Compounds for the prevention and treatment of cardiovascular diseases

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.

1 - 30 . (canceled) 
     
     
         31 . A compound of Formula II: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or hydrate thereof, wherein:
 X is CR 11 ; 
 Y is SO 2 ; 
 R 11  is selected from hydrogen, unsubstituted alkyl, unsubstituted alkenyl, and unsubstituted alkynyl; 
 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 selected from hydrogen and methyl; 
 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; 
 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. 
 
     
     
         32 - 33 . (canceled) 
     
     
         34 . The compound according to  claim 31 , or a pharmaceutically acceptable salt or hydrate thereof, wherein:
 for W-(R 10 ) p , W is N and Rio is hydrogen; and   R 7  is selected from hydroxyl and alkoxy.   
     
     
         35 . (canceled) 
     
     
         36 . The compound according to  claim 34 , or a pharmaceutically acceptable salt or hydrate thereof, 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.   
     
     
         37 . (canceled) 
     
     
         38 . The compound according to  claim 31 , or a pharmaceutically acceptable salt or hydrate thereof, 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  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. 
 
       
     
     
         39 . (canceled) 
     
     
         40 . The compound according to  claim 31 , or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound of Formula II is 6,8-dimethoxy-3-(4-hydroxy-3,5-dimethylphenyl)-2H-1,2-benzothiazine-1,1-dioxide. 
     
     
         41 . (canceled) 
     
     
         42 . A pharmaceutical composition comprising a compound according to  claim 31 , or a pharmaceutically acceptable salt or hydrate thereof, and a pharmaceutically acceptable carrier. 
     
     
         43 - 76 . (canceled)