Composition for and method of treatment using triterpenoids

Abstract

Methods and compositions for treating Kaposi's sarcoma and Epstein Barr virus using a a therapeutic derivative of a triterpenoid acid and derivatives thereof are disclosed,

I claim:  
     
         1 . A method of treating Kaposi's sarcoma comprising the steps of 
 administering to the patient a therapeutic a derivative of a triterpenoid acid and wherein the triterpenoid acid has the following structural formula:                           wherein: 
 Y═OR 1 , NR 1   2 , O--M 1 ;  
 R═H, LOWER ALKYL,  
 M + =Na + , K + , Mg ++ , Ca ++  ions;  
 R 2 ═CH 2 OR 1  or CH 3 ;  
 R 4 ═H, OH, SO 3 --M 1 , NH(CH 2 ) n NH 2 , or NH--Ph--(NH 2 ) n  wherein n=1-8 and Ph is a phenyl or naphthyl ring substituted with up to 3 amine functionalities and the remaining substitutions can be H, R 1 , R 2  or CO 2 R 1 ;  
 or both R 4  taken together are oxo;  
 X═O, S, NR 1   2 .  
   
     
     
         2 . A method of treating Kaposi's sarcoma comprising the steps of 
 administering to the patient a derivative of a triterpenoid acid and wherein the triterpenoid acid has the following structural formula:                           wherein: 
 Y═OR 1 , NR 1   2 , O--M 1 ;  
 R 1 ═H, LOWER ALKYL,  
 M 1 =Na. + , K + , Mg ++ , Ca ++  ions;  
 R 2 ═CH 2 OR 1  or CH 3 ;  
 R 3 ═H, CH 3 , lower alkyl, COY, CH 2 OH, CH 2 OCH 2 OH=CH 2 , CH 2 OSO-- 3 M 1 ;  
 Z═NR 1 , NR 1 Ac, NR 1 Bz, H, OCH 3 , lower alkyl, OH, SO 3 --M 1 , OCH 2 CH═CH 2 , OCH 2 CO 2  H or O-glucoside wherein a glucoside includes glucose, fucose, galactose, mannose, arabinose or xylose;  
 R 4 ═H, OH, SO 3 --M. 1 , NH(CH 2 ) n NH 2 , or NH--Ph--(NH 2 ) n  wherein n=1-8 and Ph is a phenyl or naphthyl ring substituted with up to 3 amine functionalities and the remaining substitutions can be H, R 1 , R 2  or CO 2 R 1 ;  
 or both R 4  taken together are oxo;  
 R 5  and R 6 ═H, R 1  or taken together to form a 5 or 6 membered carbocyclic ring;  
   X=O, S, NR 1   2  
 W═C═O, C═CR 1   2 , CR 1 CR 1   3 , CR 1 ——CR 1   2 OR 1 , COR 1 ——CR 1 OR 1   2 , COR 1 CR 1   2 OR 1 , CR 1 CR 1   2 NR 1   2 , CR 1 CR 1   2  OCR 1 COY.  
   
     
     
         3 . A pharmaceutical composition for treating Kaposi's sarcoma, comprising a therapeutically effective amount of a triterpenoid acid having the following structural formula:  
       
         
           
           
               
               
           
         
         Wherein: 
 Y═OR 1 , NR 1   2 , O--M 1 ;  
 R 1 ═H, LOWER ALKYL,  
 M 1 =Na. 30  , K 30  , Mg ++ , Ca ++  ions;  
 R 2 ═CH 2 OR 1  or CH 3 ;  
 R 4 ═H, OH, SO 3 --M 1 , NH(CH 2 ) n NH 2 , or NH--Ph--(NH 2 ) n  wherein n=1-8 and Ph is a phenyl or naphthyl ring substituted with up to 3 amine functionalities and the remaining substitutions can be H, R 1 , R 2  or CO 2 R 1 ;  
 or both R 4  taken together are oxo;  
 X=O, S, NR 1   2 .  
 
