Vinyl substituted fatty acids

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.

1 . A compound comprising a non-naturally occurring, unsaturated or polyunsaturated fatty acid having one or more electron withdrawing group associated with at least one carbon-carbon double bond or a pharmaceutically acceptable salt thereof. 
   
   
       2 . The compound of  claim 1 , wherein the non-naturally occurring, unsaturated or polyunsaturated fatty acid comprises an aliphatic chain having an odd number of carbons. 
   
   
       3 . The compound of  claim 1 , wherein the non-naturally occurring unsaturated or polyunsaturated fatty acid comprises an aliphatic chain having 5 to 23 carbons. 
   
   
       4 . The compound of  claim 1 , wherein the non-naturally occurring unsaturated or polyunsaturated fatty acid comprises an aliphatic chain having 5, 7, 9, 11, 13, 15, 17, 19, 21 or 23 carbons. 
   
   
       5 . The compound of  claim 1 , wherein the non-naturally occurring unsaturated or polyunsaturated fatty acid is selected from a glycolipid, a glycerolipid, a phospholipid and a cholesterol ester. 
   
   
       6 . The compound of  claim 1 , wherein the one or more electron withdrawing group is selected from aldehyde (—COH), acyl (—COR), carbonyl (—CO), carboxylic acid (—COOH), ester (—COOR), halides (—Cl, —F, —Br, —I), fluoromethyl (—CF n ), allyl fluoride (—CH═CHCH 2 F), cyano (—CN), sulfoxide (—SOR), sulfonyl (—SO 2 R), sulfonic acid (—SO 3 H), 1°, 2° and 3° ammonium (—NR 3   + ), and nitro (—NO 2 ), wherein R is a hydrogen, methyl or C 2 -C 6  alkyl. 
   
   
       7 . The compound of  claim 1 , wherein the one or more electron withdrawing group is a nitro (—NO 2 ) group. 
   
   
       8 . The compound of  claim 1 , wherein the one or more electron withdrawing group is positioned on an alpha carbon of a carbon-carbon double bond of the non-naturally occurring, unsaturated or polyunsaturated fatty acid. 
   
   
       9 . The compound 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. 
   
   
       10 . The compound 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. 
   
   
       11 . The compound of  claim 1 , wherein at least one of the one or more electron withdrawing group is an electron withdrawing vinyl group or an electron withdrawing allylic group. 
   
   
       12 . The compound of  claim 1 , wherein a carbon-carbon double bond associated with the one or more electron withdrawing group is in cis configuration. 
   
   
       13 . The compound of  claim 1 , wherein a carbon-carbon double bond associated with the one or more electron withdrawing group is in trans configuration. 
   
   
       14 . The compound of  claim 1 , wherein the one or more electron withdrawing group is in an absolute stereochemistry of R at an sp 3  chiral/stereogenic center. 
   
   
       15 . The compound of  claim 1 , wherein the one or more electron withdrawing group is in an absolute stereochemistry of S at an sp 3  chiral/stereogenic center. 
   
   
       16 . The compound 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. 
   
   
       17 . The compound of  claim 1 , wherein the non-naturally occurring, unsaturated or polyunsaturated fatty acid is a fatty acid with two or more conjugated carbon-carbon double bonds. 
   
   
       18 . The compound of  claim 17 , 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. 
   
   
       19 . The compound 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. 
   
   
       20 . The compound of  claim 1 , further comprising one or more non-carbon-carbon linkage selected from an ester linkage, an ether linkage, and a vinyl ether linkage. 
   
   
       21 . The compound of  claim 1 , further comprising one or more functional group other than an electron withdrawing group positioned at any carbon of the non-naturally occurring, unsaturated or polyunsaturated fatty acid. 
   
   
       22 . The compound of  claim 1 , wherein the non-naturally occurring, unsaturated or polyunsaturated fatty acid having one or more electron withdrawing group or a pharmaceutically acceptable salt thereof further comprises a pharmaceutically acceptable carrier or excipient. 
   
   
       23 . The compound of  claim 22 , 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. 
   
   
       24 . The compound of  claim 22 , wherein the non-naturally occurring, unsaturated or polyunsaturated fatty acid having one or more electron withdrawing group or a pharmaceutically acceptable salt thereof further comprising a pharmaceutically acceptable carrier or excipient is formulated as a solid, solution, powder, fluid emulsion, fluid suspension, semi-solid or dry powder. 
   
   
       25 . A compound comprising an unsaturated or polyunsaturated fatty acid having one or more electron withdrawing group associated with at least one double bond or a pharmaceutically acceptable salt thereof, with the proviso that the electron withdrawing group associated with the at least one double bond is not a nitro (—NO 2 ) group. 
   
   
       26 . The compound of  claim 25 , wherein the unsaturated or polyunsaturated fatty acid comprises a naturally occurring fatty acid or derivative thereof. 
   
   
       27 . The compound of  claim 25 , wherein the unsaturated or polyunsaturated fatty acid comprises an aliphatic carbon chain having an even number of carbons. 
   
   
       28 . The compound of  claim 25 , wherein the unsaturated or polyunsaturated fatty acid comprises an aliphatic carbon chain having from 4 to 24 carbons. 
   
   
       29 . The compound of  claim 25 , wherein the unsaturated or polyunsaturated fatty acid comprises an aliphatic carbon chain having from 12 to 18 carbons. 
   
   
       30 . The compound of  claim 25 , wherein the unsaturated or polyunsaturated fatty acid is selected from ω-2, ω-3, ω-4, ω-5, ω-6, ω-7, ω-8, ω-9 fatty acids and equivalents and derivatives thereof. 
   
   
       31 . The compound of  claim 25 , wherein the unsaturated or polyunsaturated fatty acid is selected from linolenic acid, alpha-linolenic acid, eicosapentanoic acid, docosapentaenoic acid, docosahexaenoic acid, stearidonic acid, myristoleic acid, linoleic acid, gamma-linoleic acid, dihomo-gamma-linoleic acid, arachidonic acid, palmitoleic acid, oleic acid, erucic acid and equivalents and derivatives thereof. 
   
   
       32 . The compound of  claim 25 , wherein the unsaturated fatty acid is selected from linoleic acid, oleic acid, arachidonic acid or a derivative thereof. 
   
   
       33 . The compound of  claim 25 , wherein the unsaturated fatty acid is selected from a glycolipid, a glycerolipid, a phospholipid and a cholesterol ester. 
   
   
       34 . The compound of  claim 25 , wherein the at least one electron withdrawing group is positioned at C-9, C-10, C-12, C-13 or a combination thereof. 
   
   
       35 . The compound of  claim 25 , further comprising one or more non-carbon-carbon linkage selected from an ester linkage, an ether linkage, a vinyl ether linkage or a combination thereof. 
   
   
       36 . The compound of  claim 25 , wherein the one or more electron withdrawing group is selected from aldehyde (—COH), acyl (—COR), carbonyl (—CO), carboxylic acid (—COOH), ester (—COOR), halides (—Cl, —F, —Br, —I), fluoromethyl (—CF n ), allyl fluoride (—CH═CHCH 2 F), cyano (—CN), sulfoxide (—SOR), sulfonyl (—SO 2 R), sulfonic acid (—SO 3 H), and 10, 20 and 30 ammonium (—NR 3   + ), wherein R is a hydrogen, methyl or C 2 -C 6  alkyl. 
   
   
       37 . The compound of  claim 25 , wherein the one or more electron withdrawing group is positioned on an alpha carbon of a carbon-carbon double bond of the unsaturated or polyunsaturated fatty acid. 
   
   
       38 . The compound of  claim 25 , wherein the one or more electron withdrawing group is positioned on a beta carbon of a carbon-carbon double bond of the unsaturated or polyunsaturated fatty acid. 
   
   
       39 . The compound of  claim 25 , wherein the one or more electron withdrawing group is positioned on a gamma carbon of a carbon-carbon double bond of the unsaturated or polyunsaturated fatty acid. 
   
   
       40 . The compound of  claim 25 , wherein at least one of the one or more electron withdrawing group is an electron withdrawing vinyl group or an electron withdrawing allylic group. 
   
   
       41 . The compound of  claim 25 , wherein a carbon-carbon double bond associated with the one or more electron withdrawing group is in cis configuration. 
   
   
       42 . The compound of  claim 25 , wherein a carbon-carbon double bond associated with the one or more electron withdrawing group is in trails configuration. 
   
   
       43 . The compound of  claim 25 , wherein the one or more electron withdrawing group is in an absolute stereochemistry of R at an sp 3  chiral/stereogenic center. 
   
   
       44 . The compound of  claim 25 , wherein the one or more electron withdrawing group is in an absolute stereochemistry of S at an sp 3  chiral/stereogenic center. 
   
   
       45 . The compound of  claim 25 , wherein a carbon-carbon double bond occurs at any carbon of the aliphatic chain of the unsaturated or polyunsaturated fatty acid. 
   
   
       46 . The compound of  claim 25 , wherein the non-naturally occurring, unsaturated or polyunsaturated fatty acid is a fatty acid with two or more conjugated carbon-carbon double bonds. 
   
   
       47 . The compound of  claim 46 , 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. 
   
   
       48 . The compound of  claim 25 , wherein the unsaturated or polyunsaturated fatty acid having one or more electron withdrawing group associated with at least one double bond or a pharmaceutically acceptable salt thereof, further comprises a pharmaceutically acceptable carrier or excipient. 
   
   
       49 . The compound of  claim 48 , 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. 
   
   
       50 . The compound of  claim 48 , wherein the unsaturated or polyunsaturated fatty acid having one or more electron withdrawing group associated with at least one double bond or a pharmaceutically acceptable salt thereof further comprising a pharmaceutically acceptable carrier or excipient is formulated as a solid, solution, powder, fluid emulsion, fluid suspension, semi-solid or dry powder. 
   
   
       51 . A method for treating a condition comprising administering an effective amount of an unsaturated or polyunsaturated fatty acid having one or more electron withdrawing group associated with at least one double bond with the proviso that the electron withdrawing group is not nitro (—NO 2 ) or a pharmaceutically acceptable salt thereof to a subject in need of treatment. 
   
   
       52 . The method of  claim 51 , wherein the one or more electron withdrawing group is selected from aldehyde (—COH), acyl (—COR), carbonyl (—CO), carboxylic acid (—COOH), ester (—COOR), halides (—Cl, —F, —Br, —I), fluoromethyl (—CF n ), allyl fluoride (—CH═CHCH 2 F), cyano (—CN), sulfoxide (—SOR), sulfonyl (—SO 2 R), sulfonic acid (—SO 3 H), and 1°, 2°, and 3° ammonium (—NR 3   + ), wherein R is a hydrogen, methyl or C 2 -C 6  alkyl. 
   
   
       53 . The method of  claim 51 , wherein the unsaturated or polyunsaturated fatty acid comprises an aliphatic carbon chain having from 12 to 18 carbons. 
   
   
       54 . The method of  claim 51 , wherein the unsaturated or polyunsaturated fatty acid is selected from ω-2, ω-3, ω-4, ω-5, ω-6, ω-7, ω-8, or ω-9 fatty acids and equivalents and derivatives thereof. 
   
   
       55 . The method of  claim 51 , wherein the unsaturated or polyunsaturated fatty acid is selected from linolenic acid, alpha-linolenic acid, eicosapentanoic acid, docosapentaenoic acid, docosahexaenoic acid, stearidonic acid, myristoleic acid, linoleic acid, gamma-linoleic acid, dihomo-gamma-linoleic acid, arachidonic acid, palmitoleic acid, oleic acid, erucic acid and equivalents and derivatives thereof. 
   
   
       56 . The method of  claim 51 , wherein the one or more electron withdrawing group is positioned on an alpha carbon of a carbon-carbon double bond of the unsaturated or polyunsaturated fatty acid. 
   
   
       57 . The method of  claim 51 , wherein the one or more electron withdrawing group is positioned on a beta carbon of a carbon-carbon double bond of the unsaturated or polyunsaturated fatty acid. 
   
   
       58 . The method of  claim 51 , wherein the one or more electron withdrawing group is positioned on a gamma carbon of a carbon-carbon double bond of the unsaturated or polyunsaturated fatty acid. 
   
   
       59 . The method of  claim 51 , wherein at least one of the one or more electron withdrawing group is an electron withdrawing vinyl group or an electron withdrawing allylic group. 
   
   
       60 . The method of  claim 51 , wherein a carbon-carbon double bond associated with the one or more electron withdrawing group is in cis configuration. 
   
   
       61 . The method of  claim 51 , wherein a carbon-carbon double bond associated with the one or more electron withdrawing group is in trans configuration. 
   
   
       62 . The method of  claim 51 , wherein the effective amount comprises a mixture of unsaturated or polyunsaturated fatty acids having one or more electron withdrawing group associated with at least one double bond wherein the mixture comprises electron withdrawing group positioned on alpha, beta, and gamma carbon of a carbon-carbon double bonds of the unsaturated or polyunsaturated fatty acids. 
   
