RESOLVINS: BIOTEMPLATES FOR NOVEL THERAPEUTIC INTERVENTIONS

• US 20100016432A1
• Filed: 07/08/2009
• Published: 01/21/2010
• Est. Priority Date: 08/12/2002
• Status: Abandoned Application

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: SERHAN, CHARLES N.
• Application Number:
  US12/499,528
• Publication Number:
  US 20100016432A1
• Time in Patent Office: Days
• US Class Current: 514/560
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 59/42 containing hydroxy or O-metal groups
• CPC Class Codes: C07C 59/48 containing six-membered aromatic rings
• CPC Class Codes: C07C 69/732 of unsaturated hydroxy carboxylic acids
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896

Abstract

The present invention is generally drawn to novel isolated therapeutic agents, termed resolving, generated from the interaction between a dietary omega-3 polyunsaturated fatty acid (PUFA) such as eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), cyclooxygenase-II (COX-2) and an analgesic, such as aspirin (ASA). Surprisingly, careful isolation of compounds generated from the combination of components in an appropriate environment provide di- and tri-hydroxy EPA or DHA compounds having unique structural and physiological properties. The present invention therefore provides for many new useful therapeutic di- or tri-hydroxy derivatives of EPA or DHA (resolvins) that diminish, prevent, or eliminate inflammation or PMN migration, for example. The present invention also provides methods of use, methods of preparation, and packaged pharmaceuticals for use as medicaments for the compounds disclosed throughout the specification.

Claims

1. A method of treating or preventing inflammation in a subject, comprising administering to the subject a compound having a structure of the formula:

2. A method of claim 1, wherein the compound has a structure of the formula:

3. A method of claim 1, wherein the compound has a structure of the formula:

4. A method of claim 1, wherein the compound has a structure of the formula:

5. A method of claim 4, wherein the compound has a structure of the formula:

6. The method of claim 5, wherein the carbon atom at C-17 has an R configuration.

7. The method of claim 5, wherein the C-10 carbon atom has an S configuration and the carbon atom at C-17 has an S configuration.

8. The method of claim 5, wherein the C-10 carbon atom has an R configuration and the carbon atom at C-17 has an S configuration.

9. The method of any of claims 4-8, wherein P₁ and P₂ each are hydrogen atoms, or a pharmaceutically acceptable salt thereof.

10. The method of claim 9, wherein Z is a carboxylic acid or a carboxylic ester, or a pharmaceutically acceptable salt thereof.

11. The method of claim 10, wherein Z is a carboxylic acid salt.

12. The method of any of claims 4-8, wherein Z is COOR^a, wherein R^a is hydrogen, (C1-C6)alkyl, (C3-C8)cycloalkyl, (C4-C11)cycloalkylalkyl, or (C6-C16)arylalkyl, or a pharmaceutically acceptable salt thereof.

13. The method of claim 1, wherein the compound has the structure: