Uracyl cyclopropyl nucleotides
Compounds of the formula I: including any possible stereoisomers thereof, wherein: R 1 is hydrogen or halo; R 4 is a monophosphate, diphosphate or triphosphate ester; or R 4 is a group of formula R 7 is optionally substituted phenyl; naphthyl; indolyl or N—C 1 -C 6 alkyloxycarbonyl-indolyl; R 8 is hydrogen, C 1 -C 6 alkyl, benzyl; R 8′ is hydrogen, C 1 -C 6 alkyl, benzyl; or R 8 and R 8′ together with the carbon atom to which they are attached form C 3 -C 7 cycloalkyl; R 9 is C 1 -C 10 alkyl, benzyl, or optionally substituted phenyl; or a pharmaceutically acceptable salt or solvate thereof. pharmaceutical formulations and the use of compounds I as HCV inhibitors.
1. A compound of formula I:
including any possible stereoisomers thereof, wherein:
R 1 is hydrogen or halo;
R 4 is a monophosphate, diphosphate or triphosphate ester; or R 4 is a group of formula
R 7 is phenyl, optionally substituted with 1, 2, or with 3 substituents each independently selected from halo, C 1 -C 6 alkyl, C 3 -C 6 alkenyl, C 1 -C 6 alkoxy, C 1 -C 6 alkoxycarbonyl, hydroxy, and amino; or R 7 is naphthyl; or R 7 is indolyl or N-C 1 -C 6 alkyloxy-carbonylindolyl;
R 8 is hydrogen, C 1 -C 6 alkyl, benzyl;
R 8′ is hydrogen, C 1 -C 6 alkyl, benzyl; or
R 8 and R 8′ together with the carbon atom to which they are attached form C 3 -C 7 cycloalkyl;
R 9 is C 1 -C 10 alkyl, C 3 -C 7 cycloalkyl, benzyl, or phenyl, which phenyl may be optionally substituted with 1, 2 or 3 substituents each independently selected from hydroxy, C-C 6 alkoxy, amino, mono- and diC 1 -C 6 alkylamino;
or a pharmaceutically acceptable salt or solvate thereof.
2. The compound according to claim 1 , wherein R 4 is a group of formula
3. The compound according to claim 1 , wherein R 7 is phenyl, optionally substituted with 1, 2 or 3 substituents each independently selected from halo, C 1 -C 6 alkyl, C 3 -C 6 alkenyl, and C 1 -C 6 alkoxy; or R 7 is naphthyl.
4. The compound according to claim 1 , wherein R 7 is R 7 is phenyl, optionally substituted with 1, 2 or 3 substituents each independently selected from halo and C 1 -C 6 alkyl.
5. The compound according to claim 1 , wherein R 7 is phenyl, optionally substituted with halo, or C 1 -C 6 alkyl, or R 7 is naphthyl.
6. The compound according to of claim 1 , wherein R 8 is hydrogen, and R 8′ is hydrogen or C 1 -C 6 alkyl.
7. The compound according to claim 1 , wherein the
moiety has the structure
wherein R 8 is hydrogen and R 8′ is hydrogen, C 1 -C 6 alkyl, benzyl.
8. The compound according to claim 7 , wherein R 8 is hydrogen and R 8′ is C 1 -C 2 alkyl.
9. The compound according to claim 7 , wherein R 8 is hydrogen and R 8′ is methyl.
10. The compound according to claim 1 , wherein R 9 is C 1 -C 10 alkyl, C 3 -C 7 cycloalkyl, C 3 -C 6 alkenyl, or benzyl.
11. The compound according to claim 10 , wherein R 9 is C 1 -C 8 alkyl, or benzyl.
12. The compound according to claim 10 , wherein R 9 is methyl, ethyl, isopropyl, 1-methyl-propyl, isobutyl, butyl, t-butyl, benzyl, cyclopentyl, 5-hexenyl, 2,2-dimethyl-butyl, octyl or 2-propyl-pentyl.
13. The compound according to claim 10 , wherein R 9 is ethyl, isobutyl, butyl, benzyl, cyclopentyl, 5-hexenyl, 2,2-dimethyl-butyl, or 2-propyl-pentyl.
14. A pharmaceutical composition comprising compound of formula I of claim 1 and a pharmaceutically acceptable carrier.
15. The method of treating a HCV infection comprising administrating an anti-HCV effective amount of a compound according to claim 1 to a patient in need of such treatment.