Phosphono-carboxylate compounds for treating amyloidosis

Abstract

Therapeutic compounds and methods for modulating amyloid deposition in a subject, whatever its clinical setting, are described. Amyloid deposition is modulated by the administration to a subject of an effective amount of a therapeutic compound comprising a phosphonate group and a carboxylate group, a congener thereof, or a pharmaceutically acceptable salt or ester thereof. In preferred embodiments, an interaction between an amyloidogenic protein and a basement membrane constituent is modulated.

1 . A method for modulating amyloid deposition in a subject, comprising administering to a subject an effective amount of a therapeutic compound such that modulation of amyloid deposition occurs, wherein the therapeutic compound has the formula:  
     
       
         
         
             
             
         
       
     
     in which 
 R 1  and R 2  are each independently hydrogen, a substituted or unsubstituted aliphatic group, an aryl group, a heterocyclic group, or a salt-forming cation;  
 R 3  is hydrogen, lower alkyl, aryl, or a salt-forming cation;  
 R 4  is hydrogen, lower alkyl, aryl or amino;  
 X is, independently for each occurrence, O or S;  
 Y 1  and Y 2  are each independently hydrogen, halogen, alkyl, amino, hydroxy, alkoxy, or aryloxy;  
 Z is XR 2  or R 4 ; and  
 n is an integer from 0 to 12.