   
       63 . The method of  claim 51 , wherein the condition is selected from arterial stenosis, burns, hypertension, obesity, neurodegenerative disorders, skin disorders, arthritis, autoimmune disease, autoinflammatory disease, lupus, Lyme's disease, gout, sepsis, hyperthermia, ulcers, enterocolitis, osteoporosis, viral or bacterial infections, cytomegalovirus, periodontal disease, glomerulonephritis, sarcoidosis, lung disease, chronic lung injury, respiratory distress, lung inflammation, fibrosis of the lung, asthma, acquired respiratory distress syndrome, tobacco induced lung disease, granuloma formation, fibrosis of the liver, graft vs. host disease, postsurgical inflammation, coronary and peripheral vessel restenosis following angioplasty, stent placement or bypass graft, acute and chronic leukemia, B lymphocyte leukemia, neoplastic diseases, arteriosclerosis, atherosclerosis, myocardial inflammation, psoriasis, immunodeficiency, disseminated intravascular coagulation, systemic sclerosis, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, encephalomyelitis, edema, inflammatory bowel disease, hyper IgE syndrome, cancer metastasis or growth, adoptive immune therapy, reperfusion syndrome, radiation burns, and alopecia. 
   
   
       64 . A method for treating a condition comprising administering an effective amount of a non-naturally occurring, unsaturated or polyunsaturated fatty acid having one or more electron withdrawing group or a pharmaceutically acceptable salt thereof to a subject in need of treatment. 
   
   
       65 . The method of  claim 64 , wherein the non-naturally occurring, unsaturated or polyunsaturated fatty acid comprises an aliphatic chain having an odd number of carbons. 
   
   
       66 . The method of  claim 64 , wherein the non-naturally occurring unsaturated or polyunsaturated fatty acid comprises an aliphatic chain having 5 to 23 carbons. 
   
   
       67 . The method of  claim 64 , wherein the one or more electron withdrawing group is selected from aldehyde (—COH), acyl (—COR), carbonyl (—CO), carboxylic acid (—COOH), ester (—COOR), halides (—Cl, —F, —Br, —I), fluoromethyl (—CF n ), allyl fluoride (—CH═CHCH 2 F), cyano (—CN), sulfoxide (—SOR), sulfonyl (—SO 2 R), sulfonic acid (—SO 3 H), and 1°, 2° and 3° ammonium (—NR 3   + ), and nitro (—NO 2 ) wherein R is a hydrogen, methyl or C 2 -C 6  alkyl. 
   
   
       68 . The method of  claim 64 , wherein the one or more electron withdrawing group is positioned on an alpha carbon of a carbon-carbon double bond of the unsaturated or polyunsaturated fatty acid. 
   
   
       69 . The method of  claim 64 , wherein the one or more electron withdrawing group is positioned on a beta carbon of a carbon-carbon double bond of the unsaturated or polyunsaturated fatty acid. 
   
   
       70 . The method of  claim 64 , wherein the one or more electron withdrawing group is positioned on a gamma carbon of a carbon-carbon double bond of the unsaturated or polyunsaturated fatty acid. 
   
   
       71 . The method of  claim 64 , wherein at least one of the one or more electron withdrawing group is an electron withdrawing vinyl group or an electron withdrawing allylic group. 
   
   
       72 . The method of  claim 64 , wherein a carbon-carbon double bond associated with the one or more electron withdrawing group is in cis configuration. 
   
   
       73 . The method of  claim 64 , wherein a carbon-carbon double bond associated with the one or more electron withdrawing group is in trans configuration. 
   
   
       74 . The method of  claim 64 , wherein the effective amount comprises a mixture of unsaturated or polyunsaturated fatty acids having one or more electron withdrawing group associated with at least one double bond wherein the mixture comprises electron withdrawing group positioned on alpha, beta, and gamma carbon of a carbon-carbon double bonds of the unsaturated or polyunsaturated fatty acids. 
   
   
       75 . The method of  claim 64 , wherein the condition is selected from arterial stenosis, burns, hypertension, obesity, neurodegenerative disorders, skin disorders, arthritis, autoimmune disease, autoinflammatory disease, lupus, Lyme's disease, gout, sepsis, hyperthermia, ulcers, enterocolitis, osteoporosis, viral or bacterial infections, cytomegalovirus, periodontal disease, glomerulonephritis, sarcoidosis, lung disease, chronic lung injury, respiratory distress, lung inflammation, fibrosis of the lung, asthma, acquired respiratory distress syndrome, tobacco induced lung disease, granuloma formation, fibrosis of the liver, graft vs. host disease, postsurgical inflammation, coronary and peripheral vessel restenosis following angioplasty, stent placement or bypass graft, acute and chronic leukemia, B lymphocyte leukemia, neoplastic diseases, arteriosclerosis, atherosclerosis, myocardial inflammation, psoriasis, immunodeficiency, disseminated intravascular coagulation, systemic sclerosis, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, encephalomyelitis, edema, inflammatory bowel disease, hyper IgE syndrome, cancer metastasis or growth, adoptive immune therapy, reperfusion syndrome, radiation burns, and alopecia.