Sialic acid analogs

• US 10,457,701 B2
• Filed: 07/31/2018
• Issued: 10/29/2019
• Est. Priority Date: 10/24/2011
• Status: Active Grant

• Current Assignee: Ultragenyx Pharmaceutical Inc.
• Original Assignee: Ultragenyx Pharmaceutical Inc.
• Inventors: Kakkis, Emil, Jungles, Steven, Zhao, He
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Al-Awadi, Danah
• Application Number:
  US16/050,343
• Publication Number:
  US 20190127409A1
• Time in Patent Office: 455 Days
• Field of Search: None
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: C07D 493/08 Bridged systems
• CPC Class Codes: C07H 13/04 having the esterifying carboxyl radicals attached to acyclic carbon atoms
• CPC Class Codes: C07H 13/10 having the esterifying carboxyl radicals directly attached to heterocyclic rings
• CPC Class Codes: C07H 7/02 Acyclic radicals
• CPC Class Codes: C07H 7/027 Keto-aldonic acids

Abstract

The present invention provides sialic acid analogs and their compositions useful for the treatment of sialic acid deficiencies.

Claims

1. A compound having structural Formula (Ia):

2. The compound of claim 1, wherein the compounds of Formula (Ia) has the structure of Formula (IIa):

3. The compound of claim 1, wherein R^3a in formula (f) of R⁶ is C₈ alkyl.

4. The compound of claim 1, wherein R^3a in formula (f) of R⁶ is C₁₁ alkyl.

5. The compound of claim 1, wherein R^3a in formula (f) of R⁶ is C₁₅ alkyl.

6. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

7. A sustained release pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein the release of the compound is over a period of about four hours or more.

8. A sustained release pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof, wherein the pharmacological effect from the compound lasts about four hours or more upon administration of the composition.

9. A sustained release pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof;

wherein the composition, upon administration, provides a therapeutically effective amount of the compound for about 4 hours or more.

10. A method for treating a sialic acid deficiency in a patient in need thereof comprising administering an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof.

11. The method of claim 10, wherein the sialic acid deficiency is myopathy associated with sialic acid deficiency.

12. The method of claim 11, wherein the myopathy associated with sialic acid deficiency is Hereditary Inclusion Body Myopathy (HIBM), Nonaka myopathy, or Distal Myopathy with Rimmed Vacuoles (DMRV).

13. A method for treating a sialic acid deficiency in a patient in need thereof comprising administering a compound of claim 1, or a pharmaceutically acceptable salt or solvate thereof wherein upon administration, the compound, or a pharmaceutically acceptable salt or solvate thereof, continuously provides a therapeutically effective amount of sialic acid for about 4 hours to about 24 hours.

14. The method of claim 13, wherein the sialic acid deficiency is myopathy associated with sialic acid deficiency.

15. The method of claim 14, wherein the myopathy associated with sialic acid deficiency is Hereditary Inclusion Body Myopathy (HIBM), Nonaka myopathy, or Distal Myopathy with Rimmed Vacuoles (DMRV).