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

• US 8,044,089 B2
• Filed: 11/01/2010
• Issued: 10/25/2011
• 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: Halperin, José A., Natarajan, Amarnath, Aktas, Huseyin, Fan, Yun-Hua, Chen, Han
• Primary Examiner(s): Saeed; Kamal
• Assistant Examiner(s): VAJDA, KRISTIN ANN
• Application Number:
  US12/916,956
• Publication Number:
  US 20110046367A1
• Time in Patent Office: 358 Days
• Field of Search: 514/418, 540/456, 548/487, 548/312.1, 548/181, 548/455, 548/466
• US Class Current: 514/416
• 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 inhibiting translation initiation in a cell comprising contacting the cell with a compound of formula III, formula IV, formula VI, or formula VIII wherein

the compound of formula III is:

2. The method of claim 1, wherein the cell is a cancer cell.

3. The method of claim 2 carried out in an individual by administration of the compound to the individual.

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

5. The method of claim 1 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.

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

7. The method of claim 1 wherein the compound is 4-tert-butyl-N-(5-hydroxy-4-methyl-2-(2-oxo-3-phenylindolin-3-yl)phenyl)benzenesulfonamide.

8. A method of inhibiting translation initiation in a cell comprising contacting the cell with 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.

9. A method of inhibiting translation initiation in a cell in a human or non-human mammal 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.

10. A method of inhibiting translation initiation in a cell comprising contacting the cell with a compound of formula XV,

11. The method of claim 10, wherein the cell is a cancer cell.

12. The method of claim 11 carried out in an individual by administration of the compound to the individual.

13. The method of claim 12 wherein the compound is administered by inhalation, transdermally, orally, rectally, transmucosally, intestinally, parenterally, intramuscularly, subcutaneously or intravenously.