Treating long QT syndrome

• US 9,447,027 B2
• Filed: 10/20/2011
• Issued: 09/20/2016
• Est. Priority Date: 10/22/2010
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Milan, David J., Peal, David S.
• Primary Examiner(s): Zarek, Paul
• Assistant Examiner(s): Kosturko, George W
• Application Number:
  US13/822,264
• Publication Number:
  US 20130310351A1
• Time in Patent Office: 1,797 Days
• Field of Search: 514/179, 514/617, 514/622
• US Class Current: 1/1
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/166 having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: C07C 233/75 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/56 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring

Abstract

This document relates to compounds useful for treating cardiac arrhythmias, for example, long QT syndrome. Also provided herein are methods and materials for using such compounds to shorten myocardial repolarization time in a patient.

Claims

1. A method for treating long QT syndrome in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of one or more compounds of Formula (1):

2. The method of claim 1, wherein administration of the compound of Formula (I) shortens the myocardial repolarization time in the patient.

3. The method of claim 1, wherein R² is a —

O(C₁-C₆)alkyl.

4. The method of claim 3, wherein R² is —

O(CH₃).

5. The method of claim 1, wherein the compound of Formula (1) is selected from the group consisting of:

6. The method of claim 5, wherein the compound of Formula (1) is:

7. The method of claim 1, wherein the patient has long QT syndrome type 2.

8. The method of claim 1, wherein the long QT syndrome is drug induced long QT syndrome.

9. The method of claim 1, wherein the administration of the one or more compounds of Formula (1) is acute.

10. The method of claim 1, wherein the administration of the one or more compounds of Formula (1) is chronic.

11. The method of claim 1, wherein at least two compounds are administered to the patient.

12. The method of claim 11, wherein the administration of at least one of the two compounds is acute.

13. The method of claim 11, wherein the administration of at least one of the two compounds is chronic.

14. The method of claim 1, wherein the method further comprises administering one or more glucocorticoid steroids, or a pharmaceutically acceptable salt form thereof.

15. The method of claim 14, wherein the glucocorticoid steroid is selected from the group consisting of:

alclomethasone, amicinonide, beclomethasone, betamethasone, budesonide, carbenoxolone, ciclesonide, clobetasole, clobetasone, clocortolone, cloprednol, corticosterone, corticotropin, cortisol, cortisone, cortivazol, deflazacort, descinolone, desonide, dexamethasone, desoxymethasone, diflorasone, difluocortolone, difluprednate, flucloronide, fludrocortisone, fludroxycortide, flumethasone, flunisolide, fluocortin, fluocinonide, fluocinolone, fluocortolone, fluorometholone, fluperolone, fluprednidene, fluprednisolone, flurandrenolide, fluticasone, formocortal, halcinonide, halobetasol, halomethasone, hydrocortisone, medrysone, methylprednisolone, momethasone, nivazol, paramethasone, prednicarbate, prednisolone, prednisone, prednival, prednylidene, rofleponide, ticabesone, tipredane, tralonide, and triamcinolone.

16. The method of claim 15, wherein the glucocorticoid steroid is selected from the group consisting of:

dexamethasone, flurandrenolide, fluocinonide, and fluorometholone.

24. The method of claim 14, wherein the method comprises acute administration of the one or more glucocorticoid steroids, or a pharmaceutically acceptable salt form thereof.

25. The method of claim 14, wherein the method comprises chronic administration of the compound of Formula (1), or a pharmaceutically acceptable salt form thereof.

17. A method for treating long QT syndrome in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of one or more glucocorticoid steroids, or a pharmaceutically acceptable salt form thereof.

18. The method of claim 17, wherein the patient has long QT syndrome type 2.

19. The method of claim 17, wherein the long QT syndrome is drug induced long QT syndrome.

20. The method of claim 17, wherein the administration of the one or more glucocorticoid steroids is acute.

21. The method of claim 17, wherein the administration of the one or more glucocorticoid steroids is chronic.

22. The method of claim 17, wherein the glucocorticoid steroid is selected from the group consisting of:

alclomethasone, amicinonide, beclomethasone, betamethasone, budesonide carbenoxolone, ciclesonide, clobetasole, clobetasone, clocortolone, cloprednol, corticosterone, corticotropin, cortisol, cortisone, cortivazol, deflazacort, descinolone, desonide, dexamethasone, desoxymethasone, diflorasone, difluocortolone, difluprednate, flucloronide, fludrocortisone, fludroxycortide, flumethasone, flunisolide, fluocortin, fluocinonide, fluocinolone, fluocortolone, fluorometholone, fluperolone, fluprednidene, fluprednisolone, flurandrenolide, fluticasone, formocortal, halcinonide, halobetasol, halomethasone, hydrocortisone, medrysone, methylprednisolone, momethasone, nivazol, paramethasone, prednicarbate, prednisolone, prednisone, prednival, prednylidene, rofleponide, ticabesone, tipredane, tralonide, and triamcinolone.

23. The method of claim 22, wherein the glucocorticoid steroid is selected from the group consisting of:

dexamethasone, flurandrenolide, fluocinonide, and fluorometholone.