Anti-inflammatory nitro- and thia-fatty acids

Abstract

The present invention relates to compounds of the general formula: NO 2 -A-B wherein A is a saturated or unsaturated hydrocarbon chain of 14-26 carbon atoms and B is (CH 2 ) n (COOH) m in which n is an integer from 0 to 2 and m is an integer from 0 to 2; or of general formula (I), wherein A′ is a saturated or unsaturated hydrocarbon chain of 9-26 carbon atoms, X is oxygen or is absent and B′ is (CH 2 ) j (COOH) k in which j is an integer from 1 to 3 and k is 0 or 1; and the derivatives thereof in which the hydrocarbon chain includes one or more than one substitution selected from the group consisting of hydroxy, hydroperoxy, epoxy and peroxy. These compounds have biological activity, e.g. as anti-infective or anti-inflammatory agents.

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         74 . An pharmaceutical composition effective for treating or ameliorating the symptoms of a disease state involving elevated levels of unesterified arachidonic acid or a product of arachidonic acid metabolism in a subject comprising a compound having the general formula:  
       
         
           
           
               
               
           
         
       
       wherein A is an unsaturated hydrocarbon chain of 14 to 26 carbon atoms or a derivative thereof selected from the group consisting of hydroxy, hydroperoxy, epoxy and peroxy; and B is (CH 2 ) n (COOH) m  in which n is an integer from 0 to 2 and m is 1 or 2; wherein the NO 2  group is a side group on any one of the carbon atoms of A.and a pharmaceutically acceptable carrier or diluent.  
     
     
         75 . A composition according to  claim 74  wherein the unsaturated hydrocarbon chain comprises 18 to 22 carbon atoms.  
     
     
         76 . A composition according to  claim 74  wherein the unsaturated hydrocarbon chain comprises 3 to 6 double bonds.  
     
     
         77 . A composition according to  claim 74  wherein the hydrocarbon chain comprises 18 carbon atoms and three double bonds separated by methylene groups, with the first double bond between the 3 rd  and 4 th  or 6 th  and 7 th  carbon atoms relative to the omega carbon atom.  
     
     
         78 . A composition according to  claim 74  effective for treating asthma, an autoimmune disease, multiple sclerosis, rheumatoid arthritis, adult respiratory distress syndrome, inflammatory bowel disease, cystic fibrosis, an allergy, diabetes, atopic dermatitis, systemic lupus erythematosus, ischaemia or a cardiovascular disease.  
     
     
         79 . A composition according to  claim 74  wherein the disease state is selected from the group consisting of psoriasis, allergic asthma, rhinitis, leukocytoclastic vasculitis, urticaria, angioedema, systemic lupus erythematosus, ischaemia or a cardiovascular disease.  
     
     
         80 . A method for treating a disease state involving elevated levels of unesterified arachidonic acid or a product of arachidonic acid metabolism in a subject comprising administering to the subject a therapeutic amount of a composition of  claim 1 .  
     
     
         81 . A method according to  claim 79  wherein the disease state is selected from the group consisting of psoriasis, allergic asthma, rhinitis, leukocytoclastic vasculitis, urticaria, angioedema, systemic lupus erythematosus, ischaemia and a cardiovascular disease.