ß- AND y -DIKETONES AND y -HYDROXYKETONES AS WNT/ ß -CATENIN SIGNALING PATHWAY ACTIVATORS

Abstract

The present application discloses a compound which iswhich activates Wnt/β-catenin signaling and thus treats or prevents diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries related to the differentiation and development of the central nervous system, comprising Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, comprising hair loss, hematopoiesis related diseases and tissue regeneration related diseases.

1 . A compound or pharmaceutically acceptable salt or prodrug thereof having the structure of formula I: 
       
         
           
           
               
               
           
         
         wherein R 1  is a substituted or unsubstituted heteroaryl, wherein the heteroaryl is selected from the group consisting of 
       
       
         
           
           
               
               
           
         
       
       with the proviso that a carbon atom is attached to the carbonyl;
 R 2  is selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl and substituted or unsubstituted heterocyclyl, with the proviso that a carbon atom is attached to the carbonyl; and 
 R 3 , R 4 , R 5  and R 6  are independently selected from a group consisting of —C 1-9 alkyl, —C 1-9 alkylaryl and —C 1-9 alkylheteroaryl. 
 
     
     
         2 . The compound of  claim 1 , wherein R 2  is selected from the group consisting of substituted or unsubstituted aryl, 
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound of  claim 1 , wherein R 3  and R 4  are H. 
     
     
         4 . The compound of  claim 1 , having a structure of: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt thereof. 
     
     
         5 . A pharmaceutical composition comprising a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 
     
     
         6 . A method of treating alopecia or hair loss in a mammal, comprising topically administering to the mammal a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof.