C-terminal HSP90 inhibitors

1. A method for treating or preventing a neurodegenerative disorder in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of the formula:

wherein

R 1 is hydrogen, halo, hydroxy, trifluoroalkyl, alkoxy, or sulfanyl;

R 2 is hydrogen, halo, hydroxy, trifluoroalkyl, alkoxy, sulfanyl, or alkyl;

R 3 is hydrogen, halo, hydroxy, trifluoroalkyl, alkoxy, sulfanyl, alkyl;

X is ═CR 21 —, or ═N—, wherein R 21 is hydrogen, halo, or trifluoromethyl; and

Y is ═CR 3 — or ═N—.

2. The method of claim 1 , wherein the neurodegenerative disorder is diabetic peripheral neuropathy.

3. The method of claim 1 , wherein R 2 is halo.

4. The method of claim 3 , wherein R 2 is fluoro.

5. The method of claim 1 , wherein R 1 is hydrogen.

6. The method of claim 1 , wherein R 3 is hydrogen.

7. The method of claim 1 , wherein X is ═CR 21 —, wherein R 21 is hydrogen.

8. The method of claim 1 , wherein Y is ═CR 3 —.

9. A compound of the formula:

wherein:

R 1 is hydrogen, hydroxy, halo, trifluoroalkyl, alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, aralkyl, carboxyl, amido, amino, alkoxy, sulfanyl, sulfenyl, sulfonyl, or ether;

R 2 is hydrogen, halo, hydroxy, trifluoromethyl, alkoxy, alkyl, alkenyl, alkynyl, carbocyclic, alkylcarbocyclic, alkylheterocyclic, heterocyclic, or

—R 9 —OR 10 , wherein:

R 9 is a covalent bond or alkylene, and

R 10 is hydrogen, alkyl, C-amido, or acyl; or

R 2 together with R 3 and the atoms to which they are attached form a carbocyclic ring with 5 to 7 ring members or a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen;

R 3 is hydrogen, hydroxy, halo, trifluoroalkyl, alkyl, alkoxy, sulfanyl, or

R 11 —O—R 12 , wherein:

R 11 is a covalent bond or alkylene, and

R 12 is alkyl, C-amido, or acyl; or

R 3 together with R 2 and the atoms to which they are attached form a carbocyclic ring with 5 to 7 ring members or a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen; or

R 3 is absent when Y is ═N—;

R′ is H or alkyl;

R″ is alkyl, alkoxy, haloalkyl, alkylcycloalkyl, or alkylamidoalkyl;

X is ═CR 21 — or ═N—, wherein:

R 21 is hydrogen, halo, trifluoromethyl, alkyl, alkenyl, alkynyl, alkoxy, or hydroxy; and

Y is ═CR 3 — or ═N—;

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 9 further defined as:

wherein:

R 1 is hydrogen, halo, hydroxy, trifluoroalkyl, alkoxy, or sulfanyl;

R 2 is hydrogen, halo, hydroxy, trifluoromethyl, alkoxy, or alkyl, or R 2 together with R 3 and the atoms to which they are attached form a carbocyclic ring with 5 to 7 ring members or a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen;

R 3 is hydrogen, halo, hydroxy, trifluoroalkyl, alkoxy, sulfanyl, alkyl; or R 3 together with R 2 and the atoms to which they are attached form a carbocyclic ring with 5 to 7 ring members or a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen, or R 3 is absent when Y is ═N—;

X is ═CR 21 — or ═N—, wherein R 21 is hydrogen, halo, or trifluoromethyl; and

Y is ═CR 3 — or ═N—;

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 9 , wherein R 2 is halo.

12. The compound of claim 11 , wherein R 2 is fluoro.

13. The compound of claim 9 , wherein R 1 is hydrogen.

14. The compound of claim 9 , wherein R 3 is hydrogen.

15. The compound of claim 9 , wherein X is ═CR 21 —, wherein R 21 is hydrogen.

16. The compound of claim 9 , wherein Y is ═CR 3 —.

17. The compound of claim 9 , wherein R′ is hydrogen.

18. The compound of claim 9 , wherein R″ is alkyl.

19. The compound of claim 9 further defined as:

N-(2-(5-hydroxy-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9a)

N-(2-(3′-fluoro-5-hydroxy-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9b)

N-(2-(4′-fluoro-5-hydroxy-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9c)

N-(2-(2′-chloro-5-hydroxy-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9d)

N-(2-(3′-chloro-5-hydroxy-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9e)

N-(2-(5-hydroxy-3′-(trifluoromethyl)-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9f)

N-(2-(5-hydroxy-4′-(trifluoromethyl)-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9g)

N-(2-(5-hydroxy-2′-(methylthio)-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9h)

N-(2-(5-hydroxy-2′-methoxy-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9i)

N-(2-(5-hydroxy-3′-methoxy-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9j)

N-(2-(5-hydroxy-3′-methyl-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9k)

N-(2-(5-hydroxy-3′-(morpholinomethyl)-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9l)

N-(2-(4′-((tert-butyldimethylsilyl)oxy)-5-hydroxy-[1,1′-biphenyl]-2-yl)ethyl)acetamide (9m)

N-(2-(benzo[d][1,3]dioxol-5-yl)-4-hydroxyphenethyl)acetamide (9n)

N-(4-hydroxy-2-(pyridin-3-yl)phenethyl)acetamide (9o)

N-(4-hydroxy-2-(pyridin-4-yl)phenethyl)acetamide (9p),

or a pharmaceutically acceptable salt thereof.

20. The compound of claim 9 further defined as:

or a pharmaceutically acceptable salt thereof.