Use of fluorinated derivatives of 4-aminopyridine in therapeutics and medical imaging

Abstract

The present disclosure provides novel compounds, including compounds that bind to potassium channels, methods for their manufacture, and methods for their use, including their use to diagnose and/or assess traumatic brain injury and use to treat dymeylinating diseases, and/or in vivo imaging of the central neverous system, and to diagnose and/or assess the progression of MS or other diseases.

1 - 15 . (canceled) 
     
     
         16 . A compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein: 
         R 1 , R 2 , R 3 , and R 4  are each a functional group independently selected from the group consisting of:
 H, X, (CH 2 ) n X, CH 2 OCH 2 CH 2 X, NH 2 , CH 2 OH, CX 3 , CFX 2 , CF 2 X, OCH 3 , OCH 2 X, OCHX 2 , OCHFX, or OCX 3 , OCFX 2 , and OCF 2 X; 
 
         R 5  is a functional group selected from the group consisting of:
 H, (CH 2 ) m X, OH, COOCX 3 , COOCFX 2 , COOCF 2 X, COOC(CH 3 ) 3 , and COO(CH 2 ) m X; 
 wherein n=1, 2, 3, 4, or 5; 
 wherein m=2, 3, 4, or 5; 
 wherein X represents fluorine or  18 F; and 
 
         wherein the compound contains at least one  18 F. 
       
     
     
         17 . The compound of  claim 16 , wherein at least one hydrogen atom is a deuterium isotope. 
     
     
         18 . The compound of  claim 16 , wherein the compound is [ 18 F]3-fluoro-4-aminopyridine. 
     
     
         19 . The compound of  claim 16 , wherein the compound 3-[ 18 F]fluoromethyl-4-aminopyridine. 
     
     
         20 . The compound of  claim 16 , wherein the compound 3-[ 18 F]fluoroethyl-4-aminopyridine. 
     
     
         21 . The compound of  claim 16 , wherein the compound 3-[ 18 F]trifluoromethyl-4-aminopyridine. 
     
     
         22 . A pharmaceutical composition comprising the compound of  claim 16  and a pharmaceutically acceptable carrier.