Amino ceramide-like compounds and therapeutic methods of use

• US 6,890,949 B1
• Filed: 07/07/2000
• Issued: 05/10/2005
• Est. Priority Date: 07/09/1999
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Radin, Norman S., Shayman, James A.
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US10/030,963
• Time in Patent Office: 1,768 Days
• Field of Search: 548/526, 548/568, 514/422, 514/428
• US Class Current: 514/422
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 295/12 substituted by singly or doubly bound nitrogen atoms nitro radicals C07D295/06
• CPC Class Codes: C07D 295/125 with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
• CPC Class Codes: C07D 319/18 Ethylenedioxybenzenes, not substituted on the hetero ring

Abstract

Novel amino ceramide-like compounds (1) are provided which inhibit glucosyl ceramide (GlcCer) formation by inhibiting the enzyme GlcCer synthase, thereby lowering the level of glycosphingolipids. The compounds of the present invention have improved GlcCer synthase inhibition activity and are therefore highly useful in therapeutic methods for treating various conditions and diseases associated with altered glycosphingolipid levels.

Claims

1. A method for treating a patient having a microbial or viral infection comprising the step of administering to the patient a therapeutically effective amount of a compound selected from the group consisting of D-t-3′

, 4′

-ethylenedioxy-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol, D-t-4′

-hydroxy-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol and stereoisomers and pharmaceutically acceptable salts thereof, wherein the infection is characterized by binding of the microbe, the virus, or a toxin thereof to glycosphingolipids of the patient'"'"'s cells.

2. The method of claim 1, wherein the infection is due to E. Coli, influenza A, or a verotoxin-producing microorganism.

3. The method of claim 1, wherein compound is D-t-3′

, 4′

-ethylenedioxy-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol, or a pharmaceutically-acceptable salt thereof.

4. The method of claim 1, wherein the compound is D-t-4′

-hydroxy-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol, or a pharmaceutically-acceptable salt thereof.