Novel Nucleoside Derivatives

Abstract

Compounds of Formulae I-XVI, stereoisomers, and pharmaceutically acceptable salts or prodrugs thereof, their preparation, and their uses for the treatment of viral diseases including hepatitis C viral infection, cancer, diabetes, and other diseases are described: formula (I).

1 - 29 . (canceled) 
   
   
       30 . A compound of Formula I: 
     
       
         
         
             
             
         
       
     
     or an isomer, solvate, hydrate, prodrug, or pharmaceutically acceptable salt thereof, wherein:
 X′ is O, S, S—O, or NR 20 , wherein R 20  is H or optionally substituted alkyl, aryl, arylalkyl, C 3-6  cycloalkyl, OH, OR 20′ , or O(C═O)R 20′ , wherein R 20′  is H, lower alkyl or C 3-6  cycloalkyl; Y is —O—, —S—, —N—, —C(R 20′ )—, or —CH 2 —; 
 R 19  is H or optionally substituted C 1-4  alkyl, C 2-4  alkenyl, or C 2-4  alkynyl, —OH, —O-lower alkyl, halogen, CN, or —C═CR 21 R 22 , wherein R 21  and R 22  are independently H or lower alkyl; or R 19  is absent; or R 19  is joined together with R 17  to form —(CH 2 ) p —, —O—(CH 2 ) p —, wherein p is 0 to 4; 
 R 18  is independently H, C 1-4  alkyl, C 2-4  alkenyl, or C 2-4  alkynyl; wherein said C 14  alkyl is optionally substituted with amino, hydroxy, or 1 to 3 fluorine atoms, C 1-4  alkylamino, dialkylamino, C 3-6  cycloalkylamino, halogen, or alkoxy; 
 R 17  is H, halogen, alkyl optionally substituted with 1 to 3 fluorine atoms, C 1-10  alkoxy optionally substituted with C 1-3  alkoxy or 1 to 3 fluorine atoms, C 2-6  alkenyloxy, C 1-4  alkylthio, C 1-8  alkylcarbonyloxy, aryloxycarbonyl, azido, amino, alkylamino, or dialkyl amino; 
 R 16  and R 15  are independently H, C 1-4  alkyl, C 2-4  alkenyl, or C 2-4  alkynyl; wherein said C 1-4  alkyl is optionally substituted with amino, hydroxy, or 1 to 3 fluorine atoms, and said C 2-4  alkenyl and C 2-4  alkynyl are each optionally substituted with one or more of C 1-3  alkoxy, carboxy, C 2-6  alkenyloxy, C 1-4  alkylthio, C 1-8  alkylcarbonyloxy, aryloxycarbonyl, azido, amino, alkylamino, or dialkylamino; 
 B is selected from 
 
     
       
         
         
             
             
         
       
     
     wherein:
 A, D, E, J, and G are each independently selected from the group consisting of C and N; 
 L is selected from O or S; 
 M is selected from the group consisting of O, S, and Se; 
 X 1  is absent, or X 1  is selected from the group consisting of H, —OH, —SH, —NH 2 , —COOR 11 , —CONH 2 , —CSNH 2 , alkylamino, dialkylamino, cycloalkylamino, halogen, alkyl, alkenyl, alkynyl, aryl, alkaryl, cycloalkyl, acyl, alkoxy, CF 3 , and —NHCOR X1 , wherein R X1  is H, lower alkyl, or lower alkoxy, and wherein R 11  is H or C 1-4  alkyl; 
 X 2  is absent, or X 2  is independently selected from the group consisting of H, alkenyl, alkynyl, aryl, alkaryl, cycloalkyl, acyl, and C 1 -C 6  alkyl; 
 X 3 , X 4  and X 6  are each independently absent, or X 3 , X 4  and X 6  are each independently selected from the group consisting of H, alkenyl, alkynyl, aryl, alkaryl, cycloalkyl, acyl, OH, SH, NH 2 , CF 3 , alkyl, amino, halogen, alkylamino, cycloalkylamino, and dialkylamino; 
 wherein when B contains J and G, then X 1  and X 3  cannot both be 
 (a) X 1 ═NH 2 , alkylamino, dialkylamino, cycloalkylamino or —HCOR X1 ; and 
 (b) X 3 ═NH 2 , amino, alkylamino, cycloalkylamino or dialkylamino; 
 X 5  is absent, or X 5  is selected from the group consisting of H, —CN, —NO 2 , -alkyl, alkenyl, alkynyl, aryl, alkaryl, cycloalkyl, acyl, —NHCONH 2 , —CONR 11 R 11′ , —CSNR 11 R 11′ , —COOR 11 , —C(═NH)NH 2 , -hydroxy, —C 1-3 alkoxy, -amino, -alkylamino, -dialkylamino, halogen, -(1,3-oxazol-2-yl), -(1,3-thiazol-2-yl), and -(imidazol-2-yl); wherein alkyl is unsubstituted or substituted with one to three groups independently selected from halogen, amino, hydroxy, carboxy, and C 1-3  alkoxy; and wherein R 11  and R 11′  are independently H or C 1-4  alkyl; 
 Z′ is —CH(R 23 )OH, —O—, —CH(R 23 )—, C 1-4 cycloalkyl, —OC(R 23 ) 2 PO 3 H 2 , —CH 2 C(R 23 ) 2 PO 3 H 2 , C 2-4  alkenyl, or C 2-4  alkynyl; wherein R 23  is H, F, methyl, ethyl, hydroxymethyl, or fluoromethyl or —CH 2 N 3 , —CH 2 —NR 21 R 22 , and R 21  and R 22  are as defined above; and 
 Z″ is absent, or Z″ is R 24 (C═O)—, R 24 —O—(C═O)—, or R 24 CH(NH 2 )(C═O)—, wherein R 24  is optionally substituted C 1-6  alkyl, cycloalkyl, aryl, or aralkyl; or Z″ is 
 
     
       
         
         
             
             
         
       
       wherein: 
       V, W, and W′ are independently H, optionally substituted alkyl, optionally substituted aralkyl, cycloalkyl, heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, optionally substituted 1-alkenyl, or optionally substituted 1-alkynyl; and 
       Z is —CHR z OH, —CHR z OC(O)R y , —CHR z OC(S)R y , —CHR z OC(S)OR y , —CHR z OC(O)SR y , —CHR z OCO 2 R y , —OR z , —SR z , —CHR z N 3 , —CH 2 aryl, —CH(aryl)OH, —CH(CH═CR z   2 )OH, —CH(C≡CR z )OH, —R z , —NR z   2 , —OCOR y , —OCO 2 R y , —SCOR y , —SCO 2 R y , —NHCOR z , —NHCO 2 R y , —CH 2 NHaryl, —(CH 2 ) q —OR z , and —(CH 2 ) q —SR z , halogen, —CN, —COR y , —CONR z   2 , —CO 2 R y , —SO 2 R y , or —SO 2 NR z   2 , wherein q is 2 or 3, R z  is R y  or —H, and R y  is alkyl, aryl, cycloalkyl, heterocycloalkyl, or aralkyl; or 
       Z″ is P(O)Y′R 11 Y″R 11 ; wherein each R 11  is independently H; Y′ and Y″ are each independently selected from the group consisting of —O—, and —NR v —; and 
       when Y′ and Y″ are both —O—, R 11  attached to —O— is independently selected from the group consisting of optionally substituted aryl, optionally substituted CH 2 -heterocycloakyl wherein the cyclic moiety contains a carbonate or thiocarbonate, optionally substituted -alkylaryl, —C(R z ) 2 OC(O)NR z   2 , —NR z —C(O)—R y , —C(R z ) 2 —OC(O)R y , —C(R z ) 2 —O—C(O)OR y , —C(R z ) 2 OC(O)SR y , -alkyl-S—C(O)R y , -alkyl-S—S-alkylhydroxy, and -alkyl-S—S—S-alkylhydroxy; or 
       when Y′ and Y″ are both —NR v —, then R 11  attached to —NR v — is independently selected from the group consisting of —H, —[C(R z ) 2 ] q —COOR y , —C(R x ) 2 COOR y , —[C(R z ) 2 ] q —C(O)SR y , and -cycloalkylene-COOR y ; or 
       when Y′ is —O— and Y″ is NR v , then R 11  attached to —O— is independently selected from the group consisting of optionally substituted aryl, optionally substituted CH 2 -heterocycloakyl wherein the cyclic moiety contains a carbonate or thiocarbonate, optionally substituted -alkylaryl, —C(R z ) 2 OC(O)NR z   2 , —NR z —C(O)—R y , —C(R z ) 2 —OC(O)R y —, —C(R z ) 2 —O—C(O)OR y , —C(R z ) 2 OC(O)SR y , -alkyl-S—C(O)R y , -alkyl-S—S-alkylhydroxy, and -alkyl-S—S—S-alkylhydroxy; and R 11  attached to —NR v — is independently selected from the group consisting of —H, —[C(R z ) 2 ] q —COOR y , —C(R x ) 2 COOR y , —[C(R z ) 2 ] q —C(O)SR y , and -cycloalkylene-COOR y ; or 
       when Y′ and Y″ are independently selected from —O— and —NR v —, then R 11  and R 11  together form a cyclic group comprising -alkyl-S—S-alkyl-, wherein 
       q is an integer 2 or 3; 
       each R z  is selected from the group consisting of R y  and —H; 
       each R y  is selected from the group consisting of alkyl, aryl, heterocycloalkyl, and aralkyl; 
       each R x  is independently selected from the group consisting of —H, and alkyl, or together R x  and R x  form a cycloalkyl group; and 
       each R v  is selected from the group consisting of —H, lower alkyl, acyloxyalkyl, alkoxycarbonyloxyalkyl, and lower acyl; 
       with the provisos that: 
       a) V, Z, W, W′ are not all —H; 
       b) when Z is —Rz, then at least one of V, W, and W′ is not —H, alkyl, aralkyl, cycloalkyl, or heterocycloalkyl; 
       c) when Z 1  is —CH 2 OH and R 7  is H, then one of R 15 , R 16 , R 17  and R 18  is other than H; and 
       d) when Z′ is —CH 2 O—, Z″ is —(C═O)R 24 , and R 17  is H, then one of R 15 , R 16 , R 17  and R 18  is other than H. 
     
