Deuterium substituted xanthine derivatives
This invention relates to novel compounds that are substituted xanthine derivatives and pharmaceutically acceptable salts thereof. In particular, this invention relates to novel substituted xanthine derivatives that are derivatives of a pentoxifylline metabolite. This invention also provides compositions comprising one or more compounds of this invention and a carrier and the use of the disclosed compounds and compositions in methods of treating diseases and conditions for which pentoxifylline and related compounds are beneficial. The compounds of the invention are represented by one of the following structural formulas: wherein the values of R 1 , R 2 , Y 1 and Y 2 are described herein.
1. A compound of Formula C:
or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from —CH 3 and —CD 3 ;
R 2 is selected from —CH 3 and —CD 3 ; Y 1 is hydrogen, wherein the isotopic enrichment factor for each designated deuterium atom is at least 5000.
2. The compound of claim 1 , wherein R 1 is —CH 3 .
3. The compound of claim 1 , wherein R 1 is —CD 3 .
4. The compound of claim 1 wherein R 2 is —CH 3 .
5. The compound of claim 1 wherein R 2 is —CD 3 .
6. The compound of claim 1 , wherein R 1 is —CH 3 and R 2 is —CH 3 .
7. The compound of claim 1 , wherein the compound is selected from the group consisting of the following compounds
or a pharmaceutically acceptable salt thereof.
8. A compound of Formula D:
or a pharmaceutically acceptable salt thereof, wherein R 1 —CH 3 ;
R 2 is selected from —CH 3 and —CD 3 ; Y 1 is hydrogen;
wherein the isotopic enrichment factor for each designated deuterium atom is at least 5000.
9. The compound of claim 8 , wherein R 2 is —CH 3 .
10. The compound of claim 8 , wherein R 2 is —CD 3 .
11. The compound of claim 8 , wherein the compound is represented by the following structural formula:
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.
13. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
14. A compound of the following formula:
or a pharmaceutically acceptable salt thereof, wherein the isotopic enrichment factor for each designated deuterium atom is at least 5000.
15. The compound of claim 14 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.
16. The compound of claim 8 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.
17. The compound of claim 12 , wherein isotopic enrichment factor for each designated deuterium atom is at least 6000.
18. The compound of claim 12 , wherein isotopic enrichment factor for each designated deuterium atom is at least 6600.
19. The compound of claim 15 , wherein isotopic enrichment factor for each designated deuterium atom is at least 6000.
20. The compound of claim 15 , wherein isotopic enrichment factor for each designated deuterium atom is at least 6600.
21. The compound of claim 16 , wherein isotopic enrichment factor for each designated deuterium atom is at least 6000.
22. The compound of claim 16 , wherein isotopic enrichment factor for each designated deuterium atom is at least 6600.
23. The compound of claim 1 , wherein the compound comprises less than 10% of the other stereoisomer.
24. The compound of claim 15 , wherein the compound comprises less than 10% of the other stereoisomer.
25. The compound of claim 21 , wherein the compound comprises less than 10% of the other stereoisomer.
26. The compound of claim 15 , wherein the compound comprises less than 5% of the other stereoisomer.
27. The compound of claim 21 , wherein the compound comprises less than 5% of the other stereoisomer.