Isotope-enriched 3-amino-1-propanesulfonic acid derivatives and uses thereof

1. A method for treatment of cerebral amyloid angiopathy 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 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, wherein at least one of R 1 and R 2 is a protecting group;

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.

2. The method of claim 1 , wherein:

R is a hydrogen of natural abundance and X is 15 N;

R is D and X is a nitrogen of natural abundance;

R is D and X is 15 N; or

R is a hydrogen of natural abundance; X is a nitrogen of natural abundance; and at least one atom in R 1 and/or R 2 is not of natural abundance.

3. The method of claim 1 , wherein:

R 1 and R 2 are each a hydrogen of natural abundance;

X is 15 N; and

R is a hydrogen of natural abundance, a deuterium (D) or a combination thereof.

4. The method of claim 1 , wherein one of R 1 and R 2 is a hydrogen and one of R 1 and R 2 is a protecting group.

5. A method for treatment of cerebral amyloid angiopathy 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 or hereditary cerebral hemorrhage is treated in the subject, wherein the compound is a compound of Formula (III), or a pharmaceutically acceptable salt or ester thereof:

where:

X is a nitrogen of natural abundance, a 15 N or a combination thereof;

R is a hydrogen of natural abundance, a deuterium (D) or a combination thereof;

Y is a carbon of natural abundance, a 13 C or a combination thereof;

Z is a sulfur of natural abundance, an oxygen of natural abundance, an 18 O, an 17 O or a combination thereof; and

R 3 is a substituting group selected from substituted or unsubstituted alkyl, aryl, amino alkyl, amino arylalkyl, heterocyclyl, alkoxyl, alkylthio, alkylamino, acyloxyl, and thioacyloxyl;

provided that at least one of X, R, Y and Z is not an atom of natural abundance;

provided that the compound is not N-acetyl-3-amino-1-propanesulfonic acid.

6. The method of claim 5 , wherein:

R is not a hydrogen of natural abundance when X is a nitrogen of natural abundance;

R 3 , Y, and Z taken together form an acyl group connected to X, forming an amide bond linkage; or

R 3 is a natural or unnatural amino acid residue and R 3 , Y, and Z taken together form an acyl group connected to X, the acyl group being derived from a natural or unnatural amino acid.

7. The method of claim 6 , wherein the natural or unnatural amino acid is an L-amino acid, a D-amino acid, or a mixture thereof.

8. A method for treatment of cerebral amyloid angiopathy 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 or hereditary cerebral hemorrhage is treated in the subject, wherein the compound is a compound of Formula (IV), or a pharmaceutically acceptable salt or ester thereof:

where:

R 4 is a side chain of a natural or unnatural amino acid;

O* is an oxygen atom of natural abundance, an 18 O, an 17 O or a combination thereof; and

C* is a carbon atom of natural abundance, a 13 C or a combination thereof;

X is a nitrogen of natural abundance, a 15 N or a combination thereof;

provided that at least one of O*, C*, and X is not an atom of natural abundance;

provided that the compound is not N-acetyl-3-amino-1-propanesulfonic acid.

9. The method of claim 8 , wherein the natural or unnatural amino acid is an L-amino acid, a D-amino acid, or a mixture thereof.

10. A method for treatment of cerebral amyloid angiopathy 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 or hereditary cerebral hemorrhage is treated in the subject, wherein the compound is a compound of Formula (V), or a pharmaceutically acceptable salt or ester thereof:

where:

R 4 is a side chain of a natural or unnatural amino acid;

O* is an oxygen atom of natural abundance, an 18 O, an 17 O or a combination thereof; and

C* is a carbon atom of natural abundance, a 13 C or a combination thereof;

provided that the compound is not N-acetyl-3-amino-1-propanesulfonic acid.

11. The method of claim 10 , wherein the natural or unnatural amino acid is an L-amino acid, a D-amino acid, or a mixture thereof.

12. A method for treatment of cerebral amyloid angiopathy 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 or hereditary cerebral hemorrhage is treated in the subject, wherein the compound is a compound of Formula (VI), or a pharmaceutically acceptable salt or ester thereof:

where:

R 4 is a side chain of a natural or unnatural amino acid;

O # is an oxygen atom of natural abundance, an 18 O, an 17 O or a combination thereof;

C # is a carbon atom of natural abundance, a 13 C or a combination thereof;

provided that at least one of O # and C # is an isotope-enriched atom;

provided that the compound is not N-acetyl-3-amino-1-propanesulfonic acid.

13. The method of claim 12 , wherein the natural or unnatural amino acid is an L-amino acid, a D-amino acid, or a mixture thereof.

14. The method of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt or ester thereof.

15. The method of claim 1 , wherein the level of isotope enrichment in the compound with isotopes that are not of natural abundance is about 2% or more, about 5% or more, about 10% or more, about 20% or more, about 50% or more, about 75% or more, about 90% or more, about 95% or more, or 100%.

16. The method of claim 1 , wherein the subject is ApoE4 positive.

17. A method for treatment of cerebral amyloid angiopathy 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 or hereditary cerebral hemorrhage is treated in the subject, wherein the compound is

or a pharmaceutically acceptable salt or ester thereof.