Compositions and methods to treat cardiac diseases

A phosphonate or phosphinate N-methanocarba derivative of AMP comprising,

• wherein
• Q1 is O or S;
• R1 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, halogen, or N(R6)2, wherein each R6 is independently hydrogen, optionally substituted alkyl, or optionally substituted cycloalkyl;
• R2 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkynyl, N(R6)2, or halogen;
• R3 is hydrogen, optionally substituted alkyl, N(R6)2, or halogen;
• R4 is hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted —Oaryl, or N(R6)2;
• R5 is hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, or optionally substituted —Oaryl;
• or
• alternatively, R4 and R5 form a 5- or 6-membered cyclic structure with the phosphorus atom where the cyclic structure contains at least two oxygen atoms and at least 2 or 3 carbon atoms, wherein the carbon atoms are optionally substituted with alkyl or aryl where the chain is attached;
• and
• Y is a linking group linked to the phosphorus atom by a carbon atom;
• or
• wherein X is O or S;
• n is 1, 2, or 3;
• and R7 is optionally substituted alkyl or optionally substituted aryl;
• or
• wherein Z is a bond or —O—C(═O)— where the carbonyl carbon is bonded to the oxygen of the bicycle group and the oxygen is bonded to the phosphorus atom;
• or
• wherein R8 is hydrogen or optionally substituted alkyl;
• and R8 is optionally substituted alkyl, optionally substituted alkoxy, or optionally substituted aryl;
• or
• wherein G is O or S—S;
• and R10 is hydrogen, hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, or optionally substituted aryl;
• or
• wherein R11 is hydrogen, optionally substituted alkyl, or optionally substituted aryl;
• or
• wherein
• Q1 is O or S;
• Q2 is O or S;
• R1 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, halogen, or N(R6)2, wherein each R6 is independently hydrogen, optionally substituted alkyl, or optionally substituted cycloalkyl;
• R2 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkynyl;
• N(R6)2, or halogen;
• R3 is hydrogen, optionally substituted alkyl, N(R6)2, or halogen;
• R4 is hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted —Oaryl, or N(R6)2;
• R5 is hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, or optionally substituted —Oaryl;
• or
• alternatively, R4 and R5 form a 5- or 6-membered cyclic structure with the phosphorus atom where the cyclic structure contains at least two oxygen atoms and at least 2 or 3 carbon atoms, wherein the carbon atoms are optionally substituted with alkyl or aryl where the chain is attached;
• and
• Y1 is a linking group,
• with the proviso that when Q1 and Q2 are both O, and Formula (VII) is not enriched with deuterium, then R4 and R5 are not both hydroxyl,
• a deuterium enriched isomer thereof, or a pharmaceutically acceptable salt thereof.