Anti-arrythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2)
View Patent ↗The present invention provides novel 1,4-benzothiazepine intermediates and derivatives, methods for synthesizing same, and methods for assaying same. The present invention also provides methods for using these novel compounds to limit or prevent a decrease in the level of RyR2-bound FKBP12.6 in a subject; to prevent exercise-induced sudden cardiac death in a subject; and to treat or prevent heart failure, atrial fibrillation, or exercise-induced cardiac arrhythmia in a subject. The present invention further provides methods for identifying an agent that enhances binding of RyR2 and FKBP12.6, and agents identified by these methods. Additionally, the present invention provides methods for identifying agents for use in treating or preventing heart failure, atrial fibrillation, or exercise-induced cardiac arrhythmia, and in preventing exercise-induced sudden cardiac death. Also provided are agents identified by such methods.
1. The compound S36:
2. A composition comprising S36
and a pharmaceutically acceptable carrier.
3. The composition of claim 2 wherein the carrier comprises carboxymethyl cellulose, crystalline cellulose, glycerin, gum arabic, lactose, magnesium stearate, methyl cellulose, saline, sodium alginate, sucrose, starch, talc or water.
4. The composition of claim 2 which further includes one or more of an antioxidant, colorant, flavor improving agent, preservative, sweetener, binder or lubricant.
5. The composition of claim 2 in the form of a capsule, tablet, powder, granule, or suspension.