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

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)

What is claimed is: 
     
         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.