Method for treating amyloidosis

• US 5,972,328 A
• Filed: 06/05/1995
• Issued: 10/26/1999
• Est. Priority Date: 03/29/1993
• Status: Expired due to Term

• Current Assignee: BHI Limited Partnership
• Original Assignee: Queen's University At Kingston
• Inventors: Szarek, Walter, Kisilevsky, Robert, Weaver, Donald
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US08/463,548
• Time in Patent Office: 1,604 Days
• Field of Search: 424/450, 424/78.31, 424/78.35, 424/423, 424/427, 424/430, 424/434, 424/436, 424/441, 514/772.4, 526/286, 526/281
• US Class Current: 424/78.31
• CPC Class Codes: A61K 31/185 Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids hydroxamic acids A61K31/16; peroxy acids A61K31/327
• CPC Class Codes: A61K 31/255 of sulfoxy acids or sulfur analogues thereof
• CPC Class Codes: A61K 31/41 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/737 Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate A61K31/727 takes precedence
• CPC Class Codes: A61K 31/795 Polymers containing sulfur
• CPC Class Codes: A61K 47/51 the non-active ingredient being a modifying agent
• CPC Class Codes: A61K 47/54 the modifying agent being an organic compound
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: A61K 47/55 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• CPC Class Codes: A61K 47/555 pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61L 33/08 Polysaccharides
• CPC Class Codes: C07H 11/00 Compounds containing saccharide radicals esterified by inorganic acids; Metal salts thereof halo-sugars C07H5/02; thio-, seleno-, or telluro-sugars C07H5/08
• CPC Class Codes: C07H 15/04 attached to an oxygen atom of the saccharide radical

Abstract

Therapeutic compounds and methods for inhibiting amyloid deposition in a subject, whatever its clinical setting, are described. Amyloid deposition is inhibited by the administration to a subject of an effective amount of a therapeutic compound comprising an anionic group and a carrier molecule, or a pharmaceutically acceptable salt thereof, such that an interaction between an amyloidogenic protein and a basement membrane constituent is inhibited. Preferred anionic groups are sulfonates and sulfates. Preferred carrier molecules include carbohydrates, polymers, peptides, peptide derivatives, aliphatic groups, alicyclic groups, heterocyclic groups, aromatic groups and combinations thereof.

Claims

1. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of glycerol trisulfuric acid or a pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

56. The method of any one of claims 1-7 and 15-31, wherein the therapeutic compound is administered orally.

57. The method of any one of claims 1-14 and 15-48, wherein the therapeutic compound is delivered liposomally.

58. The method of an one of claims 1-14, further comprising administering the therapeutic compound in a pharmaceutically acceptable vehicle.

2. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2-amino-2-hydroxymethyl-1,3-propanediol trisulfuric acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

3. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 3-hydroxypropylsulfamic acid sulfuric acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

4. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of methyl 5-deoxy-2,3-O-isopropylidene-β

-D-ribofuranoside-5-sulfonic acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

5. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of tetrahydro-3,4-thiophenedisulfonic acid-1,1-dioxide, or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

6. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of 3-amino-1-propanesulfonic acid or a pharmaceutically acceptable salt thereof, such that said 3-amino-1-propanesulfonic acid or a pharmaceutically acceptable salt thereof inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

7. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 5-deoxy-1,2-O-isopropylidene-α

-D-xylofuranose-5-sulfonic acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

8. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of glycerol trisulfuric acid thereof.

9. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2-amino-2-hydroxymethyl-1,3-propanediol trisulfuric acid or pharmaceutically acceptable salt thereof.

10. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 3-hydroxypropylsulfamic acid sulfuric acid or pharmaceutically acceptable salt thereof.

11. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of methyl 5-deoxy-2,3-O-isopropylidene-β

-D-ribofuranoside-5-sulfonic acid or pharmaceutically acceptable salt thereof.

12. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of, tetrahydro-3,4-thiophenedisulfonic acid-1,1-dioxide, or pharmaceutically acceptable salt thereof.

13. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of 3-amino-1-propanesulfonic acid or a pharmaceutically acceptable salt thereof.

14. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 5-deoxy-1,2-O-isopropylidene-α

-D-xylofuranose-5-sulfonic acid or pharmaceutically acceptable salt thereof.

15. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2-hydroxymethyl-1,3-propanediol trisulfuric acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

16. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2-hydroxymethyl-2-methyl-1,3-propanediol trisulfuric acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

17. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2-hydroxyethylsulfamic acid sulfuric acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

18. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 3-amino-1-propanol sulfuric acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

19. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2-benzyloxy-1,3-propanediol disulfuric acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

20. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2,2'"'"'-iminodiethanol disulfuric acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

21. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of N,N-bis(2-hydroxyethyl)sulfamic acid disulfuric acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

22. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 3-hydroxypropanesulfonic acid sulfuric acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

23. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

24. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 4-morpholine-propanesulfonic acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

25. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of methyl 5-deoxy-α

-D-arabinofuranoside-5-sulfonic acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

26. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2,5-dihydroxy-1,4-benzenedisulfonic acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

27. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 4,5-dihydroxy-1,3-benzenedisulfonic acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

28. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of (±

)-10-camphorsulfonic acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

29. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 1,3-benzenedisulfonic acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

30. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2,3-dimethoxy-1,5-benzenedisulfonic acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

31. A method for inhibiting amyloid deposition in a subject comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2,5-dimethoxy-1,4-benzenedisulfonic acid or pharmaceutically acceptable salt thereof, such that the therapeutic compound inhibits an interaction between an amyloidogenic protein and a glycoprotein or proteoglycan constituent of a basement membrane to inhibit amyloid deposition.

32. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2-hydroxymethyl-1,3-propanediol trisulfuric acid or pharmaceutically acceptable salt thereof.

33. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2-hydroxymethyl-2-methyl-1,3-propanediol trisulfuric acid or pharmaceutically acceptable salt thereof.

34. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2-hydroxyethylsulfamic acid sulfuric acid or pharmaceutically acceptable salt thereof.

35. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 3-amino-1-propanol sulfuric acid or pharmaceutically acceptable salt thereof.

36. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2-benzyloxy-1,3-propanediol disulfuric acid or pharmaceutically acceptable salt thereof.

37. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2,2'"'"'-iminodiethanol disulfuric acid or pharmaceutically acceptable salt thereof.

38. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of N,N-bis(2-hydroxyethyl)sulfamic acid disulfuric acid or pharmaceutically acceptable salt thereof.

39. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 3-hydroxypropanesulfonic acid sulfuric acid or pharmaceutically acceptable salt thereof.

40. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid or pharmaceutically acceptable salt thereof.

41. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 4-morpholine-propanesulfonic acid or pharmaceutically acceptable salt thereof.

42. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of methyl 5-deoxy-α

-D-arabinofuranoside-5-sulfonic acid or pharmaceutically acceptable salt thereof.

43. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2,5-dihydroxy-1,4-benzenedisulfonic acid or pharmaceutically acceptable salt thereof.

44. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 4,5-dihydroxy-1,3-benzenedisulfonic acid or pharmaceutically acceptable salt thereof.

45. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of (±

)-10-camphorsulfonic acid or pharmaceutically acceptable salt thereof.

46. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 1,3-benzenedisulfonic acid or pharmaceutically acceptable salt thereof.

47. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2,3-dimethoxy-1,5-benzenedisulfonic acid or pharmaceutically acceptable salt thereof.

48. A method for inhibiting amyloid deposition in a subject comprising orally administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2,5-dimethoxy-1,4-benzenedisulfonic acid or pharmaceutically acceptable salt thereof.

49. A method for reducing amyloid deposits in a subject having amyloid deposits, the method comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of glycerol trisulfuric acid, 2-hydroxymethyl-1,3-propanediol trisulfuric acid, or 2-hydroxymethyl-2-methyl-1,3-propanediol trisulfuric acid;

or a pharmaceutically acceptable salt thereof.

50. A method for reducing amyloid deposits in a subject having amyloid deposits, the method comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 2-amino-2-hydroxymethyl-1,3-propanediol trisulfuric acid, 2-hydroxyethylsulfamic acid sulfuric acid, 3-amino-1-propanol sulfuric acid, or 2-benzyloxy-1,3-propanediol disulfuric acid;

or a pharmaceutically acceptable salt thereof.

51. A method for reducing amyloid deposits in a subject having amyloid deposits, the method comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 3-hydroxypropylsulfamic acid sulfuric acid, 2,2'"'"'-iminodiethanol disulfuric acid, N,N-bis(2-hydroxyethyl)sulfamic acid disulfuric acid, or 3-hydroxypropanesulfonic acid sulfuric acid;

or a pharmaceutically acceptable salt thereof.

52. A method for reducing amyloid deposits in a subject having amyloid deposits, the method comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of methyl 5-deoxy-2,3-O-isopropylidene-β

-D-ribofuranoside-5-sulfonic acid, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, or 4-morpholine-propanesulfonic acid;

or a pharmaceutically acceptable salt thereof.

53. A method for reducing amyloid deposits in a subject having amyloid deposits, the method comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of tetrahydro-3,4-thiophenedisulfonic acid-1,1-dioxide, 2,5-dihydroxy-1,4-benzenedisulfonic acid, 4,5-dihydroxy-1,3-benzenedisulfonic acid, or (±

)-10-camphorsulfonic acid;

or a pharmaceutically acceptable salt thereof.

54. A method for reducing amyloid deposits in a subject having amyloid deposits, the method comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of 3-amino-1-propanesulfonic acid or a pharmaceutically acceptable salt thereof.

55. A method for reducing amyloid deposits in a subject having amyloid deposits, the method comprising administering to the subject an effective amount of a therapeutic compound selected from the group consisting of methyl 5-deoxy-α

-D-arabinofuranoside-5-sulfonic acid, 5-deoxy-1,2-O-isopropylidene-α

-D-xylofuranose-5-sulfonic acid, 1,3-benzenedisulfonic acid, 2,3-dimethoxy-1,5-benzenedisulfonic acid, or 2,5-dimethoxy-1,4-benzenedisulfonic acid;

or a pharmaceutically acceptable salt thereof.