US2016106750A1PendingUtilityA1

Compounds for the prevention and treatment of cardiovascular diseases

58
Assignee: HANSEN HENRIK CPriority: Feb 1, 2007Filed: Oct 26, 2015Published: Apr 21, 2016
Est. expiryFeb 1, 2027(~0.6 yrs left)· nominal 20-yr term from priority
A61P 9/10A61P 9/00A61P 3/06A61P 3/00C07D 403/12A61K 31/535A61K 31/5377A61K 31/54A61K 31/44C07D 239/91A61K 31/496A61L 2420/00A61K 31/695A61K 31/47A61L 29/16A61K 31/519A61K 31/497A61K 31/4375A61K 31/517A61K 31/472A61L 2300/204C07D 217/24A61L 2300/606C07F 7/1804C07D 401/04A61L 31/16C07D 279/02C07D 471/04C07D 405/04C07D 413/06
58
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Claims

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.

Claims

exact text as granted — not AI-modified
1 - 75 . (canceled) 
     
     
         76 . 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; 
 R 1  and R 3  are each independently selected from alkoxy, alkyl, amino, halogen, and hydrogen; 
 R 2  is selected from alkoxy, alkyl, alkenyl, alkynyl, amide, amino, halogen, and hydrogen; 
 R 6  and R 8  are each independently selected from alkyl, alkoxy, amino, halogen, and hydrogen; 
 R 5  and R 9  are each hydrogen; 
 R 7  is selected from amino, amide, alkyl, hydroxyl, and alkoxy; 
 R 10  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—(R 10 ) p , W is N and p is 1; 
 for W—(R 7 ) p , W is C and p is 1; 
 for W—(R 4 ) p , W is C, p is 1 and R 4  is H, or W is N and p is 0; 
 Z 1  is a double bond, and Z 2  and Z 3  are each a single bond; 
 with the proviso that if R 1  is hydrogen, then R 3  is alkoxy; 
 with the proviso that if R 3  is hydrogen, then R 1  is selected from amino and alkoxy; 
 with the proviso that if R 7  is selected from alkyl, hydroxyl, and alkoxy, then at least one of R 6  and R 8  is independently selected from alkyl, alkoxy, amino, and halogen. 
 
     
     
         77 . The method according to  claim 76 , wherein R 7  is amino. 
     
     
         78 . The method according to  claim 77 , 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. 
     
     
         79 . The method according to  claim 76 , wherein R 7  is selected from hydroxyl and alkoxy. 
     
     
         80 . The method according to  claim 79 , 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; and   pharmaceutically acceptable salts thereof.   
     
     
         81 . The method according to  claim 79 , wherein R 6  and R 8  are each independently alkyl;
 R 2  is hydrogen; and   R 7  is selected from hydroxyl and alkoxy substituted with a hydroxyl.   
     
     
         82 . The method according to  claim 81 , 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. 
     
     
         83 . The method according to  claim 76 , wherein R 7  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(R h ) 2 —, —S(O) 2 N(R h ) 2 —, —C(O)—, —S(O) 2 —, —C(O)O—, wherein each R h  is selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; and 
         R 20 , if present, is selected from (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkenyl, (C 1 -C 6 ) alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen. 
       
     
     
         84 . The method according to  claim 83 , 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; and   pharmaceutically acceptable salts thereof.   
     
     
         85 . The method according to  claim 76 , 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-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-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; and   pharmaceutically acceptable salts thereof.   
     
     
         86 . 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.   
     
     
         87 . 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; 
 R 1  and R 3  are each independently selected from alkoxy and hydrogen; 
 R 2  is selected from alkoxy, alkyl, and hydrogen; 
 R 6  and R 8  are each independently selected from alkyl, alkoxy, chloride, and hydrogen; 
 R 5  and R 9  are each hydrogen; 
 R 7  is selected from amino, hydroxyl, alkoxy, and alkyl substituted with a heterocyclyl; 
 R 10  is hydrogen; or 
 two adjacent substituents selected from R 6 , R 7 , and R 8  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—(R 10 ) p , W is N and p is 1; 
 for W—(R 4 ) p , W is C, p is 1 and R 4  is H, or W is N and p is 0; 
 Z 1  is a double bond, and Z 2  and Z 3  are each a single bond; 
 with the proviso that if R 2  is alkoxy or hydrogen, then least one of R 1  and R 3  is alkoxy; 
 with the proviso that if R 7  is selected from hydroxyl and alkoxy, then at least one of R 6  and R 8  are independently selected from alkyl, alkoxy, and chloride; 
 with the proviso that if for W—(R 7 ) p , W is N and p is 0, then at least one of R 6  and R 8  is selected from alkyl, alkoxy, and chloride. 
 
