Compounds of estrogen-related receptor modulators and the uses thereof

Abstract

The compounds according to formula (VIII), their pharmaceutically acceptable acid or base addition salts, and the uses thereof. These compounds and their pharmaceutically acceptable acid or base addition salts can be used for preparing medicaments for modulating estrogen related receptors (ERR), and treating metabolic diseases, such as high blood fat, fatty liver, hyperglycemia, diabetes, obesity. The substituents of the formula are defined in the description.

What is claimed is: 
     
         1 . A compound of Formula VIII or a pharmaceutically acceptable salt or stereoisomer thereof: 
       
         
           
           
               
               
           
         
       
       wherein:
 m is 0, 1 or 2; 
 n is 1 or 2; 
 in the following, a is 0 or 1, b is 0 or 1; 
 each occurrence of R 1  is independently selected from the group consisting of:
 1) Halo; 
 2) OH; 
 3) (C═O) a O b C 1 -C 4  alkyl; and 
 4) (C═O) a O b C 3 -C 6  cycloalkyl, 
 wherein one occurrence of R 1  is at the 8-position of the pyrido[1,2-a]pyrimidin-4-one ring; 
 
 each occurrence of R 2  is independently selected from the group consisting of:
 1) Halo; 
 2) OH; 
 3) (C═O) a O b C 1 -C 4  alkyl, wherein, if a is 0 and b is 1, the alkyl is substituted with C 3 -C 6  heterocyclyl; or 
 4) (C═O) a O b C 3 -C 6  cycloalkyl; 
 wherein, if one occurrence R 7  is halo or C 1 -C 4  alkyl, at least one occurrence of R 1  is OH or (C═O) a O b C 1 -C 4  alkyl wherein a is 0 and b is 1; 
 
 R 2  is selected from the group consisting of:
 1) H; 
 2) C 1 -C 3  alkyl; and 
 3) C 3 -C 6  cycloalkyl; 
 
 the alkyl mentioned above can be substituted by 0, 1 or more substituted R 4  groups wherein R 4  is selected from the group consisting of:
 1) H; and 
 2) C 3 -C 6  heterocyclyl, 
 
 
     
     
         2 . A compound or pharmaceutically acceptable salt or stereoisomer thereof wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         3 . A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or stereo isomer according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         4 . A method of treating a metabolic disease, the method comprising administering an effective amount of a composition of  claim 3  to a patient in need thereof. 
     
     
         5 . The method of  claim 4 , wherein the metabolic disease is: (1) Type II diabetes; (2) hyperglycemia; (3) reduced glucose tolerance; (4) insulin resistance; (5) obesity; (6) abnormal fat metabolism; (7) dyslipidemia; (8) hyperlipidemia; (9) hypertriglyceridemia; (10) hypercholesterolemia; (11) low levels of HDL; (12) high levels of LDL; (13) atherosclerosis; (14) vascular restenosis; (15) central obesity; (16) metabolic syndrome; or (17) fatty liver. 
     
     
         6 . A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or stereoisomer according to  claim 2  and a pharmaceutically acceptable carrier.