Phosphono-carboxylate compounds for treating amyloidosis
AssigneeQueen's University at Kingston
InventorsWalter A. Szarek, Xianqi Kong, Gregory R.J Thatcher, Boris Gorine
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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.
Claims33
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:
- 12
- in which
- R1 and R2 are each independently hydrogen, a substituted or unsubstituted aliphatic group, an aryl group, a heterocyclic group, or a salt-forming cation;
- R3 is hydrogen, lower alkyl, aryl, or a salt-forming cation;
- R4 is hydrogen, lower alkyl, aryl or amino;
- X is, independently for each occurrence, O or S;
- Y1 and Y2 are each independently hydrogen, halogen, alkyl, amino, hydroxy, alkoxy, or aryloxy;
- Z is XR2 or R4;
- and
- n is an integer from 0 to 12.
A method for treating a disease state associated with amyloidosis, comprising:
- administering to a subject an effective amount of a therapeutic compound such that a disease state associated with amyloidosis is treated, wherein the therapeutic compound has the formula 15
- in which
- R1 and R2 are each independently hydrogen, an aliphatic group, an aryl group, a heterocyclyl group, or a salt-forming cation;
- R3 is hydrogen, lower alkyl, aryl or a salt-forming cation;
- Y1 and Y2 are each independently hydrogen, halogen, lower alkyl, amino, hydroxy, alkoxy, or aryloxy;
- and
- n is an integer from 0 to 12.
A method for modulating amyloid deposition in a subject in which said amyloid deposition is characterized by interaction between an amyloidogenic protein and a constituent of a basement membrane, the method comprising administering to the subject an effective amount of a therapeutic compound such that modulation of amyloid deposition characterized by interaction between an amyloidogenic protein and a constituent of a basement membrane occurs, wherein the therapeutic compound has the formula:
- 16
- in which
- R1 and R2 are each independently hydrogen, an aliphatic group, an aryl group, a heterocyclyl group, or a salt-forming cation;
- R3 is hydrogen, lower alkyl, aryl or a salt-forming cation;
- Y1 and Y2 are each independently hydrogen, halogen, lower alkyl, amino, hydroxy, alkoxy, or aryloxy;
- and
- n is an integer from 0 to 12.
A method for preparing a compound represented by the formula:
- 17
- in which R is alkyl or aryl, and R′ is hydrogen, alkyl, or aryl;
- the method comprising:
- reacting an ester of a carbonylphosphono diacid halide with a disiylether of a vicianl diol, under conditions such that the compound of Formula V is prepared.
A compound represented by the formula (Formula IV):
- 18
- wherein G is hydrogen or one of more substituents on the aryl ring and the L is a substituted alkyl group.
Dependencies are inferred from the claim text.