INHIBITORS OF THE ENZYME UDP-GLUCOSE: N-ACYL-SPHINGOSINE GLUCOSYLTRANSFERASE

• US 20160068519A1
• Filed: 09/14/2015
• Published: 03/10/2016
• 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.
• Granted Patent: US 9,783,528 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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. A compound of claim 1, wherein each Y¹ is hydrogen.

3. A compound of claim 1, wherein each Y¹ is deuterium.

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

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

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

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

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

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

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

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

12. A compound of claim 1, wherein R¹ is selected from —

(CH₂)₆—

CH₃, —

(CH₂)₆—

CD₃, —

(CH₂)₅—

CD₂-CD₃, —

(CH₂)₄—

(CD₂)₂-CD₃, —

(CH₂)₃—

(CD₂)₃-CD₃, —

(CH₂)₂—

(CD₂)₄-CD₃, —

CH₂—

(CD₂)₅-CD₃, and —

(CD₂)₆-CD₃.

13. A compound of claim 1, wherein R¹ is selected from —

(CH₂)₆—

CH₃, —

CH₂—

(CD₂)₅-CD₃ and —

(CD₂)₆-CD₃.

14. A compound of claim 1, wherein each Y⁵ is the same as each Y⁶.

15. A compound of claim 1, wherein the compound is any one of the compounds in Table 1:

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

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

and a pharmaceutically acceptable carrier.

18. A method of inhibiting UDP-glucose:

N-acyl-sphingosine glucosyltransferase in a cell, comprising contacting a cell with a compound of claim 1.

19. A method of treating a condition selected from Tay-Sach'"'"'s disease, Gaucher'"'"'s disease, and Fabry'"'"'s disease in a subject in need of such treatment, the method comprising the step of administering to the subject a composition of claim 17.