Cyclic protein tyrosine kinase inhibitors

• US 7,125,875 B2
• Filed: 03/24/2003
• Issued: 10/24/2006
• Est. Priority Date: 04/15/1999
• Status: Expired due to Term

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Chen, Ping, Norris, Derek J., Wityak, John, Lombardo, Louis J., Das, Jagabandhu, Barrish, Joel C., Doweyko, Arthur M. P., Lee, Francis Y. F., Padmanabha, Ramesh
• Primary Examiner(s): SOLOLA, TAOFIQ A
• Application Number:
  US10/395,503
• Publication Number:
  US 20040054186A1
• Time in Patent Office: 1,310 Days
• Field of Search: 514/252.19, 514/370
• US Class Current: 514/252.19
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/16 Central respiratory analeptics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07C 237/40 : having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07D 213/81 : Amides; Imides
• CPC Class Codes: C07D 213/82 : in position 3
• CPC Class Codes: C07D 231/38 : Nitrogen atoms nitro radicals C07D231/16
• CPC Class Codes: C07D 233/90 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 239/42 : One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 263/48 : Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 277/56 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 409/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings

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.

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:

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

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:

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

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:

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:

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

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:

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:

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:

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:

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:

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:

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:

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:

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:

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:

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: