Stilbene derivatives and their use for binding and imaging amyloid plaques

• US 7,297,820 B2
• Filed: 09/06/2005
• Issued: 11/20/2007
• Est. Priority Date: 08/27/2001
• Status: Expired due to Fees

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Kung, Mei-Ping, Kung, Hank F., Zhuang, Zhi-Ping
• Primary Examiner(s): Kumar; Shailendra
• Application Number:
  US11/218,587
• Publication Number:
  US 20060002853A1
• Time in Patent Office: 805 Days
• Field of Search: 564/336, 564/340, 564/440, 514/646, 514/649
• US Class Current: 564/336
• CPC Class Codes: A61K 51/0478 complexes from non-cyclic ligands, e.g. EDTA, MAG3
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07C 211/52 the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
• CPC Class Codes: C07C 323/25 the carbon skeleton being acyclic and saturated
• CPC Class Codes: C07C 323/34 the thio group being a mercapto group
• CPC Class Codes: C07C 323/60 with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
• CPC Class Codes: C07D 213/38 having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
• CPC Class Codes: C07D 307/56 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 307/66 Nitrogen atoms
• CPC Class Codes: C07D 311/16 substituted in position 7
• CPC Class Codes: C07D 333/28 Halogen atoms

Abstract

This invention relates to a method of imaging amyloid deposits and to labeled compounds, and methods of making labeled compounds useful in imaging amyloid deposits. This invention also relates to compounds, and methods of making compounds for inhibiting the aggregation of amyloid proteins to form amyloid deposits, and a method of delivering a therapeutic agent to amyloid deposits.

Claims

1. A compound of general Formula III:

2. A compound of claim 1, wherein

R¹⁷ is NR²⁶R²⁷ wherein

R²⁶ and R²⁷ are as described above, and

R¹⁵, R¹⁶, R¹⁸, R¹⁹, R²⁰, R²¹, R²², R²³, R²⁴, R²⁵ and R²⁸ are hydrogen.

3. A compound of claim 1, wherein n is equal to zero.

4. A compound of claim 1, wherein R²⁶ and R²⁷ are independently hydrogen or C_1-4 alkyl.

5. A compound of claim 4, wherein R²⁶ and R²⁷ are methyl.

8. A pharmaceutical composition comprising a compound of claim 1.

6. A compound of general Formula V:

7. A compound of claim 6, wherein said protecting group is selected from the group consisting of methoxymethyl, methoxyethoxymethyl, p-methoxybenzyl or benzyl.

9. A compound having the following structure:

10. The compound of claim 9, one or more of R¹⁵, R¹⁶, R¹⁸, R¹⁹, R²⁰, R²¹, and R¹⁷ is hydroxy or NR²⁶R²⁷, wherein R²⁶ and R²⁷ are hydrogen or C_1-4 alkyl.