Compounds, compositions and methods useful for cholesterol mobilization

Abstract

The invention relates to classes of pharmaceutically-active heterocyclic compounds and pharmaceutically acceptable salts, and hydrates thereof, and compositions comprising the same. The invention also relates to methods for treating or preventing a disease or disorder, which comprises administering a therapeutically or prophylactically effective amount a compound described herein.

1 . A compound or a pharmaceutically acceptable salt thereof, wherein the compound is:
 (a) a compound of Formula (I):   
       
         
           
           
               
               
           
         
         wherein 
         each of R 1 , R 2 , and R 3  is independently H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O— heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ;
 R 4  is —H, —OH, —COOH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), -hydrocarbyl, —O-hydrocarbyl, -aryl, —O-aryl, -aralkyl, —O-aralkyl, -heteroaryl, —O-heteroaryl, -heterocyclyl, —O-heterocyclyl, -halo, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), or —OC(O)N(alkyl)(alkyl); 
 Z 1  is CH 2 , S, O, NH, N-hydrocarbyl, N-aryl, N-heteroaryl, or N-heterocyclyl; 
 Z 2  is CH or N; and 
 n is an integer from 1-6; 
 
         (b) a compound of Formula (II): 
       
       
         
           
           
               
               
           
         
         wherein
 each R 9  is independently —H, -hydrocarbyl, -aryl, -aralkyl, -heteroaryl, -heterocyclyl, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), or —SO 2 NH 2 ; 
 each R 10  is independently —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O— alkyl, —O-alkenyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O— heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), NHC(O)(C 2 -C 10 -alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; 
 each of Q 1 , Q 2 , and Q 3  is independently CR 10  or N; 
 X is CHR 10 , S, O, or NR 9 ; and 
 each m is independently an integer from 0-3; 
 
         (c) a compound of Formula (III): 
       
       
         
           
           
               
               
           
         
         wherein
 each of R 1 , R 2 , and R 3  is independently H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O-heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; 
 R 5  is —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralkyl, heteroaryl, —O-heteroaryl, heterocyclyl, or —O-heterocyclyl; 
 Z 1  is CH 2 , S, O, NH, N-hydrocarbyl, N-aryl, N-heteroaryl, or N-heterocyclyl; 
 Z 2  is CH or N; and 
 n is an integer from 1-6; 
 
         (d) a compound of Formula (IV): 
       
       
         
           
           
               
               
           
         
         wherein
 R 1  is H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O-heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; 
 Z 1  is CH 2 , S, O, NH, N-hydrocarbyl, N-aryl, N-heteroaryl, or N-heterocyclyl; and 
 Z 2  is CH or N; 
 
         (e) a compound of Formula (V): 
       
       
         
           
           
               
               
           
         
         wherein
 each of R 1 , R 2 , and R 3  is independently H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O-heterocyclyl, halo, OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; 
 R 4  is —H, —OH, —COOH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralkyl, heteroaryl, —O-heteroaryl, heterocyclyl, —O-heterocyclyl, halo, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), or —OC(O)N(alkyl)(alkyl); 
 R 6  is —H, —OH, —SH, —S-hydrocarbyl, —COOH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralkyl, heteroaryl, —O-heteroaryl, heterocyclyl, —O-heterocyclyl, halo, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), or —OC(O)N(alkyl)(alkyl); 
 R 7  is H, hydrocarbyl, aryl, aralkyl, heteroaryl, or heterocyclyl; 
 Z 2  is CH or N; and 
 n is an integer from 1-6; 
 
         (f) a compound of Formula (VI): 
       
       
         
           
           
               
               
           
         
         wherein
 R 1 , is H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O-heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; 
 
         R 5  is —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralkyl, heteroaryl, —O-heteroaryl, heterocyclyl, —O-heterocyclyl, or halo;
 R 6  is —H, —OH, —SH, —S-hydrocarbyl, —COOH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralkyl, heteroaryl, —O-heteroaryl, heterocyclyl, —O-heterocyclyl, halo, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), or —OC(O)N(alkyl)(alkyl); 
 R 7  is H, hydrocarbyl, aryl, aralkyl, heteroaryl, or heterocyclyl; and 
 Z 2  is CH or N; 
 
         (g) a compound of Formula (VII): 
       
       
         
           
           
               
               
           
         
         wherein
 each of R 1a , R 1b , and R 1c  is independently —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O-heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; 
 each X is independently CHR 10 , S, O, or NR 9 ; 
 
         each R 9  is independently H, hydrocarbyl, aryl, aralkyl, heteroaryl, heterocyclyl, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), or —SO 2 N H 2 ;
 each R 10  is independently —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O— hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O— heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; and 
 m is an integer from 0-3; 
 
