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|Title:||Amino ceramide-like compounds and therapeutic methods of use|
|Abstract:||Novel amino ceramide-like compounds 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.|
|Inventor(s):||Shayman; James A. (Ann Arbor, MI), Radin; Norman S. (Ann Arbor, MI)|
|Assignee:||The Regents of the University of Michigan (Ann Arbor, MI)|
|Filing Date:||Jun 26, 1997|
|Claims:||1. A method for treating a patient having sphingolipidosis by reducing glycosphingolipid synthesis comprising the step of administering to the patient a therapeutically effective amount of a compound selected from the group consisting of compounds of the formula: ##STR5## where R.sub.1 is an aromatic structure, an alicyclic structure, a branched aliphatic structure or a linear aliphatic group having 5 to 15 carbons; |
R.sub.2 is an aliphatic chain having 9 to 18 carbons; and
R.sub.3 is pyrrolidino;
and functional homologues, isomers and pharmaceutically acceptable salts thereof.
2. The method of claim 1, where R.sub.1 is a phenyl group.
3. The method of claim 1, where R.sub.1 is p-methoxyphenyl.
4. The method of claim 1, where R.sub.2 is C.sub.15 H.sub.31.
5. The method of claim 1, where the compound is 1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol and pharmaceutically acceptable salts thereof.
6. The method of claim 1, where the patient is diagnosed as having Gaucher disease.
7. The method of claim 1, where the patient is diagnosed as having Tay-Sachs disease.
8. The method of claim 1, where the patient is diagnosed as having Fabry's disease.