Compounds, compositions and methods for the treatment of inflammatory diseases

Abstract

The use of a composition comprising a compound: where R is a C 1 -C 10 alkylene group, in which, when the number of carbon atoms is at least 2, there are optionally 1 or 2 non-adjacent double bonds; 1 to 3 non-adjacent methylene groups are optionally replaced by NR 1 (where R 1 is H, alkyl, or acyl), O, or S; and 1 or 2 methylene groups are optionally replaced by a carbonyl or hydroxymethylene group for the preparation of a medicament or a pharmaceutical for the treatment of inflammatory diseases.

1 . Use of a composition for treatment of inflammatory diseases, the composition comprising a compound  
     
       
         
         
             
             
         
       
     
     where: 
 R is a C 1 -C 10  alkylene group, in which, when the number of carbon atoms is at least 2, there are optionally 1 or 2 non-adjacent double bonds; 1 to 3 non-adjacent methylene groups are optionally replaced by NR 1  (where R 1  is H, alkyl, or acyl), O, or S; and 1 or 2 methylene groups are optionally replaced by a carbonyl or hydroxymethylene group.  
 
   
   
       2 . The use of the composition of  claim 1  where the compound is selected from the group consisting of; 
 3,4,3 1 ,4 1 -tetrahydroxybenzoin (compound 1);    3,4,3 1 ,4 1 -tetrahydroxydesoxybenzoin (compound 2);    3,4,3 1 ,4 1 -tetrahydroxydiphenylmethane (compound 3);    1,2-bis(3,4-dihydroxyphenyl)ethane (compound 4);    1,3-bis(3,4-dihydroxyphenyl)propoane (compound 5);    3,4,3 1 ,4 1 -tetrahydroxychalcone (compound 6);    3,5-bis(3,4-dihydroxyphenyl)-1-methyl-2-pyrazoline (compound 7);    4,6-bis(3,4-dihydroxyphenyl)-3-cyano-2-methylpyridine (compound 8);    1,4-bis(3,4-dihydroxybenzyl)piperazine (compound 9);    N,N 1 -bis(3,4-dihydroxybenzyl)-N,N 1 -dimethylethylenediamine (compound 10);    2,5-bis(3,4-dihydroxybenzyl)-2,5-diaza[2.2.1]bicycloheptane (compound 11);    N,N 1 -bis(3,4-dihydroxybenzyl)-trans-1,2-diaminocyclohexane (compound 12);    N,N 1 -bis(3,4-dihydroxybenzyl)-trans-1,4-diaminocyclohexane (compound 13);    N,N 1 -bis(3,4-dihydroxybenzyl)-cis-1,3-bis(aminomethyl)cyclohexane (compound 14);    N-(3,4-dihydroxybenzyl)proline 3,4-dihydroxybenzylamide (compound 15);    2-(3,4-dihydroxybenzyl)isoquinoline-3-carboxylic acid 3,4-dihydroxyhenethylamide (compound 16);    2,6-bis(3,4-dihydroxybenzyl)cyclohexanone (compound 17);    3,5-bis(3,4-dihydroxybenzyl)-1-methyl-4-piperidinone (compound 18);    2,4-bis(3,4-dihydroxybenzyl)-3-tropinone (compound 19);    tris-(3,4-dihydroxybenzyl)methane (compound 20);    α-(3,4-dihydroxybenzamido)-3,4-dihydroxycinnamic acid 3,4-dihydroxybenzyl amide (compound 21);    4-(3,4-dihydroxybenzylaminomethylene)-2-(3,4-dihydroxyhenyl)oxazolin-5-one (compound 22);    1,4-bis(3,4-dihydroxybenzoyl)iperazine (compound 23);    N,N 1 -bis(3,4-dihydroxybenzoyl)-N,N 1 -dimethylethylenediamine (compound 24);    2,5-bis(3,4-dihydroxybenzoyl)-2,5-diaza[2.2.1]bicycloheptane (compound 25);    N,N 1 -bis(3,4-dihydroxybenzoyl)-trans-1,2-diaminocyclohexane (compound 26);    N,N 1 -bis(3,4-dihydroxybenzoyl)-cis-1,3-bis(aminomethyl)cyclohexane (compound 27);    3,6-bis(3,4-dihydroxybenzyl)-2,5-diketopiperazine (compound 28);    3,6-bis(3,4-dihydroxybenzylidene)-1,4-dimethyl-2,5-diketopiperazine (compound 29);    N-(3,4-dihydroxyhenylacetyl)proline 3,4-dihydroxyanilide (compound 30);    2,3-bis(3,4-dihydroxyhenyl)butane (compound 31);    1,3-bis(3,4-dihydroxybenzyl)benzene (compound 32);    1,4-bis(3,4-dihydroxybenzyl)benzene (compound 33);    