Pyrrolo[3,2-d]pyrimidine derivatives for the treatment of viral infections and other diseases
This invention concerns pyrrolo[3,2-d]pyrimidine derivatives, processes for their preparation, pharmaceutical compositions, and their use in treatment and/or therapy of diseases.
1. A compound of formula (I)
and a pharmaceutically acceptable salt or solvate thereof, wherein
R 1 is H or fluorine;
R 2 is H;
R 3 is C 1-6 alkyl substituted by a substituent selected from the group consisting of hydroxyl, phenyl, pyridinyl, thiazolyl and pyrimidinyl, wherein each substituent is optionally further substituted by one or more substituents independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkyloxy and halogen; and
R 4 is C 1-8 alkyl substituted by a substituent selected from the group consisting of hydroxyl, C 1-6 alkyl, phenyl, oxadiazolyl and isoxazolyl, wherein each substituent is optionally further substituted by C 1-6 alkyl.
2. A compound of formula (I) according to claim 1 wherein R 1 and R 2 are each hydrogen.
3. A compound of formula (I) according to claim 1 wherein R 1 is fluorine and R 2 is hydrogen.
4. A pharmaceutical composition comprising a compound according to claim 1 together with one or more pharmaceutically acceptable excipients, diluents or carriers.
5. A compound of formula (I) according to claim 1 , wherein R 3 is methyl.
6. A compound of formula (I) according to claim 5 , wherein R 3 is substituted by a substituent selected from the group consisting of phenyl, pyridinyl, thiazolyl and pyrimidinyl.
7. A compound of formula (I) according to claim 6 , wherein each substituent is optionally further substituted by methoxy or halogen.
8. A compound of formula (I) according to claim 1 , wherein R 4 is methyl.
9. A compound of formula (I) according to claim 8 , wherein R 4 is substituted by oxadiazolyl or isoxazolyl.
10. A compound of formula (I) according to claim 9 , wherein each substitutent is optionally further substituted by methyl.
11. A compound of formula (I) according to claim 1 , wherein R 3 and R 4 are each methyl.
12. A compound of formula (I) according to claim 1 , wherein R 3 is substituted with pyridinyl, and R 4 is substituted with isoxazolyl.
13. A compound according to claim 1 , wherein the compound is selected from the group consisting of:
14. A compound selected from the group consisting of
15. A pharmaceutical composition comprising a compound according to claim 13 together with one or more pharmaceutically acceptable excipients, diluents or carriers.
16. A pharmaceutical composition comprising a compound according to claim 14 together with one or more pharmaceutically acceptable excipients, diluents or carriers.
17. A method of treating HCV infection in a subject in need thereof comprising administering to said subject an effective amount of a compound of formula (I)
or a pharmaceutically acceptable salt or solvate thereof, wherein
R 1 is H, fluorine or methyl;
R 2 is H, halogen or C 1-3 alkyl;
R 3 is C 1-6 alkyl optionally substituted by aryl, wherein said aryl is optionally-substituted by one or more substituents independently selected from the group consisting of aryloxy, halogen, aryl, alkylamino, dialkylamino, C 1-6 alkyl, —CO 2 H, —C(O)OC 1-6 alkyl, —CONH 2 , —CN, and C 1-6 alkoxy; or
R 3 is C 1-6 alkyl optionally substituted by C 1-6 alkene, C 3-7 cycloalkyl or C 3-7 heterocycloalkyl; or
R 3 is C 1-6 alkyl optionally substituted by C 1-6 alkoxy, wherein said C 1-6 alkoxy is optionally substituted by aryl; and
R 4 is C 1-8 alkyl optionally substituted by one or more substituents independently selected from the group consisting of hydroxyl, C 1-6 alkoxy, C 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, aryl, heteroaryl, and C 3-7 cycloalkyl, wherein said heteroaryl and said C 3-7 cycloalkyl are optionally substituted by C 1-6 alkyl;
with the proviso that 2-amino, 4-(N-butylamino)-5-(alphamethylbenzyl)pyrrolo[3,2-d]pyrimidine is excluded, wherein administering said compound to said subject induces interferon.
18. A method of treating HCV infection in a subject in need thereof comprising administering to said subject an effective amount of a compound of claim 1 , wherein administering said compound to said subject induces interferon.
19. A method of treating HCV infection in a subject in need thereof comprising administering to said subject an effective amount of a compound of claim 13 , wherein administering said compound to said subject induces interferon.
20. A method of treating HCV infection in a subject in need thereof comprising administering to said subject an effective amount of a compound of claim 14 , wherein administering said compound to said subject induces interferon.