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

• US 10,385,042 B2
• Filed: 09/11/2017
• Issued: 08/20/2019
• 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:
  US15/700,444
• Publication Number:
  US 20180086743A1
• Time in Patent Office: 708 Days
• 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 method of treating a condition selected from Tay-Sach'"'"'s disease, Gaucher'"'"'s disease, Fabry'"'"'s disease, diabetes, fatty liver disease, polycystic kidney disease, and lupus in a subject in need of such treatment, the method comprising the step of administering to the subject a pharmaceutical composition comprising an effective amount of a compound of Formula I:

2. The method of claim 1, wherein for the compound of Formula I, each Y¹ is hydrogen.

3. The method of claim 1, wherein for the compound of Formula I, each Y¹ is deuterium.

4. The method of claim 1, wherein for the compound of Formula I, each Y² is hydrogen.

5. The method of claim 1, wherein for the compound of Formula I, each Y² is deuterium.

6. The method of claim 1, wherein for the compound of Formula I, each Y³ is hydrogen.

7. The method of claim 1, wherein for the compound of Formula I, each Y³ is deuterium.

8. The method of claim 1, wherein for the compound of Formula I, each Y⁴ is hydrogen.

9. The method of claim 1, wherein for the compound of Formula I, each Y⁴ is deuterium.

10. The method of claim 1, wherein for the compound of Formula I, each Y⁷ is hydrogen.

11. The method of claim 1, wherein for the compound of Formula I, each Y⁷ is deuterium.

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

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

14. The method of claim 1, wherein the compound of Formula I is selected from any one of the compounds in the table below:

15. The method of claim 1, wherein for the compound of Formula I, each Y⁵ is deuterium;

each Y⁶ is hydrogen; and

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

16. The method of claim 1, wherein for the compound of Formula I, the deuterium incorporation at each designated deuterium atom is at least 95%.

17. The method of claim 1, wherein for the compound of Formula I, the deuterium incorporation at each designated deuterium atom is at least 97%.