Back to results
US 2026/0216142 A1Published application
Uses of zln-005 and related compounds
OwnerSatoshi GOJOinventor
Life of this patent
Estimating the term…
Abstract
Methods of treating diseases and disorders associated with impaired lysosomal acidification, methods for increasing lysosomal acidity, and methods of treating sepsis, infection, and diseases and disorders associated with V-ATPase dysfunction with ZLN-005 and other compounds of Formula (I), and salts, hydrates, deuterated analogs, and fluorinated analogs thereof.
Claims49
A method of treating a subject having a disease or disorder associated with impaired lysosomal acidification, comprising administering to the subject a therapeutically effective amount of an agent which is a compound of Formula (I):
- or a salt, hydrate, deuterated analog, or fluorinated analog thereof, wherein:
- Ar is
- W1 is N—R1, O, or S, or when W9 is N, W1 may additionally be C—R50;
- W2 is C—R2 or N;
- W3 is C—R3 or N;
- W4 is C—R4 or N;
- W5 is C—R5 or N;
- W6 is C—R6 or N;
- W7 is C—R7 or N;
- W8 is C—R8 or N;
- W9 is C, or when W1 is C—R50, W9 may be N;
- R1 is H, (C1-C3)alkyl, CH2OC(═O)R30, CH2OP(═O)OR40OR41, C(═O)OR42, or C(═O)R43;
- each of R2, R3, R4, and R5 is independently hydrogen, deuterium, halogen, perfluoro(C1-C4)alkyl, (C1-C4)alkyl, (C1-C4)alkoxy, perfluoro(C1-C4)alkoxy, (C1-C4)acyl, (C1-4)alkoxy(C1-C4)alkyl, hydroxy(C1-C4)alkyl, hydroxy, carboxy, (C1-C4)alkoxycarbonylamino, carboxamido, (C1-C4)alkylaminocarbonyl, cyano, acetoxy, nitro, amino, (C1-C4)alkylamino, di(C1-C4)alkylamino, mercapto, (C1-C4)alkylthio, aminosulfonyl, (C1-C4)alkylsulfonyl, or (C1-C4)acylamino;
- each of R6 and R10 is independently hydrogen, deuterium, halo, (C1-C3)alkyl, perfluoro(C1-C3)alkyl, hydroxy, (C1-C3)alkoxy, perfluoro(C1-C3)alkoxy, or amino;
- each of R7 and R8 is independently hydrogen, deuterium, hydroxy, cyano, amino, halogen, halo(C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy,
- R8 is hydrogen, deuterium, halogen, halo(C1-C4)alkyl, (C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy, cyano, phenyl, phenoxy, benzyloxy, amino,
- R30 is (C1-C10)hydrocarbyl, (C1-C10)hydrocarbyl substituted with amino, (C1-C10)hydrocarbyl substituted with (C1-C4)hydrocarbyl, (C1-C10)hydrocarbyl substituted with carboxyl, carboxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkoxycarbonylamino, methylthio, heterocyclyl, (C1-C10)oxaalkyl, CHR44NHR45 and guanidine;
- each of R40 and R41 is independently hydrogen or (C1-C6)hydrocarbyl;
- R42 is (C1-C5)alkyl;
- R43 is (C1-C3)alkyl,
- R44 is a naturally occurring amino acid sidechain;
- R45 is H, methyl, or (C1-C4)alkoxycarbonyl;
- and
- R50 is H or (C1-C3)alkyl.
