Synthesis of UDP-glucose: N-acylsphingosine glucosyltransferase inhibitors

• US 7,763,738 B2
• Filed: 08/24/2007
• Issued: 07/27/2010
• Est. Priority Date: 07/16/2001
• Status: Expired due to Term

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Hirth, Bradford H., Siegel, Craig
• Primary Examiner(s): Anderson; Rebecca L
• Application Number:
  US11/895,632
• Publication Number:
  US 20080058514A1
• Time in Patent Office: 1,068 Days
• Field of Search: 548/526, 548/568, 548/569
• 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 method of preparing an acylated ceramide compound represented by the following structural formula:

2. A method of preparing an acylated ceramide compound represented by the following structural formula:

3. The method of claim 2, wherein the ceramide compound is represented by the following structural formula:

4. The method of claim 3, wherein the sphingosine-like compound is acylated with CH₃(CH₂)₆COX, wherein X is a leaving group, thereby forming the ceramide compound.

5. The method of claim 4, wherein X is —

Cl or N-hydroxysuccinimidyl.