2,6-bis(3,4-dihydroxybenzyl)yridine (compound 34);    2,5-bis(3,4-dihydroxybenzyl)thiophene (compound 35);    2,3-bis(3,4-dihydroxybenzyl)thiohene (compound 36);    1,2-bis(3,4-dihydroxyphenyl)cyclohexane (compound 37);    1,4-bis(3,4-dihydroxyphenyl)cyclohexane (compound 38);    3,7-bis(3,4-dihydroxyphenyl)bicyclo[3.3.0]octane (compound 39);    2,3-bis(3,4-dihydroxyphenyl)-1,7,7-trimethylgicyclo[2.2.1]heptane (compound 40);    1,2-bis(3,4-dihydroxyphenoxy)ethane (compound 41);    1,3-bis(3,4-dihydroxyphenoxy)propane (compound 42);    trans-1,2-bis(3,4-dihydroxyphenoxy)-cyclopentane (compound 43);    N-(3,4-dihydroxybenzyl)-3-(3,4-dihydroxyphenoxy)-2-hydroxyropylamine (compound 44);    3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxyanilide (compound 45);    3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxybenzylamide (compound 46);    3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxyphenethylamide (compound 47);    3,4-dihydroxybenzoic acid p-(3,4-dihydroxyphenoxy)anilide (compound 48);    3,4-dihydroxybenzoic acid o-(3,4-dihydroxyphenoxy)anilide (compound 49);    2,6-bis(3,4-dihydroxyphenoxy)pyridine (compound 50);    3,4-dihydroxybenzoic acid 3,4-dihydroxyanilide (compound 51);    3,4-dihydroxybenzoic acid 3,4-dihydroxybenzylamide (compound 52);    3,4-dihydroxybenzoic acid 3,4-dihydroxyphenethylamide (compound 53);    3,4-dihydroxyphenylacetic acid 3,4-dihydroxyanilide (compound 54);    3,4-dihydroxyphenylacetic acid 3,4-dihydroxybenzylamide (compound 55);    3,4-dihydroxyphenylacetic acid 3,4-dihydroxyphenethylamide (compound 56);    3-(3,4-dihydroxyphenyl)propionic acid 3,4-dihydroxyanilide (compound 57);    3-(3,4-dihydroxyphenyl)propionic acid 3,4-dihydroxybenzaylamide (compound 58);    3-(3,4-dihydroxyphenyl)propionic acid 3,4-dihydroxyphenethylamide (compound 59);    3,4-dihydroxycinnamic acid 3,4-dihydroxyanilide (compound 60);    3,4-dihydroxycinnamic acid 3,4-dihydroxybenzylamide (compound 61);    3,4-dihydroxycinnamic acid 3,4-dihydroxyphenethylamide (compound 62);    oxalic acid bis(3,4-dihydroxyanilide) (compound 63);    oxalic acid bis(3,4-dihydroxybenzylamie)(compound 64);    oxalic acid bis(3,4-dihydroxyphenethylamide) (compound 65);    succinic acid bis(3,4-dihydroxyanilide)(compound 66);    succinic acid bis(3,4-dihydroxybenzylamide) (compound 67);    succinic acid bis(3,4-dihydroxyphenethylamide) (compound 68);    maleic acid bis(3,4-dihydroxyanilide) (compound 69);    maleic acid bis(3,4-dihydroxyanilide) (compound 70);    fumaric acid bis(3,4-dihydroxyanilide) (compound 71);    fumaric acid bis(3,4-dihydroxybenzylamide) (compound 72);    bis(3,4-dihydroxybenzyl)amine (compound 73);    N(3,4-dihydroxybenzyl)-3,4-dihydroxyphenethylamine (compound 74);    tris(3,4-dihydroxybenzyl)amine (compound 75);    1,3-bis(3,4-dihydroxyhenzyl)urea (compound 76);    1-(3,4-dihydroxyphenzyl)-3-(3,4-dihydroxybenzyl)urea (compound 77);    1-(3,4-dihydroxybenzyl)-3-(3,4-dihydroxyphenethyl)urea (compound 78);    3-deoxy-3-(3,4-dihydroxybenzyl)aminoepicatechin (compound 79);    3-deoxy-3-(3,4-dihydroxyphenethyl)aminoepicatechin (compound 80);    2,3,6,7-tetrahydroxy-9,10-epoxy-9,10-dihydroacridine (compound 81);    10-aminoanthracene-1,2,7,8-tetraol (compound 82);    acridine-1,2,6,7-tetraol (compound 83);    phenoxazine-2,3,7,8,10-pentaol (compound 84);    dibenzo[c,f][2,7]napthyridine-2,3,10,11-tetraol (compound 85);    6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-2,10,11-triol (compound 86);    and methylenedioxy analogs and pharmaceutically acceptable esters or salts of the compounds.    
   
   
       3 . The use of the composition of  claim 1  or  2  wherein the inflammatory disease is selected from the group consisting of ulcerative colitis, endotoxic shock, rheumatoid arthritis, juvenile arthritis, osteoarthritis, psoriasis, Crohn's disease, inflammatory bowel disease, multiple sclerosis, insulin dependent diabetes mellitus, gout, psoriatic arthritis, reactive arthritis, viral or post-viral arthritis and ankylosing spondylarthritis.  
   
   
       4 . The use of the composition of  claim 2  wherein the inflammatory disease is rheumatoid arthritis.  
   
   
       5 . Use of a composition for preparation of a medicament for treatment of inflammatory diseases, the composition comprising a compound  
     
       
         
         
             
             
         
       
     
     where: 
 R is a C 1 -C 10  alkylene group, in which, when the number of carbon atoms is at least 2, there are optionally 1 or 2 non-adjacent double bonds; 1 to 3 non-adjacent methylene groups are optionally replaced by NR 1  (where R 1  is H, alkyl, or acyl), O, or S; and 1 or 2 methylene groups are optionally replaced by a carbonyl or hydroxymethylene group.  
 
   
   
       6 . The use of  claim 5  where the compounds are selected from the group consisting of; 
 3,4,3 1 ,4 1 -tetrahydroxybenzoin (compound 1);    3,4,3 1 ,4 1 -tetrahydroxydesoxybenzoin (compound 2);    3,4,3 1 ,4 1 -tetrahydroxydiphenylmethane (compound 3);    1,2-bis(3,4-dihydroxyphenyl)ethane (compound 4);    1,3-bis(3,4-dihydroxyphenyl)propoane (compound 5);    3,4,3 1 ,4 1 -tetrahydroxychalcone (compound 6);    3,5-bis(3,4-dihydroxyphenyl)-1-methyl-2-pyrazoline (compound 7);    4,6-bis(3,4-dihydroxyphenyl)-3-cyano-2-methylpyridine (compound 8);    1,4-bis(3,4-dihydroxybenzyl)piperazine (compound 9);    N,N 1 -bis(3,4-dihydroxybenzyl)-N,N 1 -dimethylethylenediamine (compound 10);    2,5-bis(3,4-dihydroxybenzyl)-2,5-diaza[2.2.1]bicycloheptane (compound 11);    N,N 1 -bis(3,4-dihydroxybenzyl)-trans-1,2-diaminocyclohexane (compound 12);    N,N 1 -bis(3,4-dihydroxybenzyl)-trans-1,4-diaminocyclohexane (compound 13);    N,N 1 -bis(3,4-dihydroxybenzyl)-cis-1,3-bis(aminomethyl)cyclohexane (compound 14);    N-(3,4-dihydroxybenzyl)proline 3,4-dihydroxybenzylamide (compound 15);    2-(3,4-dihydroxybenzyl)isoquinoline-3-carboxylic acid 3,4-dihydroxyhenethylamide (compound 16);    2,6-bis(3,4-dihydroxybenzyl)cyclohexanone (compound 17);    3,5-bis(3,4-dihydroxybenzyl)-1-methyl-4-piperidinone (compound 18);    2,4-bis(3,4-dihydroxybenzyl)-3-tropinone (compound 19);    tris-(3,4-dihydroxybenzyl)methane (compound 20);    α-(3,4-dihydroxybenzamido)-3,4-dihydroxycinnamic acid 3,4-dihydroxybenzyl amide (compound 21);    4-(3,4-dihydroxybenzylaminomethylene)-2-(3,4-dihydroxyhenyl)oxazolin-5-one (compound 22);    1,4-bis(3,4-dihydroxybenzoyl)iperazine (compound 23);    N,N 1 -bis(3,4-dihydroxybenzoyl)-N,N 1 -dimethylethylenediamine (compound 24);    2,5-bis(3,4-dihydroxybenzoyl)-2,5-diaza[2.2.1]bicycloheptane (compound 25);    N,N 1 -bis(3,4-dihydroxybenzoyl)-trans-1,2-diaminocyclohexane (compound 26);    N,N 1 -bis(3,4-dihydroxybenzoyl)-cis-1,3-bis(aminomethyl)cyclohexane (compound 27);    3,6-bis(3,4-dihydroxybenzyl)-2,5-diketopiperazine (compound 28);    3,6-bis(3,4-dihydroxybenzylidene)-1,4-dimethyl-2,5-diketopiperazine (compound 29);    N-(3,4-dihydroxyhenylacetyl)proline 3,4-dihydroxyanilide (compound 30);    2,3-bis(3,4-dihydroxyhenyl)butane (compound 31);    1,3-bis(3,4-dihydroxybenzyl)benzene (compound 32);    1,4-bis(3,4-dihydroxybenzyl)benzene (compound 33);    