Certain compounds, compositions and methods
View Patent ↗The present invention provides certain tetrahydrouridine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of making and using such compounds.
1. A kit comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof:
wherein the carbon marked by an asterisk may have an (R) or an (S) configuration; and wherein R 1 and R 2 are fluoro.
2. The kit of claim 1 , wherein the compound is represented by Compound 1 a or a pharmaceutically acceptable salt thereof:
3. The kit of claim 1 , wherein the compound is represented by Compound 1 a:
4. The kit of claim 1 , further comprising a second compound which is a cytidine deaminase (CDA) substrate drug selected from the group consisting of 5-azacytidine, gemcitabine, ara-C, tezacitabine, 5-fluoro-2′-deoxycytidine, and cytochlor.
5. The kit of claim 1 , further comprising a second compound which is a CDA substrate drug, wherein the CDA substrate drug is not decitabine.
6. The kit of claim 1 , further comprising a second compound which is a CDA substrate drug, wherein the CDA substrate drug is decitabine.
7. The kit of claim 1 , wherein the compound of Formula I or a pharmaceutically acceptable salt thereof is in a unit dosage form.
8. The kit of claim 1 , further comprising information.
9. A kit comprising a pharmaceutical composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof:
wherein the carbon marked by an asterisk may have an (R) or an (S) configuration; and wherein R 1 and R 2 are fluoro; and a pharmaceutically acceptable excipient.
10. The kit of claim 9 , wherein the compound is represented by Compound 1 a or a pharmaceutically acceptable salt thereof:
11. The kit of claim 9 , wherein the compound is represented by Compound 1 a:
12. The kit of claim 9 , further comprising a second compound which is a CDA substrate drug selected from the group consisting of 5-azacytidine, gemcitabine, ara-C, tezacitabine, 5-fluoro-2′-deoxycytidine, and cytochlor.
13. The kit of claim 9 , further comprising a second compound which is a CDA substrate drug, wherein the CDA substrate drug is not decitabine.
14. The kit of claim 9 , further comprising a second compound which is a CDA substrate drug, wherein the CDA substrate drug is decitabine.
15. A method for inhibiting cytidine deaminase, comprising administering to a subject in need a composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof:
wherein the carbon marked by an asterisk may have an (R) or an (S) configuration; and wherein R 1 and R 2 are fluoro;
and a pharmaceutically acceptable excipient.
16. The method of claim 15 , wherein the compound is represented by Compound 1 a or a pharmaceutically acceptable salt thereof:
17. The method of claim 15 , wherein the compound is represented by Compound 1 a:
18. A method for inhibiting degradation of a CDA substrate drug by cytidine deaminase, comprising administering to a subject that is undergoing treatment with the CDA substrate drug a composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof:
wherein the carbon marked by an asterisk may have an (R) or an (S) configuration; and wherein R 1 and R 2 are fluoro;
and a pharmaceutically acceptable excipient.
19. The method of claim 18 , wherein the compound is represented by Compound 1 a or a pharmaceutically acceptable salt thereof:
20. The method of claim 18 , wherein the compound is represented by Compound 1 a: