Cyanoisoquinoline Compounds and Methods of Use Thereof

A method of inhibiting the activity of a HIF hydroxylase enzyme, the method comprising bringing into contact the HIF hydroxylase enzyme and an inhibitory-effective amount of a compound of represented by formula I:

• wherein:
• R is selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
• R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen, halo, cyano, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, —OR7, —SR7, —SOR7, and —SOR7 wherein R7 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• R5 and R6 are independently selected from the group consisting of hydrogen or C1-3 alkyl;
• or pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, and/or prodrugs thereof.

A method of treating, pretreating, or delaying onset of a condition associated with hypoxia inducible factor (HIF), the method comprising administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising one or more compounds represented by formula I:

• wherein:
• R is selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
• R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen, halo, cyano, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, —OR7, —SR7, —SOR7, and —SO2R7 wherein R7 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• R5 and R6 are independently selected from the group consisting of hydrogen or C1-3 alkyl;
• or pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, and/or prodrugs thereof, and a pharmaceutically acceptable excipient.

A method of treating, pretreating, or delaying onset of a condition associated with erythropoietin (EPO), the method comprising administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising one or more compounds represented by formula I:

• wherein:
• R is selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
• R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen, halo, cyano, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, —OR7, —SR7, —SOR7, and —SO2R7 wherein R7 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• R5 and R6 are independently selected from the group consisting of hydrogen or C1-3 alkyl;
• or pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, and/or prodrugs thereof, and a pharmaceutically acceptable excipient.

A method of treating, pretreating, or delaying onset of anemia, the method comprising administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising one or more compounds represented by formula I:

• wherein:
• R is selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
• R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen, halo, cyano, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, —OR7, —SR7, —SOR7, and —SO2R7 wherein R7 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• R5 and R6 are independently selected from the group consisting of hydrogen or C1-3 alkyl;
• or pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, and/or prodrugs thereof, and a pharmaceutically acceptable excipient.