2-hydroxymethylcyclopropylidene methylpurines and -pyrimidines as antiviral agents
View Patent ↗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 claim 1 or 2 , wherein B is selected from the group consisting of cytosine, 5-halo substituted cytosine, 5-alkyl substituted cytosine, thyrmine, and uracil.
4. The compound of claim 1 or 2 , wherein B is cytosine-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 claim 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 claim 1 or 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 14 , wherein the additional antiviral compound is selected from the group consisting of acyclovir, ganciciclovir, zidovudine, AZT, ddl, ddC, d4T, and combinations thereof.