2,6-bis(3,4-dihydroxybenzyl)yridine (compound 34);    2,5-bis(3,4-dihydroxybenzyl)thiophene (compound 35);    2,3-bis(3,4-dihydroxybenzyl)thiohene (compound 36);    1,2-bis(3,4-dihydroxyphenyl)cyclohexane (compound 37);    1,4-bis(3,4-dihydroxyphenyl)cyclohexane (compound 38);    3,7-bis(3,4-dihydroxyphenyl)bicyclo[3.3.0]octane (compound 39);    2,3-bis(3,4-dihydroxyphenyl)-1,7,7-trimethylgicyclo[2.2.1]heptane (compound 40);    1,2-bis(3,4-dihydroxyphenoxy)ethane (compound 41);    1,3-bis(3,4-dihydroxyphenoxy)propane (compound 42);    trans-1,2-bis(3,4-dihydroxyphenoxy)-cyclopentane (compound 43);    N-(3,4-dihydroxybenzyl)-3-(3,4-dihydroxyphenoxy)-2-hydroxyropylamine (compound 44);    3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxyanilide (compound 45);    3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxybenzylamide (compound 46);    3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxyphenethylamide (compound 47);    3,4-dihydroxybenzoic acid p-(3,4-dihydroxyphenoxy)anilide (compound 48);    3,4-dihydroxybenzoic acid o-(3,4-dihydroxyphenoxy)anilide (compound 49);    2,6-bis(3,4-dihydroxyphenoxy)pyridine (compound 50);    3,4-dihydroxybenzoic acid 3,4-dihydroxyanilide (compound 51);    3,4-dihydroxybenzoic acid 3,4-dihydroxybenzylamide (compound 52);    3,4-dihydroxybenzoic acid 3,4-dihydroxyphenethylamide (compound 53);    3,4-dihydroxyphenylacetic acid 3,4-dihydroxyanilide (compound 54);    3,4-dihydroxyphenylacetic acid 3,4-dihydroxybenzylamide (compound 55);    3,4-dihydroxyphenylacetic acid 3,4-dihydroxyphenethylamide (compound 56);    3-(3,4-dihydroxyphenyl)propionic acid 3,4-dihydroxyanilide (compound 57);    3-(3,4-dihydroxyphenyl)propionic acid 3,4-dihydroxybenzaylamide (compound 58);    3-(3,4-dihydroxyphenyl)propionic acid 3,4-dihydroxyphenethylamide (compound 59);    3,4-dihydroxycinnamic acid 3,4-dihydroxyanilide (compound 60);    3,4-dihydroxycinnamic acid 3,4-dihydroxybenzylamide (compound 61);    3,4-dihydroxycinnamic acid 3,4-dihydroxyphenethylamide (compound 62);    oxalic acid bis(3,4-dihydroxyanilide) (compound 63);    oxalic acid bis(3,4-dihydroxybenzylamie)(compound 64);    oxalic acid bis(3,4-dihydroxyphenethylamide) (compound 65);    succinic acid bis(3,4-dihydroxyanilide)(compound 66);    succinic acid bis(3,4-dihydroxybenzylamide) (compound 67);    succinic acid bis(3,4-dihydroxyphenethylamide) (compound 68);    maleic acid bis(3,4-dihydroxyanilide) (compound 69);    maleic acid bis(3,4-dihydroxyanilide) (compound 70);    fumaric acid bis(3,4-dihydroxyanilide) (compound 71);    fumaric acid bis(3,4-dihydroxybenzylamide) (compound 72);    bis(3,4-dihydroxybenzyl)amine (compound 73);    N(3,4-dihydroxybenzyl)-3,4-dihydroxyphenethylamine (compound 74);    tris(3,4-dihydroxybenzyl)amine (compound 75);    1,3-bis(3,4-dihydroxyhenzyl)urea (compound 76);    1-(3,4-dihydroxyphenzyl)-3-(3,4-dihydroxybenzyl)urea (compound 77);    1-(3,4-dihydroxybenzyl)-3-(3,4-dihydroxyphenethyl)urea (compound 78);    3-deoxy-3-(3,4-dihydroxybenzyl)aminoepicatechin (compound 79);    3-deoxy-3-(3,4-dihydroxyphenethyl)aminoepicatechin (compound 80);    2,3,6,7-tetrahydroxy-9,10-epoxy-9,10-dihydroacridine (compound 81);    10-aminoanthracene-1,2,7,8-tetraol (compound 82);    acridine-1,2,6,7-tetraol (compound 83);    phenoxazine-2,3,7,8,10-pentaol (compound 84);    dibenzo[c,f][2,7]napthyridine-2,3,10,11-tetraol (compound 85);    6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-2,10,11-triol (compound 86);    and methylenedioxy analogs and pharmaceutically acceptable esters or salts of the compounds.    
   
