Myricanol Derivatives and Uses Thereof for Treatment of Neurodegenerative Diseases

Abstract

The subject invention pertains to myricanol derivatives, therapeutic compositions, and methods for treatment of neurodegenerative diseases, in particular, neurodegenerative dieses associated with abnormal accumulation of protein tau.

1 . A method of reducing intracellular tau levels, wherein said method comprises administering, to cells comprising protein tau, an effective amount of a compound of formula G, formula H, or formula I: 
       
         
           
           
               
               
           
         
         wherein each of R 1 -R 3  of formula G and formula I is, independently, —H or any group that forms an ester or ether bond; and 
         wherein each of R 1  and R 2  of formula H is, independently, —H or any group that forms an ester or ether bond; 
         whereby intracellular tau level is reduced. 
       
     
     
         2 . The method according to  claim 1 , wherein the compound has a chemical structure of formula G. 
     
     
         3 . The method according to  claim 1 , wherein the compound has a chemical structure of formula H. 
     
     
         4 . The method according to  claim 1 , wherein the compound has a chemical structure of formula I. 
     
     
         5 . The method according to  claim 1 , wherein the compound of formula G has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The method according to  claim 1 , wherein the compound of formula H has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The method according to  claim 1 , wherein the compound of formula I has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The method according to  claim 1 , wherein the cells are in a subject in need of treatment for a neurodegenerative disease. 
     
     
         9 . The method of  claim 1 , wherein the neurodegenerative disease is a tauopathy. 
     
     
         10 . The method of  claim 9 , wherein the subject is a human. 
     
     
         11 . The method of  claim 10 , wherein the neurodegenerative disease is selected from Alzheimer's disease, Parkinson's disease, frontotemporal dementia, frontotemporal dementia with Parkinsonism, frontotemporal lobe dementia, pallidopontonigral degeneration, progressive supranuclear palsy, multiple system tauopathy, multiple system tauopathy with presenile dementia, Wilhelmsen-Lynch disease, Pick's disease, or Pick's disease-like dementia. 
     
     
         12 . The method of  claim 11 , wherein the neurodegenerative disease is Alzheimer's disease. 
     
     
         13 . A compound of formula G, formula H, or formula I: 
       
         
           
           
               
               
           
         
         wherein each of R 1 -R 3  of formula G and formula I is, independently, any group that forms an ester or ether bond; and 
         wherein each of R 1  and R 2  of formula H is, independently, any group that forms an ester or ether bond. 
       
     
     
         14 . The method according to  claim 13 , wherein the compound has a chemical structure of formula G. 
     
     
         15 . The method according to  claim 14 , wherein the compound has a chemical structure of formula H. 
     
     
         16 . The method according to  claim 15 , wherein the compound has a chemical structure of formula I.