Isotope-enriched 3-amino-1-propanesulfonic acid derivatives and uses thereof
AssigneeRisen (Suzhou) Pharma Tech Co., Ltd.
InventorsJiasheng Lu, Jiamin Gu, Xinyong Lv, Guowei Song, Dongdong Wu, Daiqiang Hu, Jun Gu, Gang Chen, Xiang Ji, Xiuchun Zhang, Jinchao Ai, Xianqi Kong
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Abstract
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. R1R2X—CR2—CH2—CH2—SO3H (I)
Claims17
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:
- R1R2X—CR2—CH2—CH2—SO3H (I)
- where:
- R1 and R2 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 R1 and R2 is a protecting group;
- X is a nitrogen of natural abundance or 15N, 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, R1 and R2 comprises an atom that is not of natural abundance;
- provided that the compound is not N-acetyl-3-amino-1-propanesulfonic acid.
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 15N 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 13C or a combination thereof;
- Z is a sulfur of natural abundance, an oxygen of natural abundance, an 18O, an 17O or a combination thereof;
- and
- R3 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.
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:
- R4 is a side chain of a natural or unnatural amino acid;
- O* is an oxygen atom of natural abundance, an 18O, an 17O or a combination thereof;
- and
- C* is a carbon atom of natural abundance, a 13C or a combination thereof;
- X is a nitrogen of natural abundance, a 15N 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.
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:
- R4 is a side chain of a natural or unnatural amino acid;
- O* is an oxygen atom of natural abundance, an 18O, an 17O or a combination thereof;
- and
- C* is a carbon atom of natural abundance, a 13C or a combination thereof;
- provided that the compound is not N-acetyl-3-amino-1-propanesulfonic acid.
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:
- R4 is a side chain of a natural or unnatural amino acid;
- O# is an oxygen atom of natural abundance, an 18O, an 17O or a combination thereof;
- C# is a carbon atom of natural abundance, a 13C 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.
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.
Dependencies are inferred from the claim text.