     
     
         88 . The method according to  claim 87 , wherein the compound of Formula II is selected from:
 3-(4-hydroxy-3,5-dimethylphenyl)-6,8-dimethoxyisoquinolin-1(2H)-one;   3-(4-(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-d]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-methylphthalamide;   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; and   pharmaceutically acceptable salts thereof.   
     
     
         89 . The method according to  claim 87 , wherein R 7  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(R h ) 2 —, —S(O) 2 N(R h ) 2 —, —C(O)—, —S(O) 2 —, and —C(O)O—, wherein each R h  is independently selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; and 
         R 20 , if present, is selected from (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkenyl, (C 1 -C 6 ) alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen. 
       
     
     
         90 . The method of  claim 89 , 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-methylphthalamide;   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; and   pharmaceutically acceptable salts thereof.   
     
     
         91 . 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; 
 R 1  and R 3  are each independently selected from alkoxy, alkyl, amino, halogen, and hydrogen; 
 R 2  is selected from —N—C(O)—R 18 , —N—SO 2 —R 18 , —CH 2 —C(R 18 ) 3 , —CH 2 —N(R 18 ) 2 , and —CH 2 —O—R 18 , wherein each R 18  is independently selected from alkoxy, alkyl, alkenyl, amide, amino, aryl, arylalkyl, cycloalkyl, haloalkyl, halogen, heteroaryl, heterocyclyl, and hydrogen; 
 R 6  and R 8  are each independently selected from alkyl, alkoxy, amino, halogen, and hydrogen; 
 R 5  and R 9  are each hydrogen; 
 R 7  is selected from amino, amide, alkyl, hydroxyl, and alkoxy; 
 R 10  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—(R 10 ) p , W is N and p is 1; 
 for W—(R 7 ) p , W is C and p is 1; 
 for W—(R 4 ) p , W is C, p is 1 and R 4  is H, or W is N and p is 0; 
 Z 1  is a double bond, and Z 2  and Z 3  are each a single bond; 
 with the proviso that if R 7  is selected from alkyl, hydroxyl, and alkoxy, then at least one of R 6  and R 8  is independently selected from alkyl, alkoxy, amino, and halogen. 
 
     
     
         92 . The method according to  claim 91 , 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;   and   pharmaceutically acceptable salts thereof.   
     
     
         93 . The method according to  claim 91 , wherein R 6  and R 8  are each independently alkyl; and R 7  is selected from hydroxyl and alkoxy. 
     
     
         94 . The method according to  claim 91 , wherein R 7  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(R h ) 2 —, —S(O) 2 N(R h ) 2 —, —C(O)—, —S(O) 2 —, —C(O)O—, wherein each R h  is selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; and 
         R 20 , if present, is selected from (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkenyl, (C 1 -C 6 ) alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen. 
       
     
     
         95 . The method according to  claim 91 , wherein R 6  and R 8  are each independently alkyl. 
     
     
         96 . 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; 
 R 1  is selected from alkoxy or amino; 
 R 3  is alkoxy; 
 R 2  is selected from alkoxy, alkyl, alkenyl, alkynyl, amide, amino, halogen, and hydrogen; 
 R 6  and R 8  are each independently selected from alkyl, alkoxy, amino, halogen, and hydrogen; 
 R 5  and R 9  are each hydrogen; 
 R 7  is selected from amino, amide, alkyl, hydroxyl, and alkoxy; 
 R 10  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—(R 10 ) p , W is N and p is 1; 
 for W—(R 7 ) p , W is C and p is 1; 
 for W—(R 4 ) p , W is C, p is 1 and R 4  is H, or W is N and p is 0; 
 Z 1  is a double bond, and Z 2  and Z 3  are each a single bond. 
 
     
     
         97 . The method according to  claim 96 , wherein R 7  is selected from hydroxyl and alkoxy. 
     
     
         98 . The method according to  claim 97 , 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; and   pharmaceutically acceptable salts thereof.   
     
     
         99 . The method according to  claim 96 , wherein R 7  is selected from amide and amino. 
     
     
         100 . The method according to  claim 99 , 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; and   pharmaceutically acceptable salts thereof.   
     
     
         101 . The method according to  claim 96 , wherein R 7  is alkyl. 
     
     
         102 . The method according to  claim 101 , 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; and   pharmaceutically acceptable salts thereof.   
     
     
         103 . The method according to  claim 96 , wherein R 6  and R 8  are each independently alkyl. 
     
     
         104 . The method according to  claim 96 , wherein R 7  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(R h ) 2 —, —S(O) 2 N(R h ) 2 —, —C(O)—, —S(O) 2 —, —C(O)O—, wherein each R h  is selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; and 
         R 20 , if present, is selected from (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkenyl, (C 1 -C 6 ) alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen. 
       
     
     
         105 . The method according to  claim 104 , wherein R 6  and R 8  are each independently alkyl. 
     
     
         106 . The method of  claim 76 , 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 hypercholeasterolemia, 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. 
     
     
         107 . The method of  claim 87 , 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 hypercholeasterolemia, 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. 
     
     
         108 . The method of  claim 91 , 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 hypercholeasterolemia, 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. 
     
     
         109 . The method of  claim 96 , 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 hypercholeasterolemia, 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. 
     
     
         110 . The method of  claim 86 , 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 hypercholeasterolemia, 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. 
     
     
         111 . The method according to  claim 76 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is selected from diabetes mellitus, myocardial infarction, coronary artery disease, coronary heart disease, familial hypercholeasterolemia, acute coronary syndrome, angina, atherosclerosis, arteriosclerosis, renal artery atherosclerosis, peripheral vascular disease, congestive heart failure, stroke, and Alzheimer's disease. 
     
     
         112 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is diabetes mellitus. 
     
     
         113 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is myocardial infarction. 
     
     
         114 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is coronary artery disease. 
     
     
         115 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is coronary heart disease. 
     
     
         116 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is familial hypercholeasterolemia. 
     
     
         117 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is acute coronary syndrome. 
     
     
         118 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is angina. 
     
     
         119 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is atherosclerosis. 
     
     
         120 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is arteriosclerosis. 
     
     
         121 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is renal artery atherosclerosis. 
     
     
         122 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is peripheral vascular disease. 
     
     
         123 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is congestive heart failure. 
     
     
         124 . The method of  claim 82 , wherein the cardiovascular-, cholesterol-, or lipid-related disorder is Alzheimer's disease. 
     
     
         125 . 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; 
 R 1  and R 3  are each independently selected from alkoxy, alkyl, amino, halogen, and hydrogen; 
 R 2  is selected from alkoxy, alkyl, alkenyl, alkynyl, amide, amino, halogen, and hydrogen; 
 R 6  and R 8  are each independently selected from alkyl, alkoxy, amino, halogen, and hydrogen; 
 R 5  and R 9  are each hydrogen; 
 R 7  is selected from amino, amide, alkyl, hydroxyl, and alkoxy; 
 R 10  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—(R 10 ) p , W is N and p is 1; 
 for W—(R 7 ) p , W is C and p is 1; 
 for W—(R 4 ) p , W is C, p is 1 and R 4  is H, or W is N and p is 0; 
 Z 1  is a double bond, and Z 2  and Z 3  are each a single bond; 
 with the proviso that if R 1  is hydrogen, then R 3  is alkoxy; 
 with the proviso that if R 3  is hydrogen, then R 1  is selected from amino and alkoxy; 
 with the proviso that if R 7  is selected from alkyl, hydroxyl, and alkoxy, then at least one of R 6  and R 8  is independently selected from alkyl, alkoxy, amino, and halogen. 
 
     
     
         126 . The method of  claim 76 , wherein the surgical device is a catheter. 
     
     
         127 . The method of  claim 126 , wherein the catheter is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         128 . The method of  claim 76 , wherein the implant is a stent. 
     
     
         129 . The method of  claim 128 , wherein the stent is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         130 . The method of  claim 86 , wherein the surgical device is a catheter. 
     
     
         131 . The method of  claim 130 , wherein the catheter is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         132 . The method of  claim 86 , wherein the implant is a stent. 
     
     
         133 . The method of  claim 132 , wherein the stent is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         134 . The method of  claim 87 , wherein the surgical device is a catheter. 
     
     
         135 . The method of  claim 134 , wherein the catheter is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         136 . The method of  claim 87 , wherein the implant is a stent. 
     
     
         137 . The method of  claim 136 , wherein the stent is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         138 . The method of  claim 91 , wherein the surgical device is a catheter. 
     
     
         139 . The method of  claim 138 , wherein the catheter is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         140 . The method of  claim 91 , wherein the implant is a stent. 
     
     
         141 . The method of  claim 140 , wherein the stent is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         142 . The method of  claim 96 , wherein the surgical device is a catheter. 
     
     
         143 . The method of  claim 142 , wherein the catheter is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         144 . The method of  claim 96 , wherein the implant is a stent. 
     
     
         145 . The method of  claim 144 , wherein the stent is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         146 . The method of  claim 125 , wherein the surgical device is a catheter. 
     
     
         147 . The method of  claim 146 , wherein the catheter is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         148 . The method of  claim 125 , wherein the implant is a stent. 
     
     
         149 . The method of  claim 148 , wherein the stent is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         150 . The method of  claim 82 , wherein the surgical device is a catheter. 
     
     
         151 . The method of  claim 150 , wherein the catheter is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof. 
     
     
         152 . The method of  claim 82 , wherein the implant is a stent. 
     
     
         153 . The method of  claim 152 , wherein the stent is coated with the compound of Formula II or a pharmaceutically acceptable salt thereof.

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