Amino ceramide-like compounds and therapeutic methods of use

• US 7,253,185 B2
• Filed: 04/29/2005
• Issued: 08/07/2007
• Est. Priority Date: 04/29/2002
• Status: Expired due to Term

• 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): SHAMEEM, GOLAM M
• Application Number:
  US11/119,541
• Publication Number:
  US 20050267094A1
• Time in Patent Office: 830 Days
• Field of Search: 546/184, 546/246, 548/566, 548/567, 548/950, 514/408, 514/428, 514/315
• US Class Current: 514/315
• CPC Class Codes: A61K 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 31/5375 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 295/13 to an acyclic saturated chain
• CPC Class Codes: C07D 317/54 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 319/18 Ethylenedioxybenzenes, not substituted on the hetero ring
• CPC Class Codes: C07D 321/10 condensed with carbocyclic rings or ring systems
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides amino ceramide-like compounds which inhibit glucosyl ceramide (GlyCer) formation by inhibiting the enzyme GlyCer synthase, thereby lowering the level of glycosphingolipids. The compounds of the present invention have improved GlcCer synthase inhibition activity and are therefore useful in therapeutic methods for treating various conditions and diseases associated with altered glycosphingolipid levels.

Claims

1. A pharmaceutical composition comprising a compound represented by the following structural formula:

2. The pharmaceutical composition of claim 1, wherein R¹ is a phenyl group substituted with a functional group selected from the group consisting of a p-methoxy, hydroxyl, methylenedioxy, ethylenedioxy, trimethylenedioxy and cyclohexyl.

3. A pharmaceutical composition comprising a compound represented by the structural formula:

4. The pharmaceutical composition of claim 3, wherein R¹ is a phenyl group substituted with a functional group selected from the group consisting of a p-methoxy, hydroxyl, methylenedioxy, ethylenedioxy, trimethylenedioxy and cyclohexyl.