Sialic acid analogs

Patent metadata

Field	Value
Publication number	US-10457701-B2
Application number	US-201816050343-A
Country	US
Kind code	B2
Filing date	Jul 31, 2018
Priority date	Oct 24, 2011
Publication date	Oct 29, 2019
Grant date	Oct 29, 2019

Abstract

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

First claim

What is claimed is:

1. A compound having structural Formula (Ia):

or a pharmaceutically acceptable salt or solvate thereof;
wherein:
R 1 , R 2 , and R 4 are independently hydrogen or a moiety selected from structural formula (a), (b), (c), (f), and (g):

wherein R 3a is optionally substituted alkyl;
R 6 is structural formula (f), wherein R 3a is optionally substituted C 5 -C 20 alkyl;
X is oxygen or sulfur;
L 1 and L 2 are each independently a covalent bond, —O—, or —NR 10a —;
R 10a is hydrogen or optionally substituted alkyl;
R 1a and R 2a are each independently hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, —X a —C(O)—O—R 11a , or —X a —O—C(O)—O—R 11a ;
X a is optionally substituted alkylene;
each R 11a is independently hydrogen, optionally substituted alkyl, or optionally substituted heteroalkyl;
each R 8a and R 9a is independently hydrogen or optionally substituted alkyl;
m is 1 or 2; and
Z is hydrogen, lower alkyl, an amide group, a lactam group, an ester group, a lactone group, an urea group, a cyclic urea group, a carbonate group, a cyclic carbonate group, a carbamate group, a cyclic carbamate group, or a moiety selected from (a), (b), (c), and (f).

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 R 6 is C 8 alkyl.

4. The compound of claim 1 , wherein R 3a in formula (f) of R 6 is C 11 alkyl.

5. The compound of claim 1 , wherein R 3a in formula (f) of R 6 is C 15 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).

Assignees

• Ultragenyx Pharmaceutical Inc

Inventors

• Kakkis Emil
• Jungles Steven
• Zhao He

Classifications

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• C07H7/027

  Keto-aldonic acids · CPC title

• C07H13/04

  having the esterifying carboxyl radicals attached to acyclic carbon atoms · CPC title

• C07H7/02 Primary

  Acyclic radicals · CPC title

• C07H13/10

  having the esterifying carboxyl radicals directly attached to heterocyclic rings · CPC title