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, athero
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.
대표청구항▼
1. 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 by administering a therapeutically effective amount of a compound of Formula II: or a pharmaceutically acceptable salt
1. 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 by administering a therapeutically effective amount of a compound of Formula II: or a pharmaceutically acceptable salt 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. 2. The method according to claim 1, wherein R7 is amino. 3. The method according to claim 2, wherein the compound of Formula II is 2-(4-(bis(2-hydroxyethyl)amino)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one or a pharmaceutically acceptable salt thereof. 4. The method according to claim 1, wherein R7 is selected from hydroxyl and alkoxy. 5. The method according to claim 4, wherein the compound of Formula II is selected from: N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)methanesulfonamide;2-(4-hydroxy-3-methylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-(2-hydroxyethoxy)-3-methylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(3,5-dimethyl-4-(2-morpholinoethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one; andpharmaceutically acceptable salts thereof. 6. The method according to claim 4, wherein R6 and R3 are each independently alkyl; R2 is hydrogen; andR7 is selected from hydroxyl and alkoxy substituted with a hydroxyl. 7. The method according to claim 6, wherein the compound of Formula II is 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one or a pharmaceutically acceptable salt thereof. 8. The method according to claim 1, wherein R7 is an amino or an alkoxy selected from the group represented by Formula III: wherein:A is selected from O and N;n is selected from 0, 1, 2, 3, 4 and 5;B is selected from —C(O)N(Rh)2-, —S(O)2N(Rh)2-, —C(O)—, —S(O)2—, —C(O)O—, wherein each Rh is selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; andR20, if present, is selected from (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen. 9. The method according to claim 8, wherein the compound of Formula II is selected from: 2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl cyclohexylcarbamate;N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)acetamide;N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)isobutyramide;1-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-3-phenylurea;3-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-1,1-dimethylurea; andpharmaceutically acceptable salts thereof. 10. The method according to claim 1, wherein the compound of Formula II is selected from: 2-(3,5-dimethyl-4-(2-morpholinoethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(3,5-di-tert-butyl-4-hydroxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-hydroxy-3-methoxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(3-chloro-4-hydroxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;5,7-dimethoxy-2-(4-(4-methylpiperazin-1-yl)phenyl)quinazolin-4(3H)-one;2-(4-hydroxy-3,5-dimethylphenyl)-6,7-dimethoxyquinazolin-4(3H)-one;2-(4-(6,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)acetamide;2-(3-chloro-4-(2-hydroxyethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-(2-hydroxyethoxy)-3-methoxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-6,7-dimethoxyquinazolin-4(3H)-one;N-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenyl)-2-hydroxyacetamide;2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)acetic acid;N-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)-2-hydroxyacetamide;2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H)-one;5,7-dimethoxy-2-(4-methoxy-3-(morpholinomethyl)phenyl)quinazolin-4(3H)-one;2-(3,5-dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-hydroxy-3-(2-hydroxyethyl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-(bis(2-hydroxyethyl)amino)phenyl)-5,7-dimethoxy-pyrido[2,3-d]pyrimidin-4(3H)-one,5,7-dimethoxy-2-(4-(2-methoxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one;2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5-methoxyquinazolin-4(3H)-one;(E)-N′-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenyl)-N; N-dimethylformimidamide;2-(4-(benzyloxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-(2-aminoethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methoxyphenoxy)acetic acid;2-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethyl-phenoxy)ethyl propylcarbamate;2-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethyl-phenoxy)ethyl methylcarbamate;N-(2-(4-(5,7-Dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-4-methylbenzamide;N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)benzenesulfonamide;N-(2-(4-(5,7-dimethylphenoxy)ethyl)-4-methylbenzenesulfonamide;N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-4-methoxybenzamide;N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)benzamide;1-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-3-methylurea;1-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-3-(4-methoxyphenyl)urea; andpharmaceutically acceptable salts thereof. 