Substituted pyridines as DNMT1 inhibitors
The invention relates to substituted pyridine derivatives that are inhibitors of the activity of DNA methyltransferase 1 (DNMT1). The invention also relates to pharmaceutical compositions comprising such compounds and methods of using such compounds in the treatment of cancer, pre-cancerous syndromes, beta haemoglobinopathy disorders, and other diseases associated with inappropriate DNMT1 activity.
1. A compound of formula (I)
or a prodrug or a pharmaceutically acceptable salt thereof.
2. A compound of formula (II)
or a prodrug or a pharmaceutically acceptable salt thereof.
3. A compound of formula (IV)
or a pharmaceutically acceptable salt thereof.
4. A compound of formula (V)
or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 4 , which is a glycine salt having a formula of
6. The glycine salt according to claim 5 , wherein the salt is crystalline.
7. The glycine salt according to claim 6 , wherein the salt is anhydrous.
8. A pharmaceutical composition comprising the compound according to claim 4 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.
9. A combination comprising the compound of claim 4 , or a pharmaceutically acceptable salt thereof, and one or more other active agents.
10. The glycine salt according to claim 6 , wherein the salt is hydrated.
11. The glycine salt according to claim 10 , wherein the salt is a monohydrate.
12. A pharmaceutical composition comprising the compound according to claim 5 and one or more pharmaceutically acceptable excipients.
13. A combination comprising the compound of claim 5 and one or more other active agents.
14. The compound according to claim 1 , having formula (I)
15. The compound according to claim 2 , having formula (II)
16. The compound according to claim 3 , having formula (IV)
17. The compound according to claim 4 , having formula (V)