Uracyl spirooxetane nucleosides
The present invention relates to compounds of the formula I: including any possible stereoisomers thereof, wherein R 9 has the meaning as defined herein, or a pharmaceutically acceptable salt or solvate thereof. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HCV inhibitors, in HCV therapy.
1. A compound of formula Ib:
2. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier.
3. A method of preparing a compound of formula (7),
comprising
reacting a compound of formula (12) with POCl 3 to provide a compound of formula (6);
reacting a compound of formula (6) with a compound of formula (4),
wherein R 9 is selected from the group consisting of C 1 -C 6 alkyl, phenyl, naphtyl, C 3 -C 7 cycloalkyl, and Y, wherein Y is C 1 -C 3 alkyl substituted with 1, 2 or 3
substituents each independently selected from the group consisting of phenyl, C 3 -C 6 cycloalkyl, hydroxy and C 1 -C 6 alkoxy.
4. A method as claimed in claim 3 , wherein said reacting a compound of formula (6) with a compound of formula (4) takes place in the presence of triethylamine.
5. A method as claimed in claim 3 , wherein said reacting a compound of formula (6) with a compound of formula (4) takes place in the presence of N-methylimidazole.
6. A method as claimed in claim 3 , wherein said reacting a compound of formula (6) with a compound of formula (4) takes place in dichloromethane.
7. A method as claimed in claim 3 , wherein said reacting a compound of formula (6) with a compound of formula (4) takes place in the presence of triethylamine and N-methylimidazole in dichloromethane.
8. A method as claimed in claim 3 , wherein R 9 is C 1 -C 6 alkyl.
9. A method as claimed in claim 3 , wherein R 9 is C 3 -C 7 cycloalkyl.
10. A method as claimed in claim 3 , wherein R 9 is isopropyl.
11. A method as claimed in claim 3 , wherein R 9 is C 2 -C 4 alkyl.
12. A method as claimed in claim 3 , wherein R 9 is C 1 -C 2 alkyl substituted with phenyl.