Synthesis of UDP-glucose: N-acylsphingosine glucosyltransferase inhibitors

• US 7,196,205 B2
• Filed: 03/28/2005
• Issued: 03/27/2007
• Est. Priority Date: 07/16/2001
• Status: Active Grant

• Current Assignee: Genzyme Corporation (Sanofi ), Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Genzyme Corporation (Sanofi ), Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Siegel, Craig, Harris, David J., Shayman, James A., Nelson, Carol A., Copeland, Diane P.
• Primary Examiner(s): ANDERSON, REBECCA L
• Application Number:
  US11/091,836
• Publication Number:
  US 20050222244A1
• Time in Patent Office: 729 Days
• Field of Search: 548/526
• US Class Current: 548/526
• CPC Class Codes: A61K 31/4025 not condensed and containing further heterocyclic rings, e.g. cromakalim
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07D 295/185 from aliphatic carboxylic acids
• CPC Class Codes: C07D 319/18 Ethylenedioxybenzenes, not substituted on the hetero ring
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 498/04 Ortho-condensed systems

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.

Claims

1. A compound represented by the following structural formula:

3. The compound of claim 1, wherein the compound has an enantiomeric excess of at least 10%.

4. The compound of claim 1, wherein the compound has an enantiomeric excess of at least 25%.

5. The compound of claim 1, wherein the compound has an enantiomeric excess of at least 50%.

6. The compound of claim 1, wherein the compound has an enantiomeric excess of at least 75%.

7. The compound of claim 1, wherein the compound has an enantiomeric excess of at least 90%.

8. The compound of claim 1, wherein the compound has an enantiomeric excess of at least 95%.

9. The compound of claim 1, wherein the compound has an enantiomeric excess of at least 99%.

2. A compound represented by the following structural formula:

10. The compound of claim 2, wherein the compound has an enantiomeric excess of at least 10%.

11. The compound of claim 2, wherein the compound has an enantiomeric excess of at least 25%.

12. The compound of claim 2, wherein the compound has an enantiomeric excess of at least 50%.

13. The compound of claim 2, wherein the compound has an enantiomeric excess of at least 75%.

14. The compound of claim 2, wherein the compound has an enantiomeric excess of at least 90%.

15. The compound of claim 2, wherein the compound has an enantiomeric excess of at least 95%.

16. The compound of claim 2, wherein the compound has an enantiomeric excess of at least 99%.