Phosphono-carboxylate compounds for treating amyloidosis
First Claim
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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:
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in whichR1 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.
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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.
31 Citations
31 Claims
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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:
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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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
in which Ra and Rb are each independently hydrogen, alkyl, aryl, or heterocyclyl, or Ra and Rb, taken together with the nitrogen atom to which they are attached, form a cyclic moiety having from 3 to 8 atoms in the ring.
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15. The method of claim 14, in which Ra and Rb are each hydrogen.
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16. A method for treating a disease state associated with amyloidosis, comprising:
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administering to a subject a therapeutic compound in an amount effective to modulate amyloid deposition such that amyloid deposition is modulated in said subject and said disease state associated with amyloidosis is treated, wherein the therapeutic compound has the formula
in whichR1 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. - View Dependent Claims (17, 18, 19, 20, 21, 22, 23, 24, 25, 26)
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27. 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:
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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. - View Dependent Claims (28, 29, 30, 31)
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Specification
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Current AssigneeBellus Health (Interational) Limited
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Original AssigneeNeurochem Incorporated, Queen's University At Kingston
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InventorsKong, Xianqi, Szarek, Walter A.
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Primary Examiner(s)Reamer, James H.
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Application NumberUS09/288,583Time in Patent Office978 DaysField of Search514/120US Class Current514/120CPC Class CodesA61K 31/66 Phosphorus compoundsA61K 31/662 Phosphorus acids or esters ...A61K 31/675 having nitrogen as a ring h...A61P 25/00 Drugs for disorders of the ...
