Polyether brevetoxin derivatives as a treatment for neurotoxic shellfish poisoning and ciguatera fish poisoning

• US 20050124685A1
• Filed: 09/20/2004
• Published: 06/09/2005
• Est. Priority Date: 09/19/2003
• Status: Abandoned Application

• Current Assignee: University of North Carolina At Wilmington (University of North Carolina System)
• Original Assignee: University of North Carolina At Wilmington (University of North Carolina System)
• Inventors: Fieber, Lynne, Rein, Kathleen S., Parker, Sherry P., Baden, Daniel G.
• Application Number:
  US10/945,241
• Publication Number:
  US 20050124685A1
• Time in Patent Office: Days
• US Class Current: 514/450
• CPC Class Codes: A61K 31/335 having oxygen as the only ring hetero atom, e.g. fungichromin
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Disclosed are compounds that are derivatives of brevetoxin, or PbTx, pharmaceutical formulations comprising the compounds, and methods of administering the compounds to a subject for the treatment of neurotoxic shellfish poisoning or ciguatera fish poisoning, wherein the compounds have general Formulas (I) and (III):
wherein R, R₁, R₂, R₃, A, n, and Y are as defined herein for each compound.

Claims

1. A method of treating neurotoxic shellfish poisoning in a mammal comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of formula (I):

2. A method according to claim 1, where the compound has the formula II:

5. A method according to claim 1, wherein the therapeutically effective amount is administered in a dosage of between about 0.1 pg to about 100 mg per day.

6. A method according to claim 1, wherein the therapeutically effective amount comprises a dosage of between about 0.1 pg to about 1.0 μ

g per day.

7. A method according to claim 1, wherein the therapeutically effective amount of the compound is administered by inhalation.

8. A method according to claim 1, wherein the therapeutically effective amount of the compound is administered orally.

9. A method according to claim 1, where the compound is administered as a pharmaceutical formulation comprising the compound, or at least one pharmaceutically acceptable salt, ester, amide, solvate, hydrate, complex, or combination thereof, and at least one pharmaceutically acceptable carrier, excipient, solvent, diluent, or adjuvant.

3. A method of treating neurotoxic shellfish poisoning in a subject comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of formula (III):

4. A method according to claim 3, where the compound has the formula (IV):

10. A method according to claim 3, wherein the compound is administered as a pharmaceutical formulation comprising the compound, or at least one pharmaceutically acceptable salt, solvate, ester, amide, hydrate, complex, or combination thereof, and at least one pharmaceutically acceptable carrier, excipient, solvent, diluent, or adjuvant.

11. A method according to claim 3, wherein the therapeutically effective amount comprises a dosage of between about 0.1 pg to about 100 mg per day.

12. A method according to claim 3, wherein the therapeutically effective amount comprises a dosage of between about 0.1 pg to about 1.0 μ

g per day.

13. A method according to claim 3, wherein the therapeutically effective amount of the compound is administered by inhalation.

14. A method according to claim 3, wherein the therapeutically effective amount of the compound is administered orally.

15. A method of treating ciguatera fish poisoning in a subject comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of formula (I):

16. A method according to claim 15 where the compound has the formula (II):

19. A method according to claim 15, wherein the therapeutically effective amount is administered in a dosage of between about 0.1 pg to about 100 mg per day.

21. A method according to claim 15, wherein the therapeutically effective amount of the compound is administered by inhalation.

22. A method according to claim 15, wherein the therapeutically effective amount of the compound is administered orally.

23. A method according to claim 15, where the compound is administered as a pharmaceutical formulation comprising the compound, or a pharmaceutically acceptable salt, solvate, amide, ester, hydrate, complex, or combination thereof, and at least one pharmaceutically acceptable carrier, excipient, solvent, diluent, or adjuvant.

17. A method of treating ciguatera fish poisoning in a subject comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of the formula (III):

18. A method according to claim 17, where the compound has the formula (IV)

20. A method according to claim 17, wherein the therapeutically effective amount comprises a dosage of between about 0.1 pg to about 100 mg per day.

24. A method according to claim 17, where the compound is administered as a pharmaceutical formulation comprising the compound, or a pharmaceutically acceptable salt, solvate, ester, amide, hydrate, complex, or combination thereof, and at least one pharmaceutically acceptable carrier, excipient, solvent, diluent, or adjuvant.

25. A method according to claim 17, wherein the therapeutically effective amount of the compound is administered by inhalation.

26. A method according to claim 17, wherein the therapeutically effective amount of the compound is administered orally.