a salt thereof: ##STR00631## wherein the cancer is chronic myelogenous leukemia (CML).

12. The method of claim 11, wherein the chronic myelogenous leukemia (CML) is resistant to STI-571.

13. The method of claim 11, wherein the compound of formula (IV) is administered once daily for 5 consecutive days, followed by 2 days when there is no treatment.

14. The method of claim 11, wherein the compound of formula (IV) is administered 1 to 4 times per day.

15. A method for the oral treatment of cancer comprising administering to a subject in need thereof an effective amount of the compound of formula IV or a salt thereof: ##STR00632## wherein the cancer is gastrointestinal stromal tumor (GIST).

16. The method of claim 15, wherein the gastrointestinal stromal tumor (GIST) is resistant to STI-571.

17. The method of claim 16, wherein the compound of formula (IV) is administered once daily for 5 consecutive days, followed by 2 days when there is no treatment.

18. The method of claim 16, wherein the compound of formula (IV) is administered 1 to 4 times per day.

19. A method for the oral treatment of cancer comprising administering to a subject in need thereof an effective amount of the compound of formula IV or a salt thereof: ##STR00633## wherein the cancer is acute mylogenous leukemia (AML).

20. A method for the oral treatment of cancer comprising administering to a subject in need thereof an effective amount of the compound of formula IV or a salt thereof: ##STR00634## wherein the cancer is mastocytosis.

21. A method for the oral treatment of cancer comprising administering to a subject in need thereof an effective amount of the compound of formula IV or a salt thereof: ##STR00635## wherein the cancer is a germ cell tumor.

22. A method for the oral treatment of cancer comprising administering to a subject in need thereof an effective amount of the compound of formula IV or a salt thereof: ##STR00636## wherein the cancer is small cell lung cancer (SCLC).

23. A method for the oral treatment of cancer comprising administering to a subject in need thereof an effective amount of the compound of formula IV or a salt thereof: ##STR00637## wherein the cancer is melanoma.

24. A method for the oral treatment of cancer comprising administering to a subject in need thereof an effective amount of the compound of formula IV or a salt thereof: ##STR00638## wherein the cancer is pancreatic cancer.

25. A method for the oral treatment of cancer comprising administering to a subject in need thereof an effective amount of the compound of formula IV or a salt thereof: ##STR00639## wherein the cancer is prostate cancer.

26. A method for the oral treatment of cancer comprising administering to a subject in heed thereof an effective amount of the compound of formula IV or a salt thereof: ##STR00640## wherein the cancer is pediatric sarcoma.

27. A method for the oral treatment of cancer comprising administering to a subject in need thereof an effective amount of the compound of formula IV or a salt thereof: ##STR00641## wherein the cancer is resistant to STI-571.
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