# US 2013/0158070 A1 · Conjugates of polyunsaturated fatty acids and amine-containing compounds and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0158070 A1 - Document ID: US20130158070A1 - Status: Published application - Kind: A1 - Application number: 13/820,678 - Filed: 2011-09-06 - Published: 2013-06-20 - Earliest claimed: 2010-09-06 - Inventors: Taher Nassar - Web page: https://patentgrep.com/patent/US20130158070A1 ## CPC - A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)} - A61K 31/401: Proline; Derivatives thereof, e.g. captopril - A61K 31/616: by carboxylic acids, e.g. acetylsalicylic acid - A61K 47/542: {Carboxylic acids, e.g. a fatty acid or an amino acid} - A61P 11/06: Antiasthmatics - A61P 17/00: Drugs for dermatological disorders - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 25/16: Anti-Parkinson drugs - 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 - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - C07C 69/58: Esters of straight chain acids with eighteen carbon atoms in the acid moiety - C07C 69/587: Monocarboxylic acid esters having at least two carbon-to-carbon double bonds - C07C 233/55: having the carbon atom of the carboxamide group bound to a carbon atom of an unsaturated carbon skeleton - C07C 309/15: the nitrogen atom of at least one of the amino groups being part of any of the groups [IMAGE cpc-sch-C07C-0975.gif], X being a hetero atom, Y being any atom - C07D 207/16: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals - C07D 209/26: with an acyl radical attached to the ring nitrogen atom - C07D 213/80: in position 3 - C07D 498/04: Ortho-condensed systems - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract Novel chemical conjugates derived from unsaturated fatty acids and therapeutically active agents, are disclosed. The chemical conjugates are designed and characterized as COX-2 and/or 5-LOX inhibitors and are useful in the treatment of inflammatory diseases and disorders such as Alzheimer's disease, Parkinson's disease, asthma, osteoarthritis, rheumatoid arthritis, pain, primary dysmenorrhea, Crohn's disease and ulcerative colitis. ## Claims ### Claim at position 1 1-40. (canceled) ### Claim 41 A method for treating dermatitis in a subject in need comprising the step of administering the subject in need docosa-4,7,10,13,16,19-hexaenoic acid linked to a hydroxyproline, thereby treating dermatitis in the subject. ### Claim 42 A method of synthesizing 1-docosa-4,7,10,13,16,19-hexaenoyl-4-hydroxy-pyrrolidine-2-carboxylic acid comprising: mixing tetrahydrofurane with decosahexanoic acid; adding triethylcloroformate; adding triethylamine; stirring and filtering; adding a solution of hydroxyproline and NaOH in water; adding strong acid; adding hexane; collecting organic layer; and drying ### Claim 43 (depends on 42) The method according to claim 42, wherein the step of stirring following the addition of the hydroxyproline and NaOH in water solution, is for at 12 hours. ### Claim 44 (depends on 42) The method according to claim 42, wherein the step of drying is over anhydrous sulfate. ### Claim 45 A chemical conjugate comprising a first moiety and a second moiety covalently linked therebetween, wherein said second moiety is derived from docosa-4,7,10,13,16,19-hexaenoic acid, and wherein said first moiety is derived from a therapeutically active agent or a derivative thereof, each independently having a functional group for forming a covalent bond with said second moiety, with the proviso that said first moiety is not hydroxyproline, the chemical conjugate being a cyclooxygenase-2 (COX-2) inhibitor. ### Claim 46 (depends on 45) The chemical conjugate of claim 45, being further a 5-lipoxygenase (5-LOX) inhibitor. ### Claim 47 (depends on 45) The chemical conjugate of claim 45, wherein said functional group is selected from the group consisting of hydroxy, amine, carboxy and amide. ### Claim 48 (depends on 45) The chemical conjugate of claim 45, wherein said first moiety and said