         (h) a compound of Formula (VIII): 
       
       
         
           
           
               
               
           
         
         wherein
 R 1  is —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O-hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O-heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; 
 
         R 11  is H, hydrocarbyl, aryl, aralkyl, heteroaryl, heterocyclyl, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), or —SO 2 NH 2 ;
 each of Q 1 , Q 2 , Q 3 , and Q 4  is independently CR 10  or N; and 
 
         each R 10  is independently —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O— hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O— heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; 
         (i) a compound of Formula (IX): 
       
       
         
           
           
               
               
           
         
         wherein
 each of R 11a , R 11b , and R 11c  is independently H, hydrocarbyl, aryl, aralkyl, heteroaryl, heterocyclyl, —C(O)(alkyl), —C(O)O(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), or —SO 2 NH 2 ; 
 each of X 1  and X 2  is independently CHR 10 , S, O, NR 9 , or N-acyl; 
 each R 9  is independently H, hydrocarbyl, aryl, aralkyl, heteroaryl, heterocyclyl, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), or —SO 2 NH 2 ; 
 each R 10  is independently —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O— hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O— heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; and 
 
         each m is independently an integer from 1-3, 
         (j) a compound of Formula (XII): 
       
       
         
           
           
               
               
           
         
         wherein
 each R 9  is independently —H, -hydrocarbyl, -aryl, -aralkyl, -heteroaryl, -heterocyclyl, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), or —SO 2 NH 2 ; 
 each R 10  is independently —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O— alkyl, —O-alkenyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O— heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), NHC(O)(C 2 -C 10 -alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), —SO 2 NH 2 , —S-alkyl, —S-aryl, —S— heteroaryl, —S-heterocycle, or —S— hydrocarbyl; 
 each of Q 1 , Q 2 , and Q 3  is independently CR 10  or N; 
 X is CHR 10 , S, O, or NR 9 ; and 
 each m is independently an integer from 0-3; or 
 
         (k) a compound of Formula (XIII): 
       
       
         
           
           
               
               
           
         
         wherein
 R 1  is is independently —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O— hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O— heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; 
 
         R 11  is H, hydrocarbyl, aryl, aralkyl, heteroaryl, heterocyclyl, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), or —SO 2 NH 2 ;
 each of Q 1 , Q 2 , Q 3 , and Q 4  is independently CR 10  or N; 
 n is an integer from 1-4 and 
 
         each R 10  is independently —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O— hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O— heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 . 
       
     
     
         2 - 6 . (canceled) 
     
     
         7 . A composition comprising an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1  and a pharmaceutically acceptable vehicle or carrier. 
     
     
         8 - 10 . (canceled) 
     
     
         11 . A method for treating or preventing a disorder of lipoprotein metabolism, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1 . 
     
     
         12 . (canceled) 
     
     
         13 . A method of treating a disorder of glucose metabolism, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1 . 
     
     
         14 . (canceled) 
     
     
         15 . A method of treating a cardiovascular disorder, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1 . 
     
     
         16 - 18 . (canceled) 
     
     
         19 . A method of treating inflammation, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1 . 
     
     
         20 . A method of treating ischemic necrosis, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1 . 
     
     
         21 . A method of treating colon cancer, lung cancer, breast cancer, or skin cancer, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1 . 
     
     
         22 . A method of treating a thrombotic disorder, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1 . 
     
     
         23 . A method of treating Alzheimer's Disease, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1 . 
     
     
         24 . A method of treating Parkinson's Disease, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1 . 
     
     
         25 . A method of treating pancreatitis, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1 . 
     
     
         26 . A method of treating pancreatitius, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1 . 
     
     
         27 . A method of treating abnormal bile production, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of  claim 1 . 
     
     
         28 . A method of monitoring the progress of therapy for a cardiovascular disorder in a subject, the method comprising:
 a. determining the level of free cholesterol in the high-density lipoprotein in the blood of the subject;   b. administering to the subject a compound of  claim 1 ;   c. monitoring the level of free cholesterol in the blood of the subject for a period of time after administration of the compound; and   d. evaluating the level of improvement in the subject based on a comparison of the results of steps a. and c.   
     
     
         29 . (canceled) 
     
     
         30 . A method of determining the level of P2Y13 activity in a subject, the method comprising:
 a. determining the level of free cholesterol in the high-density lipoprotein in the blood of the subject;   b. administering to the subject a compound of  claim 1 ;   c. monitoring the level of free cholesterol in the blood of the subject for a period of time after administration of the compound; and   d. evaluating the level of P2Y13 activity in the subject based on a comparison of the results of steps a. and c.   
     
     
         31 - 91 . (canceled) 
     
     
         92 . A method for treating or preventing a disorder, the method comprising administering to a subject in need thereof an effective amount of a compound or pharmaceutically acceptable salt of the compound of:
 Formula X:   
       
         
           
           
               
               
           
         
       
       wherein
 each R 9  is independently —H, -hydrocarbyl, -aryl, -aralkyl, -heteroaryl, -heterocyclyl, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), or —SO 2 NH 2 ;
 each R 10  is independently —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O— hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O— heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; 
 each of Q 1 , Q 2 , and Q 3  is independently CR 10  or N; 
 X is CHR 10 , S, O, or NR 9 ; and 
 each m is independently an integer from 0-3; or 
 
 Formula XI: 
 
       
         
           
           
               
               
           
         
       
       wherein
 each of R 11a , R 11b , and R 11c  is independently H, hydrocarbyl, aryl, aralkyl, heteroaryl, heterocyclyl, —C(O)(alkyl), —C(O)O(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), or —SO 2 NH 2 ; 
 each of X 1  and X 2  is independently CHR 10 , S, O, NR 9 , or N-acyl; 
 each R 9  is independently H, hydrocarbyl, aryl, aralkyl, heteroaryl, heterocyclyl, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), or —SO 2 NH 2 ;
 each R 10  is independently —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O— hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O— heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; and 
 
 each m is independently an integer from 0-3, 
 wherein the disorder is a disorder of lipoprotein metabolism, a disorder of glucose metabolism, a cardiovascular disorder, inflammation, ischemic necrosis, colon cancer, lung cancer, breast cancer, skin cancer, a thrombotic disorder, Alzheimer's Disease, Parkinson's Disease, pancreatitis, pancreatitius, or abnormal bile production. 
 
     
     
         93 - 97 . (canceled) 
     
     
         98 . A method of monitoring the progress of therapy for a cardiovascular disorder in a subject, the method comprising:
 a. determining the level of free cholesterol in the high-density lipoprotein in the blood of the subject;   b. administering to the subject a compound or a pharmaceutically acceptable salt of a compound of either Formula X or Formula XI;   c. monitoring the level of free cholesterol in the blood of the subject for a period of time after administration of the compound; and   d. evaluating the level of improvement in the subject based on a comparison of the results of steps a. and c.,   wherein Formula X is:   
       
         
           
           
               
               
           
         
       
       wherein
 each R 9  is independently —H, -hydrocarbyl, -aryl, -aralkyl, -heteroaryl, -heterocyclyl, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), or —SO 2 NH 2 ;
 each R 10  is independently —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O— hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O— heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; 
 each of Q 1 , Q 2 , and Q 3  is independently CR 10  or N; 
 X is CHR 10 , S, O, or NR 9 ; and 
 each m is independently an integer from 0-3; and 
 
 Formula XI is: 
 
       
         
           
           
               
               
           
         
       
       wherein
 each of R 11a , R 11b , and R 11c  is independently H, hydrocarbyl, aryl, aralkyl, heteroaryl, heterocyclyl, —C(O)(alkyl), —C(O)O(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), or —SO 2 NH 2 ; 
 each of X 1  and X 2  is independently CHR 10 , S, O, NR 9 , or N-acyl; 
 each R 9  is independently H, hydrocarbyl, aryl, aralkyl, heteroaryl, heterocyclyl, —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), or —SO 2 NH 2 ;
 each R 10  is independently —H, —OH, —NH 2 , —NH(alkyl), —N(alkyl)(alkyl), hydrocarbyl, —O— hydrocarbyl, aryl, —O-aryl, aralkyl, —O-aralykl, heteroaryl, —O-heteroaryl, heterocyclyl, —O— heterocyclyl, halo, —OCF 3 , —C(O)O(alkyl), —OC(O)(alkyl), —C(O)NH 2 , —C(O)NH(alkyl), —C(O)N(alkyl)(alkyl), —NHC(O)(alkyl), N(alkyl)C(O)(alkyl), —OC(O)O(alkyl), —OC(O)NH 2 , —OC(O)NH(alkyl), —OC(O)N(alkyl)(alkyl), —CHNH, —CHN(alkyl), or —SO 2 NH 2 ; and 
 
 each m is independently an integer from 0-3. 
 
     
     
         99 - 100 . (canceled)