O-acetyl-ADP-ribose non-hydrolyzable analogs

Abstract

Compounds, compositions and methods for modulating cell death in target cells, particularly cancer cells are provided. The compounds are analogs of O-acetyl-ADP-ribose (OAADPr).

Description

Claims

1. A compound of the formula (1), or a salt thereof:

2. The compound of claim 1, where R1 is selected from the group consisting of —NHC(O)CH3, —CH2C(O)CH3 and —CH2C(CH3)═CH2.

3. The compound of claim 1, where R1 is —NHC(O)CH3.

4. The compound of claim 1, where R2 is selected from the group consisting of —NHC(O)CH3, —CH2C(O)CH3 and —CH2C(CH3)═CH2.

5. The compound of claim 1, where R2 is —NHC(O)CH3.

6. The compound of claim 1, where X is CH2.

7. The compound of claim 1, which is represented by formula (II) or a salt thereof:

8. The compound of claim 1, which is represented by formula (III) or a salt thereof:

9. The compound of claim 1, which is represented by formula (IV) or a salt thereof:

10. The compound of claim 1, which is represented by formula (V) or a salt thereof:

11. A composition comprising a pharmaceutically acceptable carrier and a compound according to claim 1.

12. A composition comprising a pharmaceutically acceptable carrier and a compound according to claim 8.

13. A composition comprising a pharmaceutically acceptable carrier and a compound according to claim 10.

14. A method for modulating cell death in a target cell comprising: contacting a cell expressing O-acetyl-ADP-ribose with a compound of formula (I), or a salt thereof:

15. The method of claim 14, wherein the compound is represented by formula (III) or a salt thereof:

16. The method of claim 14, wherein the compound is represented by formula (V) or a salt thereof:

17. A method for treating an O-acetyl-ADP-ribose-mediated condition comprising administering to a subject an effective amount of a compound of formula (I), or a salt thereof:

18. The method of claim 17, wherein the compound is represented by formula (III) or a salt thereof:

19. The method of claim 17, wherein the compound is represented by formula (V) or a salt thereof:

20. The method of claim 17, wherein the O-acetyl-ADP-ribose-mediated condition is cancer.

21. A method for producing 2-N-acetyl-2-deoxy-D-ribofuranose 5-hydrogen phosphate comprising: providing 1,2:5,6-di-O-isopropylidene-3-O-triflate-α-D-glucofuranose; transforming 1,2:5,6-di-O-isopropylidene-3-O-triflate-α-D-glucofuranose to 2-N-acetyl-2-deoxy-D-ribofuranose 5-hydrogen phosphate; isolating 2-N-acetyl-2-deoxy-D-ribofuranose 5-hydrogen phosphate.

22. The method of claim 21, further comprising transforming 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose to 1,2:5,6-di-O-isopropylidene-3-O-triflate-α-D-glucofuranose.

23. A method for producing 3-N-acetyl-3-deoxy-D-ribofuranose 5-hydrogen phosphate comprising: providing 5-O-benzyl-3-triflyl-1,2-O-isopropylidene-α-D-xylofuranose; transforming 5-O-benzyl-3-triflyl-1,2-O-isopropylidene-α-D-xylofuranose to 3-N-Acetyl-3-deoxy-D-ribofuranose 5-hydrogen phosphate; and isolating 3-N-Acetyl-3-deoxy-D-ribofuranose 5-hydrogen phosphate.

24. The method of claim 23, further comprising transforming 1,2-O-isopropylidne-α-D-xylofuranose to 5-O-benzyl-3-triflyl-1,2-O-isopropylidene-α-D-xylofuranose.