11. 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 by administering a therapeutically effective amount of a compound 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-methylquinazolin-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; and5-hydroxy-2-(4-hydroxy-3,5-dimethylphenyl)-7-methoxyquinazolin-4(3H)-one, and pharmaceutically acceptable salts thereof. 12. 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 by administering a therapeutically effective amount of a compound of Formula II; or a pharmaceutically acceptable salt thereof, whereinX 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; ortwo 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), 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. 13. The method according to claim 12, wherein the compound of Formula II is selected from: 3-(4-hydroxy-3,5-dimethylphenyl)-6,8-dimethoxyisoquinolin-1(2H)-one;3-O-(2-hydroxyethoxy)-3,5-dimethylphenyl)-6,8-dimethoxyisoquinolin-1(2H)-one;2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one);2-(4-hydroxy-3-methoxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-(bis(2-hydroxyethyl)amino)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-(bis(2-hydroxyethyl)amino)phenyl)-6,7-dimethoxyquinazolin-4(3H)-one;2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6,7-dimethoxyquinazolin-4(3H)-one;2-(4-((4-ethylpiperazin-1-yl)methyl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxypyrido[2,3-c]pyrimidin-4(3H)-one;2-(2-chloro-6-methylpyridin-4-yl)-5,7-dimethoxyquinazolin-4(3H)-one;5,7-dimethoxy-2-(4-methoxy-3,5-dimethylphenyl)quinazolin-4(3H)-one;2-(4-amino-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;N1-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-N2-methylphthalimide;2-(4-(2-aminoethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;4-chloro-N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)benzenesulfonamide; andpharmaceutically acceptable salts thereof. 14. The method according to claim 12, wherein R7 is selected from an amino or an alkoxy selected from the group represented by Formula III: wherein:A is selected from O and N;n is selected from 0, 1, 2, 3, 4 and 5;B is selected from —C(O)N(Rh)2-, —S(O)2N(Rh)2-, —C(O)—, —S(O)2—, and —C(O)O—, wherein each Rh is independently selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; andR20, if present, is selected from (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen. 15. The method of claim 14, wherein the compound of Formula II is selected from: N1-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-N2-methylphthalimide;2-(4-(2-aminoethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;4-chloro-N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)benzenesulfonamide; andpharmaceutically acceptable salts thereof. 16. 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 by administering a therapeutically effective amount of a compound Formula II: or a pharmaceutically acceptable salt 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—, —CH2—C(R13)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—(R1), 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. 17. The method according to claim 16, wherein the compound of Formula II is selected from: N-(2-(4-hydroxy-3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-6-yl)acetamide,2-(4-hydroxy-3,5-dimethylphenyl)-6-(morpholinomethyl)quinazolin-4(3H)-one;N-(2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-6-yl)acetamide;andpharmaceutically acceptable salts thereof. 18. The method according to claim 16, wherein R6 and R8 are each independently alkyl; and R7 is selected from hydroxyl and alkoxy. 19. The method according to claim 16, wherein R7 is selected from an amino or an alkoxy selected from the group represented by Formula III: wherein:A is selected from O and N;n is selected from 0, 1, 2, 3, 4 and 5;Bis selected from —C(O)N(Rh)2-, —S(O)2N(Rh)2-, —C(O)—, —S(O)2—, —C(O)O—, wherein each Rh is selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; andR20, if present, is selected from (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl, aryl, aryalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen. 20. The method according to claim 16, wherein R6 and R8 are each independently alkyl. 21. 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 by administering a therapeutically effective amount of a compound of Formula II: or a pharmaceutically acceptable salt thereof wherein:X is N;Y is CO;R1 is selected from alkoxy or amino;R3 is alkoxy;R7 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 Rs 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. 