Details for Patent: 7,615,573
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Title: | Synthesis of UDP-glucose: N-acylsphingosine glucosyltransferase inhibitors |
Abstract: | Disclosed is a novel enantiomeric synthesis ceramide-like inhibitors of UDP-glucose: N-acylsphingosine glucosyltransferase. Also disclosed are novel intermediates formed during the synthesis. |
Inventor(s): | Siegel; Craig (Woburn, MA), Shayman; James A. (Ann Arbor, MI), Nelson; Carol A. (Westford, MA), Harris; David J. (Lexington, MA), Copeland; Diane P. (North Billerica, MA) |
Assignee: | The Regents of the University of Michigan (Ann Arbor, MI) Genzyme Corporation (Cambridge, MA) |
Filing Date: | Feb 05, 2007 |
Application Number: | 11/702,425 |
Claims: | 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: ##STR00032## 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: ##STR00033## 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: ##STR00034## 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: ##STR00035## 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: ##STR00036## 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: ##STR00037## 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%. |