Amyloid binding agents

1. A method of detecting an amyloid peptide, the method comprising:

(i) contacting an amyloid peptide with a compound having the structure of formula (I), or a pharmaceutical acceptable salt thereof, thereby forming a detectable amyloid complex; and

(ii) detecting said detectable amyloid complex;

wherein formula (I) has the structure:

wherein

EDG is an electron donor group;

πCE is a pi-conjugation element; and

WSG is a water soluble group;

wherein

said EDG is R 1 -substituted or unsubstituted alkyl, R 1 -substituted or unsubstituted cycloalkyl, R 1 -substituted or unsubstituted heteroalkyl, R 1 -substituted or unsubstituted heterocycloalkyl, R 1 -substituted or unsubstituted aryl, R 1 -substituted or unsubstituted heteroaryl, —OR 2 NR 4 C(O)R 3 , —NR 4 R 5 , —SR 6 , or —PR 7 R 8 ,

wherein

R 1 is halogen, —OR 9 , —NR 10 R 11 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl;

R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are independently hydrogen, R 12 -substituted or unsubstituted alkyl, R 12 -substituted or unsubstituted heteroalkyl, R 12 -substituted or unsubstituted cycloalkyl, R 12 -substituted or unsubstituted heterocycloalkyl, R 12 -substituted or unsubstituted aryl or R 12 -substituted or unsubstituted heteroaryl, wherein R 4 and R 5 are optionally joined together to form an R 12 -substituted or unsubstituted heterocycloalkyl, or R 12 -substituted or unsubstituted heteroaryl;

R 9 , R 10 and are independently hydrogen, R 12 -substituted or unsubstituted alkyl, R 12 -substituted or unsubstituted heteroalkyl, R 12 -substituted or unsubstituted cycloalkyl, R 12 -substituted or unsubstituted heterocycloalkyl, R 12 -substituted or unsubstituted aryl, or R 12 -substituted or unsubstituted heteroaryl, wherein R 10 and are optionally joined together to form an R 12 -substituted or unsubstituted heterocycloalkyl, or R 12 -substituted or unsubstituted heteroaryl;

R 12 is halogen, —OR 13 , —NR 14 R 15 , R 16 -substituted or unsubstituted alkyl, R 16 -substituted or unsubstituted heteroalkyl, R 16 -substituted or unsubstituted cycloalkyl, R 16 -substituted or unsubstituted heterocycloalkyl, R 16 -substituted or unsubstituted aryl, or R 16 -substituted or unsubstituted heteroaryl;

R 13 , R 14 and R 15 are independently hydrogen or unsubstituted alkyl; and

R 16 is unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl;

wherein

said pi-conjugation element has the formula:

-L 1 -(A 1 ) q -L 2 -(A 2 ) r -L 3 - or -L 1 -(A 1 ) q -L 4 -A 3 -L 2 -(A 2 ) r -L 3 -,

wherein

q and r are independently 0 or 1, wherein at least one of q or r is 1;

A 1 , A 2 and A 3 are independently R 17 -substituted or unsubstituted arylene or R 17 -substituted or unsubstituted heteroarylene;

L 1 , L 2 , L 3 and L 4 are independently a bond or a linking group having the formula:

wherein x is an integer from 1 to 50;

R 17 is halogen, —OR 18 —NR 19 R 20 , R 21 -substituted or unsubstituted alkyl, R 21 -substituted or unsubstituted heteroalkyl, R 21 -substituted or unsubstituted cycloalkyl, R 21 -substituted or unsubstituted heterocycloalkyl, R 21 -substituted or unsubstituted aryl, or R 21 -substituted or unsubstituted heteroaryl;

R 18 , R 19 and R 20 are independently hydrogen, R 21 -substituted or unsubstituted alkyl, R 21 -substituted or unsubstituted heteroalkyl, R 21 -substituted or unsubstituted cycloalkyl, R 21 -substituted or unsubstituted heterocycloalkyl, R 21 -substituted or unsubstituted aryl, or R 21 -substituted or unsubstituted heteroaryl;

R 21 is halogen, —OR 22 , —NR 23 R 24 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl;

R 22 , R 23 and R 24 are independently hydrogen or unsubstituted alkyl; and

wherein

said water soluble group is R 25 -substituted or unsubstituted alkyl, R 25 -substituted or unsubstituted heteroalkyl, R 25 -substituted or unsubstituted cycloalkyl, R 25 -substituted or unsubstituted heterocycloalkyl, R 25 -substituted or unsubstituted aryl, R 25 -substituted or unsubstituted heteroaryl;

wherein

R 25 is halogen, —OR 26 , —NR 27 R 28 , R 29 -substituted or unsubstituted alkyl, R 29 -substituted or unsubstituted heteroalkyl, R 29 -substituted or unsubstituted cycloalkyl, R 29 -substituted or unsubstituted heterocycloalkyl, R 29 -substituted or unsubstituted aryl, or R 29 -substituted or unsubstituted heteroaryl;

