3-3-di-substituted-oxindoles as inhibitors of translation initiation

• US 7,737,172 B2
• Filed: 08/09/2006
• Issued: 06/15/2010
• Est. Priority Date: 02/13/2004
• Status: Expired due to Fees

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Fan, Yun-Hua, Natarajan, Amarnath, Aktas, Huseyin, Chen, Han, Halperin, Jose A.
• Primary Examiner(s): Saeed; Kamal A
• Assistant Examiner(s): BIANCHI, KRISTIN A
• Application Number:
  US11/463,421
• Publication Number:
  US 20070099976A1
• Time in Patent Office: 1,406 Days
• Field of Search: None
• US Class Current: 514/418
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: C07D 209/34 in position 2
• CPC Class Codes: C07D 209/36 in position 3, e.g. adrenochrome
• CPC Class Codes: C07D 403/02 containing two hetero rings
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/10 linked by a carbon chain containing aromatic rings

Abstract

Compositions and methods for inhibiting translation using 3-(5-tert-Butyl-2-Hydroxy-phenyl)-3-phenyl-1,3-dihydro-indol-2-one and/or its derivatives are provided. Compositions, methods and kits for treating (1) cellular proliferative disorders, (2) non-proliferative, degenerative disorders, (3) viral infections, and/or (4) disorders associated with viral infections, using 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3-dihydro-indol-2-one and/or its derivatives are described.

Claims

1. A method of treating cancer in a human or non-human mammal in need thereof, the method comprising administering to the human or non-human mammal a compound of formula III

2. The method of claim 1 wherein the compound is 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one.

3. The method of claim 1, wherein the compound is administered by inhalation, transdermally, orally, rectally, transmucosally, intestinally, parenterally, intramuscularly, subcutaneously or intravenously.

4. A method of treating cancer in a human or non-human mammal in need thereof, the method comprising administering to the human or non-human mammal a compound of formula IV

5. The method of claim 4, wherein the compound is administered by inhalation, transdermally, orally, rectally, transmucosally, intestinally, parenterally, intramuscularly, subcutaneously or intravenously.

6. A method of treating cancer in a human or non-human mammal in need thereof, the method comprising administering to the human or non-human mammal a compound of formula VI

7. The method of claim 6, wherein the compound is administered by inhalation, transdermally, orally, rectally, transmucosally, intestinally, parenterally, intramuscularly, subcutaneously or intravenously.

8. A method of treating cancer in a human or non-human mammal in need thereof, the method comprising administering to the human or non-human mammal a compound of formula VIII

9. The method of claim 8, wherein the compound is administered by inhalation, transdermally, orally, rectally, transmucosally, intestinally, parenterally, intramuscularly, subcutaneously or intravenously.

10. The method of claim 8 wherein the compound is 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.

11. A method of treating breast cancer in a human or non-human mammal, the method comprising administering to the human or non-human mammal a compound of

20. The method of claim 11 wherein the compound is 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one or 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.

12. A method of treating lung cancer in a human or non-human mammal, the method comprising administering to the human or non-human mammal a compound of

21. The method of claim 12 wherein the compound is 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one or 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.

13. A method of treating melanoma in a human or non-human mammal, the method comprising administering to the human or non-human mammal a compound of

22. The method of claim 13 wherein the compound is 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one or 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.

14. A method of prostate cancer in a human or non-human mammal, the method comprising administering to the human or non-human mammal a compound of

23. The method of claim 14 wherein the compound is 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one or 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.

15. A method of treating leukemia in a human or non-human mammal, the method comprising administering to the human or non-human mammal a compound of

24. The method of claim 15 wherein the compound is 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one or 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.

16. A method of treating multiple myeloma in a human or non-human mammal, the method comprising administering to the human or non-human mammal a compound of

25. The method of claim 16 wherein the compound is 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one or 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.

17. A method of treating plasmocytoma in a human or non-human mammal, the method comprising administering to the human or non-human mammal a compound of

26. The method of claim 17 wherein the compound is 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one or 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.

18. A method of treating pancreatic cancer in a human or non-human mammal, the method comprising administering to the human or non-human mammal a compound of

27. The method of claim 18 wherein the compound is 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one or 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.

19. A method of treating colon cancer in a human or non-human mammal, the method comprising administering to the human or non-human mammal a compound of

28. The method of claim 19 wherein the compound is 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one or 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.

29. A method of treating cancer in a human or non-human mammal in need thereof, the method comprising administering to the human or non-human mammal 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one or 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide wherein the cancer is a member selected from the group consisting of breast cancer, lung cancer, melanoma, prostate cancer, leukemia, multiple myeloma, plasmocytoma, pancreatic cancer and colon cancer.

30. The method of claim 29 comprising administering 3-(5-tert-butyl-2-hydroxy-phenyl)-3-phenyl-1,3,-dihydro-indol-2-one.