Hdac inhibitors for the treatment of diabetic peripheral neuropathy

Abstract

The invention relates to HDAC inhibitors for use in the treatment of diabetic peripheral neuropathy in a subject in need thereof. Also provided herein are methods for treating diabetic peripheral neuropathy in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an HDAC inhibitor.

1 . A method for treating or preventing diabetic peripheral neuropathy in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an HDAC6 inhibitor. 
     
     
         2 . The method of  claim 1 , wherein the HDAC6 inhibitor is an HDAC6-specific inhibitor. 
     
     
         3 . The method of  claim 1 , wherein the HDAC6 inhibitor is a compound of Formula Ia: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein, 
         R x  is selected from H and C 1-6 -alkyl; 
         R y  is selected from H and C 1-6 -alkyl; 
         or R x  and R y  together with the carbon to which each is attached, form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; 
         each R A  is independently C 1-6 -alkyl, C 1-6 -alkoxy, halo, OH, or haloalkyl; and 
         m is 0, 1, or 2. 
       
     
     
         4 . The method of  claim 3 , wherein the compound of Formula Ia is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt thereof. 
       
     
     
         5 . The method of  claim 1 , wherein the HDAC6 inhibitor is a compound of Formula II: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein ring B is aryl or heteroaryl optionally substituted by OH, halo, or C 1-6 -alkyl; 
         R 1  is aryl or heteroaryl optionally substituted by OH, halo, or C 1-6 -alkyl; and 
         R is H or C 1-6 -alkyl. 
       
     
     
         6 . The method of  claim 5 , wherein the compound of Formula II is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         7 . The method of  claim 5 , wherein the compound of Formula II is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         8 . A compound which is 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.