Fatty Acid Inhibitors

Abstract

Fatty acid inhibitors, pharmaceutical compositions including fatty acid inhibitors, methods for using fatty acid inhibitors to treat a variety of diseases, and methods for preparing fatty acid inhibitors are provided herein.

What is claimed is: 
     
         1 . A compound comprising an unsaturated or polyunsaturated fatty acid or pharmaceutically Formulae: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       Wherein:
 R 1  is H or an electron withdrawing group selected from the group consisting of aldehyde (—COH), acyl (—COR), carbonyl (—CO), carboxylic acid (—COOH), ester (—COOR), halides 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; 
 R 2  when present is H or an electron withdrawing group selected from the group consisting of 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 and the other is —H; 
 X is a leaving group selected from the group consisting of diazonium salts (—N 2   + ), nonaflates (R—OSO 2 C 4 F 9 ), triflates (—OSO 2 CF 3 ), fluorosulfonates (—OSO 2 F), tosylates (—OTs), mesylates (—OMs), halides, (—F, —Cl, —Br, —I), conjugate acid of alcohols (—OH 2   + ), acyl chlorides (—R(O)Cl), conjugate acid of an ethers (—OHR′ + ), nitrates (—ONO 2 ), phosphates (—OPO(OH) 2 ), tetraalkylammonium salts (—NR′ 3   + ), esters (—OC(O)R′), acid anhydrides (—C(O)OC(O)R′), ammonium salts (—NH 3   + ), phenoxides (—OAr), alcohols (—OH), carboxylic acids (—C(O)OH), ethers (—OR′), and esters (—C(O)OR′); 
 each R′ is, independently, selected from the group consisting of hydrogen (—H) or C 1  to C 6  alkyl, alkenyl, or alkynyl; and 
 Y is a leaving group within the main chain selected from the group consisting of —O—, NR″—, —S—, —SO—, —SO 2 —, and —POR″—; 
 Q is a heteroatom selected from the group consisting of —O—, —S—, —NR′″—, —CR′″ 2 —, and C═CR′″ 2 , wherein R′″ is —H, C 1  to C 6  alkyl, alkenyl, alkynyl, or aryl; 
 Z is a ketone, ester, amide, or thioester; and 
 m and n can, independently, be 1-20; 
 
     
     
         2 . The compound of  claim 1 , wherein the unsaturated or polyunsaturated fatty acid comprises an aliphatic chain having 5 to 23 carbons. 
     
     
         3 . The compound of  claim 1 , wherein the unsaturated or polyunsaturated fatty acid is selected from a glycolipid, a glycerolipid, a phospholipid and a cholesterol ester. 
     
     
         4 . The compound of  claim 1 , wherein R 1  is nitro (—NO 2 ). 
     
     
         5 . 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. 
     
     
         6 . The compound of  claim 1 , wherein a carbon-carbon double bond associated with R 1  is in cis configuration. 
     
     
         7 . The compound of  claim 1 , wherein a carbon-carbon double bond associated with R 1  is in trans configuration. 
     
     
         8 . The compound of  claim 1 , wherein the unsaturated or polyunsaturated fatty acid comprises two or more conjugated carbon-carbon double bonds. 
     
     
         9 . The compound of  claim 8 , wherein R 1  is at any carbon in the two or more conjugated carbon-carbon double bonds. 
     
     
         10 . The compound of  claim 1 , wherein at least R 1  is positioned at C-9, C-10, C-12, C-13 or a combination thereof. 
     
     
         11 . 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. 
     
     
         12 . The compound of  claim 1 , further comprising one or more functional group other than an electron withdrawing group positioned at any carbon of the unsaturated or polyunsaturated fatty acid. 
     
     
         13 . The compound of  claim 1 , further comprising a pharmaceutically acceptable carrier, excipient, or combination thereof. 
     
     
         14 . The compound of  claim 13 , 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. 
     
     
         15 . The compound of  claim 13 , wherein the unsaturated or polyunsaturated fatty acid or 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. 
     
     
         16 . A pharmaceutical composition comprising an effective amount of an unsaturated or polyunsaturated fatty acid of  claim 1  and at least one pharmaceutically acceptable carrier, excipient, or combination thereof. 
     
     
         17 . The pharmaceutical composition of  claim 16 , 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. 
     
     
         18 . The pharmaceutical composition of  claim 16 , wherein the pharmaceutical composition is formulated as a solid, solution, powder, fluid emulsion, fluid suspension, semi-, solid, or dry powder. 
     
     
         19 . A method for treating a condition comprising administering to an individual in need of treatment an effective amount of an unsaturated or polyunsaturated fatty acid of  claim 1 . 
     
     
         20 . The method of  claim 17 , 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 hums, and alopecia.