3-beta-D-ribofuranosylthiazolo[4,5-d]pyridimine nucleosides and uses thereof

Abstract

The invention is directed to 3-β-D-ribofuranosylthiazolo[4,5-d]pyridimine nucleosides and pharmaceutical compositions containing such compounds that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds.

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         11 . A method of modulating immune cytokine activities in a patient comprising: 
 providing a compound or pharmaceutically acceptable salt of formula I; and    treating a patient in need thereof with the compound or pharmaceutically acceptable salt, wherein formula I comprises:                          R 1  is independently H, —C(O)R 3 , or a racemic, L-, or D-amino acid group —C(O)CHNH 2 R 4 , wherein R 3  is alkyl and R 4  is H or alkyl, wherein alkyl is optionally substituted by one or more groups selected from halogen, —C 1 -C 6 , —OH, —NO 2 , —CN, —CO 2 H, —O—C 1 -C 6 , -aryl, -aryl-C 1 -C 6 , —CO 2 CH 3 , —CONH 2 , —OCH 2 CONH 2 , —NH 2 , —SO 2 NH 2 , haloalkyl, and —O-haloalkyl;    R 2  is OR 5  or N(R 6 ) 2 , wherein R 5  is H and wherein R 6  is independently H, alkyl, cycloalkyl, or together with nitrogen forms a heterocycloalkyl ring; wherein the alkyl, cycloalkyl, and heterocycloalkyl are optionally substituted by one or more groups selected from halogen, —C 1 -C 6 , —OH, —NO 2 , —CN, —CO 2 H, —O—C 1 -C 6 , -aryl, -aryl-C 1 -C 6 , —CO 2 CH 3 , —CONH 2 , —OCH 2 CONH 2 , —NH 2 , —SO 2 NH 2 , haloalkyl, and —O-haloalkyl; and    wherein at least one of the R 1  groups is a racemic L-, or D-amino acid group —C(O)CHNH 2 R 4 ;    or a pharmaceutically acceptable salt.    
     
     
         12 . The method of  claim 11 , wherein R 4  is alkyl, and wherein the remaining R 1  groups are H; R 2  is OR 5  or N(R 6 ) 2 , wherein R 5  is H, and wherein R 6  is independently H, alkyl, cycloalkyl, or together with nitrogen forms a heterocycloalkyl ring.  
     
     
         13 . The method of  claim 12 , wherein R 6  is independently H or alkyl.  
     
     
         14 . The method of  claim 11 , wherein R 4  is —CH(CH 3 ) 2 , and wherein the remaining R 1  groups are H; and R 2  is OH.  
     
     
         15 . The method of  claim 11 , wherein the compound or pharmaceutically acceptable salt is selected from the group consisting of: