Immunomodulatory compounds and method of use thereof

Abstract

The present invention is directed to methods of treating diseases and disorders related to immune responses by administering one or more immunomodulatory compounds. In particular, the invention is directed to methods of stimulating and reducing immune responses, treating autoimmune conditions, treating allergic reactions and asthma, and preventing ischemic damage and asthma by administering one or more immunomodulatory compounds.

What is claimed is:  
     
         1 . A method of inducing or stimulating an immune response in a subject comprising administering an effective amount of a compound of the formula I, II, or III, as the active ingredient:  
       
         
           
           
               
               
           
         
       
       Wherein for each of formula I, II, or III: 
 R 1  is selected from the group consisting of 
 (a) C(O);  
 (b) C(O)—C 1-14  alkyl-C(O), wherein said C 1-14  alkyl is optionally substituted with hydroxy, C 1-5  alkoxy, C 1-5  alkylenedioxy, C 1-5  alkylamino, or C 1-5 -alkyl-aryl, wherein said aryl moiety of said C 1-15 -alkyl-aryl is optionally substituted with C 1-5  alkoxy, C 1-5  alkyl amino, C 1-5  alkoxy-amino, C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl C(O)OH, —O—C- 1-5  alkylamino-C(O)—C 1-5  alkyl-C(O)—C 1-5  alkyl;  
 (c) C 2  to C 15  straight or branched chain alkyl optionally substituted with hydroxy or alkoxy; and  
 (d) —C(O)—C 6-12  arylene-C(O)— wherein said arylene is optionally substituted with hydroxy, halogen, nitro or armno;  
 
 a and b are independently 0, 1, 2, 3 or 4;  
 d, d′, d″, e, e′ and e″ are independently an integer from 1 to 4;  
 X 1 , X 2 , Y 1  and Y 2  are independently selected from the group consisting of null, oxygen, NH and N(C(O)C 1-4  alkyl), and N(C 1-4  alkyl) 2 ;  
 W 1  and W 2  are independently selected from the group consisting of carbonyl, methylene, sulfone and sulfoxide;  
 R 2  and R 5  are independently selected from the group consisting of: 
 (a) C 2  to C 20  straight chain or branched chain alkyl which is optionally substituted with oxo, hydroxy or alkoxy,  
 (b) C 2  to C 20  straight chain or branched chain alkenyl or dialkenyl which is optionally substituted with oxo, hydroxy or alkoxy;  
 (c) C 2  to C 20  straight chain or branched chain alkoxy which is optionally substituted with oxo, hydroxy or alkoxy;  
 (d) —NH—C 2  to C 20  straight chain or branched chain alkyl, wherein said alkyl group is optionally substituted with oxo, hydroxy or alkoxy; and  
 (e)  
                     
 wherein Z is selected from the group consisting of O and NH, and M and N are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl, alkenyl, alkoxy, acyloxy, alkylamino, and acylamino; R 1  and R 6  are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl or alkenyl optionally substituted with oxo or fluoro;  
 
 R 4  and R 7  are independently selected from the group consisting of C(O)C 2  to C 20  straight chain or branched chain alkyl or alkenyl; C 2  to C 20  straight chain or branched chain alkyl; C 2  to C 20  straight chain or branched chain alkoxy; C 2  to C 20  straight chain or branched chain alkenyl; wherein said alkyl, alkenyl or alkoxy groups can be independently and optionally substituted with hydroxy, fluoro or C 1  to C 5  alkoxy;  
 G 1 , G 2 , G 3  and G 4  are independently selected from the group consisting of oxygen, methylene, amino, thiol, —NHC(O)—, and —N(C(O)C 1-4  alkyl)—;  
 or G 2 R 4  or G 4 R 7  may together be a hydrogen atom or hydroxyl;  
 or a pharmaceutically acceptable salt thereof;  
 and wherein for Formula II:  
 a′ and b′ are independently 2, 3, 4, 5, 6, 7, or 8, preferably 2;  
 Z 1  is selected from the group consisting of —OP(O)(OH) 2 , —P(O)(OH) 2 ,—OP(O)(OR 8 )(OH) where R 8 is a C1-C4 alkyl chain, —OS(O) 2 OH,—S(O) 2 OH—,—CO 2 H, —OB(OH) 2 , —OH, —CH 3 , —NH 2 , NR 9   3  where R 9  is a C1-C4 alkyl chain;  
 Z 2  is —OP(O)(OH) 2 , —P(O)(OH) 2′ , —OP(O)(OR 10 )(OH) where R 10  is a C1-C4 alkyl chain, —OS (O) 2 OH,—S(O) 2 OH, CO 2 H, —OB(OH) 2 , —OH, CH 3 , —NH 2 , —NR 11 , where R 11  is a C1-C4 alkyl chain;  
 and wherein for Formula 3:  
 R 12  is selected from H and a C1-C4 alkyl chain;  
 or a pharmaceutical salt thereof, 
 with the proviso that the compounds of formula I, II, or III are not  
                     
 
 
     
     
         2 . The method of  claim 1 , wherein the compounds bind a Toll-like receptor.  
     
     
         3 . The method of  claim 2 , wherein the Toll-like receptor is Toll-like receptor 4.  
     
     
         4 . The method of  claim 1 , wherein the subject is a human.  
     
     
         5 . The method of  claim 1 , wherein the subject is a mammal, fish, or reptile.  
     
     
         6 . The method of  claim 1 , wherein the immune response stimulates the production of at least one cytokine selected from the group consisting of IL-1α, IL-1β, IL-6, IL-10, IL12, interferon-α, interferon-γ, and GM-CSF.  
     
     
         7 . A method for upregulation of the immune system comprising administering a therapeutically effective amount of a compound of formula I, II, or III,  
       
         
           
           
               
               
           
         
       
       Wherein for each of formula I, II, or III: 
 R 1  is selected from the group consisting of 
 (a) C(O);  
 (b) C(O)—C 1-14  alkyl-C(O), wherein said C 1-14  alkyl is optionally substituted with hydroxy, C 1-5  alkoxy, C 1-5  alkylenedioxy, C 1-5  alkylamino, or C 1-5 -alkyl-aryl, wherein said aryl moiety of said C 1-15 -alkyl-aryl is optionally substituted with C 1-5  alkoxy, C 1-5  alkyl amino, C 1-5  alkoxy-amino, C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl C(O)OH, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl-C(O)—C 1-5  alkyl;  
 (c) C 2  to C 15  straight or branched chain alkyl optionally substituted with hydroxy or alkoxy; and  
 (d) —C(O)—C 6-12  arylene-C(O)— wherein said arylene is optionally substituted with hydroxy, halogen, nitro or amino;  
 
 a and b are independently 0, 1, 2, 3 or 4;  
 d, d′, d″, e, e′ and e″ are independently an integer from 1 to 4;  
 X 1 , X 2 , Y 1  and Y 2  are independently selected from the group consisting of null, oxygen, NH and N(C(O)C 1-4  alkyl), and N(C 1-4  alkyl) 2 ;  
 W 1  and W 2  are independently selected from the group consisting of carbonyl, methylene, sulfone and sulfoxide;  
 R 2  and R 5  are independently selected from the group consisting of: 
 (a) C 2  to C 20  straight chain or branched chain alkyl which is optionally substituted with oxo, hydroxy or alkoxy,  
 (b) C 2  to C 20  straight chain or branched chain alkenyl or dialkenyl which is optionally substituted with oxo, hydroxy or alkoxy;  
 (c) C 2  to C 20  straight chain or branched chain alkoxy which is optionally substituted with oxo, hydroxy or alkoxy;  
 (d) —NH—C 2  to C 20  straight chain or branched chain alkyl, wherein said alkyl group is optionally substituted with oxo, hydroxy or alkoxy; and  
 (e)  
                     
 wherein Z is selected from the group consisting of O and NH, and M and N are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl, alkenyl, alkoxy, acyloxy, alkylamino, and acylamino; R 1  and R 6  are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl or alkenyl optionally substituted with oxo or fluoro;  
 
 R 4  and R 7  are independently selected from the group consisting of C(O)C 2  to C 20  straight chain or branched chain alkyl or alkenyl; C 2  to C 20  straight chain or branched chain alkyl; C 2  to C 20  straight chain or branched chain alkoxy; C 2  to C 20  straight chain or branched chain alkenyl; wherein said alkyl, alkenyl or alkoxy groups can be independently and optionally substituted with hydroxy, fluoro or C, to C 5  alkoxy;  
 G 1 , G 2 , G 3  and G 4  are independently selected from the group consisting of oxygen, methylene, amino, thiol, —NHC(O)—, and —N(C(O)C 1-4  alkyl)—;  
 or G 2 R 4  or G 4 R 7  may together be a hydrogen atom or hydroxyl;  
 or a pharmaceutically acceptable salt thereof;  
 and wherein for Formula II:  
 a′ and b′ are independently 2, 3, 4, 5, 6, 7, or 8, preferably 2;  
 Z 1  is selected from the group consisting of —OP(O)(OH) 2 ,—P(O)(OH) 2 ,—OP(O)(OR 8 )(OH) where R 8  is a C1-C4 alkyl chain, —OS(O) 2 OH,—S(O) 2 OH—,—CO 2 H, —OB(OH) 2 , —OH, —CH 3 , —NH 2 , NR 9   3  where R 9  is a C1-C4 alkyl chain;  
 Z 2  is —OP(O)(OH) 2 , —P(O)(OH) 2′ , —OP(O)(OR 10 ) (OH) where R 10 is a C1-C4 alkyl chain, —OS (O) 2 OH,—S(O) 2 OH, CO 2 H, —OB(OH) 2 , —OH, CH 3 , —NH 2 , —NR 11 , where R 11  is a C1-C4 alkyl chain;  
 and wherein for Formula 3:  
 R 12  is selected from H and a C1-C4 alkyl chain;  
 or a pharmaceutical salt thereof, 
 with the proviso that the compounds of formula I, II, or III are not  
                     
 wherein said compound has immunostimulatory activity.  
 