   
   
       31 . The compound of  claim 30 , wherein Z″ is absent, or Z″ is R 24 (C═O)—, R 24 —O—(C═O)—, or R 24 CH(NH 2 )(C═O)—, wherein R 24  is optionally substituted C 1-6  alkyl, cycloalkyl, aryl, or aralkyl. 
   
   
       32 . The compound of  claim 32 , wherein X′ is O, Y is O, and R 19  is absent. 
   
   
       33 . The compound of  claim 31 , wherein X′ is S. 
   
   
       34 . The compound of  claim 31 , wherein R 16  is —CH 3 . 
   
   
       35 . The compound of  claim 32 , wherein Z″ is absent, Z′ is —CH(R 23 )OH, R 16  is C 1-4  alkyl, and R 15  is H or C 1-4  alkyl. 
   
   
       36 . The compound of  claim 35 , wherein said compound is selected from the group consisting of: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       37 . The compound of  claim 30 , wherein:
 V and Z are connected together via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, wherein 0-1 atoms are heteroatoms and the remaining atoms are carbon substituted with hydroxy, acyloxy, alkylthiocarbonyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both 0 groups attached to the phosphorus; or   V and Z are connected together via an additional 3-5 atoms to form a cyclic group, wherein 0-1 atoms are heteroatoms and the remaining atoms are carbon, that is fused to an aryl group at the beta and gamma position to the 0 attached to the phosphorus; or   V and W are connected together via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from an O attached to the phosphorus; or   Z and W are connected together via an additional 3-5 atoms to form a cyclic group, wherein 0-1 atoms are heteroatoms and the remaining atoms are carbon, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl; or   W and W′ are connected together via an additional 2-5 atoms to form a cyclic group, wherein 0-2 atoms are heteroatoms and the remaining atoms are carbon, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl.   
   
