Ion channel modulating compounds and uses thereof

• US 7,259,184 B2
• Filed: 01/27/2006
• Issued: 08/21/2007
• Est. Priority Date: 10/06/2000
• Status: Expired due to Term

• Current Assignee: Correvio International SARL (ADVANZ PHARMA Corp. Ltd.)
• Original Assignee: Cardiome Pharma Corp. (ADVANZ PHARMA Corp. Ltd.)
• Inventors: Sheng, Tao, Zhu, Jeff Jiqun, Beatch, Gregory N, Zolotoy, Alexander B, Yong, Sandro L, Walker, Michael J A, Plouvier, Bertrand M C, Wall, Richard A
• Primary Examiner(s): Shameem; Golam
• Assistant Examiner(s): Cheng; Karen
• Application Number:
  US11/342,270
• Publication Number:
  US 20060189677A1
• Time in Patent Office: 571 Days
• Field of Search: 548/541, 514/424
• US Class Current: 514/424
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: C07D 207/12 Oxygen or sulfur atoms
• CPC Class Codes: C07D 209/36 in position 3, e.g. adrenochrome

Abstract

Ion channel modulating compounds are disclosed. The compounds of the present invention may be incorporated in compositions and kits. The present invention also discloses a variety of in vitro and in vivo uses for the compounds and compositions, including the treatment of arrhythmia and the production of analgesia and local anesthesia.

Claims

1. A method of treating arrhythmia in a warm-blooded animal, comprising administering to said animal a therapeutically effective amount of a composition comprising a compound having the following structure:

2. The method of claim 1 wherein administration is by a route selected from the group consisting of oral, topical, parenteral, sublingual, rectal, vaginal, and intranasal.

3. The method of claim 2 wherein the parenteral administration is selected from the group consisting of subcutaneous injection, intravenous injection, intramuscular injection, epidural injection, intrastemal injection, and infusion.

4. The method of claim 2 wherein the oral administration comprises administering an oral dosage form selected from the group consisting of a powder, a granule, a compressed tablet, a pill, a capsule, a cachet, a chewing gum, a wafer, and a lozenge.

5. The method of claim 1 wherein the arrhythmia is atrial arrhythmia.

6. The method of claim 5 wherein the atrial arrhythmia is atrial fibrillation.

7. The method of claim 1 wherein the arrhythmia is ventricular arrhythmia.

8. The method of claim 7 wherein the ventricular arrhythmia is ventricular fibrillation.

9. The method of claim 8 wherein the ventricular fibrillation occurs during acute ischemia.

17. The method of any one of claims 1-6 and 7-16 wherein the compound is a mixture of isomers.

18. The method of claim 17 wherein the compound has the following structure:

19. The method of claim 17 wherein the compound has the following structure:

20. The method of any one of claims 1-6 and 7-16 wherein the compound is an isolated enantiomeric or diastereomeric isomer.

21. The method of claim 20 wherein the compound has the following structure:

22. The method of claim 20 wherein the compound has the following structure:

23. The method of claim 20 wherein the compound has the following structure:

24. The method of claim 20 wherein the compound has the following structure:

25. The method of claim 22 wherein the pharmaceutically acceptable salt is a monohydrochloride salt.

10. A method for blocking cardiac early repolarizing currents and cardiac sodium currents in a patient in need thereof comprising administering to said patient a therapeutically effective amount of a composition comprising a compound having the following structure:

11. The method of claim 10 wherein the blocking occurs in the presence of an arrhythmogenic substrate in the heart.

12. A method to block sodium or potassium ion channels in vitro comprising contacting a preparation containing sodium ion channels or potassium ion channels with an effective amount of a composition comprising a compound having the following structure:

13. A method to block sodium or potassium ion channels in a patient in need thereof comprising administering to said patient a therapeutically effective amount of a composition comprising a compound having the following structure:

14. A method for treating atrial arrhythmia in a warm-blooded animal, the method comprising administering to said animal a therapeutically effective amount of a compound having the following structure:

15. A method to produce local analgesia or anesthesia in a warm-blooded animal comprising administering to said animal a therapeutically effective amount of a composition comprising a compound having the following structure:

16. A method for treating atrial fibrillation in a warm-blooded animal, the method comprising administering to said animal a therapeutically effective amount of a compound having the following structure: