Uracyl spirooxetane nucleosides
Compounds of the formula I: including any possible stereoisomers thereof, wherein: R 4 is a monophosphate, diphosphate or triphosphate ester; or R 4 is R 7 is optionally substituted phenyl, optionally substituted naphthyl, or optionally substituted indolyl; R 8 and R 8′ are hydrogen, C 1 -C 6 alkyl, benzyl, or phenyl; or R 8 and R 8′ form C 3 -C 7 cycloalkyl; R 9 is C 1 -C 10 alkyl, C 3 -C 7 cycloalkyl, phenyl or phenyl-C 1 -C 6 alkyl, wherein the phenyl moiety in phenyl or phenyl-C 1 -C 6 alkyl is optionally substituted; 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 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, hydroxy, and amino; or R 7 is naphthyl, 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, hydroxy, and amino; or R 7 is indolyl, optionally substituted with one C 1 -C 6 alkyloxy-carbonyl group and optionally further 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, hydroxy, and amino;
R 8 is hydrogen, C 1 -C 6 alkyl, benzyl, or phenyl;
R 8′ is hydrogen, C 1 -C 6 alkyl, benzyl, or phenyl; 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 or phenyl-C 1 -C 6 alkyl, wherein the phenyl moiety in phenyl or phenyl-C 1 -C 6 alkyl is optionally substituted with 1, 2 or 3 substituents each independently selected from hydroxy, C 1 -C 6 alkoxy, amino, mono- and diC 1 -C 6 alkylamino;
or a pharmaceutically acceptable salt or solvate thereof.
2. A compound according to claim 1 , wherein R 4 is a group of formula
3. A compound according to claim 1 , wherein R 7 is phenyl, optionally substituted with halo or with one or two C 1 -C 6 alkyl groups, or R 7 is naphthyl or indolyl.
4. A compound according to claim 1 , wherein R 7 is phenyl, optionally substituted with halo, or with two C 1 -C 6 alkyl groups, or R 7 is naphthyl.
5. A compound according to claim 1 , wherein R 7 is phenyl or naphtyl.
6. A compound according to claim 1 , wherein R 8 is hydrogen, and R 8′ is hydrogen or C 1 -C 6 alkyl.
7. A compound according to claim 1 , wherein R 8 is hydrogen and R 8′ is methyl or ethyl.
8. A compound according to claim 1 , wherein R 9 is C 1 -C 6 alkyl or benzyl.
9. A compound according to claim 1 , wherein R 9 is n.butyl or benzyl.
10. A compound which is:
11. A pharmaceutical composition comprising an anti-virally effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
12. A method for inhibiting HCV, comprising administering to a patient in need thereof an effective amount of a compound of claim 1 .
13. A compound according to claim 10 which is :
14. A pharmaceutical composition comprising an anti-virally effective amount of a compound of claim 13 and a pharmaceutically acceptable carrier.
15. A method for inhibiting HCV, comprising administering to a patient in need thereof an effective amount of a compound of claim 13 .