Compositions and methods for treating galactosemia
AssigneeApplied Therapeutics, Inc.
InventorShoshana Shendelman
Life of this patent
Estimating the term…
Abstract
The disclosure relates to methods for treating galactosemia and manifestations of galactosemia using aldose reductase inhibitors.
Claims29
A method of treating galactosemia or preventing complications associated with galactosemia, comprising administering a therapeutically effective amount of an aldose reductase inhibitor to a subject in need thereof, wherein the aldose reductase inhibitor is a compound of Formula (III) or pharmaceutically acceptable salt thereof:
- wherein,
- R1 is CO2R2;
- R2 is H, (C1-C6)-alkyl, (C1-C6)-hydroxyalkyl, or (C1-C6)-aminoalkyl;
- X1 is H or halogen;
- X2 is H or halogen;
- Y is a bond, C═O, C═S, C═NH, or C═N(C1-C4)-alkyl;
- Z is
- A1 is NR7, O, S or CH2;
- A2 is N or CH;
- A3 is NR7, O, or S;
- R3, R4, R5, and R6 are independently hydrogen, halogen, cyano, acyl, haloalkyl, haloalkoxy, haloalkylthio, trifluoroacetyl, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, or (C1-C4)-alkyl sulfonyl;
- and
- R7 is hydrogen, C1-C4-alkyl, or C(O)O—(C1-C4)-alkyl.
A method of reducing the amount or level of galactitol in a subject with galactosemia, comprising administering a therapeutically effective amount of an aldose reductase inhibitor to the subject, wherein the aldose reductase inhibitor is a compound of Formula (III) or pharmaceutically acceptable salt thereof:
- wherein,
- R1 is CO2R2;
- R2 is H, (C1-C6)-alkyl, (C1-C6)-hydroxyalkyl, or (C1-C6)-aminoalkyl;
- X1 is H or halogen;
- X2 is H or halogen;
- Y is a bond, C═O, C═S, C═NH, or C═N(C1-C4)-alkyl;
- Z is
- A1 is NR7, O, S or CH2;
- A2 is N or CH;
- A3 is NR7, O, or S;
- R3, R4, R5, and R6 are independently hydrogen, halogen, cyano, acyl, haloalkyl, haloalkoxy, haloalkylthio, trifluoroacetyl, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, or (C1-C4)-alkyl sulfonyl;
- and
- R7 is hydrogen, C1-C4-alkyl, or C(O)O—(C1-C4)-alkyl.
A method for treating cataracts, comprising administering a therapeutically effective amount of an aldose reductase inhibitor to a subject in need thereof, wherein the aldose reductase inhibitor is a compound of Formula (III) or pharmaceutically acceptable salt thereof:
- wherein,
- R1 is CO2R2;
- R2 is H, (C1-C6)-hydroxyalkyl, or (C1-C6)-aminoalkyl;
- X1 is H or halogen;
- X2 is H or halogen;
- Y is a bond, C═O, C═S, C═NH, or C═N(C1-C4)-alkyl;
- Z is
- A1 is NR7, O, S or CH2;
- A2 is N or CH;
- A3 is NR7, O, or S;
- R3, R4, R5, and R6 are independently hydrogen, halogen, cyano, acyl, haloalkyl, haloalkoxy, haloalkylthio, trifluoroacetyl, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, or (C1-C4)-alkyl sulfonyl;
- and
- R7 is hydrogen, C1-C4-alkyl, or C(O)O—(C1-C4)-alkyl.
A method for treating or preventing cognitive or neurological deficiency associated with galactosemia, comprising administering a therapeutically effective amount of an aldose reductase inhibitor to a subject with galactosemia, wherein the aldose reductase inhibitor is a compound of Formula (III) or pharmaceutically acceptable salt thereof:
- wherein,
- R1 is CO2R2;
- R2 is H, (C1-C6)-hydroxyalkyl, or (C1-C6)-aminoalkyl;
- X1 is H or halogen;
- X2 is H or halogen;
- Y is a bond, C═O, C═S, C═NH, or C═N(C1-C4)-alkyl;
- Z is
- A1 is NR7, O, S or CH2;
- A2 is N or CH;
- A3 is NR7, O, or S;
- R3, R4, R5, and R6 are independently hydrogen, halogen, cyano, acyl, haloalkyl, haloalkoxy, haloalkylthio, trifluoroacetyl, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, or (C1-C4)-alkyl sulfonyl;
- and
- R7 is hydrogen, C1-C4-alkyl, or C(O)O—(C1-C4)-alkyl.
Dependencies are inferred from the claim text.