       
     
     
         4 . A pharmaceutical composition for treating Kaposi's sarcoma, comprising a therapeutically effective amount of a triterpenoid acid having the following structural formula:  
       
         
           
           
               
               
           
         
         wherein: 
 Y═OR 1 , NR 1   2 , O--M 1 ;  
 R 1 ═H, LOWER ALKYL,  
 M 1 =Na. + , K + , Mg ++ , Ca ++  ions;  
 R 2 ═CH 2 OR 1  or CH 3 ;  
 R 3 ═H, CH 3 , lower alkyl, COY, CH 2 OH, CH 2 OCH 2 CH═CH 2 , CH 2 OSO-- 3 M 1 ;  
 Z═NR 1 , NR 1 Ac, NR 1 Bz, H, OCH 3 , lower alkyl, OH, SO 3 --M 1 , OCH 2 CH═CH 2 , OCH 2 CO 2  H or O-glucoside wherein a glucoside includes glucose, fucose, galactose, mannose, arabinose or xylose;  
 R 4 ═H, OH, SO 3 --M. 1 , NH(CH 2 ) n NH 2 , or NH--Ph--(NH 2 ) n  wherein n=1-8 and Ph is a phenyl or naphthyl ring substituted with up to 3 amine functionalities and the remaining substitutions can be H, R 1 , R 2  or CO 2 R 1 ;  
 or both R 4  taken together are oxo;  
 R 5  and R 6 ═H,R 1  or taken together to form a 5 or 6 membered carbocyclic ring;  
 X═O, S, NR 1   2    
 W═C═O, C═CR 1   2 , CR 1 CR 1   3 , CR 1 ——CR 1   2 OR 1 , COR 1 ——CR 1 OR 1   2 , COR 1 CR 1   2 OR 1 , CR 1 CR 1   2  NR 1   2 , CR 1 CR 1   2 OCR 1 COY.  
 
       
     
     
         5 . A method of treating Epstein Barr virus comprising the steps of administering to the patient a therapeutic a derivative of a triterpenoid acid and wherein the triterpenoid acid has the following structural formula:  
       
         
           
           
               
               
           
         
          wherein: 
 Y═OR 1 , NR 1   2 , O--M 1 ;  
 R 1 ═H, LOWER ALKYL,  
 M 1 =Na. + , K + , Mg ++ , Ca ++  ions;  
 R 2 ═CH 2 OR 1  or CH 3 ;  
 R 4 ═H, OH, SO 3 --M 1 , NH(CH 2 ) n NH 2 , or NH--Ph--(NH 2 ) n  wherein n=1-8 and Ph is a phenyl or naphthyl ring substituted with up to 3 amine functionalities and the remaining substitutions can be H, R 1 , R 2  or CO 2  R 1 ;  
 or both R 4  taken together are oxo;  
 X=O, S, NR 1  2.  
 
       
     
     
         6 . A method of treating Epstein Barr virus comprising the steps of 
 administering to the patient a derivative of a triterpenoid acid and wherein the triterpenoid acid has the following structural formula:                           wherein: 
 Y═OR 1 , NR 1   2 , O--M 1 ;  
 R 1 ═H, LOWER ALKYL,  
 M 1 =Na. + , K + , Mg ++ , Ca ++  ions;  
 R 2 ═CH 2 OR 1  or CH 3 ;  
 R 3 ═H, CH 3 , lower alkyl, COY, CH 2 OH, CH 2 OCH 2 CH═CH 2 , CH 2 OSO-- 3 M 1 ;  
 Z═NR 1 , NR 1 Ac, NR 1 Bz, H, OCH 3 , lower alkyl, OH, SO 3 --M 1 , OCH 2 CH═CH 2 , OCH 2 CO 2  H or O-glucoside wherein a glucoside includes glucose, fucose, galactose, mannose, arabinose or xylose;  
 R 4 ═H, OH, SO 3 --M. 1 , NH(CH 2 ) n NH 2 , or NH--Ph--(NH 2 ) n wherein n=1-8 and Ph is a phenyl or naphthyl ring substituted with up to 3 amine functionalities and the remaining substitutions can be H, R 1 , R 2  or CO 2 R 1 ;  
 or both R 4  taken together are oxo;  
 R 5  and R 6 ═H, R 1  or taken together to form a 5 or 6 membered carbocyclic ring;  
 X═O, S, NR 1   2    
 W═C═O, C═CR 1   2 , CR 1 CR 1   3 , CR 1 ——CR 1   2 OR 1 , COR 1 ——CR 1 OR 1   2 , COR 1 CR 1   2 OR 1 , CR 1 CR 1   2  NR 1   2 , CR 1 CR 1   2 OCR 1 COY.  
   