 
     
     
         8 . A method of reducing an immune response in a subject, the method comprising administering to the subject a compound of formula I, II, or III  
       
         
           
           
               
               
           
         
       
       Wherein for each of formula I, IT, or III: 
 R 1  is selected from the group consisting of 
 (a) C(O);  
 (b) C(O)—C 1-14  alkyl-C(O), wherein said C 1-14  alkyl is optionally substituted with hydroxy, C 1-5  alkoxy, C 1-5  alkylenedioxy, C 1-5 alkylamino, or C 1-5 -alkyl-aryl, wherein said aryl moiety of said C 1-15 -alkyl-aryl is optionally substituted with C 1-5  alkoxy, C 1-5  alkyl amino, C 1-5  alkoxy-amino, C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C 5  alkoxy, —O—C 1-5  alkylamino-C (O)—C 1-5  alkyl C(O)OH, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl-C(O)—C 1-5  alkyl;  
 (c) C 2  to C 15  straight or branched chain alkyl optionally substituted with hydroxy or alkoxy; and  
 (d) —C(O)—C 6-12  arylene-C(O)— wherein said arylene is optionally substituted with hydroxy, halogen, nitro or amino;  
 
 a and b are independently 0, 1, 2, 3 or 4;  
 d, d′, d″, e, e′ and e″ are independently an integer from 1 to 4;  
 X 1 , X 2 , Y 1  and Y 2  are independently selected from the group consisting of null, oxygen, NH and N(C(O)C 1-4  alkyl), and N(C 1-4  alkyl) 2 ;  
 W 1  and W 2  are independently selected from the group consisting of carbonyl, methylene, sulfone and sulfoxide;  
 R 2  and R 5  are independently selected from the group consisting of: 
 (a) C 2  to C 20  straight chain or branched chain alkyl which is optionally substituted with oxo, hydroxy or alkoxy,  
 (b) C 2  to C 20  straight chain or branched chain alkenyl or dialkenyl which is optionally substituted with oxo, hydroxy or alkoxy;  
 (c) C 2  to C 20  straight chain or branched chain alkoxy which is optionally substituted with oxo, hydroxy or alkoxy;  
 (d) —NH—C 2  to C 20  straight chain or branched chain alkyl, wherein said alkyl group is optionally substituted with oxo, hydroxy or alkoxy; and  
 (e)  
                     
 wherein Z is selected from the group consisting of O and NH, and M and N are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl, alkenyl, alkoxy, acyloxy, alkylamino, and acylamino; R 1  and R 6  are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl or alkenyl optionally substituted with oxo or fluoro;  
 
 R 4  and R 7  are independently selected from the group consisting of C(O)C 2  to C 20  straight chain or branched chain alkyl or alkenyl; C 2  to C 20  straight chain or branched chain alkyl; C 2  to C 20  straight chain or branched chain alkoxy; C 2  to C 20  straight chain or branched chain alkenyl; wherein said alkyl, alkenyl or alkoxy groups can be independently and optionally substituted with hydroxy, fluoro or C 1  to C 5  alkoxy;  
 G 1 , G 2 , G 3  and G 4  are independently selected from the group consisting of oxygen, methylene, amino, thiol, —NHC(O)—, and —N(C(O)C 1-4  alkyl)-;  
 or G 2 R 4  or G 4 R 7  may together be a hydrogen atom or hydroxyl;  
 or a pharmaceutically acceptable salt thereof;  
 and wherein for Formula II:  
 a′ and b′ are independently 2, 3, 4, 5, 6, 7, or 8, preferably 2;  
 Z 1  is selected from the group consisting of —OP(O)(OH) 2 ,—P(O)(OH) 2 ,—OP(O)(OR 8 )(OH) where R 8  is a C1-C4 alkyl chain, —OS(O) 2 OH,—S(O) 2 OH—,—CO 2 H, —OB(OH) 2 , —OH, —CH 3 , —NH 2 , NR 9   3  where R 9  is a C1-C4 alkyl chain;  
 Z 2  is —OP(O)(OH) 2 , —P(O)(OH) 2′ , —OP(O)(OR 10 )(OH) where R 10 is a C1-C4 alkyl chain, —OS (O) 2 OH,—S(O) 2 OH, CO 2 H, —OB(OH) 2 , —OH, CH 3 , —NH 2 , —NR 11 , where R 11  is a C1-C4 alkyl chain;  
 and wherein for Formula 3:  
 R 12  is selected from H and a C1-C4 alkyl chain;  
 or a pharmaceutical salt thereof, 
 with the proviso that the compounds of formula I, II, or III are not  
                     
 in an amount sufficient to reduce an immune response in the subject and thereby induce a therapeutic effect.  
 