   
       38 . A compound of Formula II′: 
     
       
         
         
             
             
         
       
     
     or an isomer, solvate, hydrate, prodrug, or pharmaceutically acceptable salt thereof, wherein:
 X′ is O, S, S—O, or NR 20 , wherein R 20  is H or optionally substituted alkyl, aryl, arylalkyl, C 3-6  cycloalkyl, OH, OR 20′ , or O(C═O)R 20′ , wherein R 20′  is H, lower alkyl or C 3-6  cycloalkyl; 
 Y is —O—, —S—, —N—, —C(R 20 )—, or —CH 2 —R 19  is H or optionally substituted C 1-4  alkyl, C 2-4  alkenyl, or C 2-4  alkynyl, —OH, —O-lower alkyl, halogen, CN, or —C═CR 21  R 22 , wherein R 21  and R 22  are independently H or lower alkyl; 
 or R 19  is absent; or R 19  is joined together with R 17  to form —(CH 2 ) p —, —O—(CH 2 ) p —, wherein p is 0 to 4; 
 R 18  is independently H, C 1-4  alkyl, C 2-4  alkenyl, or C 2-4  alkynyl; wherein said C 1-4  alkyl is optionally substituted with amino, hydroxy, or 1 to 3 fluorine atoms, C 1-4  alkylamino, dialkylamino, C 3-6  cycloalkylamino, halogen, or alkoxy; 
 R 17  is H, halogen, alkyl optionally substituted with 1 to 3 fluorine atoms, C 1-10  alkoxy optionally substituted with C 1-3  alkoxy or 1 to 3 fluorine atoms, C 2-6  alkenyloxy, C 1-4  alkylthio, C 1-8  alkylcarbonyloxy, aryloxycarbonyl, azido, amino, alkylamino, or dialkylamino; 
 R 16  and R 15  are independently H, C 1-4  alkyl, C 2-4  alkenyl, or C 2-4  alkynyl; wherein said C 1-4  alkyl is optionally substituted with amino, hydroxy, or 1 to 3 fluorine atoms, and said C 2-4  alkenyl and C 2-4  alkynyl are each optionally substituted with one or more of C 1-3  alkoxy, carboxy, C 2-6  alkenyloxy, C 1-4  alkylthio, C 1-8  alkylcarbonyloxy, aryloxycarbonyl, azido, amino, alkylamino, or dialkylamino; 
 B is selected from the group consisting of: 
 
     
       
         
         
             
             
         
       