R 26 , R 27 and R 28 are independently hydrogen, R 29 -substituted or unsubstituted alkyl, R 29 -substituted or unsubstituted heteroalkyl, R 29 -substituted or unsubstituted cycloalkyl, R 29 -substituted or unsubstituted heterocycloalkyl, R 29 -substituted or unsubstituted aryl, or R 29 -substituted or unsubstituted heteroaryl, wherein R 27 and R 28 are optionally joined together to form an R 29 -substituted or unsubstituted heterocycloalkyl, or R 29 -substituted or unsubstituted heteroaryl;

R 29 is halogen, —OR 30 , —NR 31 R 32 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl; and

R 30 , R 31 and R 32 are independently hydrogen or unsubstituted alkyl.

2. The method of claim 1 , wherein at least one of A 1 or A 2 is R 17 -substituted or unsubstituted

3. The method of claim 1 , wherein x is an integer from 1 to 10.

4. The method of claim 1 , wherein said water soluble group is an ethylene glycol moiety having the formula:

wherein y is an integer from 1 to 50.

5. The method of claim 4 , wherein R 29 is unsubstituted alkyl.

6. The method of claim 1 , wherein said compound has the structure:

7. A method of detecting an amyloid peptide, the method comprising:

(i) contacting an amyloid peptide with a compound having the structure of formula (IVa) or formula (IVb), or a pharmaceutical acceptable salt thereof, thereby forming a detectable amyloid complex; and

(ii) detecting said detectable amyloid complex;

wherein formula (IVa) has the structure:

and

formula (IVb) has the structure:

wherein R 4 and R 5 are independently hydrogen, R 12 -substituted or unsubstituted alkyl, R 12 -substituted or unsubstituted heteroalkyl, R 12 -substituted or unsubstituted cycloalkyl, R 12 -substituted or unsubstituted heterocycloalkyl, R 12 -substituted or unsubstituted aryl or R 12 -substituted or unsubstituted heteroaryl, wherein R 4 and R 5 are optionally joined together to form an R 12 -substituted or unsubstituted heterocycloalkyl, or R 12 -substituted or unsubstituted heteroaryl;

R 12 is halogen, —OR 13 , —NR 14 R 15 , R 16 -substituted or unsubstituted alkyl, R 16 -substituted or unsubstituted heteroalkyl, R 16 -substituted or unsubstituted cycloalkyl, R 16 -substituted or unsubstituted heterocycloalkyl, R 16 -substituted or unsubstituted aryl, or R 16 -substituted or unsubstituted heteroaryl;

R 13 , R 14 and R 15 are independently hydrogen or unsubstituted alkyl;

R 16 is unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl;

R 17 is halogen, —OR 18 , —NR 19 R 20 , R 21 -substituted or unsubstituted alkyl, R 21 -substituted or unsubstituted heteroalkyl, R 21 -substituted or unsubstituted cycloalkyl, R 21 -substituted or unsubstituted heterocycloalkyl, R 21 -substituted or unsubstituted aryl, or R 21 -substituted or unsubstituted heteroaryl;

R 18 , R 19 and R 20 are independently hydrogen, R 21 -substituted or unsubstituted alkyl, R 21 -substituted or unsubstituted heteroalkyl, R 21 -substituted or unsubstituted cycloalkyl, R 21 -substituted or unsubstituted heterocycloalkyl, R 21 -substituted or unsubstituted aryl, or R 21 -substituted or unsubstituted heteroaryl;

R 21 is halogen, —OR 22 , —NR 23 R 24 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl;

R 22 , R 23 and R 24 are independently hydrogen or unsubstituted alkyl;

R 29 is halogen, —OR 30 , —NR 31 R 32 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl;

R 30 , R 31 and R 32 are independently hydrogen or unsubstituted alkyl;

y is an integer from 1 to 10; and

z is an integer from 0 to 4 when the amyloid peptide is contacted with a compound having the structure of formula IVa, and is an integer from 0 to 6 when the amyloid peptide is contacted with a compound having the structure of formula IVb.

8. The method of claim 7 , wherein said compound has the structure:

9. The method of claim 7 , wherein R 4 and R 5 are optionally joined together to form an R 12 -substituted or unsubstituted heterocycloalkyl.

10. The method of claim 7 , wherein said R 12 -substituted or unsubstituted heterocycloalkyl is a substituted or unsubstituted piperidinyl.

11. The method of claim 7 , wherein y is 2 and z is 0.

12. The method of claim 1 , wherein said amyloid peptide is Aβ peptide, prion, protein, α-synuclein, or superoxide dismutase.

13. The method of claim 12 , wherein said amyloid peptide forms part of an amyloid.

14. The method of claim 1 , wherein said compound has the structure:

15. The method of claim 7 , wherein said compound has the structure: