Fluorinated benzofuran derivatives
The invention relates to fluorinated compounds and their use in the field of pathological syndromes of the cardiovascular system. Novel fluorinated benzofuran derivatives of amiodarone and pharmaceutically acceptable salts or solvates thereof and their use for the treatment of arrhythmias are described.
1. A method of treating a disorder selected from a pathological syndrome of the cardiovascular system, angina pectoris, hypertension, arrhythmia, and cerebral circulatory insufficiency in a subject in need thereof comprising administering to the subject an effective amount of a compound of formula II:
or a pharmaceutically acceptable salt thereof, wherein X 2 is CF 3 and X 3 is selected from hydrogen, I, F, CF 3 , CHF 2 , CH 2 F, OCF 3 , OCHF 2 , and OCH 2 F.
2. The method of claim 1 , wherein X 3 is selected from hydrogen, I, F, CF 3 , CHF 2 , and CH 2 F.
3. The method of claim 1 , wherein X 3 is selected from hydrogen, I, and CF 3 .
4. The method of claim 1 , wherein the compound of formula II is of formula VII:
5. The method of claim 1 , wherein the disorder is arrhythmia.
6. The method of claim 5 , wherein the arrhythmia is selected from tachycardia, bradycardia, ventricular arrhythmia, supraventricular arrhythmia, atrial fibrillation, reentrant tachyarrhythmia, atrial flutter, supraventricular tachycardia, Wolff-Parkinson-White syndrome, premature supraventricular contraction or premature atrial contraction, sick sinus syndrome, sinus arrhythmia, sinus tachycardia, multifocal atrial tachycardia, premature ventricular contraction, ventricular fibrillation, ventricular tachycardia, and shock-refractory ventricular fibrillation.
7. A method of treating a disorder selected from a pathological syndrome of the cardiovascular system, angina pectoris, hypertension, arrhythmia, and cerebral circulatory insufficiency in a subject in need thereof comprising administering to the subject an effective amount of a compound of formula II:
or a pharmaceutically acceptable salt thereof, wherein X 3 is hydrogen and X 2 is selected from F, CF 3 , CHF 2 , CH 2 F, OCF 3 , OCHF 2 , and OCH 2 F.
8. The method of claim 7 , wherein X 2 is selected from F, CF 3 , CHF 2 , and CH 2 F.
9. The method of claim 7 , wherein the disorder is arrhythmia.
10. The method of claim 9 , wherein the arrhythmia is selected from tachycardia, bradycardia, ventricular arrhythmia, supraventricular arrhythmia, atrial fibrillation, reentrant tachyarrhythmia, atrial flutter, supraventricular tachycardia, Wolff-Parkinson-White syndrome, premature supraventricular contraction or premature atrial contraction, sick sinus syndrome, sinus arrhythmia, sinus tachycardia, multifocal atrial tachycardia, premature ventricular contraction, ventricular fibrillation, ventricular tachycardia, and shock-refractory ventricular fibrillation.
11. A method of treating a disorder selected from a pathological syndrome of the cardiovascular system, angina pectoris, hypertension, arrhythmia, and cerebral circulatory insufficiency in a subject in need thereof comprising administering to the subject an effective amount of a compound selected from
or a pharmaceutically acceptable salt thereof.
12. The method of claim 11 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
13. The method of claim 11 , wherein the disorder is arrhythmia.
14. The method of claim 13 , wherein the arrhythmia is selected from tachycardia, bradycardia, ventricular arrhythmia, supraventricular arrhythmia, atrial fibrillation, reentrant tachyarrhythmia, atrial flutter, supraventricular tachycardia, Wolff-Parkinson-White syndrome, premature supraventricular contraction or premature atrial contraction, sick sinus syndrome, sinus arrhythmia, sinus tachycardia, multifocal atrial tachycardia, premature ventricular contraction, ventricular fibrillation, ventricular tachycardia, and shock-refractory ventricular fibrillation.
15. A method of treating a disorder selected from a pathological syndrome of the cardiovascular system, angina pectoris, hypertension, arrhythmia, and cerebral circulatory insufficiency in a subject in need thereof comprising administering to the subject an effective amount of a compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein X 1 , X 2 , X 3 , and X 4 are each independently selected from hydrogen, I, F, CF 3 , CHF 2 , CH 2 F, OCF 3 , OCHF 2 , and OCH 2 F, provided that at least one of X 1 , X 2 , X 3 , and X 4 is F or a group of atoms containing at least one fluorine atom; and wherein at least one hydrogen in the compound is substituted with a deuterium.
16. The method of claim 15 , wherein the compound is
17. The method of claim 15 , wherein the disorder is arrhythmia.
18. The method of claim 17 , wherein the arrhythmia is selected from tachycardia, bradycardia, ventricular arrhythmia, supraventricular arrhythmia, atrial fibrillation, reentrant tachyarrhythmia, atrial flutter, supraventricular tachycardia, Wolff-Parkinson-White syndrome, premature supraventricular contraction or premature atrial contraction, sick sinus syndrome, sinus arrhythmia, sinus tachycardia, multifocal atrial tachycardia, premature ventricular contraction, ventricular fibrillation, ventricular tachycardia, and shock-refractory ventricular fibrillation.