Phosphono-carboxylate compounds for treating amyloidosis
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.