Deuterated analogs of acetyl-leucine
AssigneeIntrabio Ltd.
InventorMICHIKO MANN
Life of this patent
Estimating the term…
Abstract
The present disclosure provides compounds represented by Formula I: I, and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are as defined as set forth in the specification, and the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more. The present disclosure also provides compounds having Formula I for use to treat or delay the progression of a lysosomal storage disorder or a neurodegenerative disease in a subject, provide neuroprotection in a subject having a lysosomal disorder, treat or prevent a migraine, and the symptoms associated therewith, in a subject, or improve mobility and/or cognitive function in a subject.
Claims56
A compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more,
- with the provisos that:
- (a) at least one of R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12 is hydrogen when R13 is hydrogen;
- and
- (b) and the compound is not:
A method of treating or delaying the progression of a lysosomal storage disorder, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more.
A method of providing neuroprotection in a subject having a lysosomal storage disorder, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more.
A method of treating or delaying the progression of a neurodegenerative disease, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more.
A method of treating or delaying the progression of a neurodegenerative disease associated with defects in lysosomal storage, treating or preventing a migraine, and the symptoms associated therewith, improving mobility and/or cognitive function, treating or preventing restless legs syndrome, or treating or preventing vertigo, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more.
A compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more,
- for use in a method of treating or delaying progression of a lysosomal storage disorder, treating or delaying the progression of a neurodegenerative disease, treating or delaying the progression of a neurodegenerative disease associated with defects in lysosomal storage, treating or preventing a migraine, and the symptoms associated therewith, treating or preventing restless legs syndrome, and the symptoms associated therewith, treating or preventing vertigo, and the symptoms associated therewith, or improving mobility and/or cognitive function.
A compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more,
- for use in providing neuroprotection in a subject having a lysosomal disorder.
Use of a compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more,
- in the manufacture of a medicament for treating or delaying progression of a lysosomal storage disorder, treating or delaying the progression of a neurodegenerative disease, treating or delaying the progression of a neurodegenerative disease associated with defects in lysosomal storage, treating or preventing a migraine, and the symptoms associated therewith, treating or preventing restless legs syndrome, and the symptoms associated therewith, treating or preventing vertigo, and the symptoms associated therewith, or improving mobility and/or cognitive function.
Use of a compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more,
- in the manufacture of a medicament for providing neuroprotection in a subject having a lysosomal disorder.
A pharmaceutical composition comprising a compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more, and
- a pharmaceutically acceptable carrier,
- for use in a method of treating or delaying progression of a lysosomal storage disorder, treating or delaying the progression of a neurodegenerative disease, treating or delaying the progression of a neurodegenerative disease associated with defects in lysosomal storage, treating or preventing a migraine, and the symptoms associated therewith, treating or preventing restless legs syndrome, and the symptoms associated therewith, treating or preventing vertigo, and the symptoms associated therewith, or improving mobility and cognitive function.
A pharmaceutical composition comprising a compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more, and
- a pharmaceutically acceptable carrier,
- for use in providing neuroprotection in a subject having a lysosomal disorder.
A kit comprising a compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more, and instructions for administering the compound to a subject to treat or delay progression of a lysosomal storage disorder, treating or delaying the progression of a neurodegenerative disease, treating or delaying the progression of a neurodegenerative disease associated with defects in lysosomal storage, treating or preventing a migraine, and the symptoms associated therewith, treating or preventing restless legs syndrome, and the symptoms associated therewith, treating or preventing vertigo, and the symptoms associated therewith, or improving mobility and cognitive function.
A kit comprising a compound having Formula I:
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R2 is C1-6 alkyl;
- and
- R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently selected from the group consisting of hydrogen and deuterium,
- wherein the deuterium enrichment of any one or more of R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 is about 15% or more, and instructions for administering the compound to provide neuroprotection in a subject having a lysosomal disorder.
Dependencies are inferred from the claim text.