Cyanoisoquinoline Compounds and Methods of Use Thereof

1 - 36 . (canceled)

37 . 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;

R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of hydrogen, halo, cyano, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, —OR 7 , —SR 7 , —SOR 7 , and —SOR 7 wherein R 7 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;

R 5 and R 6 are independently selected from the group consisting of hydrogen or C 1-3 alkyl;

or pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, and/or prodrugs thereof.

38 . The method of claim 37 , wherein the HIF hydroxylase enzyme is an asparaginyl hydroxylase.

39 . The method of claim 38 , wherein the asparaginyl hydroxylase is a factor inhibiting HIF.

40 . The method of claim 37 , wherein the HIF hydroxylase enzyme is a prolyl hydroxylase.

41 . The method of claim 40 , wherein the prolyl hydroxylase is selected from the group consisting of human EGLN1, EGLN2, and EGLN3.

42 . 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;

R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of hydrogen, halo, cyano, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, —OR 7 , —SR 7 , —SOR 7 , and —SO 2 R 7 wherein R 7 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;

R 5 and R 6 are independently selected from the group consisting of hydrogen or C 1-3 alkyl;

or pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, and/or prodrugs thereof, and a pharmaceutically acceptable excipient.

43 . The method of claim 42 , wherein the condition associated with HIF is tissue damage associated with ischemia or hypoxia.

44 . The method of claim 43 , wherein the ischemia is an acute ischemic event selected from the group consisting of myocardial infarction, pulmonary embolism, intestinal infarction, ischemic stroke, and renal ischemic-reperfusion injury.

45 . The method of claim 43 , wherein the ischemia is chronic ischemic event selected from the group consisting of cardiac cirrhosis, macular degeneration, chronic kidney failure, and congestive heart failure.

46 . 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;

R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of hydrogen, halo, cyano, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, —OR 7 , —SR 7 , —SOR 7 , and —SO 2 R 7 wherein R 7 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;

R 5 and R 6 are independently selected from the group consisting of hydrogen or C 1-3 alkyl;

or pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, and/or prodrugs thereof, and a pharmaceutically acceptable excipient.

47 . 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;

R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of hydrogen, halo, cyano, hydroxyl, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, amino, substituted amino, —OR 7 , —SR 7 , —SOR 7 , and —SO 2 R 7 wherein R 7 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;

R 5 and R 6 are independently selected from the group consisting of hydrogen or C 1-3 alkyl;

or pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, and/or prodrugs thereof, and a pharmaceutically acceptable excipient.