C-terminal Hsp90 inhibitors
Hsp90 C-terminal inhibitors and pharmaceutical compositions containing such compounds are provided. The compounds of the disclosure are useful for the treatment and/or prevention of neurodegenerative disorders such as diabetic peripheral neuropathy.
1. A method of 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:
2. The method of claim 1 , wherein the neurodegenerative disorder is sensory neuron glucotoxicity.
3. The method of claim 2 , wherein the sensory neuron glucotoxicity results from hyperglycemia.
4. The method of claim 3 , wherein the hyperglycemia is associated with a diabetic condition.
5. The method of claim 2 , wherein the sensory neuron glucotoxicity results in diabetic peripheral neuropathy.
6. The method of claim 5 , wherein the diabetic peripheral neuropathy is third nerve palsy.
7. The method of claim 5 , wherein the diabetic peripheral neuropathy is mononeuropathy.
8. The method of claim 5 , wherein the diabetic peripheral neuropathy is mononeuropathy multiplex.
9. The method of claim 5 , wherein the diabetic peripheral neuropathy is diabetic amyotrophy.
10. The method of claim 5 , wherein the diabetic peripheral neuropathy is autonomic neuropathy.
11. The method of claim 5 , wherein the diabetic peripheral neuropathy is thoracoabdominal neuropathy.
12. The method of claim 1 , wherein the method comprises treating the neurodegenerative disorder.
13. The method of claim 12 , wherein the method comprises delaying or slowing the progression of the neurodegenerative disorder.
14. The method of claim 12 , wherein the method ameliorates one or more symptoms of the neurodegenerative disorder.
15. The method of claim 1 , wherein the method comprises preventing the neurodegenerative disorder.
16. The method of claim 15 , wherein the method comprises preventing the neurodegenerative disorder in a patient who is at increased risk for the neurodegenerative disorder.
17. The method of claim 15 , wherein the method comprises delaying the onset of the neurodegenerative disorder.
18. The method of claim 15 , wherein the method comprises preventing the individual from developing the neurodegenerative disorder.
19. The method of claim 1 , wherein the therapeutically effective amount is an amount sufficient to inhibit the progression of the disorder.
20. The method of claim 1 , wherein the therapeutically effective amount comprises an amount of the compound sufficient to alleviate one or more symptoms of the disorder.
21. The method of claim 14 , wherein the symptom of the neurodegenerative disorder is pain.