Ultra short acting anti-arrhythmic agents
Some aspects provide novel dofetilide derivatives and pharmaceutical compositions containing the same that are useful as pharmaceutical agents in the treatment of supraventricular and ventricular arrhythmias.
1. A compound of Formula I-III or a stereoisomer thereof:
Formula
Formula
I
II
III
wherein:
R is selected from H, C 1-6 alkyl, C 3-6 alkenyl, and C 3-6 alkynyl; and,
m is selected from 0 and 1;
or a pharmaceutically acceptable salt thereof.
2. A compound of claim 1 , wherein the compound is of Formula I:
wherein the compound is selected from the following table:
R
m
1.
CH 3
0
2.
CH 2 CH 3
0
3.
CH 2 CH 2 CH 3
0
4.
CH 2 CH═CH 2
0
5.
CH 3
1
6.
CH 2 CH 3
1
7.
CH 2 CH 2 CH 3
1
8.
CH 2 CH═CH 2
1
9.
CH 3
2
10.
CH 2 CH 3
2
11.
CH 2 CH 2 CH 3
2
12.
CH 2 CH═CH 2
2
or pharmaceutically acceptable salt thereof.
3. A compound of claim 1 , wherein the compound is of Formula II:
wherein the compound is selected from the following table:
R
M
1.
CH 3
0
2.
CH 2 CH 3
0
3.
CH 2 CH 2 CH 3
0
4.
CH 2 CH=CH 2
0
5.
CH 3
1
6.
CH 2 CH 3
1
7.
CH 2 CH 2 CH 3
1
8.
CH 2 CH=CH 2
1
9.
CH 3
2
10.
CH 2 CH 3
2
11.
CH 2 CH 2 CH 3
2
12.
CH 2 CH=CH 2
2
or pharmaceutically acceptable salt thereof.
4. A compound of claim 1 , wherein the compound is of Formula III:
wherein the compound is selected from the following table:
R
m
1.
CH 3
0
2.
CH 2 CH 3
0
3.
CH 2 CH 2 CH 3
0
4.
CH 2 CH═CH 2
0
5.
CH 3
1
6.
CH 2 CH 3
1
7.
CH 2 CH 2 CH 3
1
8.
CH 2 CH═CH 2
1
9.
CH 3
2
10.
CH 2 CH 3
2
11.
CH 2 CH 2 CH 3
2
12.
CH 2 CH═CH 2
2
or pharmaceutically acceptable salt thereof.
5. A pharmaceutical composition, comprising: a therapeutically effective amount of a compound of claim 1 or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
6. A pharmaceutical composition, comprising: a therapeutically effective amount of a compound of claim 2 or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
7. A pharmaceutical composition, comprising: a therapeutically effective amount of a compound of claim 3 or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition, comprising: a therapeutically effective amount of a compound of claim 4 or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
9. A method of terminating or blocking the occurrence of an arrhythmia, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or pharmaceutically acceptable salt thereof, wherein the arrhythmia is selected from: paroxysmal atrial tachycardia, junctional ectopic tachycardia, atrial flutter, atrial fibrillation, atrial tachycardia, ventricular tachycardia, junctional tachycardia, and ventricular fibrillation.
10. A method of terminating or blocking the occurrence of an arrhythmia, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of claim 2 or pharmaceutically acceptable salt thereof, wherein the arrhythmia is selected from: paroxysmal atrial tachycardia, junctional ectopic tachycardia, atrial flutter, atrial fibrillation, atrial tachycardia, ventricular tachycardia, junctional tachycardia, and ventricular fibrillation.
11. A method of terminating or blocking the occurrence of an arrhythmia, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of claim 3 or pharmaceutically acceptable salt thereof, wherein the arrhythmia is selected from: paroxysmal atrial tachycardia, junctional ectopic tachycardia, atrial flutter, atrial fibrillation, atrial tachycardia, ventricular tachycardia, junctional tachycardia, and ventricular fibrillation.
12. A method of terminating or blocking the occurrence of an arrhythmia, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of claim 4 or pharmaceutically acceptable salt thereof, wherein the arrhythmia is selected from: paroxysmal atrial tachycardia, junctional ectopic tachycardia, atrial flutter, atrial fibrillation, atrial tachycardia, ventricular tachycardia, junctional tachycardia, and ventricular fibrillation.