Synthesis of UDP-glucose: N-acylsphingosine glucosyltransferase inhibitors
View Patent ↗Disclosed is a novel enantiomeric synthesis ceramide-like inhibitors of UDP-glucose: N-acylsphingosine glucosyltransferase. Also disclosed are novel intermediates formed during the synthesis.
1. A method of inhibiting glucosylceramide synthase or lowering glycosphingolipid concentrations in a subject in need thereof, comprising administering to the subject an effective amount of a compound represented by the following structural formula:
or a physiologically acceptable salt thereof.
2. The method of claim 1 , wherein the compound has an enantiomeric excess of at least 25%.
3. The method of claim 1 , wherein the compound has an enantiomeric excess of at least 50%.
4. The method of claim 1 , wherein the compound has an enantiomeric excess of at least 90%.
5. The method of claim 1 , wherein the compound has an enantiomeric excess of at least 99%.
6. A method of treating a subject with Fabry disease, comprising administering to the subject an effective amount of a compound represented by the following structural formula:
or a physiologically acceptable salt thereof.
7. The method of claim 6 , wherein the compound has an enantiomeric excess of at least 25%.
8. The method of claim 6 , wherein the compound has an enantiomeric excess of at least 50%.
9. The method of claim 6 , wherein the compound has an enantiomeric excess of at least 90%.
10. The method of claim 6 , wherein the compound has an enantiomeric excess of at least 99%.
11. A method of inhibiting glucosylceramide synthase or lowering glycosphingolipid concentrations in a subject in need thereof, comprising administering to the subject an effective amount of a compound represented by the following structural formula:
or a physiologically acceptable salt thereof.
12. The method of claim 11 , wherein the compound has an enantiomeric excess of at least 25%.
13. The method of claim 11 , wherein the compound has an enantiomeric excess of at least 50%.
14. The method of claim 11 , wherein the compound has an enantiomeric excess of at least 90%.
15. The method of claim 11 , wherein the compound has an enantiomeric excess of at least 99%.
16. A method of treating a subject with Fabry disease, comprising administering to the subject an effective amount of a compound represented by the following structural formula:
or a physiologically acceptable salt thereof.
17. The method of claim 16 , wherein the compound has an enantiomeric excess of at least 25%.
18. The method of claim 16 , wherein the compound has an enantiomeric excess of at least 50%.
19. The method of claim 16 , wherein the compound has an enantiomeric excess of at least 90%.
20. The method of claim 16 , wherein the compound has an enantiomeric excess of at least 99%.
21. A method of treating a subject with Gaucher disease, comprising administering to the subject an effective amount of a compound represented by the following structural formula:
or a physiologically acceptable salt thereof.
22. The method of claim 21 , wherein the compound has an enantiomeric excess of at least 25%.
23. The method of claim 21 , wherein the compound has an enantiomeric excess of at least 50%.
24. The method of claim 21 , wherein the compound has an enantiomeric excess of at least 90%.
25. The method of claim 21 , wherein the compound has an enantiomeric excess of at least 99%.
26. A method of treating a subject with Gaucher disease, comprising administering to the subject an effective amount of a compound represented by the following structural formula:
or a physiologically acceptable salt thereof.
27. The method of claim 26 , wherein the compound has an enantiomeric excess of at least 25%.
28. The method of claim 26 , wherein the compound has an enantiomeric excess of at least 50%.
29. The method of claim 26 , wherein the compound has an enantiomeric excess of at least 90%.
30. The method of claim 26 , wherein the compound has an enantiomeric excess of at least 99%.