Thyroid hormone receptor agonist and use thereof

Abstract

A thyroid hormone receptor agonist and its use in the treatment of a disease associated thyroid hormone receptor beta are described. The compound can be effective in lowering cholesterol with minimum or no adverse effects on the heart or thyroid hormone axis.

What is claimed is: 
     
         1 . A compound having a structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof 
       
     
     
         2 . A pharmaceutical composition comprising the compound of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         3 . A method for the treatment of a disease that is associated with thyroid hormone receptor β, comprising administering an effective amount of the compound of  claim 1  to a subject in need thereof. 
     
     
         4 . The method of  claim 3 , wherein the disease is selected from the group consisting of obesity, hyperlipidemia, hypercholesterolemia and diabetes, non-alcoholic fatty liver disease, NASH (nonalcoholic steatohepatitis), atherosclerosis, cardiovascular diseases, hypothyroidism, and thyroid cancer. 
     
     
         5 . A method of agonizing thyroid hormone receptor β, comprising contacting the thyroid hormone receptor β with an effective amount of the compound of  claim 1  to a subject in need thereof. 
     
     
         6 . A method for lowering cholesterol levels comprising administering an effective amount of the compound of  claim 1  to a subject in need thereof. 
     
     
         7 . A method for lowering triglyceride levels comprising administering an effective amount of the compound of  claim 1  to a subject in need thereof. 
     
     
         8 . A method of preventing or treating a metabolic disease comprising administering to a subject in need thereof a pharmaceutically effective amount of the compound of  claim 1 . 
     
     
         9 . The method of  claim 8 , wherein the metabolic disease is selected from the group consisting of obesity, hypercholesterolemia, hyperlipidemia, atherosclerosis, coronary heart disease, and hypertension. 
     
     
         10 . The method of  claim 3 , further comprising administering an additional therapeutic agent. 
     
     
         11 . The method of  claim 3 , wherein the compound has a plasma half-life of less than 6 hours. 
     
     
         12 . The method of  claim 3 , wherein the LDL level of the subject is reduced by at least 10% post administration compared to pre-administration level. 
     
     
         13 . The method of  claim 3 , wherein the LDL level of the subject is reduced by at least 20% post administration compared to pre-administration level. 
     
     
         14 . The method of  claim 3 , wherein the triglyceride level of the subject is reduced by at least 10% post administration compared to pre-administration level. 
     
     
         15 . The method of  claim 3 , wherein the triglyceride level of the subject is reduced by at least 20% post administration compared to pre-administration level. 
     
     
         16 . The method of  claim 3 , wherein the level of total T4 in the subject has a change of less than 50% post administration compared to pre-administration level. 
     
     
         17 . The method of  claim 3 , wherein the level of total T3 in the subject has a change of less than 50% post administration compared to pre-administration levels. 
     
     
         18 . The method of  claim 3 , wherein the level of thyroid-stimulating hormone (THS) in the subject has a change of less than 50% post administration compared to pre-administration level. 
     
     
         19 . The method of  claim 3 , wherein the compound is administered parenterally. 
     
     
         20 . The method of  claim 3 , wherein the compound is administered orally.