ISOTOPE-ENRICHED 3-AMINO-1-PROPANESULFONIC ACID DERIVATIVES AND USES THEREOF
There are provided isotope-enriched compounds of Formula (I) and pharmaceutically acceptable salts or esters thereof, as well as pharmaceutical compositions thereof and methods of use thereof for prevention and treatment of amyloid-β related diseases, such as Alzheimer's disease. R 1 R 2 X—CR 2 —CH 2 —CH 2 —SO 3 H (I)
1 .- 41 . (canceled)
42 . A method for treatment of mild cognitive impairment in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound, such that mild cognitive impairment is treated in the subject, wherein the compound is a compound of Formula (I), or a pharmaceutically acceptable salt or ester thereof:
R 1 R 2 X—CR 2 —CH 2 —CH 2 —SO 3 H (I)
where:
R 1 and R 2 are independently a hydrogen of natural abundance or a protecting group, wherein said protecting group is isotope-enriched or non-isotope enriched, said protecting group being selected from acyl, carbonyl, thiocarbonyl, and carbamoyl groups;
X is a nitrogen of natural abundance or 15 N, or a combination thereof; and
R is a hydrogen of natural abundance, a deuterium (D) or a combination thereof;
provided that at least one of X, R, R 1 and R 2 comprises an atom that is not of natural abundance;
provided that the compound is not N-acetyl-3-amino-1-propanesulfonic acid.
43 . A method for treatment of Alzheimer's disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound, such that Alzheimer's disease is treated in the subject, wherein the compound is a compound of Formula (I), or a pharmaceutically acceptable salt or ester thereof:
R 1 R 2 X—CR 2 —CH 2 —CH 2 —SO 3 H (I)
where:
R 1 and R 2 are independently a hydrogen of natural abundance or a protecting group, wherein said protecting group is isotope-enriched or non-isotope enriched, said protecting group being selected from acyl, carbonyl, thiocarbonyl, and carbamoyl groups;
X is a nitrogen of natural abundance or 15 N, or a combination thereof; and
R is a hydrogen of natural abundance, a deuterium (D) or a combination thereof;
provided that at least one of X, R, R 1 and R 2 comprises an atom that is not of natural abundance;
provided that the compound is not N-acetyl-3-amino-1-propanesulfonic acid.
44 . A method for treatment of cerebral amyloid angiopathy (CAA) or hereditary cerebral hemorrhage in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound, such that cerebral amyloid angiopathy (CAA) or hereditary cerebral hemorrhage is treated in the subject, wherein the compound is a compound of Formula (I), or a pharmaceutically acceptable salt or ester thereof:
R 1 R 2 X—CR 2 —CH 2 —CH 2 —SO 3 H (I)
where:
R 1 and R 2 are independently a hydrogen of natural abundance or a protecting group, wherein said protecting group is isotope-enriched or non-isotope enriched, said protecting group being selected from acyl, carbonyl, thiocarbonyl, and carbamoyl groups;
X is a nitrogen of natural abundance or 15 N, or a combination thereof; and
R is a hydrogen of natural abundance, a deuterium (D) or a combination thereof;
provided that at least one of X, R, R 1 and R 2 comprises an atom that is not of natural abundance;
provided that the compound is not N-acetyl-3-amino-1-propanesulfonic acid.
45 . A method for treatment of inclusion body myositis in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound, such that inclusion body myositis is treated in the subject, wherein the compound is a compound of Formula (I), or a pharmaceutically acceptable salt or ester thereof:
R 1 R 2 X—CR 2 —CH 2 —CH 2 —SO 3 H (I)
where:
R 1 and R 2 are independently a hydrogen of natural abundance or a protecting group, wherein said protecting group is isotope-enriched or non-isotope enriched, said protecting group being selected from acyl, carbonyl, thiocarbonyl, and carbamoyl groups;
X is a nitrogen of natural abundance or 15 N, or a combination thereof; and
R is a hydrogen of natural abundance, a deuterium (D) or a combination thereof;
provided that at least one of X, R, R 1 and R 2 comprises an atom that is not of natural abundance;
provided that the compound is not N-acetyl-3-amino-1-propanesulfonic acid.
46 . A method for treatment of age-related macular degeneration in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound, such that age-related macular degeneration is treated in the subject, wherein the compound is a compound of Formula (I), or a pharmaceutically acceptable salt or ester thereof:
R 1 R 2 X—CR 2 —CH 2 —CH 2 —SO 3 H (I)
where:
R 1 and R 2 are independently a hydrogen of natural abundance or a protecting group, wherein said protecting group is isotope-enriched or non-isotope enriched, said protecting group being selected from acyl, carbonyl, thiocarbonyl, and carbamoyl groups;
X is a nitrogen of natural abundance or 15 N, or a combination thereof; and
R is a hydrogen of natural abundance, a deuterium (D) or a combination thereof;
provided that at least one of X, R, R 1 and R 2 comprises an atom that is not of natural abundance;
provided that the compound is not N-acetyl-3-amino-1-propanesulfonic acid.