Compounds for the prevention and treatment of cardiovascular diseases
AssigneeResverlogix Corp.
InventorHenrik C. Hansen
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.
Claims79
1-75. (canceled)
A method of treating or reducing the risk of acquiring a cardiovascular-, cholesterol-, or lipid-related disorder in a mammal suffering from or at risk of acquiring such disorder comprising administering a therapeutically effective amount of a compound via surgical device or implant, wherein the compound is selected from compounds of Formula II:
- and pharmaceutically acceptable salts thereof, wherein:
- X is N;
- Y is CO;
- R1 and R3 are each independently selected from alkoxy, alkyl, amino, halogen, and hydrogen;
- R2 is selected from alkoxy, alkyl, alkenyl, alkynyl, amide, amino, halogen, and hydrogen;
- R6 and R8 are each independently selected from alkyl, alkoxy, amino, halogen, and hydrogen;
- R5 and R9 are each hydrogen;
- R7 is selected from amino, amide, alkyl, hydroxyl, and alkoxy;
- R10 is hydrogen;
- each W is independently selected from C and N, wherein if W is N, then p is 0 or 1, and if W is C, then p is 1;
- for W—(R10)p, W is N and p is 1;
- for W—(R7)p, W is C and p is 1;
- for W—(R4)p, W is C, p is 1 and R4 is H, or W is N and p is 0;
- Z1 is a double bond, and Z2 and Z3 are each a single bond;
- with the proviso that if R1 is hydrogen, then R3 is alkoxy;
- with the proviso that if R3 is hydrogen, then R1 is selected from amino and alkoxy;
- with the proviso that if R7 is selected from alkyl, hydroxyl, and alkoxy, then at least one of R6 and R8 is independently selected from alkyl, alkoxy, amino, and halogen.
A method of treating or reducing the risk of acquiring a cardiovascular-, cholesterol-, or lipid-related disorder in a mammal suffering from or at risk of acquiring such disorder comprising administering a therapeutically effective amount of a compound via surgical device or implant, wherein the compound is selected from:
- 2-(3,5-dimethyl-4-(2-morpholinoethoxy)phenyl)quinazolin-4(3H)-one;
- 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;
- 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)quinazolin-4(3H)-one;
- 2-(4-(4-oxo-3,4-dihydroquinazolin-2-yl)phenoxy)acetic acid;
- 2-(4-(dimethylamino)naphthalen-1-yl)quinazolin-4(3H)-one;
- 2-(4-(4-oxo-3,4-dihydroquinazolin-2-yl)phenoxy)acetamide;
- 2-(4-(bis(2-hydroxyethyl)amino)phenyl)quinazolin-4(3H)-one;
- 2-(4-(5,7-dimethoxyquinazolin-2-yl)-2,6-dimethylphenoxy)ethanol;
- 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethylquinazolin-4(3H)-one;
- 5,7-dichloro-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;
- 6-bromo-2-(4-hydroxy-3,5-dimethylphenyl)quinazolin-4(3H)-one;
- 6-bromo-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;
- 6-bromo-2-(4-(2-(tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;
- 5,7-dimethoxy-2-(pyridin-4-yl)quinazolin-4(3H)-one;
- 2-(4-(dimethylamino)naphthalen-1-yl)-5,7-dimethoxyquinazolin-4(3H)-one;
- 2-(4-(dimethylamino)pyridin-1-yl)-6,7-dimethoxyquinazolin-4(3H)-one;
- 2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxy-1-methylquinazol-4(1H)-one;
- 2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxy-6-(morpholinomethyl)quinazolin-4(3H)-one;
- 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-6-methoxyquinazolin-4(3H)-one;
- and
- 5-hydroxy-2-(4-hydroxy-3,5-dimethylphenyl)-7-methoxyquinazolin-4(3H)-one, and pharmaceutically acceptable salts thereof.
A method of treating or reducing the risk of acquiring a cardiovascular-, cholesterol-, or lipid-related disorder in a mammal suffering from or at risk of acquiring such disorder comprising administering a therapeutically effective amount of a compound via surgical device or implant, wherein the compound is selected from compounds of Formula II:
- and pharmaceutically acceptable salts thereof, wherein:
- X is N;
- Y is CO;
- R1 and R3 are each independently selected from alkoxy and hydrogen;
- R2 is selected from alkoxy, alkyl, and hydrogen;
- R6 and R8 are each independently selected from alkyl, alkoxy, chloride, and hydrogen;
- R5 and R9 are each hydrogen;
- R7 is selected from amino, hydroxyl, alkoxy, and alkyl substituted with a heterocyclyl;
- R10 is hydrogen;
- or
- two adjacent substituents selected from R6, R7, and R8 are connected to form a heterocyclyl;
- each W is independently selected from C and N, wherein if W is N, then p is 0 or 1, and if W is C, then p is 1;
- for W—(R10)p, W is N and p is 1;
- for W—(R4)p, W is C, p is 1 and R4 is H, or W is N and p is 0;
- Z1 is a double bond, and Z2 and Z3 are each a single bond;
- with the proviso that if R2 is alkoxy or hydrogen, then least one of R1 and R3 is alkoxy;
- with the proviso that if R7 is selected from hydroxyl and alkoxy, then at least one of R6 and R8 are independently selected from alkyl, alkoxy, and chloride;
- with the proviso that if for W—(R7)p, W is N and p is 0, then at least one of R6 and R8 is selected from alkyl, alkoxy, and chloride.
