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, solvate or polymorph 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 substituted by heterocycle; or
R 3 is an C 1 alkylaryl optionally substituted by one or more substituents independently selected from the group consisting of halogen, aryloxy, aryl, alkylamino, dialkylamino, C 1-6 alkyl, —CO 2 H, —CO 2 C 1-6 alkyl, —CO 2 NH 2 ,—SO 2 NH 2 , —CN and C 1-6 alkoxy; and
R 4 is C 1-6 alkyl optionally substituted by one or more substituents independently selected from the group consisting of hydroxyl, C 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl and aryl wherein said aryl is optionally further substituted by C 1-6 alkyl, and said C 3-7 cycloalkyl is optionally further substituted by C 1-6 alkyl;
or
R 4 is an alkylaryl optionally substituted by one or more substituents independently selected from the group consisting of halogen, aryloxy, aryl, alkylamino, dialkylamino, C 1-6 alkyl, —CO 2 H, —CO 2 C 1-6 alkyl, —CO 2 NH 2 ,—SO 2 NH 2 ,—CN and C 1-6 alkoxy, provided that when R 4 is C 1-6 alkyl, R 3 is C 1-6 alkyl optionally substituted by one or more substituents independently selected from the group consisting of aryloxy, heterocycle, halogen, aryl, alkylamino, dialkylamino, C 1-6 alkyl, —CO 2 H, —CO 2 C 1-6 alkyl, —CO 2 NH 2 , —CN and C 1-6 alkoxy.
2. A compound according to claim 1 wherein R 1 is fluorine and R 2 is hydrogen.
3. A compound according to claim 1 having the following chemical structure:
4. A compound as claimed in claim 1 , wherein R 2 and R 1 are H.
5. A compound as claimed in claim 4 , wherein R 3 is
6. A compound as claimed in claim 1 , wherein R 4 is alkylaryl.
7. A compound as claimed in claim 5 , wherein R 4 is alkylaryl.
8. A compound as claimed in claim 5 , wherein R 4 is selected from the group consisting of
9. A compound as claimed in claim 1 , wherein R 4 is C 1-6 alkyl.
10. A compound as claimed in claim 5 , wherein R 4 is C 1-6 alkyl.
11. A compound as claimed in claim 1 , wherein
R 2 and R 1 are H,
12. A compound as claimed in claim 1 wherein
R 2 and R 1 are H,
R 3 is
and
R 4 is butane.
13. A compound as claimed in claim 1 , wherein
R 2 and R 1 are H,
14. The compound of claim 1 , wherein R 3 is methyl phenyl optionally substituted with one or more C 1-6 alkoxy.
15. The compound of claim 1 , wherein R 3 is methyl pyridinyl optionally substituted with one or more C 1-6 alkoxy.
16. A compound selected from the group consisting of
17. A pharmaceutical composition comprising a compound according to claim 1 together with one or more pharmaceutically acceptable excipients, diluents or carriers.
18. A pharmaceutical composition comprising a compound as claimed in claim 3 together with one or more pharmaceutically acceptable excipients, diluents or carriers.
19. A method of modulating TLR 7 to treat a viral infection comprising adminstering a therapeutically effective amount of at least one compound as claimed in claim 1 .