2-Hydroxymethylcyclopropylidenemethylpurines and - pyrimidines as antiviral agents

Abstract

Compounds which are active against viruses have the following Formulas: wherein B is a purine or pyrimidine heterocyclic ring and is preferably selected from the group consisting of 6-aminopurine (adenine), 2,6-diaminopurine, 2-amino-6-azidopurine, 2-amino-6-cyclopropylaminopurine, 6-hydroxypurine (hypoxanthine), 2-amino-6-halo substituted purines, 2-amino-6-alkoxy substituted purines, 2-amino-6-hydroxypurine (guanine), 3-deazapurines, 7-deaza-purines, 8-azapurines, cytosine, 5-halo substituted cytosines, 5-alkyl substituted cytosines, thymine, uracil and 6-azapyrimidines; X is O; and, R 1 and R 2 are alkyl or aryl groups. The compounds of the present invention also include the R- and S-enantiomers of the above compounds. The R 1 X and/or R 2 X can also be amino acid residues with X as NH.

1 . A compound having the formula:  
     
       
         
         
             
             
         
       
     
     wherein B is a pyrimidine moiety, and pharmaceutically acceptable salts, and prodrugs, thereof.  
   
   
       2 . A compound having the formula:  
     
       
         
         
             
             
         
       
     
     wherein B is a pyrimidine moiety, and pharmaceutically acceptable salts, and prodrugs, thereof.  
   
   
       3 . The compound of claims  1  or  2 , wherein B is selected from the group consisting of 7-deazapurine, 8-azapurine, cytosine, 5-halo substituted cytosine, 5-alkyl substituted cytosine, thymine, uracil and 6-azapyrimidine.  
   
   
       4 . The compound of claims  1  or  2 , wherein B is selected from the group consisting of cytosin-N 1 -yl.  
   
   
       5 . An antiviral compound selected from the group consisting of syn-N 1 -(2-hydroxymethylcyclopropylidenemethyl)-cytosine and syn-N 1 -(2-carbomethoxycyclopropylidenemethyl)cytosine, and pharmaceutically acceptable salts and prodrugs, thereof.  
   
   
       6 . An antiviral compound selected from the group consisting of anti-N 1 -(2-hydroxymethylcyclopropylidenemethyl)-cytosine and anti-N 1 -(2-carbomethoxycyclopropylidenemethyl)-cytosine, and pharmaceutically acceptable salts and prodrugs, thereof.  
   
   
       7 . A composition comprising a compound of claims  1  or  2  and a pharmaceutically acceptable carrier.  
   
   
       8 . A method of treating mammals infected with a virus selected from the group consisting of HCMV, HSV-1, HSV-2, HHV-6, HIV, EBV, and HBV comprising the step of administering to the mammal an antiviral compound selected from the group consisting of the compounds of claims  1  and  2 .  
   
   
       9 . The method of  claim 8 , wherein said mammal is a human.  
   
   
       10 . The method of  claim 8 , wherein said virus is a human herpes virus.  
   
   
       11 . The method of  claim 8 , wherein said virus is Epstein-Barr virus.  
   
   
       12 . The method of  claim 8 , wherein said virus is a human immunodeficiency virus.  
   
   
       13 . The method of  claim 8 , wherein said virus is hepatitis B virus.  
   
   
       14 . The method of  claim 8 , further comprising the step of administering an additional antiviral compound.  
   
   
       15 . The method of  claim 13 , wherein the additional antiviral compound is selected from the group consisting of acyclovir, ganciclovir, zidovudine, AZT, ddI, ddC, d4T, and combinations thereof.