PROLYL HYDROXYLASE INHIBITORS AND METHODS OF USE
The present disclosure relates to HIF-1α prolyl hydroxylase inhibitors, compositions which comprise the HIF-1α prolyl hydroxylase inhibitors described herein and to methods for controlling, inter alia, Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), heart failure, ischemia, and anemia.
1 - 32 . (canceled)
33 . A method for treating a patient having ischemia, Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), or heart failure, comprising administering to the patient a compound having a structure:
wherein
R is selected from
i) 3-chlorophenyl; and
ii) 2,3-dihydrobenzo[1,4]dioxin-6-yl;
R 2 is selected from
i) OR 6 ; and
ii) NR 7a R 7b ;
R 6 is selected from hydrogen, methyl, and ethyl;
R 7a and R 7b are each independently selected from:
i) hydrogen; and
ii) methyl;
or a pharmaceutically acceptable salt thereof.
34 . The method of claim 33 , wherein the patient has ischemia.
35 . The method of claim 33 , wherein the patient has Peripheral Vascular Disease (PVD).
36 . The method of claim 33 , wherein the patient has Coronary Artery Disease (CAD).
37 . The method of claim 33 , wherein the patient has heart failure.
38 . The method of claim 35 , wherein the PVD results from atherosclerosis.
39 . The method of claim 38 , wherein the atherosclerosis presents as asymptomatic PVD, intermittent claudication, or critical limb ischemia.
40 . A method of vascularizing ischemic tissue, improving blood flow, improving oxygen delivery, improving energy utilization, enhancing the ability to revascularize damaged tissues, or increasing vasculature in a patient in need thereof, comprising administering to the patient a compound having a structure:
wherein
R is selected from
i) 3-chlorophenyl; and
ii) 2,3-dihydrobenzo[1,4]dioxin-6-yl;
R 2 is selected from
i) OR 6 ; and
ii) NR 7a R 7b ;
R 6 is selected from hydrogen, methyl, and ethyl;
R 7a and R 7b are each independently selected from:
i) hydrogen; and
ii) methyl;
or a pharmaceutically acceptable salt thereof.
41 . The method of claim 33 or 40 , wherein the compound has a structure:
wherein
R 2 is selected from
i) OR 6 ; and
ii) NR 7a R 2b ;
R 6 is selected from hydrogen, methyl, and ethyl;
R 7a and R 7b are each independently selected from:
i) hydrogen; and
ii) methyl;
or a pharmaceutically acceptable salt thereof.
42 . The method of claim 33 , wherein the compound has a structure:
wherein
R 2 is selected from
i) OR 6 ; and
ii) NR 7a R 7b ;
R 6 is selected from hydrogen, methyl, and ethyl;
R 7a and R 7b are each independently selected from:
i) hydrogen; and
ii) methyl;
or a pharmaceutically acceptable salt thereof.
43 . The method of claim 41 , wherein the compound is selected from:
{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid methyl ester;
{[5-(3-Chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid;
5-(3-Chlorophenyl)-N-(2-amino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide;
5-(3-Chlorophenyl)-N-(2-methylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide; and
5-(3-Chlorophenyl)-N-(2-dimethylamino-2-oxoethyl)-3-hydroxylpyridin-2-yl amide.
or a pharmaceutically acceptable salt thereof.
44 . The method of claim 43 , wherein the compound has a structure:
or a pharmaceutically acceptable salt thereof.
45 . The method of claim 43 , wherein the compound has a structure:
or a pharmaceutically acceptable salt thereof.
46 . The method of claim 43 , wherein the compound has a structure:
or a pharmaceutically acceptable salt thereof.
47 . The method of claim 43 . wherein the compound has a structure:
or a pharmaceutically acceptable salt thereof.
48 . The method of claim 43 . wherein the compound has a structure:
or a pharmaceutically acceptable salt thereof.
49 . The method of claim 42 , wherein the compound has a structure:
or a pharmaceutically acceptable salt thereof.