 
     
     
         9 . A method of desensitizing a subject against the occurrence of an allergic reaction in response to contact with a particular antigen or allergen, comprising administering to the subject an effective amount of an immunostimulatory compound of the formula I, II, or III  
       
         
           
           
               
               
           
         
       
       Wherein for each of formula I, II, or III: 
 R 1  is selected from the group consisting of 
 (a) C(O);  
 (b) C(O)—C 1-14  alkyl-C(O), wherein said C 1-14  alkyl is optionally substituted with hydroxy, C 1-5  alkoxy, C 1-5  alkylenedioxy, C 1-5  alkylamino, or C  1-5 -alkyl-aryl, wherein said aryl moiety of said C 1-15 -alkyl-aryl is optionally substituted with C 1-5  alkoxy, C 1-5  alkyl amino, C 1-5  alkoxy-amino, C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl C(O)OH, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl-C(O)—C 1-5  alkyl;  
 (c) C 2  to C 15  straight or branched chain alkyl optionally substituted with hydroxy or alkoxy; and  
 (d) —C(O)—C 6-12  arylene-C(O)— wherein said arylene is optionally substituted with hydroxy, halogen, nitro or amino;  
 
 a and b are independently 0, 1, 2, 3 or 4;  
 d, d′, d″, e, e′ and e″ are independently an integer from 1 to 4;  
 X 1 , X 2 , Y 1  and Y 2  are independently selected from the group consisting of null, oxygen, NH and N(C(O)C 1-4  alkyl), and N(C 1-4  alkyl) 2 ;  
 W 1  and W 2  are independently selected from the group consisting of carbonyl, methylene, sulfone and sulfoxide;  
 R 2  and R 5  are independently selected from the group consisting of: 
 (a) C 2  to C 20  straight chain or branched chain alkyl which is optionally substituted with oxo, hydroxy or alkoxy,  
 (b) C 2  to C 20  straight chain or. branched chain alkenyl or dialkenyl which is optionally substituted with oxo, hydroxy or alkoxy;  
 (c) C 2  to C 20  straight chain or branched chain alkoxy which is optionally substituted with oxo, hydroxy or alkoxy;  
 (d) —NH—C 2  to C 20  straight chain or branched chain alkyl, wherein said alkyl group is optionally substituted with oxo, hydroxy or alkoxy; and  
 (e)  
                     
 wherein Z is selected from the group consisting of O and NH, and M and N are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl, alkenyl, alkoxy, acyloxy, alkylamino, and acylamino; R 1  and R 6  are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl or alkenyl optionally substituted with oxo or fluoro;  
 
 R 4  and R 7  are independently selected from the group consisting of C(O)C 2  to C 20  straight chain or branched chain alkyl or alkenyl; C 2  to C 20  straight chain or branched chain alkyl; C 2  to C 20  straight chain or branched chain alkoxy; C 2  to C 20  straight chain or branched chain alkenyl; wherein said alkyl, alkenyl or alkoxy groups can be independently and optionally substituted with hydroxy, fluoro or C 1  to C 5  alkoxy;  
 G 1 , G 2 , G 3  and G 4  are independently selected from the group consisting of oxygen, methylene, amino, thiol, —NHC(O)—, and —N(C(O)C 1-4 alkyl)—;  
 or G 2 R 4  or G 4 R 7  may together be a hydrogen atom or hydroxyl;  
 or a pharmaceutically acceptable salt thereof;  
 and wherein for Formula II:  
 a′ and b′ are independently 2, 3, 4, 5, 6, 7, or 8, preferably 2;  
 Z 1  is selected from the group consisting of —OP(O)(OH 2 ,—P(O)(OH) 2 ,—OP(O)(OR 8 )(OH) where R 8  is a C1-C4 alkyl chain, —OS(O) 2 OH,—S(O) 2 OH—,—CO 2 H, —OB(OH) 2 , —OH, —CH 3 , —NH 2 , NR 9   3  where R 9  is a C1-C4 alkyl chain;  
 Z 2  is —OP(O)(OH) 2 , —P(O)(OH) 2′ , —OP(O)(OR 10 )(OH) where R 10 is a C1-C4 alkyl chain, —OS(O) 2 OH,—S(O) 2 OH, CO 2 H, —OB(OH) 2 , —OH, CH 3 , —NH 2 , —NR 11 , where R 11  is a C1-C4 alkyl chain;  
 and wherein for Formula 3:  
 R 12  is selected from H and a C1-C4 alkyl chain;  
 or a pharmaceutical salt thereof, 
 with the proviso that the compounds of formula I, II, or III are not  
                     
 as the active ingredient.  
 
 
     
     
         10 . The method of  claim 9 , wherein the subject suffers from asthma, atopic dermatitis, or allergic rhinitis.  
     
     
         11 . A method of treating an autoimmune disease, the method comprising administering to a subject diagnosed as having an autoimmune disease a pharmaceutical composition comprising (a) a compound of formula I, II, or III,  
       
         
           
           
               
               
           
         
       
       Wherein for each of formula I, II, or III: 
 R 1  is selected from the group consisting of 
 (a) C(O);  
 (b) C(O)—C 1-14  alkyl-C(O), wherein said C 1-14  alkyl is optionally substituted with hydroxy, C 1-5  alkoxy, C 1-5  alkylenedioxy, C 1-5  alkylamino, or C 1-5 -alkyl-aryl, wherein said aryl moiety of said C 1-15 -alkyl-aryl is optionally substituted with C 1-5  alkoxy, C 1-5  alkyl amino, C 1-5  alkoxy-amino, C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl C(O)OH, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl-C(O)—C 1-5  alkyl;  
 (c) C 2  to C 15  straight or branched chain alkyl optionally substituted with hydroxy or alkoxy; and  
 (d) —C(O)—C 6-12  arylene-C(O)— wherein said arylene is optionally substituted with hydroxy, halogen, nitro or amino;  
 
 a and b are independently 0, 1, 2, 3 or 4;  
 d, d′, d″, e, e′ and e″ are independently an integer from 1 to 4;  
 X 1 , X 2 , Y 1  and Y 2  are independently selected from the group consisting of null, oxygen, NH and N(C(O)C 1-4  alkyl), and N(C 1-4  alkyl) 2 ;  
 W 1  and W 2  are independently selected from the group consisting of carbonyl, methylene, sulfone and sulfoxide;  
 R 2  and R 5  are independently selected from the group consisting of: 
 (a) C 2  to C 20  straight chain or branched chain alkyl which is optionally substituted with oxo, hydroxy or alkoxy,  
 (b) C 2  to C 20  straight chain or branched chain alkenyl or dialkenyl which is optionally substituted with oxo, hydroxy or alkoxy;  
 (c) C 2  to C 20  straight chain or branched chain alkoxy which is optionally substituted with oxo, hydroxy or alkoxy;  
 (d) —NH—C 2  to C 20  straight chain or branched chain alkyl, wherein said alkyl group is optionally substituted with oxo, hydroxy or alkoxy; and  
 (e)  
                     
 wherein Z is selected from the group consisting of O and NH, and M and N are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl, alkenyl, alkoxy, acyloxy, alkylamino, and acylamino; R 1  and R 6  are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl or alkenyl optionally substituted with oxo or fluoro;  
 
 R 4  and R 7  are independently selected from the group consisting of C(O)C 2  to C 20  straight chain or branched chain alkyl or alkenyl; C 2  to C 20  straight chain or branched chain alkyl; C 2  to C 20  straight chain or branched chain alkoxy; C 2  to C 20  straight chain or branched chain alkenyl; wherein said alkyl, alkenyl or alkoxy groups can be independently and optionally substituted with hydroxy, fluoro or C 1  to C 5  alkoxy;  
 G 1 , G 2 , G 3  and G 4  are independently selected from the group consisting of oxygen, nethylene, amino, thiol, —NHC(O)—, and —N(C(O)C 1-4  alkyl)—;  
 or G 2 R 4  or G 4 R 7  may together be a hydrogen atom or hydroxyl;  
 or a pharmaceutically acceptable salt thereof;  
 and wherein for Formula II:  
 a′ and b′ are independently 2, 3, 4, 5, 6, 7, or 8, preferably 2;  
 Z 1  is selected from the group consisting of —OP(O)(OH) 2 ,—P(O)(OH) 2 ,—OP(O)(OR 8 )(OH) where R 8  is a C1-C4 alkyl chain, —OS(O) 2 OH,—S(O) 2 OH—,—CO 2 H, —OB(OH) 2 , —OH, —CH 3 , —NH 2 , NR 9   3  where R 9  is a C1-C4 alkyl chain;  
 Z 2  is —OP(O)(OH) 2 , —P(O)(OH) 2′ , —OP(O)(OR 10 )(OH) where R 10 is a C1-C4 alkyl chain, —OS(O) 2 OH,—S(O) 2 OH, CO 2 H,—OB(OH) 2 , —OH, CH 3 , —NH 2 , —NR 11 , where R 11  is a C1-C4 alkyl chain;  
 and wherein for Formula 3:  
 R 12  is selected from H and a C1-C4 alkyl chain;  
 or a pharmaceutical salt thereof, 
 with the proviso that the compounds of formula I, II, or III are not  
                     
 or a salt thereof, and (b) a pharmaceutically acceptable carrier therefor, wherein the compound is an immunoinhibitory compound.  
 
