Stilbene derivatives and their use for binding and imaging amyloid plaques

• US 7,250,525 B2
• Filed: 08/27/2002
• Issued: 07/31/2007
• 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:
  US10/228,275
• Publication Number:
  US 20030149250A1
• Time in Patent Office: 1,799 Days
• Field of Search: 556/81, 556/87, 558/303, 558/418, 560/21, 560/388, 564/305, 564/374, 564/441, 564/442, 564/443, 568/700, 568/705, 568/707, 568/745, 514/646, 514/739, 514/525, 424/1.11, 424/1.65, 424/1.81, 424/1.85, 424/1.89
• US Class Current: 556/81
• 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 I:

2. A compound of claim 1, wherein

R⁵ is hydrogen or methyl;

and

R³ is hydrogen.

3. A compound of claim 1, wherein

R¹ and R² are hydrogen or C_1-4 alkyl.

4. A compound of claim 3, wherein

R⁵ is hydrogen.

5. A compound of claim 4, wherein

R¹ is hydrogen, and

R⁴ is C_1-4 alkylthio, halo(C_1-4)alkoxy, hydroxy, C_1-4 alkoxy or

NR⁶R⁷, wherein

R⁶ and R⁷ are hydrogen, fluoro(C_1-4)alkyl or C_1-4 alkyl.

6. A compound of claim 5, wherein

R² is hydrogen.

7. A compound of claim 1, wherein

R⁴ is methylthio, hydroxy, methoxy or NR⁶R⁷,

wherein R⁶ and R⁷ are hydrogen, fluoro(C_1-4)alkyl or methyl.

8. A compound of claim 1, wherein

X′

is ¹²³I. the other of R²⁹ and R³² represents an unsubstituted postion.

9. A compound of claim 8, wherein X′

is ¹⁸Fluoromethyl, ¹⁸Fluoroethyl or ¹⁸Fluoropropyl.

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

11. A diagnostic composition for imaging amyloid deposits, comprising a radiolabeled compound of claim 1;

and

a pharmaceutically acceptable excipient or diluent.

12. A method of imaging amyloid deposits, comprising:

a. introducing into a mammal a detectable quantity of a diagnostic composition of claim 11; and

b. allowing sufficient time for the labeled compound to be associated with amyloid deposits; and

c. detecting the labeled compound associated with one or more amyloid deposits.

13. A method of inhibiting amyloid plaque aggregation in a mammal, comprising administering a composition of claim 10 in an amount effective to inhibit amyloid plaque aggregation.