Methods for treating spinocerebellar ataxia type 3

Abstract

The present description relates to methods of treating spinocerebellar ataxia type 3 (SCA3) using substituted pyrrolo[2,3-d]pyrimidine compounds, forms, and pharmaceutical compositions thereof.

What is claimed is: 
     
         1 . A method for treating spinocerebellar ataxia type 3 (SCA3) in a subject in need thereof, comprising administering to said subject an effective amount of a compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a form thereof, wherein 
         R 1  is selected from the group consisting of phenyl and heteroaryl, wherein heteroaryl is a membered monocyclic or bicyclic aromatic carbon atom ring structure radical containing 1-3 heteroatoms selected from N, O, and S, and wherein phenyl or heteroaryl are optionally substituted with one, two, three, or four, independently selected R 1a  substituents; 
         R 1a  is independently selected from the group consisting of cyano, halo, hydroxy, C 1-6  alkyl, halo-C 1-6 alkyl, deutero-C 1-6 alkyl, and C 1-6 alkoxy; 
         R 2  is selected from the group consisting of hydrogen, halo, and C 1-6  alkyl; 
         R 3  is C 2-6  alkyl, wherein C 2-6  alkyl optionally contains a chiral carbon having an (R) or (S) configuration, and wherein C 2-6  alkyl is optionally substituted with one, two, three, or four independently selected R 3a  substituents; 
         R 3a  is independently selected from the group consisting of cyano, halo, hydroxy, C 1-6  alkyl, halo-C 1-6 alkyl, deutero-C 1-6 alkyl, C 1-6 alkoxy, amino, C 1-6 alkyl-amino, deutero-C 1-6 alkyl-amino, and (C 1-6 alkyl) 2 -amino; 
         R 4  is selected from the group consisting of hydrogen, C 1-6  alkyl, and phenyl, wherein C 1-6  alkyl or phenyl are optionally substituted with one, two, three, or four independently selected R 4a  substituents; 
         R 4a  is independently selected from the group consisting of cyano, halo, hydroxy, C 1-6 alkyl, halo-C 1-6 alkyl, and C 1-6 alkoxy; and 
         R 5  is selected from the group consisting of hydrogen, halo, and C 1-6  alkyl; 
         wherein the form of the compound is selected from the group consisting of a salt, hydrate, solvate, and tautomer form thereof. 
       
     
     
         2 . The method of  claim 1 , wherein R 1  is selected from the group consisting of phenyl, furanyl, thiophenyl, 1H-pyrazolyl, 1H-imidazolyl, isoxazolyl, 1,3-thiazolyl, 1,3-oxazolyl, tetrazolyl, 1,2,3-triazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzofuranyl, and quinolinyl. 
     
     
         3 . The method of  claim 1 , wherein R 1  is heteroaryl selected from the group consisting of furanyl, thiophenyl, 1,3-thiazolyl, 1,3-oxazolyl, and pyridinyl. 
     
     
         4 . The method of  claim 1 , wherein R 3  is C 2-6  alkyl, wherein C 2-6  alkyl contains a chiral carbon having the (S) configuration. 
     
     
         5 . The method of  claim 1 , wherein R 3  is C 2-6  alkyl, wherein C 2-6  alkyl contains a chiral carbon having the (R) configuration. 
     
     
         6 . A method for treating spinocerebellar ataxia type 3 (SCA3) in a subject in need thereof, comprising administering to said subject an effective amount of a compound or form thereof selected form the group consisting of:
 6-(3-aminopropyl)-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-(3-aminopropyl)-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   2-chloro-N-[(furan-2-yl)methyl]-6-[2-(methylamino)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   2-chloro-N-[(furan-2-yl)methyl]-6-[2-(methylamino)propyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   2-chloro-6-[2-(methylamino)ethyl]-N-[(1,3-thiazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-6-[2-(methylamino)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   2-chloro-6-[2-(dimethylamino)ethyl]-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-(2-aminoethyl)-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   2-chloro-N-[(furan-2-yl)methyl]-6-2-[( 2 H 3 )methylamino]ethyl 1-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2R)-2-amino-3-methylbutyl]-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2R)-2-amino-3-methylbutyl]-2-chloro-N-[(pyridin-4-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2,5-dichloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2R)-2-amino-3-methylbutyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2R)-2-amino-3-methylbutyl]-2-chloro-5-fluoro-N-[(pyridin-4-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   2,5-dichloro-N-[(furan-2-yl)methyl]-6-[2-(methyl amino)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   5-bromo-2-chloro-N-[(furan-2-yl)methyl]-6-[2-(methyl amino)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-5-bromo-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(pyridin-4-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminobutyl]-2,5-dichloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(1,3-thiazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2,5-dichloro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(thiophen-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminobutyl]-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(1,3-oxazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-5-butyl-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2R)-2-amino-3,3-dim ethylbutyl]-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-3-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(3-fluoropyridin-4-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2R,3S)-2-amino-3-methylpentyl]-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-5-fluoro-N-[(furan-2-yl)methyl]-2-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-5,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(1,3-thiazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2R)-2-amino-3-methoxypropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(1,3-thiazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   (2R)-2-amino-3-(2-chloro-5-fluoro-4-{[(furan-2-yl)methyl]amino}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)propan-1-ol;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(thiophen-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(3-fluoropyridin-4-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-7-ethyl-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(pyridin-4-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminobutyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminobutyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-(4-methoxyphenyl)-N-[(thiophen-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(1,3-thiazol-5-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(thiophen-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-N-benzyl-2-chloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-N-benzyl-2-chloro-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(2-fluorophenyl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(2-fluorophenyl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(pyridin-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(pyridin-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(pyridin-3-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(pyridin-3-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminobutyl]-2-chloro-5-fluoro-N-[(thiophen-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminobutyl]-2-chloro-5-fluoro-N-[(1,3-thiazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2R)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(1,3-thiazol-4-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine; and   6-[(2S)-2-aminopropyl]-2-bromo-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;
 wherein the form of the compound is selected from the group consisting of a salt, hydrate, solvate, and tautomer form thereof. 
   
