Method of lowering blood glucose

Patent metadata

Field	Value
Publication number	US-9532976-B2
Application number	US-201414464432-A
Country	US
Kind code	B2
Filing date	Aug 20, 2014
Priority date	Nov 10, 2004
Publication date	Jan 3, 2017
Grant date	Jan 3, 2017

Abstract

The invention provides methods of treating a diabetic subject comprising administering a glucosylceramide synthase inhibitor to the subject.

First claim

The invention claimed is:

1. A method of lowering blood glucose in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising a compound of Formula Ib, or a pharmaceutically acceptable salt thereof,

where R 1 is an optionally substituted aromatic ring or an optionally substituted heterocycle; R 2 is an optionally substituted alkyl group; and R 3 is an optionally substituted tertiary cyclic amine,
with the proviso that R 3 is not morpholine.

2. The method of claim 1 , wherein R 1 is an optionally substituted aromatic ring.

3. The method of claim 2 , wherein R 1 is an optionally substituted phenyl group.

4. The method of claim 3 , wherein R 1 is a phenyl group; R 2 is an alkyl group; and R 3 is a tertiary cyclic amine.

5. The method of claim 3 , wherein R 1 is a substituted phenyl group.

6. The method of claim 5 , wherein R 1 is (3′,4′-ethylenedioxy)phenyl.

7. The method of claim 1 , wherein R 3 is pyrrolidine.

8. The method of claim 1 , wherein R 2 comprises at least 7 carbon atoms.

9. The method of claim 8 , wherein R 2 is an optionally substituted C 7 -C 18 alkyl group.

10. The method of claim 9 , wherein R 2 is an optionally substituted C 7 alkyl group.

11. The method of claim 10 , wherein R 2 is chosen from 1-(1-hydroxyheptyl) and 1-(6-hydroxyheptyl).

12. The method of claim 9 , wherein R 2 is an optionally substituted C 8 alkyl group.

13. The method of claim 12 , wherein R 2 is chosen from 1-(1-hydroxyoctyl) and 1-(7-hydroxyoctyl).

14. The method of claim 1 , wherein the compound of Formula Ib is in the form of a free base.

15. The method of claim 1 , wherein the compound of Formula Ib is in the form of a pharmaceutically acceptable salt.

16. The method of claim 15 , wherein the pharmaceutically acceptable salt is chosen from citrate, tartrate, hydrochloride, hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, dihydrogenphosphate, acetate, succinate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate).

17. The method of claim 1 , wherein the compound of Formula Ib is a D-threo isomer or L-threo isomer.

18. The method of claim 1 , wherein the compound of Formula Ib is an L-erythro isomer or D-erythro isomer.

19. The method of claim 1 , wherein the compound of Formula Ib is a tartrate salt, and wherein R 1 is D-threo-(3′,4′-ethylenedioxy)phenyl, R 3 is pyrrolidine, and R 2 is a C 7 alkyl group.

20. The method of claim 1 , wherein the compound of Formula Ib is a tartrate salt, and wherein R 1 is D-threo-(3′,4′-ethylenedioxy)phenyl, R 3 is pyrrolidine, and R 2 is a C 8 alkyl group.

21. The method of claim 1 , wherein the compound of Formula Ib is 1-(3′,4′-ethylenedioxy)phenyl-2-nonanoylamino-3-pyrrolidino-1-propanol.

22. The method of claim 1 , wherein the compound of Formula Ib is 1-(3′,4′-ethylenedioxy)phenyl-2-octanoylamino-3-pyrrolidino-1-propanol.

23. The method of claim 4 , wherein R 1 is a substituted phenyl group.

24. The method of claim 23 , wherein the substituted phenyl group is (3′,4′-ethylenedioxy)phenyl.

25. The method of claim 4 , wherein R 3 is pyrrolidine.

26. The method of claim 4 , wherein R 2 comprises at least 7 carbon atoms.

27. The method of claim 26 , wherein R 2 is a C 7 -C 18 alkyl group.

28. The method of claim 27 , wherein the alkyl group is a C 7 alkyl group.

29. The method of claim 26 , wherein R 2 is a C 8 alkyl group.

30. The method of claim 4 , wherein the compound is a D-threo isomer or L-threo isomer.

31. The method of claim 4 , wherein the compound is a L-erythro isomer or D-erythro isomer.

32. The method of claim 4 , wherein the compound is a tartrate salt and wherein R 1 is D-threo-(3′,4′-ethylenedioxy)phenyl, R 3 is pyrrolidine, and is a C 7 alkyl group.

33. The method of claim 4 , wherein the compound is a tartrate salt, and wherein the R 1 is D-threo-(3′,4′-ethylenedioxy)phenyl, R 3 is pyrrolidine, and R 2 is a C 8 alkyl group.

Assignees

• Genzyme Corp

Inventors

• Cheng Seng H
• Yew Nelson S
• Scheule Ronald K
• Zhao Hongmei

Classifications

• A61P3/08

  for glucose homeostasis (pancreatic hormones A61P5/48) · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title