The present teachings provide compounds of Formulae I and II: and pharmaceutically acceptable salts, hydrates, complexes, esters, and prodrugs thereof, wherein R1, R1′, R2, R2′, R3, R3′, and X are as defined herein. The present teachings also provide methods of making the compounds of formulae I and II, and methods of treating RyR-associated conditions, disorders, and diseases that include administering a therapeutically effective amount of a compound of formula I or II to a subject in need thereof. In addition, the present teachings relate to methods of reducing the open probability of a ryanodine receptor, and methods of reducing Ca2+ release across a ryanodine receptor (e.g., into the cytoplasm of a cell), by contacting a compound of formula I or II with a ryanodine receptor.
