Methods and compositions for treating amyloid-related diseases

• US 7,598,269 B2
• Filed: 05/30/2007
• Issued: 10/06/2009
• Est. Priority Date: 06/23/2003
• Status: Expired due to Fees

• Current Assignee: Bellus Health (Interational) Limited (GSK plc)
• Original Assignee: Bellus Health (Interational) Limited (GSK plc)
• Inventors: Kong, Xianqi, Szarek, Walter A., Gervais, Francine
• Primary Examiner(s): Shameem; Golam M. M.
• Assistant Examiner(s): CHUNG, SUSANNAH LEE
• Application Number:
  US11/807,759
• Publication Number:
  US 20080015180A1
• Time in Patent Office: 860 Days
• Field of Search: 514/315, 546/184
• US Class Current: 514/315
• 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 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 2601/14 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 309/46 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 335/32 : having sulfur atoms of isothiourea groups bound to acyclic carbon atoms
• CPC Class Codes: C07C 381/02 : Thiosulfates
• 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: C07F 9/1651 : with hydroxyalkyl compounds with further substituents on alkyl
• CPC Class Codes: C07F 9/2458 : of aliphatic amines

Abstract

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

Claims

1. A compound of Formula III:

8. The compound of claim 1, wherein said compound is:

9. The compound of claim 1, wherein A is oxygen.

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

11. The compound of claim 1, wherein m is 0.

12. The compound of claim 1, wherein R^A, R^B, R^C, R^D and R^E are each hydrogen.

13. The compound of claim 1, wherein R³ and R⁴ are taken together with the carbon atoms to which they are attached to form a double bond.

14. The compound of claim 1, wherein R³, R^3a, R⁵, R^5a, R⁶, R^6a, R⁷ and R^7a are each hydrogen.

2. The compound selected from the group consisting of:

3. A pharmaceutical composition comprising a pharmaceutically acceptable vehicle and an effective amount of a compound of Formula III:

4. The pharmaceutical composition of claim 3, wherein said pharmaceutical composition further comprises a pharmaceutically acceptable acid, base, buffering agent, inorganic salt, solvent.

5. The pharmaceutical composition of claim 3, wherein said compound is dissolved in a liquid pharmaceutically acceptable vehicle.

6. The pharmaceutical composition of claim 3, wherein said compound is present as a homogenous mixture in a capsule or pill.

7. The pharmaceutical composition of claim 3, wherein said compound is: