Compounds for treating huntington's disease

Abstract

The present description relates to compounds, forms, and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease. In particular, the present description relates to substituted monocyclic heteroaryl compounds of Formula (I) or Formula (II), forms and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease.

1 . A compound of Formula (I) or Formula (II): 
       
         
           
           
               
               
           
         
         or a form thereof, wherein: 
         X is CHR 1a , C═O, O, NR 1b , or a bond; 
         R 1a  is hydrogen, halogen, hydroxyl, cyano, C 1-4 alkyl, deutero-C 1-4 alkyl, halo-C 1-4 alkyl, amino or hydroxyl-C 1-4 alkyl; 
         R 1b  is hydrogen, C 1-4 alkyl, deutero-C 1-4 alkyl, halo-C 1-4 alkyl or hydroxyl-C 1-4 alkyl; 
         B is heterocyclyl, 
         wherein heterocyclyl is a saturated or partially unsaturated 3-7 membered monocyclic, 6-10 membered bicyclic or 13-16 membered polycyclic ring system having 1, 2, or 3 heteroatom ring members independently selected from N, O, or S, each optionally substituted with 1, 2, 3, 4, or 5 substituents each selected from R 2 ; 
         R 2  is independently selected from halogen, hydroxyl, cyano, C 1-4 alkyl, deutero-C 1-4 alkyl, halo-C 1-4 alkyl, amino, C 1-6 alkyl-amino, (C 1-6 alkyl) 2 -amino, halo-C 1-4 alkyl-amino, (halo-C 1-6 alkyl) 2 -amino, hydroxy-C 1-4 alkyl-amino, C 1-4 alkoxy-C 1-4 alkyl-amino, amino-C 1-4 alkyl, C 1-4 alkyl-amino-C 1-4 alkyl, (C 1-4 alkyl-amino) 2 -C 1-4 alkyl, C 1-4 alkoxy, halo-C 1-4 alkoxy, hydroxyl-C 1-4 alkoxy, C 1-4 alkyl-C 1-4 alkoxy, C 3-10 cycloalkyl, C 3-10 cycloalkyl-amino, C 3-10 cycloalkyl-amino-C 1-4 alkyl, heteroaryl-C 1-4 alkyl, heteroaryl-amino, heteroaryl-C 1-4 alkyl-amino, heterocyclyl, heterocyclyl-C 1-4 alkyl, heterocyclyl-amino, heterocyclyl-amino-C 1-4 alkyl, heterocyclyl-C 1-4 alkoxy, heterocyclyl-amino-C 3-10 cycloalkyl, phenyl, and phenyl-C 1-4 alkoxy, 
         wherein heteroaryl is a 3-7 membered monocyclic or 6-10 membered bicyclic ring system having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, or S, 
         wherein heterocyclyl is a saturated or partially unsaturated 3-7 membered monocyclic, 6-10 membered bicyclic or 13-16 membered polycyclic ring system having 1, 2, or 3 heteroatom ring members independently selected from N, O, or S, wherein C 3-10 cycloalkyl is a saturated or partially unsaturated 3-7 membered monocyclic ring system, and 
         wherein each instance of phenyl, heteroaryl, heterocyclyl, or C 3-10 cycloalkyl is optionally substituted with 1 or 2 substituents each selected from R 3 ; 
         R 3  is independently selected from halogen, hydroxyl, cyano, C 1-4 alkyl, deutero-C 1-4 alkyl, halo-C 1-4 alkyl, amino, C 1-4 alkoxy, and halo-C 1-4 alkoxy; 
         n is 1 or 2; 
         R 4  is independently selected from halogen, hydroxyl, cyano, C 1-4 alkyl, deutero-C 1-4 alkyl, halo-C 1-4 alkyl, amino, C 1-4 alkyl-amino, (C 1-4 alkyl) 2 -amino, C 1-4 alkoxy, halo-C 1-4 alkoxy, heteroaryl, heterocyclyl, and phenyl, 
         wherein heteroaryl is a 3-7 membered monocyclic or 6-10 membered bicyclic ring system having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, or S, 
         wherein heterocyclyl is a saturated or partially unsaturated 3-6 membered monocyclic or 9-10 membered bicyclic ring system having 1, 2, or 3 heteroatom ring members selected from N, O, and S, and 
         wherein each instance of phenyl, heteroaryl or heterocyclyl is optionally substituted with 1, or 2 substituents each selected from R 5 ; 
         R 5  is independently selected from halogen, hydroxyl, cyano, nitro, C 1-4 alkyl, deutero-C 1-4 alkyl, halo-C 1-4 alkyl, amino, C 1-4 alkyl-amino, (C 1-4 alkyl) 2 -amino, amino-C 1-4 alkyl, hydroxyl-C 1-4 alkyl, C 1-4 alkyl-carbonyl, C 1-4 alkoxy, C 1-4 alkylthio, halo-C 1-4 alkoxy, and C 3-10 cycloalkyl; 
         wherein a form of the compound is selected from the group consisting of a salt, hydrate, solvate, racemate, enantiomer, diastereomer, stereoisomer, and tautomer form thereof. 
       
     
     
         2 . The compound of  claim 1 , or form thereof, wherein X is selected from NR 1b  and a bond. 
     
     
         3 . The compound of  claim 1 , or form thereof, wherein B is heterocyclyl selected from azetidinyl, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, piperazinyl, 1,4-diazepanyl, 1,2-dihydropyridinyl, 1,2,5,6-tetrahydropyridinyl, 1,2,3,6-tetrahydropyridinyl, hexahydrocyclopentapyrrol-(1H)-yl, hexahydropyrrolo[3,2-b]pyrrol-(2H)-yl, hexahydropyrrolo[3,4-b]pyrrol-(2H)-yl, (3aS,6aS)-hexahydropyrrolo[3,4-b]pyrrol-(2H)-yl, hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl, (3aS,6aS)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl, hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl, (3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl, octahydro-2H-pyrrolo[3,4-c]pyridinyl, octahydro-5H-pyrrolo[3,2-c]pyridinyl, octahydro-6H-pyrrolo[3,4-b]pyridinyl, (4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridinyl, (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridinyl, hexahydropyrrolo[1,2-a]pyrazin-(2H)-one, hexahydropyrrolo[1,2-a]pyrazin-(1H)-yl, (7R,8aS)-hexahydropyrrolo[1,2-a]pyrazin-(1H)-yl, (8aS)-hexahydropyrrolo[1,2-a]pyrazin-(1H)-yl, (8aR)-hexahydropyrrolo[1,2-a]pyrazin-(1H)-yl, hexahydro-1H-cyclobuta[1.2-c:1,4-c′]dipyrrol-(3H)-yl, (8aS)-octahydropyrrolo[1,2-a]pyrazin-(1H)-yl, (8aR)-octahydropyrrolo[1,2-a]pyrazin-(1H)-yl, octahydro-2H-pyrido[1,2-a]pyrazinyl, hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl, 5-azaspiro[2.4]heptanyl, 2-oxa-6-azaspiro[3.4]octanyl, 3-azabicyclo[3.1.0]hexanyl, 8-azabicyclo[3.2.1]octanyl, (1R,5S)-8-azabicyclo[3.2.1]octanyl, 8-azabicyclo[3.2.1]oct-2-en-yl, (1R,5S)-8-azabicyclo[3.2.1]oct-2-en-yl, 9-azabicyclo[3.3.1]nonanyl, (1R,5S)-9-azabicyclo[3.3.1]nonanyl, 2,5-diazabicyclo[2.2.1]heptanyl, (1S,4S)-2,5-diazabicyclo[2.2.1]heptanyl, 1,4-diazabicyclo[3.1.1]heptanyl, 3,6-diazabicyclo[3.2.0]heptanyl, 2,5-diazabicyclo[2.2.2]octanyl, 1,4-diazabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, (1R,5S)-3,8-diazabicyclo[3.2.1]octanyl, 1,4-diazabicyclo[3.2.2]nonanyl, azaspiro[3.3]heptanyl, 4,7-diazaspiro[2.5]octanyl, 2,6-diazaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.4]octanyl, 1,7,-diazaspiro[4.4]nonanyl, 1,7-diazaspiro[3.5]nonanyl, 2,6-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[3.5]nonanyl, 5,8-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2,7-diazaspiro[4.5]decanyl, 2,8-diazaspiro[4.5]decanyl, 6,9-diazaspiro[4.5]decyl, and 7-azadispiro[5.1.5 8 .3 6 ]hexadecanyl, optionally substituted with 1, 2, 3, 4, or 5 R 2  substituents. 
     
     
         4 . The compound of  claim 1 , or form thereof, wherein B is selected from pyrrolidinyl, piperidinyl, piperazinyl, hexahydrocyclopentapyrrol-(1H)-yl, hexahydropyrrolo[3,2-b]pyrrol-(2H)-yl, hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl, hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl, octahydro-2H-pyrrolo[3,4-c]pyridinyl, octahydro-5H-pyrrolo[3,2-c]pyridinyl, octahydro-6H-pyrrolo[3,4-b]pyridinyl, hexahydropyrrolo[1,2-a]pyrazin-(1H)-yl, hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl, 5-azaspiro[2.4]heptanyl, 2-oxa-6-azaspiro[3.4]octanyl, 3-azabicyclo[3.1.0]hexanyl, 8-azabicyclo[3.2.1]octanyl, 9-azabicyclo[3.3.1]nonanyl, 2,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.4]octanyl, 1,7,-diazaspiro[4.4]nonanyl, 1,7-diazaspiro[3.5]nonanyl, 2,6-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2,7-diazaspiro[4.5]decanyl, 2,8-diazaspiro[4.5]decanyl, 6-oxa-2,9-diazaspiro[4.5]decanyl, and 2,9-diazaspiro[5.5]undecanyl, optionally substituted with 1, 2, 3, 4, or 5 R 2  substituents. 
     
     
         5 . The compound of  claim 1 , or form thereof, wherein R 4  is heteroaryl selected from thienyl, 1H-pyrazolyl, 1H-imidazolyl, 1,3-thiazolyl, oxazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl, 1H-tetrazolyl, 2H-tetrazolyl, pyridinyl, pyridin-2(1H)-on-yl, pyrimidinyl, pyrimidin-4(3H)-on-yl, pyridazinyl, pyridazin-3(2H)-on-yl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1H-indolyl, 1H-indazolyl, 2H-indazolyl, indolizinyl, benzofuranyl, benzothienyl, 1H-benzimidazolyl, 1,3-benzoxazolyl, 1,3-benzothiazolyl, 1,3-benzodioxolyl, 1,2,3-benzotriazolyl, 9H-purinyl, furo[3,2-b]pyridinyl, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl, 1,3-oxazolo[5,4-b]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3-d]pyrimidinyl, 1H-pyrrolo[2,3-b]pyridinyl, 1H-pyrrolo[2,3-c]pyridinyl, pyrrolo[1,2-a]pyrimidinyl, pyrrolo[1,2-a]pyrazinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridin-yl, pyrazolo[1,5-a]pyridinyl, 1H-pyrazolo[3,4-b]pyrazinyl, 1H-pyrazolo[3,4-b]pyridinyl, 1H-pyrazolo[3,4-b]pyridinyl, 1H-pyrazolo[3,4-c]pyridinyl, 1H-pyrazolo[3,4-c]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, 1H-pyrazolo[4,3-d]pyrimidinyl, 2H-pyrazolo[4,3-b]pyridinyl, 2H-pyrazolo[4,3-c]pyridin-yl, 5H-pyrrolo[2,3-b]pyrazinyl, pyrazolo[1,5-a]pyrazinyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-a]pyrimidinyl, imidazo[1,2-a]pyrimidinyl, imidazo[1,2-c]pyrimidinyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrazinyl, imidazo[1,2-a]pyrazinyl, 1H-imidazo[4,5-b]pyridinyl, 3H-imidazo[4,5-b]pyridinyl, imidazo[2,1-b][1,3]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, [1,3]oxazolo[4,5-b]pyridinyl, [1,2,3]triazolo[1,5-a]pyridinyl, [1,2,3]triazolo[1,5-a]pyridinyl, 1H-[1,2,3]triazolo[4,5-b]pyridinyl, 3H-[1,2,3]triazolo[4,5-b]pyridinyl, tetrazolo[1,5-a]pyridinyl, tetrazolo[1,5-b]pyridazinyl, quinolinyl, isoquinolinyl, and quinoxalinyl, optionally substituted with 1 or 2 R 5  substituents. 
     
     
         6 . The compound of  claim 1 , or form thereof, wherein R 4  is heteroaryl selected from thienyl, 1H-pyrazolyl, 1H-imidazolyl, 1,3-thiazolyl, oxazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl, 2H-tetrazolyl, pyridinyl, pyrimidinyl, pyrimidin-4(3H)-on-yl, pyridazinyl, pyridazin-3(2H)-on-yl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1H-indazolyl, 1H-benzimidazolyl, 1,3-benzoxazolyl, 1,3-benzodioxolyl, 1,2,3-benzotriazolyl, 1,3-oxazolo[5,4-b]pyridinyl, 1H-pyrazolo[3,4-b]pyrazinyl, 1H-pyrazolo[3,4-b]pyridinyl, 1H-pyrazolo[3,4-c]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, 1H-pyrazolo[4,3-d]pyrimidinyl, 5H-pyrrolo[2,3-b]pyrazinyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrazinyl, 1H-imidazo[4,5-b]pyridinyl, 3H-imidazo[4,5-b]pyridinyl, [1,2,3]triazolo[1,5-a]pyridinyl, 1H-[1,2,3]triazolo[4,5-b]pyridinyl, 3H-[1,2,3]triazolo[4,5-b]pyridinyl, tetrazolo[1,5-a]pyridinyl, tetrazolo[1,5-b]pyridazinyl, and quinolinyl, optionally substituted with 1 or 2 R 5  substituents. 
     
     
         7 . The compound of  claim 1 , wherein the form of the compound is a compound salt selected from hydrochloride, hydrobromide, trifluoroacetate, formate, dihydrochloride, dihydroiodide, trihydrochloride, tetrahydrochloride, dihydrobromide and ditrifluoroacetate. 
     
     
         8 - 9 . (canceled) 
     
     
         10 . A method for treating or ameliorating Huntington's Disease (HD) in a subject in need thereof comprising, administering to the subject an effective amount of the compound or form thereof of  claim 1 . 
     
     
         11 . The method of  claim 10 , wherein the effective amount of the compound or form thereof is in a range of from about 0.001 mg/kg/day to about 500 mg/kg/day. 
     
     
         12 - 17 . (canceled) 
     
     
         18 . A pharmaceutical composition comprising the compound or form thereof of  claim 1  in admixture with one or more pharmaceutically acceptable excipients. 
     
     
         19 . A compound of Formula (I) or Formula (II): 
       
         
           
           
               
               
           
         
         or a form thereof, wherein: 
         X is CHR 1a , C═O, O, NR 1b , or a bond; 
         R 1a  is hydrogen, halogen, hydroxyl, cyano, C 1-4 alkyl, deutero-C 1-4 alkyl, halo-C 1-4 alkyl, amino or hydroxyl-C 1-4 alkyl; 
         R 1b  is hydrogen, C 1-4 alkyl, deutero-C 1-4 alkyl, halo-C 1-4 alkyl or hydroxyl-C 1-4 alkyl; 
         B is heterocyclyl, 
         wherein heterocyclyl is a saturated or partially unsaturated 3-7 membered monocyclic, 6-10 membered bicyclic or 13-16 membered polycyclic ring system having 1, 2, or 3 heteroatom ring members independently selected from N, O, or S, each optionally substituted with 1, 2, 3, 4, or 5 substituents each selected from R 2 ; 
         R 2  is independently selected from halogen, hydroxyl, cyano, C 1-4 alkyl, deutero-C 1-4 alkyl, halo-C 1-4 alkyl, amino, C 1-6 alkyl-amino, (C 1-6 alkyl) 2 -amino, halo-C 1-4 alkyl-amino, (halo-C 1-6 alkyl) 2 -amino, hydroxy-C 1-4 alkyl-amino, C 1-4 alkoxy-C 1-4 alkyl-amino, amino-C 1-4 alkyl, C 1-4 alkyl-amino-C 1-4 alkyl, (C 1-4 alkyl-amino) 2 -C 1-4 alkyl, C 1-4 alkoxy, halo-C 1-4 alkoxy, hydroxyl-C 1-4 alkoxy, C 1-4 alkyl-C 1-4 alkoxy, C 3-10 cycloalkyl, C 3-10 cycloalkyl-amino, C 3-10 cycloalkyl-amino-C 1-4 alkyl, heteroaryl-C 1-4 alkyl, heteroaryl-amino, heteroaryl-C 1-4 alkyl-amino, heteroaryl-C 1-4 alkyl-amino-C 1-4 alkyl, heterocyclyl, heterocyclyl-C 1-4 alkyl, heterocyclyl-amino, heterocyclyl-amino-C 1-4 alkyl, heterocyclyl-C 1-4 alkoxy, heterocyclyl-amino-C 3-10 cycloalkyl, phenyl, and phenyl-C 1-4 alkoxy, 
         wherein heteroaryl is a 3-7 membered monocyclic or 6-10 membered bicyclic ring system having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, or S, 
         wherein heterocyclyl is a saturated or partially unsaturated 3-7 membered monocyclic, 6-10 membered bicyclic or 13-16 membered polycyclic ring system having 1, 2, or 3 heteroatom ring members independently selected from N, O, or S, 
         wherein C 3-10 cycloalkyl is a saturated or partially unsaturated 3-7 membered monocyclic ring system, and 
         wherein each instance of phenyl, heteroaryl, heterocyclyl, or C 3-10 cycloalkyl is optionally substituted with 1 or 2 substituents each selected from R 3 ; 
         R 3  is independently selected from halogen, hydroxyl, cyano, C 1-4 alkyl, deutero-C 1-4 alkyl, halo-C 1-4 alkyl, amino, C 1-4 alkoxy, and halo-C 1-4 alkoxy; 
         n is 1 or 2; 
         R 4  is independently selected from halogen, hydroxyl, cyano, C 1-4 alkyl, deutero-C 1-4 alkyl, halo-C 1-4 alkyl, amino, C 1-4 alkyl-amino, (C 1-4 alkyl) 2 -amino, C 1-4 alkoxy, halo-C 1-4 alkoxy, heteroaryl, heterocyclyl, and phenyl, 
         wherein heteroaryl is a 3-7 membered monocyclic or 6-10 membered bicyclic ring system having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, or S, 
         wherein heterocyclyl is a saturated or partially unsaturated 3-6 membered monocyclic or 9-10 membered bicyclic ring system having 1, 2, or 3 heteroatom ring members selected from N, O, and S, and 
         wherein each instance of phenyl, heteroaryl or heterocyclyl is optionally substituted with 1, or 2 substituents each selected from R 5 ; 
         R 5  is independently selected from halogen, hydroxyl, cyano, nitro, C 1-4 alkyl, deutero-C 1-4 alkyl, halo-C 1-4 alkyl, amino, C 1-4 alkyl-amino, (C 1-4 alkyl) 2 -amino, amino-C 1-4 alkyl, hydroxyl-C 1-4 alkyl, C 1-4 alkyl-carbonyl, C 1-4 alkoxy, C 1-4 alkylthio, halo-C 1-4 alkoxy, and C 3-10 cycloalkyl; 
         wherein a form of the compound is selected from the group consisting of a salt, hydrate, solvate, racemate, enantiomer, diastereomer, stereoisomer, and tautomer form thereof. 
       
     
     
         20 . The compound of  claim 19 , or form thereof, wherein X is selected from NR 1b  and a bond. 
     
     
         21 . The compound of  claim 19 , or form thereof, wherein B is heterocyclyl selected from azetidinyl, tetrahydrofuranyl, pyrrolidinyl, piperidinyl, piperazinyl, 1,4-diazepanyl, 1,2-dihydropyridinyl, 1,2,5,6-tetrahydropyridinyl, 1,2,3,6-tetrahydropyridinyl, hexahydrocyclopentapyrrol-(1H)-yl, hexahydropyrrolo[3,2-b]pyrrol-(2H)-yl, hexahydropyrrolo [3,4-b]pyrrol-(2H)-yl, (3aS,6aS)-hexahydropyrrolo[3,4-b]pyrrol-(2H)-yl, hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl, (3aS,6aS)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl, hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl, (3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl, octahydro-2H-pyrrolo[3,4-c]pyridinyl, octahydro-5H-pyrrolo[3,2-c]pyridinyl, octahydro-6H-pyrrolo[3,4-b]pyridinyl, (4aR,7aR)-octahydro-6H-pyrrolo[3,4-b]pyridinyl, (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridinyl, hexahydropyrrolo[1,2-a]pyrazin-(2H)-one, hexahydropyrrolo[1,2-a]pyrazin-(1H)-yl, (7R,8aS)-hexahydropyrrolo[1,2-a]pyrazin-(1H)-yl, (8aS)-hexahydropyrrolo[1,2-a]pyrazin-(1H)-yl, (8aR)-hexahydropyrrolo[1,2-a]pyrazin-(1H)-yl, hexahydro-1H-cyclobuta[1.2-c:1,4-c′]dipyrrol-(3H)-yl, (8aS)-octahydropyrrolo[1,2-a]pyrazin-(1H)-yl, (8aR)-octahydropyrrolo[1,2-a]pyrazin-(1H)-yl, octahydro-2H-pyrido[1,2-a]pyrazinyl, hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl, 5-azaspiro[2.4]heptanyl, 2-oxa-6-azaspiro[3.4]octanyl, 3-azabicyclo[3.1.0]hexanyl, 8-azabicyclo[3.2.1]octanyl, (1R,5S)-8-azabicyclo[3.2.1]octanyl, 8-azabicyclo[3.2.1]oct-2-en-yl, (1R,5S)-8-azabicyclo[3.2.1]oct-2-en-yl, 9-azabicyclo[3.3.1]nonanyl, (1R,5S)-9-azabicyclo[3.3.1]nonanyl, 2,5-diazabicyclo[2.2.1]heptanyl, (1S,4S)-2,5-diazabicyclo[2.2.1]heptanyl, 1,4-diazabicyclo[3.1.1]heptanyl, 3,6-diazabicyclo[3.2.0]heptanyl, 2,5-diazabicyclo[2.2.2]octanyl, 1,4-diazabicyclo[3.2.1]octanyl, 3,8-diazabicyclo[3.2.1]octanyl, (1R,5S)-3,8-diazabicyclo[3.2.1]octanyl, 1,4-diazabicyclo[3.2.2]nonanyl, azaspiro[3.3]heptanyl, 4,7-diazaspiro[2.5]octanyl, 2,6-diazaspiro[3.3]heptan-2-yl, 2,6-diazaspiro[3.4]octanyl, 1,7,-diazaspiro[4.4]nonanyl, 1,7-diazaspiro[3.5]nonanyl, 2,6-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[3.5]nonanyl, 5,8-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2,7-diazaspiro[4.5]decanyl, 2,8-diazaspiro[4.5]decanyl, 6,9-diazaspiro[4.5]decyl, and 7-azadispiro[5.1.5 8 .3 6 ]hexadecanyl, optionally substituted with 1, 2, 3, 4, or 5 R 2  substituents. 
     
     
         22 . The compound of  claim 19 , or form thereof, wherein B is selected from pyrrolidinyl, piperidinyl, piperazinyl, hexahydrocyclopentapyrrol-(1H)-yl, hexahydropyrrolo[3,2-b]pyrrol-(2H)-yl, hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl, hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl, octahydro-2H-pyrrolo[3,4-c]pyridinyl, octahydro-5H-pyrrolo[3,2-c]pyridinyl, octahydro-6H-pyrrolo[3,4-b]pyridinyl, hexahydropyrrolo[1,2-a]pyrazin-(1H)-yl, hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl, 5-azaspiro[2.4]heptanyl, 2-oxa-6-azaspiro[3.4]octanyl, 3-azabicyclo[3.1.0]hexanyl, 8-azabicyclo[3.2.1]octanyl, 9-azabicyclo[3.3.1]nonanyl, 2,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.4]octanyl, 1,7,-diazaspiro[4.4]nonanyl, 1,7-diazaspiro[3.5]nonanyl, 2,6-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2,7-diazaspiro[4.5]decanyl, 2,8-diazaspiro[4.5]decanyl, 6-oxa-2,9-diazaspiro[4.5]decanyl, and 2,9-diazaspiro[5.5]undecanyl, optionally substituted with 1, 2, 3, 4, or 5 R 2  substituents. 
     
     
         23 . The compound of  claim 19 , or form thereof, wherein R 4  is heteroaryl selected from thienyl, 1H-pyrazolyl, 1H-imidazolyl, 1,3-thiazolyl, oxazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl, 1H-tetrazolyl, 2H-tetrazolyl, pyridinyl, pyridin-2(1H)-on-yl, pyrimidinyl, pyrimidin-4(3H)-on-yl, pyridazinyl, pyridazin-3(2H)-on-yl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1H-indolyl, 1H-indazolyl, 2H-indazolyl, indolizinyl, benzofuranyl, benzothienyl, 1H-benzimidazolyl, 1,3-benzoxazolyl, 1,3-benzothiazolyl, 1,3-benzodioxolyl, 1,2,3-benzotriazolyl, 9H-purinyl, furo[3,2-b]pyridinyl, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl, 1,3-oxazolo[5,4-b]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3-d]pyrimidinyl, 1H-pyrrolo[2,3-b]pyridinyl, 1H-pyrrolo[2,3-c]pyridinyl, pyrrolo[1,2-a]pyrimidinyl, pyrrolo[1,2-a]pyrazinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridin-yl, pyrazolo[1,5-a]pyridinyl, 1H-pyrazolo[3,4-b]pyrazinyl, 1H-pyrazolo[3,4-b]pyridinyl, 1H-pyrazolo[3,4-b]pyridinyl, 1H-pyrazolo[3,4-c]pyridinyl, 1H-pyrazolo[3,4-c]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, 1H-pyrazolo[4,3-d]pyrimidinyl, 2H-pyrazolo[4,3-b]pyridinyl, 2H-pyrazolo[4,3-c]pyridin-yl, 5H-pyrrolo[2,3-b]pyrazinyl, pyrazolo[1,5-a]pyrazinyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-a]pyrimidinyl, imidazo[1,2-a]pyrimidinyl, imidazo[1,2-c]pyrimidinyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrazinyl, imidazo[1,2-a]pyrazinyl, 1H-imidazo[4,5-b]pyridinyl, 3H-imidazo[4,5-b]pyridinyl, imidazo[2,1-b][1,3]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, [1,3]oxazolo[4,5-b]pyridinyl, [1,2,3]triazolo[1,5-a]pyridinyl, [1,2,3]triazolo[1,5-a]pyridinyl, 1H-[1,2,3]triazolo[4,5-b]pyridinyl, 3H-[1,2,3]triazolo[4,5-b]pyridinyl, tetrazolo[1,5-a]pyridinyl, tetrazolo[1,5-b]pyridazinyl, quinolinyl, isoquinolinyl, and quinoxalinyl, optionally substituted with 1 or 2 R 5  substituents. 
     
     
         24 . The compound of  claim 19 , or form thereof, wherein R 4  is heteroaryl selected from thienyl, 1H-pyrazolyl, 1H-imidazolyl, 1,3-thiazolyl, oxazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl, 2H-tetrazolyl, pyridinyl, pyrimidinyl, pyrimidin-4(3H)-on-yl, pyridazinyl, pyridazin-3(2H)-on-yl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1H-indazolyl, 1H-benzimidazolyl, 1,3-benzoxazolyl, 1,3-benzodioxolyl, 1,2,3-benzotriazolyl, 1,3-oxazolo[5,4-b]pyridinyl, 1H-pyrazolo[3,4-b]pyrazinyl, 1H-pyrazolo[3,4-b]pyridinyl, 1H-pyrazolo[3,4-c]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, 1H-pyrazolo[4,3-d]pyrimidinyl, 5H-pyrrolo[2,3-b]pyrazinyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrazinyl, 1H-imidazo[4,5-b]pyridinyl, 3H-imidazo[4,5-b]pyridinyl, [1,2,3]triazolo[1,5-a]pyridinyl, 1H-[1,2,3]triazolo[4,5-b]pyridinyl, 3H-[1,2,3]triazolo[4,5-b]pyridinyl, tetrazolo[1,5-a]pyridinyl, tetrazolo[1,5-b]pyridazinyl, and quinolinyl, optionally substituted with 1 or 2 R 5  substituents. 
     
     
         25 . The compound of  claim 19 , wherein the form of the compound is a compound salt selected from hydrochloride, hydrobromide, trifluoroacetate, formate, dihydrochloride, dihydroiodide, trihydrochloride, tetrahydrochloride, dihydrobromide and ditrifluoroacetate. 
     
     
         26 . A method for treating or ameliorating Huntington's Disease (HD) in a subject in need thereof comprising, administering to the subject an effective amount of the compound or form thereof of  claim 19 . 
     
     
         27 . The method of  claim 26 , wherein the effective amount of the compound or form thereof is in a range of from about 0.001 mg/kg/day to about 500 mg/kg/day. 
     
     
         28 . The compound of  claim 1 , wherein the compound is a compound salt, wherein the compound salt is 4-(3-hydroxy-4-13-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-6-ylphenyl)-1,3,5-triazin-2-ol dihydrochloride.