   
       7 . The use of claims  5  or  6  wherein the inflammatory disease is selected from the group consisting of ulcerative colitis, endotoxic shock, rheumatoid arthritis, juvenile arthritis, osteoarthritis, psoriasis, Crohn's disease, inflammatory bowel disease, multiple sclerosis, insulin dependent diabetes mellitus, gout, psoriatic arthritis, reactive arthritis, viral or post-viral arthritis and ankylosing spondylarthritis.  
   
   
       8 . The use of  claim 5  wherein the inflammatory disease is rheumatoid arthritis.  
   
   
       9 . Use of a composition for inhibition of the inflammatory cascade, the composition comprising a compound  
     
       
         
         
             
             
         
       
     
     where: 
 R is a C 1 -C 10  alkylene group, in which, when the number of carbon atoms is at least 2, there are optionally 1 or 2 non-adjacent double bonds; 1 to 3 non-adjacent methylene groups are optionally replaced by NR 1  (where R 1  is H, alkyl, or acyl), O, or S; and 1 or 2 methylene groups are optionally replaced by a carbonyl or hydroxymethylene group.  
 
   
   
       10 . The use of the composition of  claim 9  where the compound is selected from the group consisting of; 
 3,4,3 1 ,4 1 -tetrahydroxybenzoin (compound 1);    3,4,3 1 ,4 1 -tetrahydroxydesoxybenzoin (compound 2);    3,4,3 1 ,4 1 -tetrahydroxydiphenylmethane (compound 3);    1,2-bis(3,4-dihydroxyphenyl)ethane (compound 4);    1,3-bis(3,4-dihydroxyphenyl)propoane (compound 5);    3,4,3 1 ,4 1 -tetrahydroxychalcone (compound 6);    3,5-bis(3,4-dihydroxyphenyl)-1-methyl-2-pyrazoline (compound 7);    4,6-bis(3,4-dihydroxyphenyl)-3-cyano-2-methylpyridine (compound 8);    1,4-bis(3,4-dihydroxybenzyl)piperazine (compound 9);    N,N 1 -bis(3,4-dihydroxybenzyl)-N,N 1 -dimethylethylenediamine (compound 10);    2,5-bis(3,4-dihydroxybenzyl)-2,5-diaza[2.2.1]bicycloheptane (compound 11);    N,N 1 -bis(3,4-dihydroxybenzyl)-trans-1,2-diaminocyclohexane (compound 12);    N,N 1 -bis(3,4-dihydroxybenzyl)-trans-1,4-diaminocyclohexane (compound 13);    N,N 1 -bis(3,4-dihydroxybenzyl)-cis-1,3-bis(aminomethyl)cyclohexane (compound 14);    N-(3,4-dihydroxybenzyl)proline 3,4-dihydroxybenzylamide (compound 15);    2-(3,4-dihydroxybenzyl)isoquinoline-3-carboxylic acid 3,4-dihydroxyhenethylamide (compound 16);    2,6-bis(3,4-dihydroxybenzyl)cyclohexanone (compound 17);    3,5-bis(3,4-dihydroxybenzyl)-1-methyl-4-piperidinone (compound 18);    2,4-bis(3,4-dihydroxybenzyl)-3-tropinone (compound 19);    tris-(3,4-dihydroxybenzyl)methane (compound 20);    α-(3,4-dihydroxybenzamido)-3,4-dihydroxycinnamic acid 3,4-dihydroxybenzyl amide (compound 21);    4-(3,4-dihydroxybenzylaminomethylene)-2-(3,4-dihydroxyhenyl)oxazolin-5-one (compound 22);    1,4-bis(3,4-dihydroxybenzoyl)iperazine (compound 23);    N,N 1 -bis(3,4-dihydroxybenzoyl)-N,N 1 -dimethylethylenediamine (compound 24);    2,5-bis(3,4-dihydroxybenzoyl)-2,5-diaza[2.2.1]bicycloheptane (compound 25);    N,N 1 -bis(3,4-dihydroxybenzoyl)-trans-1,2-diaminocyclohexane (compound 26);    N,N 1 -bis(3,4-dihydroxybenzoyl)-cis-1,3-bis(aminomethyl)cyclohexane (compound 27);    3,6-bis(3,4-dihydroxybenzyl)-2,5-diketopiperazine (compound 28);    3,6-bis(3,4-dihydroxybenzylidene)-1,4-dimethyl-2,5-diketopiperazine (compound 29);    N-(3,4-dihydroxyhenylacetyl)proline 3,4-dihydroxyanilide (compound 30);    2,3-bis(3,4-dihydroxyhenyl)butane (compound 31);    1,3-bis(3,4-dihydroxybenzyl)benzene (compound 32);    1,4-bis(3,4-dihydroxybenzyl)benzene (compound 33);    2,6-bis(3,4-dihydroxybenzyl)yridine (compound 34);    2,5-bis(3,4-dihydroxybenzyl)thiophene (compound 35);    2,3-bis(3,4-dihydroxybenzyl)thiohene (compound 36);    1,2-bis(3,4-dihydroxyphenyl)cyclohexane (compound 37);    1,4-bis(3,4-dihydroxyphenyl)cyclohexane (compound 38);    3,7-bis(3,4-dihydroxyphenyl)bicyclo[3.3.0]octane (compound 39);    2,3-bis(3,4-dihydroxyphenyl)-1,7,7-trimethylgicyclo[2.2.1]heptane (compound 40);    1,2-bis(3,4-dihydroxyphenoxy)ethane (compound 41);    1,3-bis(3,4-dihydroxyphenoxy)propane (compound 42);    trans-1,2-bis(3,4-dihydroxyphenoxy)-cyclopentane (compound 43);    N-(3,4-dihydroxybenzyl)-3-(3,4-dihydroxyphenoxy)-2-hydroxyropylamine (compound 44);    3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxyanilide (compound 45);    3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxybenzylamide (compound 46);    3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxyphenethylamide (compound 47);    3,4-dihydroxybenzoic acid p-(3,4-dihydroxyphenoxy)anilide (compound 48);    3,4-dihydroxybenzoic acid o-(3,4-dihydroxyphenoxy)anilide (compound 49);    2,6-bis(3,4-dihydroxyphenoxy)pyridine (compound 50);    3,4-dihydroxybenzoic acid 3,4-dihydroxyanilide (compound 51);    3,4-dihydroxybenzoic acid 3,4-dihydroxybenzylamide (compound 52);    3,4-dihydroxybenzoic acid 3,4-dihydroxyphenethylamide (compound 53);    3,4-dihydroxyphenylacetic acid 3,4-dihydroxyanilide (compound 54);    3,4-dihydroxyphenylacetic acid 3,4-dihydroxybenzylamide (compound 55);    3,4-dihydroxyphenylacetic acid 3,4-dihydroxyphenethylamide (compound 56);    3-(3,4-dihydroxyphenyl)propionic acid 3,4-dihydroxyanilide (compound 57);    3-(3,4-dihydroxyphenyl)propionic acid 3,4-dihydroxybenzaylamide (compound 58);    3-(3,4-dihydroxyphenyl)propionic acid 3,4-dihydroxyphenethylamide (compound 59);    3,4-dihydroxycinnamic acid 3,4-dihydroxyanilide (compound 60);    3,4-dihydroxycinnamic acid 3,4-dihydroxybenzylamide (compound 61);    3,4-dihydroxycinnamic acid 3,4-dihydroxyphenethylamide (compound 62);    oxalic acid bis(3,4-dihydroxyanilide) (compound 63);    oxalic acid bis(3,4-dihydroxybenzylamie)(compound 64);    oxalic acid bis(3,4-dihydroxyphenethylamide) (compound 65);    succinic acid bis(3,4-dihydroxyanilide)(compound 66);    succinic acid bis(3,4-dihydroxybenzylamide) (compound 67);    succinic acid bis(3,4-dihydroxyphenethylamide) (compound 68);    maleic acid bis(3,4-dihydroxyanilide) (compound 69);    maleic acid bis(3,4-dihydroxyanilide) (compound 70);    fumaric acid bis(3,4-dihydroxyanilide) (compound 71);    fumaric acid bis(3,4-dihydroxybenzylamide) (compound 72);    bis(3,4-dihydroxybenzyl)amine (compound 73);    N(3,4-dihydroxybenzyl)-3,4-dihydroxyphenethylamine (compound 74);    tris(3,4-dihydroxybenzyl)amine (compound 75);    1,3-bis(3,4-dihydroxyhenzyl)urea (compound 76);    1-(3,4-dihydroxyphenzyl)-3-(3,4-dihydroxybenzyl)urea (compound 77);    1-(3,4-dihydroxybenzyl)-3-(3,4-dihydroxyphenethyl)urea (compound 78);    3-deoxy-3-(3,4-dihydroxybenzyl)aminoepicatechin (compound 79);    3-deoxy-3-(3,4-dihydroxyphenethyl)aminoepicatechin (compound 80);    2,3,6,7-tetrahydroxy-9,10-epoxy-9,10-dihydroacridine (compound 81);    10-aminoanthracene-1,2,7,8-tetraol (compound 82);    acridine-1,2,6,7-tetraol (compound 83);    phenoxazine-2,3,7,8,10-pentaol (compound 84);    dibenzo[c,f][2,7]napthyridine-2,3,10,11-tetraol (compound 85);    6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-2,10,11-triol (compound 86);    and methylenedioxy analogs and pharmaceutically acceptable esters or salts of the compounds.    
   