22. The method according to claim 21, wherein R7 is selected from hydroxyl and alkoxy. 23. The method according to claim 22, wherein the compound of Formula II is selected from: 2-(4-hydroxyphenyl)-5,7-dimethoxyquinazolin-4(3H)-one;2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenoxy)acetic acid;5,7-dimethoxy-2-(4-methoxyphenyl)quinazolin-4(3H)-one,2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenoxy)acetamide; andpharmaceutically acceptable salts thereof. 24. The method according to claim 21, wherein R7 is selected from amide and amino. 25. The method according to claim 24, wherein the compound of Formula II is selected from: 5,7-dimethoxy-2(4(4-methylpiperazin-1-yl)phenyl)quinazolin-4(3H)-one;2-(4-(bis(2-hydroxyethyl)amino)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one;5,7-dimethoxy-2-(4-morpholinophenyl)quinazolin-4(3H)-one;N-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)-2-hydroxyacetamide;2-(4-(bis(2-hydroxyethyl)amino)phenyl)-5,7-dimethoxy-pyrido[2,3-d]pyrimidin-4(3H)one; andpharmaceutically acceptable salts thereof. 26. The method according to claim 21, wherein R7 is alkyl. 27. The method according to claim 26, wherein the compound of Formula II is selected from: 3-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)propanoic acid;5,7-dimethoxy-2-(4((4-methylpiperazin-1-yl)methyl)phenyl)quinazolin-4(3H)-one;5,7-dimethoxy-2-(4-(morpholinomethyl)phenyl)quinazolin-4(3H)-one;2-(4-((4-ethylpiperazin-1-yl)methyl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one; andpharmaceutically acceptable salts thereof. 28. The method according to claim 21, wherein R6 and R8 are each independently alkyl. 29. The method according to claim 21, wherein R7 is selected from an amino or an alkoxy selected from the group represented by Formula III: wherein:A is selected from O and N;n is selected from 0, 1, 2, 3, 4 and 5;B is selected from —C(O)N(Rh)2-, —S(O)2N(Rh)2-, —C(O)—, —S(O)2—, —C(O)O—, wherein each Rh is selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; andR20, if present, is selected from (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen. 30. The method according to claim 29, wherein R6 and R8 are each independently alkyl. 31. The method of claim 1, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is selected from acute coronary syndrome, angina, arteriosclerosis, atherosclerosis, carotid atherosclerosis, cerebrovascular disease, cerebral infarction, congestive heart failure, congenital heart disease, coronary heart disease, coronary artery disease, coronary plaque stabilization, dyslipidemias, dyslipoproteinemias, endothelium dysfunctions, familial hypercholesterolemia, familial combined hyperlipidemia, hypoalphalipoproteinemia, hypertriglyceridemia, hyperbetalipoproteinemia, hypercholesterolemia, hypertension, hyperlipidemia, intermittent claudication, ischemia, ischemia reperfusion injury, ischemic heart diseases, cardiac ischemia, metabolic syndrome, multi-infarct dementia, myocardial infarction, obesity, peripheral vascular disease, reperfusion injury, restenosis, renal artery atherosclerosis, rheumatic heart disease, stroke, thrombotic disorder, transitory ischemic attacks, lipoprotein abnormalities associated with Alzheimer's disease, diabetes mellitus, syndrome X, impotence, multiple sclerosis, and Parkinson's disease. 32. The method of claim 12, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is selected from acute coronary syndrome, angina, arteriosclerosis, atherosclerosis, carotid atherosclerosis, cerebrovascular disease, cerebral infarction, congestive heart failure, congenital heart disease, coronary heart disease, coronary artery disease, coronary plaque stabilization, dyslipidemias, dyslipoproteinemias, endothelium dysfunctions, familial hypercholesterolemia, familial combined hyperlipidemia, hypoaiphalipoproteinemia, hypertriglyceridemia, hyperbetalipoproteinemia, hypercholesterolemia, hypertension, hyperlipidemia, intermittent claudication, ischemia, ischemia reperfusion injury, ischemic heart diseases, cardiac ischemia, metabolic syndrome, multi-infarct dementia, myocardial infarction, obesity, peripheral vascular disease, reperfusion injury, restenosis, renal artery atherosclerosis, rheumatic heart disease, stroke, thrombotic disorder, transitory ischemic attacks, lipoprotein abnormalities associated with Alzheimer's disease, diabetes mellitus, syndrome X, impotence, multiple sclerosis, and Parkinson's disease. 