21 more elements
A method for increasing lysosomal acidity in a subject, comprising administering to the subject an amount of an agent which is a compound of Formula (I):
- or a salt, hydrate, deuterated analog, or fluorinated analog thereof effective to increase lysosomal acidity in the subject, wherein:
- Ar is
- W1 is N—R1, O, or S, or when W9 is N, W1 may additionally be C—R50;
- W2 is C—R2 or N;
- W3 is C—R3 or N;
- W4 is C—R4 or N;
- W5 is C—R5 or N;
- W6 is C—R6 or N;
- W7 is C—R7 or N;
- W8 is C—R8 or N;
- W9 is C, or when W1 is C—R50, W9 may be N;
- R1 is H, (C1-C3)alkyl, CH2OC(═O)R30, CH2OP(═O)OR40OR41, C(═O)OR42, or C(═O)R43;
- each of R2, R3, R4, and R5 is independently hydrogen, deuterium, halogen, perfluoro(C1-C4)alkyl, (C1-C4)alkyl, (C1-C4)alkoxy, perfluoro(C1-C4)alkoxy, (C1-C4)acyl, (C1-4)alkoxy(C1-C4)alkyl, hydroxy(C1-C4)alkyl, hydroxy, carboxy, (C1-C4)alkoxycarbonylamino, carboxamido, (C1-C4)alkylaminocarbonyl, cyano, acetoxy, nitro, amino, (C1-C4)alkylamino, di(C1-C4)alkylamino, mercapto, (C1-C4)alkylthio, aminosulfonyl, (C1-C4)alkylsulfonyl, or (C1-C4)acylamino;
- each of R6 and R10 is independently hydrogen, deuterium, halo, (C1-C3)alkyl, perfluoro(C1-C3)alkyl, hydroxy, (C1-C3)alkoxy, perfluoro(C1-C3)alkoxy, or amino;
- each of R7 and R9 is independently hydrogen, deuterium, hydroxy, cyano, amino, halogen, halo(C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy,
- R8 is hydrogen, deuterium, halogen, halo(C1-C4)alkyl, (C1-C4)alkyl, (C1-C4)alkoxy, halo(C1—C4)alkoxy, cyano, phenyl, phenoxy, benzyloxy, amino,
- R30 is (C1-C10)hydrocarbyl, (C1-C10)hydrocarbyl substituted with amino, (C1-C10)hydrocarbyl substituted with (C1-C4)hydrocarbyl, (C1-C10)hydrocarbyl substituted with carboxyl, carboxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkoxycarbonylamino, methylthio, heterocycyl, (C1-C10)oxaalkyl, CHR44NHR45 and guanidine;
- each of R40 and R41 is independently hydrogen or (C1-C6)hydrocarbyl;
- R42 is (C1-C5)alkyl;
- R43 is (C1-C3)alkyl,
- R44 is a naturally occurring amino acid sidechain;
- R45 is H, methyl, or (C1-C4)alkoxycarbonyl;
- and
- R50 is H or (C1-C3)alkyl.
21 more elements
A method of treating a subject having sepsis, an infection, or a disease or disorder associated with V-ATPase dysfunction, comprising administering to the subject a therapeutically effective amount of an agent which is a compound of Formula (I):
- or a salt, hydrate, deuterated analog, or fluorinated analog thereof, wherein:
- Ar is
- W1 is N—R1, O, or S, or when W9 is N, W1 may additionally be C—R50;
- W2 is C—R2 or N;
- W3 is C—R3 or N;
- W4 is C—R4 or N;
- W5 is C—R5 or N;
- W6 is C—R6 or N;
- W7 is C—R7 or N;
- W8 is C—R8 or N;
- W9 is C, or when W1 is C—R50, W9 may be N;
- R1 is H, (C1-C3)alkyl, CH2OC(═O)R30, CH2OP(═O)OR40OR41, C(═O)OR42, or C(═O)R43;
- each of R2, R3, R4, and R5 is independently hydrogen, deuterium, halogen, perfluoro(C1-C4)alkyl, (C1-C4)alkyl, (C1-C4)alkoxy, perfluoro(C1-C4)alkoxy, (C1-C4)acyl, (C1-4)alkoxy(C1-C4)alkyl, hydroxy(C1-C4)alkyl, hydroxy, carboxy, (C1-C4)alkoxycarbonylamino, carboxamido, (C1-C4)alkylaminocarbonyl, cyano, acetoxy, nitro, amino, (C1-C4)alkylamino, di(C1-C4)alkylamino, mercapto, (C1-C4)alkylthio, aminosulfonyl, (C1-C4)alkylsulfonyl, or (C1-C4)acylamino;
- each of R6 and R10 is independently hydrogen, deuterium, halo, (C1-C3)alkyl, perfluoro(C1-C3)alkyl, hydroxy, (C1-C3)alkoxy, perfluoro(C1-C3)alkoxy, or amino;
- each of R7 and R9 is independently hydrogen, deuterium, hydroxy, cyano, amino, halogen, halo(C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy,
- R8 is hydrogen, deuterium, halogen, halo(C1-C4)alkyl, (C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy, cyano, phenyl, phenoxy, benzyloxy, amino,
- R30 is (C1-C10)hydrocarbyl, (C1-C10)hydrocarbyl substituted with amino, (C1-C10)hydrocarbyl substituted with (C1-C4)hydrocarbyl, (C1-C10)hydrocarbyl substituted with carboxyl, carboxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkoxycarbonylamino, methylthio, heterocyclyl, (C1-C10)oxaalkyl, CHR44NHR45 and guanidine;
- each of R40 and R41 is independently hydrogen or (C1-C6)hydrocarbyl;
- R42 is (C1-C5)alkyl;
- R43 is (C1-C3)alkyl,
- R44 is a naturally occurring amino acid sidechain;
- R45 is H, methyl, or (C1-C4)alkoxycarbonyl;
- and
- R50 is H or (C1-C3)alkyl.
21 more elements
Dependencies are inferred from the claim text.