   
       11 . Use of a composition for preparation of a medicament for inhibition of the inflammatory cascade, the composition comprising a compound  
     
       
         
         
             
             
         
       
     
     where: 
 R is a C 1 -C 10  alkylene group, in which, when the number of carbon atoms is at least 2, there are optionally 1 or 2 non-adjacent double bonds; 1 to 3 non-adjacent methylene groups are optionally replaced by NR 1  (where R 1  is H, alkyl, or acyl), O, or S; and 1 or 2 methylene groups are optionally replaced by a carbonyl or hydroxymethylene group.  
 
   
   
       12 . The use of the composition of  claim 11  where the compound is selected from the group consisting of; 
 3,4,3 1 ,4 1 -tetrahydroxybenzoin (compound 1);    3,4,3 1 ,4 1  tetrahydroxydesoxybenzoin (compound 2);    3,4,3 1 ,4 1 -tetrahydroxydiphenylmethane (compound 3);    1,2-bis(3,4-dihydroxyphenyl)ethane (compound 4);    1,3-bis(3,4-dihydroxyphenyl)propoane (compound 5);    3,4,3 1 ,4 1 -tetrahydroxychalcone (compound 6);    3,5-bis(3,4-dihydroxyphenyl)-1-methyl-2-pyrazoline (compound 7);    4,6-bis(3,4-dihydroxyphenyl)-3-cyano-2-methylpyridine (compound 8);    1,4-bis(3,4-dihydroxybenzyl)piperazine (compound 9);    N,N 1 -bis(3,4-dihydroxybenzyl)-N,N 1 -dimethylethylenediamine (compound 10);    2,5-bis(3,4-dihydroxybenzyl)-2,5-diaza[2.2.1]bicycloheptane (compound 11);    N,N 1 -bis(3,4-dihydroxybenzyl)-trans-1,2-diaminocyclohexane (compound 12);    N,N 1 -bis(3,4-dihydroxybenzyl)-trans-1,4-diaminocyclohexane (compound 13);    N,N 1 -bis(3,4-dihydroxybenzyl)-cis-1,3-bis(aminomethyl)cyclohexane (compound 14);    N-(3,4-dihydroxybenzyl)proline 3,4-dihydroxybenzylamide (compound 15);    2-(3,4-dihydroxybenzyl)isoquinoline-3-carboxylic acid 3,4-dihydroxyhenethylamide (compound 16);    2,6-bis(3,4-dihydroxybenzyl)cyclohexanone (compound 17);    3,5-bis(3,4-dihydroxybenzyl)-1-methyl-4-piperidinone (compound 18);    2,4-bis(3,4-dihydroxybenzyl)-3-tropinone (compound 19);    tris-(3,4-dihydroxybenzyl)methane (compound 20);    α-(3,4-dihydroxybenzamido)-3,4-dihydroxycinnamic acid 3,4-dihydroxybenzyl amide (compound 21);    4-(3,4-dihydroxybenzylaminomethylene)-2-(3,4-dihydroxyhenyl)oxazolin-5-one (compound 22);    1,4-bis(3,4-dihydroxybenzoyl)iperazine (compound 23);    N,N 1 -bis(3,4-dihydroxybenzoyl)-N,N 1 -dimethylethylenediamine (compound 24);    2,5-bis(3,4-dihydroxybenzoyl)-2,5-diaza[2.2.1]bicycloheptane (compound 25);    N,N 1 -bis(3,4-dihydroxybenzoyl)-trans-1,2-diaminocyclohexane (compound 26);    N,N 1 -bis(3,4-dihydroxybenzoyl)-cis-1,3-bis(aminomethyl)cyclohexane (compound 27);    3,6-bis(3,4-dihydroxybenzyl)-2,5-diketopiperazine (compound 28);    3,6-bis(3,4-dihydroxybenzylidene)-1,4-dimethyl-2,5-diketopiperazine (compound 29);    N-(3,4-dihydroxyhenylacetyl)proline 3,4-dihydroxyanilide (compound 30);    2,3-bis(3,4-dihydroxyhenyl)butane (compound 31);    1,3-bis(3,4-dihydroxybenzyl)benzene (compound 32);    1,4-bis(3,4-dihydroxybenzyl)benzene (compound 33);    2,6-bis(3,4-dihydroxybenzyl)yridine (compound 34);    2,5-bis(3,4-dihydroxybenzyl)thiophene (compound 35);    2,3-bis(3,4-dihydroxybenzyl)thiohene (compound 36);    1,2-bis(3,4-dihydroxyphenyl)cyclohexane (compound 37);    1,4-bis(3,4-dihydroxyphenyl)cyclohexane (compound 