33. The method of claim 16, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is selected from acute coronary syndrome, angina, arteriosclerosis, atherosclerosis, carotid atherosclerosis, cerebrovascular disease, cerebral infarction, congestive heart failure, congenital heart disease, coronary heart disease, coronary artery disease, coronary plaque stabilization, dyslipidemias, dyslipoproteinemias, endothelium dysfunctions, familial hypecholeasterolemia, familial combined hyperlipidemia, hypoalphalipoproteinemia, hypertriglyceridemia, hyperbetalipoproteinemia, hypercholesterolemia, hypertension, hyperlipidemia, intermittent claudication, ischemia, ischemia reperfusion injury, ischemic heart diseases, cardiac ischemia, metabolic syndrome, multi-infarct dementia, myocardial infarction, obesity, peripheral vascular disease, reperfusion injury, restenosis, renal artery atherosclerosis, rheumatic heart disease, stroke, thrombotic disorder, transitory ischemic attacks, lipoprotein abnormalities associated with Alzheimer's disease, diabetes mellitus, syndrome X, impotence, multiple sclerosis, and Parkinson's disease. 34. The method of claim 21, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is selected from acute coronary syndrome, angina, arteriosclerosis, atherosclerosis, carotid atherosclerosis, cerebrovascular disease, cerebral infarction, congestive heart failure, congenital heart disease, coronary heart disease, coronary artery disease, coronary plaque stabilization, dyslipidemias, dyslipoproteinemias, endothelium dysfunctions, familial hypercholesterolemia, familial combined hyperlipidemia, hypoalphalipoproteinemia, hypertriglyceridemia, hyperbetalipoproteinemia, hypercholesterolemia, hypertension, hyperlipidemia, intermittent claudication, ischemia, ischemia reperfusion injury, ischemic heart diseases, cardiac ischemia, metabolic syndrome, multi-infarct dementia, myocardial infarction, obesity, peripheral vascular disease, reperfusion injury, restenosis, renal artery atherosclerosis, rheumatic heart disease, stroke, thrombotic disorder, transitory ischemic attacks, lipoprotein abnormalities associated with Alzheimer's disease, diabetes mellitus, syndrome X, impotence, multiple sclerosis, and Parkinson's disease. 35. The method of claim 11, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is selected from acute coronary syndrome, angina, arteriosclerosis, atherosclerosis, carotid atherosclerosis, cerebrovascular disease, cerebral infarction, congestive heart failure, congenital heart disease, coronary heart disease, coronary artery disease, coronary plaque stabilization, dyslipidemias, dyslipoproteinemias, endothelium dysfunctions, familial hypercholesterolemia, familial combined hyperlipidemia, hypoaiphalipoproteinemia, hypertriglyceridemia, hyperbetalipoproteinemia, hypercholesterolemia, hypertension, hyperlipidemia, intermittent claudication, ischemia, ischemia reperfusion injury, ischemic heart diseases, cardiac ischemia, metabolic syndrome, multi-infarct dementia, myocardial infarction, obesity, peripheral vascular disease, reperfusion injury, restenosis, renal artery atherosclerosis, rheumatic heart disease, stroke, thrombotic disorder, transitory ischemic attacks, lipoprotein abnormalities associated with Alzheimer's disease, diabetes mellitus, syndrome X, impotence, multiple sclerosis, and Parkinson's disease. 36. The method according to claim 1, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is selected from diabetes mellitus, myocardial infarction, coronary artery disease, coronary heart disease, familial hypercholesterolemia, acute coronary syndrome, angina, atherosclerosis, arteriosclerosis, renal artery atherosclerosis, peripheral vascular disease, congestive heart failure, stroke, and Alzheimer's disease. 37. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is diabetes mellitus. 38. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is myocardial infarction. 39. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is coronary artery disease. 40. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is coronary heart disease. 41. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is familial hypercholesterolemia. 42. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is acute coronary syndrome. 43. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is angina. 44. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is atherosclerosis. 45. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is arteriosclerosis. 46. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is renal artery atherosclerosis. 47. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is peripheral vascular disease. 48. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is congestive heart failure. 49. The method of claim 7, wherein the cardiovascular-, cholesterol-, or lipid-related disorder is Alzheimer's disease. 50. A method of increasing levels of high density lipoprotein cholesterol (HDL-C) in a mammal by administering a therapeutically effective amount of a compound of Formula II: or a pharmaceutically acceptable salt 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), W is N and p is 1;for W—(R7)p, W is C and p is 1;for W—(R4), 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.
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