 
     
     
         12 . The method of  claim 11 , wherein the autoimmune disease is systemic lupus erythematosis, sceleroderma, Sjögren's syndrome, multiple sclerosis and other demyelinating diseases, rheumatoid arthritis, juvenile arthritis, systemic lupus erythamatosus, myocarditis, Graves'disease, uveitis, Reiter's syndrome, gout, osteoarthritis, polymyositis, myocarditis, primary biliary cirrhosis, Crohn's disease, ulcerative colitis, aplastic anemia, Addison's disease, or insulin-dependent diabetes mellitus.  
     
     
         13 . A method of treating an inflammmatory condition in a subject comprising administering to the subject an effective amount of a compound of the formula I, II, or III  
       
         
           
           
               
               
           
         
       
       Wherein for each of formula I, II, or III: 
 R 1  is selected from the group consisting of 
 (a) C(O);  
 (b) C(O)—C 1-14  alkyl-C(O), wherein said C 1-14  alkyl is optionally substituted with hydroxy, C 1-5  alkoxy, C 1-5  alkylenedioxy, C 1-5  alkylamino, or C 1-5 -alkyl-aryl, wherein said aryl moiety of said C 1-15 -alkyl-aryl is optionally substituted with C 1-5  alkoxy, C 1-5  alkyl amino, C 1-5  alkoxy-amino, C 1-5  alkylamino-C 1-5  alkoxy, —O-C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C (O)—C 1-5  alkyl C(O)OH, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl-C(O)—C 1-5  alkyl;  
 (c) C 2  to C 15  straight or branched chain alkyl optionally substituted with hydroxy or alkoxy; and  
 (d) —C(O)—C 6-12  arylene-C(O)— wherein said arylene is optionally substituted with hydroxy, halogen, nitro or amino;  
 
 a and b are independently 0, 1, 2, 3 or 4;  
 d, d′, d″, e, e′ and e″ are independently an integer from 1 to 4;  
 X 1 , X 2 , Y 1  and Y 2  are independently selected from the group consisting of null, oxygen, NH and N(C(O)C 1-4  alkyl), and N(C 1-4  alkyl) 2 ;  
 W 1  and W 2  are independently selected from the group consisting of carbonyl, methylene, sulfone and sulfoxide;  
 R 2  and R 5  are independently selected from the group consisting of: 
 (a) C 2  to C 20  straight chain or branched chain alkyl which is optionally substituted with oxo, hydroxy or alkoxy,  
 (b) C 2  to C 20  straight chain or branched chain alkenyl or dialkenyl which is optionally substituted with oxo, hydroxy or alkoxy;  
 (c) C 2  to C 20  straight chain or branched chain alkoxy which is optionally substituted with oxo, hydroxy or alkoxy;  
 (d) —NH—C 2  to C 20  straight chain or branched chain alkyl, wherein said alkyl group is optionally substituted with oxo, hydroxy or alkoxy; and  
 (e)  
                     
 wherein Z is selected from the group consisting of O and NH, and M and N are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl, alkenyl, alkoxy, acyloxy, alkylamino, and acylamino; R 1  and R 6  are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl or alkenyl optionally substituted with oxo or fluoro;  
 
 R 4  and R 7  are independently selected from the group consisting of C(O)C 2  to C 20  straight chain or branched chain alkyl or alkenyl; C 2  to C 20  straight chain or branched chain alkyl; C 2  to C 20  straight chain or branched chain alkoxy; C 2  to C 20  straight chain or branched chain alkenyl; wherein said alkyl, alkenyl or alkoxy groups can be independently and optionally substituted with hydroxy, fluoro or C 1  to C 5  alkoxy;  
 G 1 , G 2 , G 3  and G 4  are independently selected from the group consisting of oxygen, methylene, amino, thiol, —NHC(O)—, and —N(C(O)C 1-4  alkyl)—;  
 or G 2 R 4  or G 4 R 7  may together be a hydrogen atom or hydroxyl;  
 or a pharmaceutically acceptable salt thereof;  
 and wherein for Formula II:  
 a′ and b′ are independently 2, 3, 4, 5, 6, 7, or 8, preferably 2;  
 Z 1  is selected from the group consisting of —OP(O)(OH) 2 ,—P(O)(OH) 2 ,—OP(O)(OR 8 )(OH) where R 8 is a C1-C4 alkyl chain, —OS(O) 2 OH,—S(O) 2 OH—,—CO 2 H, —OB(OH) 2 , —OH, —CH 3 , —NH 2 , NR 9   3  where R 9  is a C1-C4 alkyl chain;  
 Z 2  is —OP(O)(OH) 2 , —P(O)(OH) 2′ , —OP(O)(OR 10 )(OH) where R 10 is a C1-C4 alkyl chain, —OS(O) 2 OH,—S(O) 2 OH, CO 2 H, —OB(OH) 2 , —OH, CH 3 , —NH 2 , —NR 11 , where, R 11  is a C1-C4 alkyl chain;  
 and wherein for Formula 3:  
 R 12  is selected from H and a C1-C4 alkyl chain;  
 or a pharmaceutical salt thereof, 
 with the proviso that the compounds of formula I, II, or III are not  
                     
 as the active ingredient.  
 
