Methods and compositions for treating amyloid-related diseases

• US 8,642,801 B2
• Filed: 11/05/2009
• Issued: 02/04/2014
• Est. Priority Date: 06/23/2003
• Status: Expired due to Fees

• Current Assignee: BHI Limited Partnership
• Original Assignee: BHI Limited Partnership
• Inventors: Kong, Xianqi, Migneault, David, Valade, Isabelle, Wu, Xinfu, Gervais, Francine
• Primary Examiner(s): HAVLIN, ROBERT H
• Application Number:
  US12/613,412
• Publication Number:
  US 20100113591A1
• Time in Patent Office: 1,552 Days
• Field of Search: 562/44, 514/576
• US Class Current: 562/44
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 2601/04 with a four-membered ring
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 2601/10 the ring being unsaturated
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2601/18 with a ring being at least seven-membered
• CPC Class Codes: C07C 2602/08 the other ring being five-membered, e.g. indane
• CPC Class Codes: C07C 2602/10 the other ring being six-membered, e.g. tetraline
• CPC Class Codes: C07C 2602/42 the bicyclo ring system containing seven carbon atoms
• CPC Class Codes: C07C 2603/74 Adamantanes
• CPC Class Codes: C07C 307/02 Monoamides of sulfuric acids or esters thereof, e.g. sulfamic acids
• CPC Class Codes: C07C 309/13 containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
• CPC Class Codes: C07C 309/14 containing amino groups bound to the carbon skeleton
• CPC Class Codes: C07C 309/15 the nitrogen atom of at least one of the amino groups being part of any of the groups , X being a hetero atom, Y being any atom
• CPC Class Codes: C07C 309/19 of a saturated carbon skeleton containing rings
• CPC Class Codes: C07C 309/23 of an unsaturated carbon skeleton containing rings other than six-membered aromatic rings
• CPC Class Codes: C07C 309/46 having the sulfo groups bound to carbon atoms of non-condensed six-membered aromatic rings
• CPC Class Codes: C07C 309/69 : of a carbon skeleton substituted by nitrogen atoms, not being part of nitro or nitroso groups
• CPC Class Codes: C07C 311/32 : of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 311/46 : Y being a hydrogen or a carbon atom
• CPC Class Codes: C07C 323/25 : the carbon skeleton being acyclic and saturated
• CPC Class Codes: C07C 323/58 : with amino groups bound to the carbon skeleton
• CPC Class Codes: C07C 335/12 : the carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 335/32 : having sulfur atoms of isothiourea groups bound to acyclic carbon atoms
• CPC Class Codes: C07C 381/02 : Thiosulfates
• CPC Class Codes: C07D 209/08 : with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 209/14 : Radicals substituted by nitrogen atoms, not forming part of a nitro radical
• CPC Class Codes: C07D 209/18 : Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 209/20 : substituted additionally by nitrogen atoms, e.g. tryptophane
• CPC Class Codes: C07D 209/44 : Iso-indoles; Hydrogenated iso-indoles
• CPC Class Codes: C07D 209/48 : with oxygen atoms in positions 1 and 3, e.g. phthalimide
• CPC Class Codes: C07D 211/46 : having a hydrogen atom as the second substituent in position 4
• CPC Class Codes: C07D 211/64 : having an aryl radical as the second substituent in position 4
• CPC Class Codes: C07D 211/70 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 217/04 : with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 217/10 : Quaternary compounds
• CPC Class Codes: C07D 235/28 : Sulfur atoms
• CPC Class Codes: C07D 257/04 : Five-membered rings
• CPC Class Codes: C07D 295/084 : with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/088 : to an acyclic saturated chain
• CPC Class Codes: C07D 317/50 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 453/02 : containing not further condensed quinuclidine ring systems
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07F 9/1651 : with hydroxyalkyl compounds with further substituents on alkyl
• CPC Class Codes: C07F 9/2458 : of aliphatic amines
• CPC Class Codes: C07K 5/0812 : and aromatic or cycloaliphatic

Abstract

Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.

Claims

1. A compound of Formula V:

2. The compound of claim 1, wherein n is 4.

3. The compound of claim 1, wherein n is 3.

4. The compound of claim 1, wherein m is 1 or 2.

5. The compound of claim 4, wherein m is 1.

6. The compound of claim 4, wherein m is 2.

7. The compound of claim 1, wherein A-R¹¹ is a residue of a natural amino acid, or a salt or ester thereof.

8. The compound of claim 7, wherein A-R¹¹ is a phenylalanine residue.

9. The compound of claim 1, wherein A is an oxygen and R¹¹ is a hydrogen or a salt-forming cation.

10. The compound of claim 1, wherein aa is a residue of a natural amino acid.

11. The compound of claim 1, wherein (aa)_m is a residue of phenylalanine or phe-phe.

12. The compound of claim 1, wherein aa is a residue of an unnatural amino acid.

13. The compound of claim 1, wherein R¹⁵ is hydrogen or substituted alkyl.

14. The compound of claim 13, wherein R¹⁵ is arylalkyl.

15. The compound of claim 13, wherein R¹⁵ is hydrogen.

16. The compound of claim 1, wherein R¹⁴ and R¹⁵ are both hydrogen.

17. The compound of claim 1, wherein said compound is selected from the group consisting of: