Treating Various Disorders Using TrkB Agonists

Abstract

Novel compounds and methods for activating the TrkB receptor are provided. The methods include administering in vivo or in vitro a therapeutically effective amount of a compound containing four six-membered rings and a substituted or unsubstituted C 5 or C 6 heteroaryl or heterocycloalkyl ring and pharmaceutically acceptable salts, prodrugs, and derivatives thereof. Specifically, methods and compounds for the treatment of disorders including neurologic, neuropsychiatric, and metabolic disorders are provided. For example, a method is provided of treating or reducing the risk of depression, anxiety, or obesity in a subject, which includes selecting a subject with or at risk of developing depression, anxiety, or obesity, and administering to the subject a therapeutically effective amount of the described compounds. A further method of promoting neuroprotection in a subject is provided, which includes selecting a subject in need of neuroprotection, and administering to the subject a therapeutically effective amount of the described compounds.

What is claimed is: 
     
         1 . A method of enhancing memory comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising a compound of the following formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or prodrug thereof, wherein: 
         R 1  and R 2  are each independently selected from hydrogen, substituted or unsubstituted C 1-12  alkyl, substituted or unsubstituted C 1-12  haloalkyl, substituted or unsubstituted C 2-12  alkenyl, substituted or unsubstituted C 2-12  alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkylalkyl, and substituted or unsubstituted heterocycloalkylalkyl; 
         R 3  is hydrogen, carbonyl, hydroxyl, —O—R 1 , —O—(C═O)—R 1 , or —NR 5 R 6 , wherein R 5  and R 6 , are each independently selected from R 1 ; 
         R 4  is carbonyl, —R 1 , —O—R 1 , or —O—(C═O)—R 1 ; 
         A is a substituted or unsubstituted C 5  or C 6  heteroaryl or C 5  or C 6  heterocycloalkyl; 
            is a single or double bond, wherein two double bonds are not adjacent; and 
           is a double bond or 
       
       
         
           
           
               
               
           
         
       
     
     
         2 . The method of  claim 1  wherein the compound is 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         3 . The method of  claim 1 , wherein the subject is diagnosed with a disease associated with neurodegeneration. 
     
     
         4 . The method of  claim 1 , wherein the subject is diagnosed with Alzheimer's disease. 
     
     
         5 . The method of  claim 1 , wherein the subject is diagnosed with Parkinson's disease. 
     
     
         6 . The method of  claim 1 , wherein the subject is diagnosed with Huntington's disease.