     
     
         7 . The method of  claim 6 , wherein the compound or form thereof is selected from the group consisting of:
 6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   2,5-dichloro-N-[(furan-2-yl)methyl]-6-[2-(methylamino)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2,5-dichloro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-5,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(1,3-thiazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(3-fluoropyridin-4-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(pyridin-4-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine; and   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(thiophen-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine;
 wherein the form of the compound is selected from the group consisting of a salt, hydrate, solvate, and tautomer form thereof. 
   
     
     
         8 . A method for treating spinocerebellar ataxia type 3 (SCA3) in a subject in need thereof, comprising administering to said subject an effective amount of a compound salt or form thereof selected form the group consisting of:
 6-(3-aminopropyl)-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-(3-aminopropyl)-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   2-chloro-N-[(furan-2-yl)methyl]-6-[2-(methylamino)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   2-chloro-N-[(furan-2-yl)methyl]-6-[2-(methylamino)propyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   2-chloro-6-[2-(methylamino)ethyl]-N-[(1,3-thiazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-6-[2-(methylamino)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-(2-aminoethyl)-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   2-chloro-N-[(furan-2-yl)methyl]-6-2-[( 2 H 3 )methylamino]ethyl 1-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2R)-2-amino-3-methylbutyl]-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2R)-2-amino-3-methylbutyl]-2-chloro-N-[(pyridin-4-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride;   6-[(2S)-2-aminopropyl]-2,5-dichloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2R)-2-amino-3-methylbutyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2R)-2-amino-3-methylbutyl]-2-chloro-5-fluoro-N-[(pyridin-4-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride;   2,5-dichloro-N-[(furan-2-yl)methyl]-6-[2-(methylamino)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   5-bromo-2-chloro-N-[(furan-2-yl)methyl]-6-[2-(methylamino)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-5-bromo-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminobutyl]-2,5-dichloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(1,3-thiazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2,5-dichloro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(thiophen-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(1,3-oxazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-5-butyl-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2R)-2-amino-3,3-dimethylbutyl]-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-3-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(3-fluoropyridin-4-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride;   6-[(2R,3S)-2-amino-3-methylpentyl]-2-chloro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-5-fluoro-N-[(furan-2-yl)methyl]-2-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-5,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(1,3-thiazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2R)-2-amino-3-methoxypropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(1,3-thiazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   (2R)-2-amino-3-(2-chloro-5-fluoro-4-{[(furan-2-yl)methyl]amino}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)propan-1-ol hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(thiophen-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(3-fluoropyridin-4-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-7-ethyl-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(pyridin-4-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride;   6-[(2S)-2-aminobutyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminobutyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-(4-methoxyphenyl)-N-[(thiophen-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(1,3-thiazol-5-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(thiophen-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-N-benzyl-2-chloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-N-benzyl-2-chloro-5-fluoro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(2-fluorophenyl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(2-fluorophenyl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(pyridin-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(pyridin-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(pyridin-3-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(pyridin-3-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride;   6-[(2S)-2-aminobutyl]-2-chloro-5-fluoro-N-[(thiophen-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminobutyl]-2-chloro-5-fluoro-N-[(1,3-thiazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride; and   6-[(2R)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;
 wherein the form of the compound salt is selected from the group consisting of a hydrate, solvate, and tautomer form thereof. 
   
     
     
         9 . The method of  claim 8 , wherein the compound or form thereof is selected from the group consisting of:
 6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   2,5-dichloro-N-[(furan-2-yl)methyl]-6-[2-(methylamino)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2,5-dichloro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-N-[(furan-2-yl)methyl]-5,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(1,3-thiazol-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(3-fluoropyridin-4-yl)methyl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride;   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(pyridin-4-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride; and   6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-7-methyl-N-[(thiophen-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine hydrochloride;
 wherein the form of the compound salt is selected from the group consisting of a hydrate, solvate, and tautomer form thereof. 
   
     
     
         10 . The method of any one of  claim 1  or  6 - 9 , wherein the effective amount of the compound or form thereof inducing exon skipping in ATXN3 pre-mRNA in the subject. 
     
     
         11 . The method of any one of  claim 1  or  6 - 10 , wherein the effective amount of the compound or form thereof induces exon skipping. 
     
     
         12 . The method of any one of  claim 1  or  6 - 10 , wherein the effective amount of the compound or form thereof is in an admixture with one or more pharmaceutically acceptable excipient(s).