DERIVATIVES OF SULINDAC, USE THEREOF AND PREPARATION THEREOF

• US 20140094492A1
• Filed: 03/30/2012
• Published: 04/03/2014
• Est. Priority Date: 04/01/2011
• Status: Active Grant

• Current Assignee: Southwest Research Institute
• Original Assignee: Southwest Research Institute
• Inventors: Reynolds, Robert, Piazza, Gary A., Mathew, Bini
• Granted Patent: US 9,365,528 B2
• Time in Patent Office: Days
• US Class Current: 514/319
• 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 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 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: C07C 211/19 containing condensed ring systems
• CPC Class Codes: C07D 211/26 with hydrocarbon radicals, substituted by nitrogen atoms
• CPC Class Codes: C07D 213/38 having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
• CPC Class Codes: C07D 295/13 to an acyclic saturated chain
• CPC Class Codes: C07D 307/52 Radicals substituted by nitrogen atoms not forming part of a nitro radical

Abstract

Derivatives of sulindac that lack cyclooxygenase inhibitory activity are provided along with pharmaceutical compositions containing them and use for treatment or prevention of cancer. The derivatives of sulindac are also suitable for treating chronic inflammatory conditions. A method for preparing the derivatives is also provided.

Claims

1. Compound represented by the formula:

2. The compound of claim 1 being represented by the following formula:

3. The compound of claim 1 being represented by the following formula:

4. The compound of claim 1 being represented by the following formula:

5. The compound of claim 1 being represented by the following formula:

6. The compound of claim 1 being represented by the following formula:

7. The compound of claim 1 being represented by the following formula:

8. The compound of claim 1 being represented by the following formula:

9. The compound of claim 1 being represented by the following formula:

10. The compound of claim 1 being represented by the following formula:

11. The compound of claim 1 being represented by the following formula:

13. The compound of claim 1 being represented by the following formula:

22. A method for preparing a compound of claim 1 which comprise converting an ester of sulindac or a derivative therefore represented by the following formula:

12. A compound being represented by the following formula:

14. A pharmaceutical composition comprising a compound represented by the formula:

15. A method of treating a precancerous condition or cancer in a mammal comprising administering to the mammal an effective treatment amount of a compound represented by the formula:

16. The method of claim 15 wherein the derivative is administered orally, intravenously or intraperitoneally.

17. The method of claim 15 wherein the mammal is human.

18. A method for treating a patient with a chronic inflammatory disease, which comprises administering to the patient an effective treatment amount of a compound represented by the formula:

19. The method according to claim 18, wherein the chronic inflammatory disease is inflammatory bowel disease.

20. A method for treating a patient having a neurodegenerative disease, which comprises administering to the patient an effective treatment amount of a compound represented by the formula:

21. The method according to claim 20, wherein the neurodegenerative disease is Alzheimer'"'"'s disease.