38);    3,7-bis(3,4-dihydroxyphenyl)bicyclo[3.3.0]octane (compound 39);    2,3-bis(3,4-dihydroxyphenyl)-1,7,7-trimethylgicyclo[2.2.1]heptane (compound 40);    1,2-bis(3,4-dihydroxyphenoxy)ethane (compound 41);    1,3-bis(3,4-dihydroxyphenoxy)propane (compound 42);    trans-1,2-bis(3,4-dihydroxyphenoxy)-cyclopentane (compound 43);    N-(3,4-dihydroxybenzyl)-3-(3,4-dihydroxyphenoxy)-2-hydroxyropylamine (compound 44);    3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxyanilide (compound 45);    3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxybenzylamide (compound 46);    3,4-dihydroxyphenoxyacetic acid 3,4-dihydroxyphenethylamide (compound 47);    3,4-dihydroxybenzoic acid p-(3,4-dihydroxyphenoxy)anilide (compound 48);    3,4-dihydroxybenzoic acid o-(3,4-dihydroxyphenoxy)anilide (compound 49);    2,6-bis(3,4-dihydroxyphenoxy)pyridine (compound 50);    3,4-dihydroxybenzoic acid 3,4-dihydroxyanilide (compound 51);    3,4-dihydroxybenzoic acid 3,4-dihydroxybenzylamide (compound 52);    3,4-dihydroxybenzoic acid 3,4-dihydroxyphenethylamide (compound 53);    3,4-dihydroxyphenylacetic acid 3,4-dihydroxyanilide (compound 54);    3,4-dihydroxyphenylacetic acid 3,4-dihydroxybenzylamide (compound 55);    3,4-dihydroxyphenylacetic acid 3,4-dihydroxyphenethylamide (compound 56);    3-(3,4-dihydroxyphenyl)propionic acid 3,4-dihydroxyanilide (compound 57);    3-(3,4-dihydroxyphenyl) propionic acid 3,4-dihydroxybenzaylamide (compound 58);    3-(3,4-dihydroxyphenyl)propionic acid 3,4-dihydroxyphenethylamide (compound 59);    3,4-dihydroxycinnamic acid 3,4-dihydroxyanilide (compound 60);    3,4-dihydroxycinnamic acid 3,4-dihydroxybenzylamide (compound 61);    3,4-dihydroxycinnamic acid 3,4-dihydroxyphenethylamide (compound 62);    oxalic acid bis(3,4-dihydroxyanilide) (compound 63);    oxalic acid bis(3,4-dihydroxybenzylamie)(compound 64);    oxalic acid bis(3,4-dihydroxyphenethylamide) (compound 65);    succinic acid bis(3,4-dihydroxyanilide)(compound 66);    succinic acid bis(3,4-dihydroxybenzylamide) (compound 67);    succinic acid bis(3,4-dihydroxyphenethylamide) (compound 68);    maleic acid bis(3,4-dihydroxyanilide) (compound 69);    maleic acid bis(3,4-dihydroxyanilide) (compound 70);    fumaric acid bis(3,4-dihydroxyanilide) (compound 71);    fumaric acid bis(3,4-dihydroxybenzylamide) (compound 72);    bis(3,4-dihydroxybenzyl)amine (compound 73);    N(3,4-dihydroxybenzyl)-3,4-dihydroxyphenethylamine (compound 74);    tris(3,4-dihydroxybenzyl)amine (compound 75);    1,3-bis(3,4-dihydroxyhenzyl)urea (compound 76);    1-(3,4-dihydroxyphenzyl)-3-(3,4-dihydroxybenzyl)urea (compound 77);    1-(3,4-dihydroxybenzyl)-3-(3,4-dihydroxyphenethyl)urea (compound 78);    3-deoxy-3-(3,4-dihydroxybenzyl)aminoepicatechin (compound 79);    3-deoxy-3-(3,4-dihydroxyphenethyl)aminoepicatechin (compound 80);    2,3,6,7-tetrahydroxy-9,10-epoxy-9,10-dihydroacridine (compound 81);    10-aminoanthracene-1,2,7,8-tetraol (compound 82);    acridine-1,2,6,7-tetraol (compound 83);    phenoxazine-2,3,7,8,10-pentaol (compound 84);    dibenzo[c,f][2,7]napthyridine-2,3,10,11-tetraol (compound 85);    6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-2,10,11-triol (compound 86);    and methylenedioxy analogs and pharmaceutically acceptable esters or salts of the compounds.