 
     
     
         14 . The method of  claim 13 , wherein the inflammatory condition is selected from the group consisting of inflammatory bowel disease, multiple sclerosis and autoimmune diabetes.  
     
     
         15 . An immunostimulatory remedy containing, as the active ingredient, a compound of the formula I, II, or III:  
       
         
           
           
               
               
           
         
       
       Wherein for each of formula I, II, or III: 
 R 1  is selected from the group consisting of 
 (a) C(O);  
 (b) C(O)—C 1-4  alkyl-C(O), wherein said C 1-4  alkyl is optionally substituted with hydroxy, C 1-5  alkoxy, C 1-5  alkylenedioxy, C 1-5  alkylamino, or C 1-5 -alkyl-aryl, wherein said aryl moiety of said C 1-15 -alkyl-aryl is optionally substituted with C 1-5  alkoxy, C 1-5  alkyl amino, C 1-5  alkoxy-amino, C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl C(O)OH, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl-C(O)—C 1-5  alkyl;  
 
 (c) C 2  to C 15  straight or branched chain alkyl optionally substituted with hydroxy or alkoxy; and  
 (d) —C(O)—C 6-12  arylene-C(O)— wherein said arylene is optionally substituted with hydroxy, halogen, nitro or amino;  
 a and b are independently 0, 1, 2, 3 or 4;  
 d, d′, d″, e, e′ and e″ are independently an integer from 1 to 4;  
 X 1 , X 2 , Y 1  and Y 2  are independently selected from the group consisting of null, oxygen, NH and N(C(O)C 1-4  alkyl), and N(C 1-4  alkyl) 2 ;  
 W 1  and W 2  are independently selected from the group consisting of carbonyl, methylene, sulfone and sulfoxide;  
 R 2  and R 5  are independently selected from the group consisting of: 
 (a) C 2  to C 20  straight chain or branched chain alkyl which is optionally substituted with oxo, hydroxy or alkoxy,  
 (b) C 2  to C 20  straight chain or branched chain alkenyl or dialkenyl which is optionally substituted with oxo, hydroxy or alkoxy;  
 (c) C 2  to C 20  straight chain or branched chain alkoxy which is optionally substituted with oxo, hydroxy or alkoxy;  
 (d) —NH—C 2  to C 20  straight chain or branched chain alkyl, wherein said alkyl group is optionally substituted with oxo, hydroxy or alkoxy; and  
 (e)  
                     
 wherein Z is selected from the group consisting of O and NH, and M and N are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl, alkenyl, alkoxy, acyloxy, alkylamino, and acylamino; R 1  and R 6  are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl or alkenyl optionally substituted with oxo or fluoro;  
 
 R 4  and R 7  are independently selected from the group consisting of C(O)C 2  to C 20  straight chain or branched chain alkyl or alkenyl; C 2  to C 20  straight chain or branched chain alkyl; C 2  to C 20  straight chain or branched chain alkoxy; C 2  to C 20  straight chain or branched chain alkenyl; wherein said alkyl, alkenyl or alkoxy groups can be independently and optionally substituted with hydroxy, fluoro or C 1  to C 5  alkoxy;  
 G 1 , G 2 , G 3  and G 4  are independently selected from the group consisting of oxygen, methylene, amino, thiol, —NHC(O)—, and —N(C(O)C 1-4  alkyl)—;  
 or G 2 R 4  or G 4 R 7  may together be a hydrogen atom or hydroxyl;  
 or a pharmaceutically acceptable salt thereof;  
 and wherein for Formula II:  
 a′ and b′ are independently 2, 3, 4, 5, 6, 7, or 8, preferably 2;  
 Z 1  is selected from the group consisting of —OP(O)(OH) 2 ,—P(O)(OH) 2 ,—OP(O)(OR 8 )(OH) where R 8  is a C1-C4 alkyl chain, —OS(O) 2 OH,—S(O) 2 OH—,—CO 2 H, —OB(OH) 2 , —OH, —CH 3 , —NH 2 , NR 9   3  where R 9  is a C1-C4 alkyl chain;  
 Z 2  is —OP(O)(OH) 2 , —P(O)(OH) 2′ , ′OP(O)(OR 10 )(OH) where R 10  is a C1-C4 alkyl chain, —OS (O) 2 OH,—S(O) 2 OH, CO 2 H, —OB(OH) 2 , —OH, CH 3 , —NH 2 , —NR 11 , where R 11  is a C1-C4 alkyl chain;  
 and wherein for Formula 3:  
 R 2  is selected from H and a C1-C4 alkyl chain;  
 or a pharmaceutical salt thereof, 
 with the proviso that the compounds of formula I, II, or III are not  
                     
 
 
     
     
         16 . A method of preventing or reducing ischemic damage in a subject, the method comprising administering to the subject an effective amount of a compound of the formula I, II, or III prior to performing surgery on the patient.  
     