second moiety are covalently bound via a bond selected from the group consisting of an amide bond and an ester bond. ### Claim 49 (depends on 45) The chemical conjugate of claim 45, wherein said therapeutically active agent is an anti-inflammatory agent or a cyclooxygenase (COX) inhibitor or a non-steroidal anti-inflammatory drug (NSAID). ### Claim 50 (depends on 45) The chemical conjugate of claim 45, wherein said therapeutically active agent is selected from the group consisting of: 5-hydroxy-indol-3-yl-acetic acid, 2-amino-nicotinic acid, salicyclic acid, mesalazine and quercetin. ### Claim 51 A chemical conjugate comprising a first moiety and a second moiety covalently linked therebetween, wherein said second moiety is derived from y-linolenic acid, and wherein said first moiety is derived from a therapeutically active agent or a derivative thereof, each independently having a functional group for forming a covalent bond with said second moiety, with the proviso that said first moiety is not hydroxyproline or taurine, the chemical conjugate being a cyclooxygenase-2 (COX-2) inhibitor. ### Claim 52 (depends on 51) The chemical conjugate of claim 51, being further a 5-lipoxygenase (5-LOX) inhibitor. ### Claim 53 (depends on 51) The chemical conjugate of claim 51, wherein said functional group is selected from the group consisting of hydroxy, amine, carboxy and amide. ### Claim 54 (depends on 51) The chemical conjugate claim 51, wherein said first moiety and said second moiety are covalently bound via a bond selected from the group consisting of an amide bond and an ester bond. ### Claim 55 (depends on 51) The chemical conjugate of claim 51, wherein said therapeutically active agent is an anti-inflammatory agent, a cyclooxygenase (COX) inhibitor, a non-steroidal anti-inflammatory drug (NSAID) or selected from the group consisting of salicyclic acid and mesalazine. ### Claim 56 A chemical conjugate comprising a first moiety and a second moiety covalently linked therebetween, wherein said first moiety is derived from a compound selected from the group consisting of 5-hydroxy-indol-3-yl-acetic acid, 2-amino-nicotinic acid, salicyclic acid, mesalazine, quercetin and resveratrol, and wherein said second moiety is derived from a fatty acid. ### Claim 57 (depends on 56) The chemical conjugate of claim 56, wherein said first moiety and said second moiety are covalently linked therebetween via a bon selected from the group consisting of an ester bond and an amide bond and the fatty acid is docosa-4,7,10,13,16,19-hexaenoic acid or γ-linolenic acid. ### Claim 58 A chemical conjugate selected from the group consisting of: N-(docosa-4,7,10,13,16,19-hexaenoyl)-5-hydroxy-indol-3-yl-aceticacid (MWL004); N-(docosa-4,7,10,13,16,19-hexaenoyl)-2-amino-nicotinic acid (MWL005); N-(docosa-4,7,10,13,16,19-hexaenoyl)-2-amino-phenyl-acetic acid (MWL006); N-oleoyl-5-hydroxy-indol-3-yl-acetic acid (MWL007); N-oleoyl-2-amino-nicotinic acid (MWL008); O-oleoyl-salicylic acid (MWL009); O-(docosa-4,7,10,13,16,19-hexaenoyl)-salicylic acid (MWL013); O-(y-linolenoyl)-salicylic acid (MWL014); N-(y-linolenoyl)-5-amino-salicylic acid (MWL015); N-(docosa-4,7,10,13,16,19-hexaenoyl)-5-amino-salicylic acid (MWL016); N-oleoyl-5-amino-salicylic acid (MWL017); and N-docosa-4,7,10,13,16,19-hexaenoyl-taurine (MWL002). ### Claim 59 (depends on 45) A pharmaceutical composition comprising the chemical conjugate of claim 45 and a pharmaceutically acceptable carrier. ### Claim 60 (depends on 45) A method of treating an inflammatory disease or disorder, the method comprising administering to a subject in need thereof an effective amount of the chemical conjugate of claim 45. ### Claim 61 (depends on 60) The method of claim 60, wherein said inflammatory disease or disorder is selected from the group consisting of Alzheimer's disease, Parkinson's disease, asthma, osteoarthritis, rheumatoid arthritis, pain associated with inflammation, primary dysmenorrhea, Crohn's disease and ulcerative colitis.