Vinyl substituted fatty acids

• US 9,790,167 B2
• Filed: 09/12/2012
• Issued: 10/17/2017
• Est. Priority Date: 05/01/2008
• Status: Expired due to Fees

• Current Assignee: Complexa, Inc., Life Technologies Corporation (Thermo Fisher Scientific Incorporated), University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: Complexa, Inc., University of Pittsburgh of The Commonwealth System of Higher Education
• Inventors: Freeman, Bruce A., Branchaud, Bruce
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): Karol, Jody
• Application Number:
  US13/611,112
• Publication Number:
  US 20130012583A1
• Time in Patent Office: 1,861 Days
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• 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 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• 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 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• 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: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07C 205/50 : having nitro groups and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton

Abstract

Activated fatty acids, pharmaceutical compositions including activated fatty acids, methods for using activated fatty acids to treat a variety of diseases, and methods for preparing activated fatty acids are provided herein.

Claims

1. A pharmaceutical composition comprising an unsaturated or polyunsaturated fatty acid having an aliphatic chain comprised of an odd number of carbons;

and one or more electron withdrawing groups selected from the group consisting of an aldehyde (—

COH), acyl (—

COR), carbonyl (—

CO), cyano (—

CN), sulfoxide (—

SOR), sulfonyl (—

SO₂R), and sulfonic acid (—

SO₃H), wherein R is a hydrogen, methyl or C₂-C₆ alkyl, associated with at least one carbon-carbon double bond, or a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutical acceptable carrier or excipient.

2. The pharmaceutical composition of claim 1, wherein the aliphatic chain of the unsaturated or polyunsaturated fatty acid comprises 5 to 23 carbons.

3. The pharmaceutical composition of claim 1, wherein the unsaturated or polyunsaturated fatty acid comprises an aliphatic chain having 5, 7, 9, 11, 13, 15, 17, 19, 21 or 23 carbons.

4. The pharmaceutical composition of claim 1, wherein the unsaturated or polyunsaturated fatty acid prodrug is selected from the group consisting of a cholesterol ester, a glycolipid, a glycerolipid, and a phospholipid.

5. The pharmaceutical composition of claim 1, wherein the one or more electron withdrawing group is positioned on a sp² carbon of a carbon-carbon double bond of the unsaturated or polyunsaturated fatty acid.

6. The pharmaceutical composition of claim 1, wherein the one or more electron withdrawing group is positioned on a beta carbon of a carbon-carbon double bond of the non-naturally occurring, unsaturated or polyunsaturated fatty acid.

7. The pharmaceutical composition of claim 1, wherein the one or more electron withdrawing group is positioned on a gamma carbon of a carbon-carbon double bond of the non-naturally occurring, unsaturated or polyunsaturated fatty acid.

8. The pharmaceutical composition of claim 1, wherein a carbon-carbon double bond associated with the one or more electron withdrawing group is in cis configuration.

9. The pharmaceutical composition of claim 1, wherein a carbon-carbon double bond associated with the one or more electron withdrawing group is in trans configuration.

10. The pharmaceutical composition of claim 1, wherein the one or more electron withdrawing group is in an absolute stereochemistry of R at an sp³ chiral/stereogenic center.

11. The pharmaceutical composition of claim 1, wherein the one or more electron withdrawing group is in an absolute stereochemistry of S at an sp³ chiral/stereogenic center.

12. The pharmaceutical composition of claim 1, wherein a carbon-carbon double bond occurs at any carbon of the aliphatic chain of the non-naturally occurring, unsaturated or polyunsaturated fatty acid.

13. The pharmaceutical composition of claim 1, wherein the unsaturated or polyunsaturated fatty acid is a fatty acid with two or more conjugated carbon-carbon double bonds.

14. The pharmaceutical composition of claim 13, wherein at least one of the one or more electron withdrawing group is at any carbon in the two or more conjugated carbon-carbon double bonds.

15. The pharmaceutical composition of claim 1, wherein at least one of the one or more electron withdrawing group is positioned at C-9, C-10, C-12, C-13 or a combination thereof.

16. The pharmaceutical composition of claim 1, further comprising one or more of diluents, fillers, disintegrants, binders, lubricants, surfactants, hydrophobic vehicles, water soluble vehicles, emulsifiers, buffers, humectants, moisturizers, solubilizers, antioxidants, preservatives or combinations thereof.

17. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable carrier or excipient is formulated as a solid solution, powder, fluid emulsion, fluid suspension, semi-solid or dry powder.

18. The pharmaceutical composition of claim 1, wherein the unsaturated or polyunsaturated fatty acid is selected from the group consisting of ω

-2, ω

-3, ω

-4, ω

-5, ω

-6, ω

-7, ω

-8, and ω

-9 fatty acids.

19. The pharmaceutical composition of claim 1, wherein the unsaturated or polyunsaturated fatty acid is selected from the group consisting of (E)-10-acetylheptadec-9-enoic acid, (E)-9-acetylheptadec-9-enoic acid, (E)-11-acetyloctahepta-9-enoic acid, (E)-8-acetylheptadec-9-enoic acid, (E)-10-methylsulfonylnonadec-9-enoic acid, (E)-9-methylsulfonylnonadec-9-enoic acid, (E)-11-methylsulfonylnonadec-9-enoic acid, (E)-8-methylsulfonylnonadec-9-enoic acid, (E)-10-acetylnonadec-10,13-ienoic acid, (E)-9-acetylnonadec-9,12-enoic acid, (E)-11-acetylnonadec-10,13-ienoic acid, (E)-8-acetylnonadec-9,12-enoic acid, (E)-10-methylsulfonylpentadec-9,11-ienoic acid, (E)-9-methylsulfonylpentadec-8,9-ienoic acid, (E)-11-methylsulfonylpentadec-9,10-ienoic acid, (E)-8-methylsulfonylpentadec-8,9-ienoic acid, (Z)-10-acetylheptadec-9-enoic acid, (Z)-9-acetylheptadec-9-enoic acid, (Z)-11-acetyloctahepta-9-enoic acid, (Z)-8-acetylheptadec-9-enoic acid, (Z)-10-methylsulfonylnonadec-9-enoic acid, (Z)-9-methylsulfonylnonadec-9-enoic acid, (Z)-11-methylsulfonylnonadec-9-enoic acid, (Z)-8-methylsulfonylnonadec-9-enoic acid, (Z)-10-acetylnonadec-10,13-ienoic acid, (Z)-9-acetylnonadec-9,12-enoic acid, (Z)-11-acetylnonadec-10,13-ienoic acid, (Z)-8-acetylnonadec-9,12-enoic acid, (Z)-10-methylsulfonylpentadec-9,11-ienoic acid, (Z)-9-methylsulfonylpentadec-8,9-ienoic acid, (Z)-11-methylsulfonylpentadec-9,10-ienoic acid, and (Z)-8-methylsulfonylpentadec-8,9-ienoic acid or a pharmaceutically acceptable salt or prodrug thereof.