     
     wherein:
 A, D, E, J, and G are each independently selected from the group consisting of C and N; 
 L is selected from O or S; 
 M is selected from the group consisting of O, S, and Se; 
 X 1  is absent, or X 1  is selected from the group consisting of H, —OH, —SH, —NH 12 , —COOR 11 , —CONH 2 , —CSNH 2 , alkylamino, dialkylamino, cycloalkylamino, halogen, alkyl, alkoxy, CF 3 , and —NHCOR X1 , wherein R X1  is H, lower alkyl, or lower alkoxy, and wherein R 11  is H or C 1-4  alkyl; 
 X 2  is absent, or X 2  is independently selected from the group consisting of H and C 11 C 6  alkyl; 
 X 3 , X 4  and X 6  are each independently absent, or X 3 , X 4  and X 6  are each independently selected from the group consisting of H, OH, SH, NH 2 , CF 3 , alkyl, amino, halogen, alkylamino, cycloalkylamino, and dialkylamino; 
 wherein when B contains J and G, then X 1  and X 3  cannot both be 
 (a) X 1 ═NH 2 , alkylamino, dialkylamino, cycloalkylamino or —HCOR X1 ; and 
 (b) X 3 ═NH 2 , amino, alkylamino, cycloalkylamino or dialkylamino; 
 X 5  is absent, or X 5  is selected from the group consisting of H, —CN, —NO 2 , -alkyl, —NHCONH 2 , —CONR 11 R 11′ , —CSNR 11 R 11′ , —COOR 11 , —C(═NH)NH 2 , -hydroxy, —C 1-3  alkoxy, -amino, -alkylamino, -dialkylamino, halogen, -(1,3-oxazol-2-yl), -(1,3-thiazol-2-yl), and -(imidazol-2-yl); wherein alkyl is unsubstituted or substituted with one to three groups independently selected from the group consisting of halogen, amino, hydroxy, carboxy, and C 1-3  alkoxy; and wherein R 11  and R 11′  are independently H or C 1-4  alkyl; 
 Z′ is —O—, —CH(R 23 )—O—, C 1-4  cycloalkylene, C 2-4  alkenylene, or C 2-4  alkynylene; wherein R 23  is methyl, ethyl, hydroxymethyl, fluoromethyl, —CH 2 N 3 , —CH 2 —NR 21 R 22 ; and R 21  and R 22  are as defined above; 
 V, W, and W′ are independently H, optionally substituted alkyl, optionally substituted aralkyl, cycloalkyl, heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, optionally substituted 1-alkenyl, or optionally substituted 1-alkynyl; and 
 Z is —CHR z OH, —CHR z OC(O)R y , —CHR z OC(S)R y , —CHR z OC(S)OR y , —CHR z OC(O)SR y , —CHR z CO 2 R Y , —OR z , —SR z , —CHR z N 3 , —CH 2 aryl, —CH(aryl)OH, —CH(CH═CR z   2 )OH, —CH(C≡CR z )OH, —R z , —NR z   2 , —OCOR y , —OCO 2 R y , —SCOR y , —SCO 2 R y , —NHCOR z , —NHCO 2 R y , —CH 2 NHaryl, —(CH 2 ) q —OR z , and —(CH 2 ) q —SR 1 , halogen, —CN, —COR y , —CONR z   2 , —CO 2 R y , —SO 2 R y , or —SO 2 NR z   2 , wherein q is 2 or 3, R z  is R y  or —H, and R y  is alkyl, aryl, cycloalkyl, heterocycloalkyl, or aralkyl; 
 with the provisos that: 
 a) V, Z, W, W′ are not all —H; and 
 b) when Z is —Rz, then at least one of V, W, and W′ is not —H, alkyl, aralkyl, cycloalkyl, or heterocycloalkyl. 
 
   
   
       39 . The compound of  claim 38 , wherein X′ is O, Y is O, and R 19  is absent. 
   
   
       40 . The compound of  claim 39 , wherein R 15 , R 16 , R 17 , and R 18  are independently H or C 1-4  alkyl. 
   
   
       41 . The compound of  claim 38 , wherein:
 V is selected from the group consisting of phenyl; substituted phenyl with 1-3 substituents independently selected from the group consisting of halogen, C 1-6  alkyl, —CF 3 , —OR 3 , —OR 12 , —COR 3 , —CO 2 R 3 , —N(R 3 ) 2 , —N(R 12 ) 2 , —CO 2 N(R 2 ) 2 , —SR 3 , —SO 2 R 3 , —SO 2 N(R 2 ) 2  and —CN; monocyclic heteroaryl; and substituted monocyclic heteroaryl with 1-2 substituents independently selected from the group consisting of halogen, C 1-6  alkyl, —CF 3 , —OR 3 , —OR 12 , —COR 3 , —CO 2 R 3 , —N(R 3 ) 2 , —N(R 12 ) 2 , —CO 2 N(R 2 ) 2 , —SR 3 , —SO 2 R 3 , —SO 2 N(R 2 ) 2  and —CN;   wherein said monocyclic heteroaryl and substituted monocyclic heteroaryl has 1-2 heteroatoms that are independently selected from the group consisting of N, O, and S; wherein R 2  is H or R 3 , R 3  is C 1-6  alkyl, aryl, heterocycloalkyl, or aralkyl, and R 12  is H or lower acyl; with the provisos that   a) when there are two heteroatoms and one is O, then the other can not be O or S, and   b) when there are two heteroatoms and one is S, then the other can not be O or S; or   V and Z together are connected via an additional 3-5 atoms to form a cyclic group, optionally containing I heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus.   
   
   
       42 . The compound of  claim 41 , wherein V is selected from the group consisting of phenyl; substituted phenyl with 1-2 substituents independently selected from the group consisting of —Cl, —Br, —F, C 1-3  alkyl, and —CF 3 ; pyridyl; substituted pyridyl with 1 substituent independently selected from the group consisting of —Cl, —Br, —F, C 1-3  alkyl, and —CF 3 ; furanyl; substituted furanyl with 1 substituent independently selected from the group consisting of —Cl, —Br, —F, C 1-3  alkyl, and —CF 3 ; thienyl; and substituted thienyl with 1 substituent independently selected from the group consisting of —Cl, —Br, —F, C 1-3  alkyl, and —CF 3 . 
   
   
       43 . The compound of  claim 38 , wherein Z″ is: 
     
       
         
         
             
             
         
       
     
   
   
       44 . The compound of  claim 38 , wherein Z″ is: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       45 . A pharmaceutical composition comprising a compound of  claim 30 , and a pharmaceutically acceptable excipient or carrier. 
   
   
       46 . A pharmaceutical composition comprising a compound of  claim 38 , and a pharmaceutically acceptable excipient or carrier. 
   
   
       47 . A method of inhibiting viral replication in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 30 . 
   
   
       48 . The method of  claim 47 , wherein said viral replication is RNA-dependent RNA viral replication. 
   
   
       49 . The method of  claim 48 , wherein said viral replication is HCV replication. 
   
   
       50 . A method of inhibiting viral replication in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 38 . 
   
   
       51 . The method of  claim 50 , wherein said viral replication is RNA-dependent RNA viral replication. 
   
   
       52 . The method of  claim 51 , wherein said viral replication is HCV replication. 
   
   
       53 . A method of treating a viral infection in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 30 . 
   
   
       54 . The method of  claim 53 , wherein said viral infection is an RNA-dependent RNA viral infection. 
   
   
       55 . The method of  claim 54 , wherein said viral infection is an HCV infection. 
   
   
       56 . The method of  claim 55 , wherein said compound is used in combination with a therapeutically effective amount of a second agent active against HCV. 
   
   
       57 . The method of  claim 56 , wherein said second agent active against HCV is ribavirin; levovirin; viramidine; thymosin alpha-1; interferon-β; an inhibitor of NS3 serine protease; an inhibitor of inosine monophosphate dehydrogenase; interferon-α or pegylated interferon-α, alone or in combination with ribavirin or levovirin. 
   
   
       58 . A method of treating a viral infection in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 38 . 
   
   
       59 . The method of  claim 58 , wherein said viral infection is an RNA-dependent RNA viral infection. 
   
   
       60 . The method of  claim 59 , wherein said viral infection is an HCV infection. 
   
   
       61 . The method of  claim 60 , wherein said compound is used in combination with a therapeutically effective amount of a second agent active against HCV. 
   
   
       62 . The method of  claim 61 , wherein said second agent active against HCV is ribavirin; levovirin; viramidine; thymosin alpha-1; interferon-β; an inhibitor of NS3 serine protease; an inhibitor of inosine monophosphate dehydrogenase; interferon-α or pegylated interferon-α, alone or in combination with ribavirin or levovirin. 
   
   
       63 . A method of treating cancer, liver fibrosis, diabetes, hyperlipidemia, obesity or non-alcoholic steatohepatitis in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 30 . 
   
   
       64 . A method of treating cancer, liver fibrosis, diabetes, hyperlipidemia, obesity or non-alcoholic steatohepatitis in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 38 . 
   
   
       65 . A method of treating a platelet disorder or diabetes in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 30 , wherein said compound is a P2 receptor antagonist. 
   
   
       66 . A method of treating a platelet disorder or diabetes in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 38 , wherein said compound is a P2 receptor antagonist. 
   
   
       67 . A method of treating diabetes in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 30 , wherein said compound is an AMPK activator. 
   
   
       68 . A method of treating diabetes in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 38 , wherein said compound is an AMPK activator. 
   
   
       69 . A method of treating diabetes or cardiovascular disease in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 30 , wherein said compound binds an adenosine receptor. 
   
   
       70 . A method of treating diabetes or cardiovascular disease in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 38 , wherein said compound binds an adenosine receptor. 
   
   
       71 . A method of treating inflammation or a CNS disorder in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 30 , wherein said compound acts as an adenosine analogue. 
   
   
       72 . A method of treating inflammation or a CNS disorder in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound of  claim 38 , wherein said compound acts as an adenosine analogue.