Inhibitors of the enzyme UDP-glucose: N-acyl-sphingosine glucosyltransferase

• US 9,783,528 B2
• Filed: 09/14/2015
• Issued: 10/10/2017
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Sun Pharmaceutical Industries, Inc. (Sun Pharmaceutical Industries Limited)
• Original Assignee: Concert Pharmaceuticals Inc. (Sun Pharmaceutical Industries Limited)
• Inventors: Harbeson, Scott L.
• Primary Examiner(s): Bakshi, Pancham
• Application Number:
  US14/853,900
• Publication Number:
  US 20160068519A1
• Time in Patent Office: 757 Days
• Field of Search: 514422, 5142288, 514359, 514408
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07B 59/002 Heterocyclic compounds
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/10 linked by a carbon chain containing aromatic rings

Abstract

This invention relates to novel inhibitors of UDP-glucose: N-acyl-sphingosine glucosyltransferase and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering inhibitors of UDP-glucose: N-acyl-sphingosine glucosyltransferase.

Claims

1. A compound of Formula I:

2. The compound of claim 1, wherein each Y¹ is hydrogen.

3. The compound of claim 1, wherein each Y¹ is deuteriutn.

4. The compound of claim 1, 2 or 3, wherein each Y² is hydrogen.

5. The compound of claim 1, 2 or 3, wherein each Y² is deuterium.

6. The compound of claim 1, wherein Y³ is hydrogen.

7. The compound of claim 1, wherein Y³ is deuterium.

8. The compound of claim 6 or 7, wherein Y⁴ is hydrogen.

9. The compound of claim 6 or 7, wherein Y⁴ is deuterium.

10. The compound of claim 1, wherein each Y⁷ is hydrogen.

11. The compound of claim 1, wherein each Y⁷ is deuterium.

12. The compound of claim 1, wherein each Y⁵ is the same as each Y⁶.

13. The compound of claim 1, wherein the compound is selected from any one of the compounds in the table below:

14. The compound of claim 1, wherein any atom not designated as deuterium is present at its natural isotopic abundance.

15. A pharmaceutical composition comprising an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt of said compound;

and a pharmaceutically acceptable carrier.

16. A compound of claim 1, wherein the compound is selected from any one of the compounds in the table below:

17. A compound of claim 1, wherein each Y⁵ is deuterium;

each Y⁶ is hydrogen; and

the compound is selected from any one of the compounds in the table below;

18. The compound of claim 1, wherein the deuterium incorporation at each designated deuterium atom is at least 90%.

19. The compound of claim 18, wherein the deuterium incorporation at each designated deuterium atom is at least 95%.

20. The compound of claim 19, wherein the deuterium incorporation at each designated deuterium atom is at least 97%.