Amino ceramide-like compounds and therapeutic methods of use

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.

1 . A compound represented by the following structural formula: 
     
       
         
         
             
             
         
       
     
     wherein
 R 1  is a phenyl group substituted with p-methoxy, hydroxy, methylenedioxy, ethylenedioxy or trimethylenedioxy; 
 R 2  is an alkyl group 6, 7 or 8 carbons long; and 
 R 3  is a pyrrolidine, or 
 a pharmaceutically acceptable salt thereof. 
 
   
   
       2 . The compound of  claim 1 , wherein R 2  is an alkyl group 7 carbons long. 
   
   
       3 . A pharmaceutical composition comprising a compound of  claim 1  and a pharmaceutically acceptable carrier or an excipient. 
   
   
       4 . A pharmaceutical composition comprising a compound of  claim 2  and a pharmaceutically acceptable carrier or an excipient. 
   
   
       5 . A method of treating a patient having Gaucher disease, comprising the step of administering to the patient a therapeutically effective amount of a composition comprising the compound of  claim 1 . 
   
   
       6 . A method of treating a patient having Gaucher disease, comprising the step of administering to the patient a therapeutically effective amount of a composition comprising the compound of  claim 2 .