Details for Patent: 5,916,911

Title:	Amino ceramide--like compounds and therapeutic methods of use
Abstract:	Novel amino 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:	Sep 05, 1996
Application Number:	08/708,574
Claims:	1. A method for inhibiting the growth of cancer cells in a mammal, wherein said cancer cells are sensitive to the compounds below, comprising the step of administering to the mammal 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.sup.2 is an aliphatic chain having 10 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 the growth of the cancer cells is inhibited by increasing ceramide levels in the cancer cells to a toxic level. 3. The method of claim 1, where R.sub.1 is a phenyl group. 4. The method of claim 1, where R.sub.1 is p-methoxyphenyl. 5. The method of claim 1, where R.sub.2 is C.sub.15 H.sub.31. 6. The method of claim 1, where the compound is 1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol and pharmaceutically acceptable salts thereof. 7. A method for treating a patient having a drug resistant tumor sensitive to the compounds below, 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: ##STR6## 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. 8. The method of claim 7, where R.sub.1 is a phenyl group. 9. The method of claim 7, where R.sub.1 is p-methoxyphenyl. 10. The method of claim 7, where R.sub.2 is C.sub.15 H.sub.31. 11. The method of claim 7, where the compound is 1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol and pharmaceutically acceptable salts thereof. 12. A method for reducing tumor angiogenesis in a patient, wherein said angiogenesis is sensitive to the compounds below, 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: ##STR7## 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. 13. The method of claim 12, where R.sub.1 is a phenyl group. 14. The method of claim 12, where R.sub.1 is p-methoxyphenyl. 15. The method of claim 12, where R.sub.2 is C.sub.15 H.sub.31. 16. The method of claim 12, where the compound is 1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol and pharmaceutically acceptable salts thereof.