     
         17 . A method of preventing, ameliorating, or delaying asthma in a subject, the method comprising administering to the subject an effective amount of a compound of the formula I, II, or III  
       
         
           
           
               
               
           
         
       
       Wherein for each of formula I, II, or III: 
 R 1  is selected from the group consisting of 
 (a) C(O);  
 (b) C(O)—C 1-14  alkyl-C(O), wherein said C 1-14  alkyl is optionally substituted with hydroxy, C 1-5  alkoxy, C 1-5  alkylenedioxy, C 1-5  alkylamino, or C 1-5 -alkyl-aryl, wherein said aryl moiety of said C 1-15 -alkyl-aryl is optionally substituted with C 1-5  alkoxy, C 1-5  alkyl amino, C 1-5  alkoxy-amino, C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C 1-5  alkoxy, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl C(O)OH, —O—C 1-5  alkylamino-C(O)—C 1-5  alkyl-C(O)—C 1-5  alkyl;  
 (c) C 2  to C 15  straight or branched chain alkyl optionally substituted with hydroxy or alkoxy; and  
 (d) —C(O)—C 6-12  arylene-C(O)— wherein said arylene is optionally substituted with hydroxy, halogen, nitro or amino;  
 
 a and b are independently 0, 1, 2, 3 or 4;  
 d, d′, d″, e, e′ and e″ are independently an integer from 1 to 4;  
 X 1 , X 2 , Y 1  and Y 2  are independently selected from the group consisting of null, oxygen, NH and N(C(O)C 1-4  alkyl), and N(C 1-4  alkyl) 2 ;  
 W 1  and W 2  are independently selected from the group consisting of carbonyl, methylene, sulfone and sulfoxide;  
 R 2  and R 5  are independently selected from the group consisting of: 
 (a) C 2  to C 20  straight chain or branched chain alkyl which is optionally substituted with oxo, hydroxy or alkoxy,  
 (b) C 2  to C 20  straight chain or branched chain alkenyl ordialkenyl which is optionally substituted with oxo, hydroxy or alkoxy;  
 (c) C 2  to C 20  straight chain or branched chain alkoxy which is optionally substituted with oxo, hydroxy or alkoxy;  
 (d) —NH—C 2  to C 20  straight chain or branched chain alkyl, wherein said alkyl group is optionally substituted with oxo, hydroxy or alkoxy; and  
 (e)  
                     
 wherein Z is selected from the group consisting of O and NH, and M and N are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl, alkenyl, alkoxy, acyloxy, alkylamino, and acylamino; R 1  and R 6  are independently selected from the group consisting of C 2  to C 20  straight chain or branched chain alkyl or alkenyl optionally substituted with oxo or fluoro;  
 
 R 4  and R 7  are independently selected from the group consisting of C(O)C 2  to C 20  straight chain or branched chain alkyl or alkenyl; C 2  to C 20  straight chain or branched chain alkyl; C 2  to C 20  straight chain or branched chain alkoxy; C 2  to C 20  straight chain or branched chain alkenyl; wherein said alkyl, alkenyl or alkoxy groups can be independently and optionally substituted with hydroxy, fluoro or C 1  to C 5  alkoxy;  
 G 1 , G 2 , G 3  and G 4  are independently selected from the group consisting of oxygen, methylene, amino, thiol, —NHC(O)—, and —N(C(O)C 1-4  alkyl)—;  
 or G 2 R 4  or G 4 R 7  may together be a hydrogen atom or hydroxyl;  
 or a pharmaceutically acceptable salt thereof;  
 and wherein for Formula II:  
 a′ and b′ are independently 2, 3, 4, 5, 6, 7, or 8, preferably 2;  
 Z 1  is selected from the group consisting of —OP(O)(OH) 2 ,—P(O)(OH) 2 ,—OP(O)(OR 8 )(OH) where R 8  is a C1-C4 alkyl chain, —OS(O) 2 OH,—S(O) 2 OH—,—CO 2 H, —OB(OH) 2 , —OH, —CH 3 , —NH 2 , NR 9   3  where R 9  is a C1-C4 alkyl chain;  
 Z 2  is —OP(O)(OH) 2 , —P(O)(OH) 2′ , —OP(O)(OR 10 )(OH) where R 10 is a C1-C4 alkyl chain, —OS(O) 2 OH,—S(O) 2 OH, CO 2 H, —OB(OH) 2 , —OH, CH 3 , —NH 2 , —NR 11 , where R 11  is a C1-C4 alkyl chain;  
 and wherein for Formula 3:  
 R 12  is selected from H and a C1-C4 alkyl chain;  
 or a pharmaceutical salt thereof, 
 with the proviso that the compounds of formula I, II, or III are not  
                     
 as the active ingredient.