A method of treating or reducing the risk of acquiring a cardiovascular-, cholesterol-, or lipid-related disorder in a mammal suffering from or at risk of acquiring such disorder comprising administering a therapeutically effective amount of a compound via surgical device or implant, wherein the compound is selected from compounds of Formula II:
- and pharmaceutically acceptable salts thereof, wherein:
- X is N;
- Y is CO;
- R1 and R3 are each independently selected from alkoxy, alkyl, amino, halogen, and hydrogen;
- R2 is selected from —N—C(O)—R18, —N—SO2—R18, —CH2—C(R18)3, —CH2—N(R18)2, and —CH2—O—R18, wherein each R18 is independently selected from alkoxy, alkyl, alkenyl, amide, amino, aryl, arylalkyl, cycloalkyl, haloalkyl, halogen, heteroaryl, heterocyclyl, and hydrogen;
- R6 and R8 are each independently selected from alkyl, alkoxy, amino, halogen, and hydrogen;
- R5 and R9 are each hydrogen;
- R7 is selected from amino, amide, alkyl, hydroxyl, and alkoxy;
- R10 is hydrogen;
- each W is independently selected from C and N, wherein if W is N, then p is 0 or 1, and if W is C, then p is 1;
- for W—(R10)p, W is N and p is 1;
- for W—(R7)p, W is C and p is 1;
- for W—(R4)p, W is C, p is 1 and R4 is H, or W is N and p is 0;
- Z1 is a double bond, and Z2 and Z3 are each a single bond;
- with the proviso that if R7 is selected from alkyl, hydroxyl, and alkoxy, then at least one of R6 and R8 is independently selected from alkyl, alkoxy, amino, and halogen.
A method of treating or reducing the risk of acquiring a cardiovascular-, cholesterol-, or lipid-related disorder in a mammal suffering from or at risk of acquiring such disorder comprising administering a therapeutically effective amount of a compound via surgical device or implant, wherein the compound is selected from compounds of Formula II:
- and pharmaceutically acceptable salts thereof, wherein:
- X is N;
- Y is CO;
- R1 is selected from alkoxy or amino;
- R3 is alkoxy;
- R2 is selected from alkoxy, alkyl, alkenyl, alkynyl, amide, amino, halogen, and hydrogen;
- R6 and R8 are each independently selected from alkyl, alkoxy, amino, halogen, and hydrogen;
- R5 and R9 are each hydrogen;
- R7 is selected from amino, amide, alkyl, hydroxyl, and alkoxy;
- R10 is hydrogen;
- each W is independently selected from C and N, wherein if W is N, then p is 0 or 1, and if W is C, then p is 1;
- for W—(R10)p, W is N and p is 1;
- for W—(R7)p, W is C and p is 1;
- for W—(R4)p, W is C, p is 1 and R4 is H, or W is N and p is 0;
- Z1 is a double bond, and Z2 and Z3 are each a single bond.
A method of increasing levels of high density lipoprotein cholesterol (HDL-C) in a mammal comprising administering a therapeutically effective amount of a compound via surgical device or implant, wherein the compound is selected from compounds of Formula II:
- and pharmaceutically acceptable salts thereof, wherein:
- X is N;
- Y is CO;
- R1 and R3 are each independently selected from alkoxy, alkyl, amino, halogen, and hydrogen;
- R2 is selected from alkoxy, alkyl, alkenyl, alkynyl, amide, amino, halogen, and hydrogen;
- R6 and R8 are each independently selected from alkyl, alkoxy, amino, halogen, and hydrogen;
- R5 and R9 are each hydrogen;
- R7 is selected from amino, amide, alkyl, hydroxyl, and alkoxy;
- R10 is hydrogen;
- each W is independently selected from C and N, wherein if W is N, then p is 0 or 1, and if W is C, then p is 1;
- for W—(R10)p, W is N and p is 1;
- for W—(R7)p, W is C and p is 1;
- for W—(R4)p, W is C, p is 1 and R4 is H, or W is N and p is 0;
- Z1 is a double bond, and Z2 and Z3 are each a single bond;
- with the proviso that if R1 is hydrogen, then R3 is alkoxy;
- with the proviso that if R3 is hydrogen, then R1 is selected from amino and alkoxy;
- with the proviso that if R7 is selected from alkyl, hydroxyl, and alkoxy, then at least one of R6 and R8 is independently selected from alkyl, alkoxy, amino, and halogen.
Dependencies are inferred from the claim text.