Cardioprotective phosphonates and malonates

A method of treating ischemia reperfusion injury in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula I

• 47
• in which
• R1 is hydrogen or alkyl;
• R2 is —CHO, —CH2OH, —CH3, —CO2R6 in which R6 is hydrogen, alkyl, or aryl;
• or
• R2 is —CH2—O-alkyl- in which alkyl is covalently bonded to the oxygen at the 3-position instead of R1;
• R3 is hydrogen and R4 is hydroxy, halo, alkoxy, alkylcarbonyloxy, alkylamino or arylamino;
• or
• R3 and R4 are halo;
• and
• R5 is hydrogen, alkyl, aryl, aralkyl, or —CO2R7 in which R7 is hydrogen, alkyl, aryl, or aralkyl;
• or a pharmaceutically acceptable acid addition salt thereof in a unit dosage form.

A method of treating myocardial ischemia in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula I

• 48
• in which
• R1 is hydrogen or alkyl;
• R2 is —CHO, —CH2OH, —CH3, —CO2R6 in which R6 is hydrogen, alkyl, or aryl;
• or
• R2 is —CH2—O-alkyl- in which alkyl is covalently bonded to the oxygen at the 3-position instead of R1;
• R3 is hydrogen and R4 is hydroxy, halo, alkoxy, alkylcarbonyloxy, alkylamino or arylamino;
• or
• R3 and R4 are halo;
• and
• R5 is hydrogen, alkyl, aryl, aralkyl, or —CO2R7 in which R7 is hydrogen, alkyl, aryl, or aralkyl;
• or a pharmaceutically acceptable acid addition salt thereof in a unit dosage form.

A method of treating congestive heart failure in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula I

• 49
• in which
• R1 is hydrogen or alkyl;
• R2 is —HO, —CH2OH, —CH3, —CO2R6 in which R6 is hydrogen, alkyl, or aryl;
• or
• R2 is —CH2—O-alkyl- in which alkyl is covalently bonded to the oxygen at the 3-position instead of R1;
• R3 is hydrogen and R4 is hydroxy, halo, alkoxy, alkylcarbonyloxy, alkylamino or arylamino;
• or
• R3 and R4 are halo;
• and
• R5 is hydrogen, alkyl, aryl, aralkyl, or —CO2R7 in which R7 is hydrogen, alkyl, aryl, or aralkyl;
• or a pharmaceutically acceptable acid addition salt thereof in a unit dosage form.

A method of treating arrhythmia in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula I

• 50
• in which
• R1 is hydrogen or alkyl;
• R2 is —CHO, —CH2OH, —CH3, —CO2R6 in which R6 is hydrogen, alkyl, or aryl;
• or
• R2 is —CH2—O-alkyl- in which alkyl is covalently bonded to the oxygen at the 3-position instead of R1;
• R3 is hydrogen and R4 is hydroxy, halo, alkoxy, alkylcarbonyloxy, alkylamino or arylamino;
• or
• R3 and R4 are halo;
• and
• R5 is hydrogen, alkyl, aryl, aralkyl, or —CO2R7 in which R7 is hydrogen, alkyl, aryl, or aralkyl;
• or a pharmaceutically acceptable acid addition salt thereof in a unit dosage form.

A method of reducing blood clots in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula I

• 51
• in which
• R1 is hydrogen or alkyl;
• R2 is —CHO, —CH2OH, —CH3, —CO2R6 in which R6 is hydrogen, alkyl, or aryl;
• or
• R2 is —CH2—O-alkyl- in which alkyl is covalently bonded to the oxygen at the 3-position instead of R1;
• R3 is hydrogen and R4 is hydroxy, halo, alkoxy, alkylcarbonyloxy, alkylamino or arylamino;
• or
• R3 and R4 are halo;
• and
• R5 is hydrogen, alkyl, aryl, aralkyl, or —CO2R7 in which R7 is hydrogen, alkyl, aryl, or aralkyl;
• or a pharmaceutically acceptable acid addition salt thereof in a unit dosage form.

A method of treating a disease that arises from thrombotic and prothrombotic states in which the coagulation cascade is activated in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula I

• 52
• in which
• R1 is hydrogen or alkyl;
• R2 is —CHO, —CH2OH, —CH3, —CO2R6 in which R6 is hydrogen, alkyl, or aryl;
• or
• R2 is —CH2—O-alkyl- in which alkyl is covalently bonded to the oxygen at the 3-position instead of R1;
• R3 is hydrogen and R4 is hydroxy, halo, alkoxy, alkylcarbonyloxy, alkylamino or arylamino;
• or
• R3 and R4 are halo;
• and
• R5 is hydrogen, alkyl, aryl, aralkyl, or —CO2R7 in which R7 is hydrogen, alkyl, aryl, or aralkyl;
• or a pharmaceutically acceptable acid addition salt thereof, in a unit dosage form.