Anti-arrhythmicity agents

A compound of structure of Formula Ic:

• wherein:
• R1 is an alkane, phenyl, heteroaryl, or substituted phenyl group;
• R2 is a phenyl, heteroaryl, substituted phenyl, or hydrocarbyl group with or without a heteroatom;
• and
• R3 is an alkoxy, amino, amino ether, N-Boc-protected 2-aminoethoxyethoxyethylamino group, or a C1-C10 straight or branched, acyclic or cyclic alkyloxy group, aryloxy, or amino group with or without heteroatom;
• and
• wherein the compound is effective to potentiate mitochondrial Ca2+ uptake so as to modulate cardiac rhythmicity in a subject.

A method of regulating cardiac rhythmicity in a subject, comprising potentiating mitochondrial Ca2+ uptake by

• i) inducing VDAC2 or VDAC1 overexpression in the subject to restore rhythmic contraction,
• ii) inducing overexpression of
• VDAC2 or VDAC1 and/or
• MCU or MICU1 complex,
• iii) administering to the subject in need thereof an agent effective to activate
• VDAC2 or VDAC1 and/or
• MCU or MICU1 complex, or
• iv) administering to the subject in need thereof an agent effective to induce Ca2+ transporting activity of VDAC2 or VDAC1.

A method of forming the compound of Formula Ic:

• where R1 is substituted phenyl or substituted or unsubstituted heteroaryl;
• and R2 is substituted phenyl or substituted or unsubstituted heteroaryl;
• and R3 is R3 is an alkoxy, amino, amino ether, N-Boc-protected 2-aminoethoxyethoxyethylamino group, or a C1-C10 straight or branched, acyclic or cyclic alkyloxy group, aryloxy, or amino group with or without heteroatom
• comprising reacting
• according to a reaction of Scheme III
• to form the compound of Formula Ic.