     
     
         7 . A pharmaceutical composition for treating Epstein Barr virus, comprising a therapeutically effective amount of a triterpenoid acid having the following structural formula:  
       
         
           
           
               
               
           
         
         wherein: 
 Y═OR 1 , NR 1   2 , O--M 1 ;  
 R 1 ═H, LOWER ALKYL,  
 M 1 =Na. + , K + , Mg ++ , Ca ++  ions;  
 R 2 ═CH 2 OR 1  or CH 3 ;  
 R 4 ═H, OH, SO 3 --M. 1 , NH(CH 2 ) n NH 2 , or NH--Ph--(NH 2 ) n wherein n=1-8 and is a phenyl or naphthyl ring substituted with up to 3 amine functionalities and the remaining substitutions can be H, R 1 , R 2  or CO 2  R 1 ;  
 or both R 4  taken together are oxo;  
 X═O, S, NR 1   2 .  
 
       
     
     
         8 . A pharmaceutical composition for treating Epstein Barr virus, comprising a therapeutically effective amount of a triterpenoid acid having the following structural formula:  
       
         
           
           
               
               
           
         
         wherein: 
 Y═OR 1 , NR 1   2 , O--M 1 ;  
 R 1 ═H, LOWER ALKYL,  
 M 1 =Na. + , K + , Mg ++ , Ca ++  ions;  
 R 2 ═CH 2 OR 1  or CH 3 ;  
 R 3 ═H, CH 3 , lower alkyl, COY, CH 2 OH, CH 2 OCH 2 CH═CH 2 , CH 2 OSO-- 3  M 1 ;  
 Z═NR 1 , NR 1 Ac, NR 1 Bz, H, OCH 3 , lower alkyl, OH, SO 3 --M 1 , OCH 2 CH═CH 2 , OCH 2 CO 2  H or O-glucoside wherein a glucoside includes glucose, fucose, galactose, mannose, arabinose or xylose;  
 R 4 ═H, OH, SO 3 --M. 1 , NH(CH 2 ) n NH 2 , or NH--Ph--(NH 2 ) n  wherein n=1-8 and Ph is a phenyl or naphthyl ring substituted with up to 3 amine functionalities and the remaining substitutions can be H, R 1 , R 2  or CO 2 R 1 ;  
 or both R 4  taken together are oxo;  
 R 5  and R 6 ═H,R 1  or taken together to form a 5 or 6 membered carbocyclic ring;  
 X═O, S, NR 1   2    
 W═C═O, C═CR 1   2 , CR 1 CR 1   3 , CR 1 ——CR 1   2 OR 1 , COR 1 ——CR 1 OR 1   2 , COR 1 CR 1   2 OR 1 , CR 1 CR 1   2 NR 1   2 , CR 1 CR 1   2  OCR 1 COY.  
 
       
     
     
         9 . The method according to  claim 1  wherein the dosage is in the range of 2.5 mg to 50 mg/kg.  
     
     
         10 . The method according to  claim 5  wherein the dosage is in the range of 2.5 mg to 50 mg/kg.