Polyether brevetoxin derivatives as a treatment for cystic fibrosis, mucociliary dysfunction, and pulmonary diseases

• US 7,399,782 B2
• Filed: 09/20/2004
• Issued: 07/15/2008
• Est. Priority Date: 09/19/2003
• Status: Active Grant

• 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: Baden, Daniel G., Bourdelais, Andrea J., Abraham, William M.
• Primary Examiner(s): Andres; Janet L.
• Assistant Examiner(s): Robinson; Binta M
• Application Number:
  US10/945,467
• Publication Number:
  US 20050124686A1
• Time in Patent Office: 1,394 Days
• Field of Search: 514/450, 549/348
• US Class Current: 514/450
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/12 Mucolytics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 493/22 in which the condensed system contains four or more hetero rings

Abstract

Disclosed are compounds that are derivatives of brevetoxin, or PbTx, pharmaceutical formulations comprising the compounds, and methods of regulating mucus transport in a cell, treating mucociliary dysfunction and diseases related to decreased mucus transport, wherein the compounds are of the Formula (I), and Formula (III):

wherein R, R₁, R₂, R₃, A, n, and Y are as defined herein for each compound.

Claims

1. A method of reducing the severity of or delaying the onset of symptoms associated with cystic fibrosis or asthma in a subject comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of Formula X, or a pharmaceutically acceptable salt, where Formula X is:

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

4. A method according to claim 3, wherein the therapeutically effective amount is a dosage of between about 0.1 pg to about 10 μ

g per day.

2. A method of treating cystic fibrosis or asthma in a subject comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of Formula (III), or a pharmaceutically acceptable salt, where Formula (III) is:

5. A method according to claim 2, wherein the therapeutically effective amount is a dosage of between about 0.1 pg to about 100 mg per day.