US 12,139,499 B2
Heteroaryl compounds for treating Huntington's disease
Nanjing Zhang, Princeton, NJ (US); Suresh Babu, Pennington, NJ (US); Scott J. Barraza, Piscataway, NJ (US); Anuradha Bhattacharyya, Edison, NJ (US); Guangming Chen, Bridgewater, NJ (US); Gary Mitchell Karp, Princeton Junction, NJ (US); Andrew J. Kassick, Wexford, PA (US); Anthony R. Mazzotti, Rahway, NJ (US); Young-Choon Moon, Belle Mead, NJ (US); Jana Narasimhan, Scotch Plains, NJ (US); Nadiya Sydorenko, Princeton, NJ (US); Anthony Turpoff, Hillsborough, NJ (US); Matthew G. Woll, Dunellen, NJ (US); and Wuming Yan, Wayne, NJ (US)
Assigned to PTC THERAPEUTICS, INC., Warren, NJ (US)
Appl. No. 17/254,828
Filed by PTC THERAPEUTICS, INC., Warren, NJ (US)
PCT Filed Jun. 25, 2019, PCT No. PCT/US2019/038895
§ 371(c)(1), (2) Date Dec. 21, 2020,
PCT Pub. No. WO2020/005877, PCT Pub. Date Jan. 2, 2020.
Claims priority of provisional application 62/690,540, filed on Jun. 27, 2018.
Prior Publication US 2021/0284660 A1, Sep. 16, 2021
Int. Cl. C07D 519/00 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01); C07D 513/04 (2006.01)
CPC C07D 519/00 (2013.01) [C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01); C07D 513/04 (2013.01)] 9 Claims
 
1. A method for treating or ameliorating Huntington's Disease in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula (I):

OG Complex Work Unit Chemistry
or a form thereof, wherein:
W1, W2 and W3 are independently C—Ra or N;
Ra is, in each instance, independently selected from the group consisting of hydrogen, cyano, halogen, hydroxy, C1-6alkyl, halo-C1-6alkyl, C1-6alkyl-carbonyl, C1-6alkoxy, halo-C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-carbonyl, amino, C1-6alkyl-amino, (C1-6alkyl)2-amino, amino-C1-6alkyl, and hydroxy-C1-6alkyl;
X is selected from the group consisting of N—Rb, O, and a bond;
Rb is selected from the group consisting of hydrogen and C1-6alkyl;
R1 is selected from the group consisting of C3-10cycloalkyl and 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, and
wherein each instance of C3-10cycloalkyl and heterocyclyl is optionally substituted with one, two three, or four R3 substituents and optionally, with one additional R4 substituent, or,
wherein, alternatively, each instance of C3-10cycloalkyl and heterocyclyl is optionally substituted with one, two, three, four, or five R3 substituents;
R2 is selected from the group consisting of phenyl and heteroaryl,
wherein heteroaryl is selected from the group consisting of furanyl, 1H-imidazolyl, 1H -1,2,3-triazolyl, 4H-1,2,4-triazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1H-indolyl, 2H-indolyl, 1H-indazolyl, 2H-indazolyl, indolizinyl, benzofuranyl, 1H-benzimidazolyl, 1,3-benzoxazolyl, furo[2,3-b]pyridinyl, furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl, furo[3,2-c]pyridinyl, 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]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, 2H-pyrazolo[4,3-b]pyridinyl, 2H-pyrazolo[4,3-c]pyridinyl, pyrazolo[1,5-a]pyrazinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-a]pyrimidinyl, imidazo[1,2-a]pyraziny, imidazo[1,2-b]pyridazinyl, imidazo[1,2-c]pyrimidinyl, imidazo[1,5-a]pyridinyl, imidazo[2,1-b][1,3]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazoly, [1,3]oxazolo[4,5-b]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, [1,2,4]triazolo[1,5-b]pyridazinyl, and quinolinyl,
wherein each instance of phenyl and heteroaryl is optionally substituted with one, two or three R5 substituents and optionally, with one additional R6 substituent, or,
wherein, alternatively, each instance of phenyl and heteroaryl is optionally substituted with one, two, three or four R5 substituents;
R3 is, in each instance, independently selected from the group consisting of cyano, halogen, hydroxy, C1-6alkyl, halo-C1-6alkyl, C1-6alkyl-carbonyl, C1-6alkoxy, halo-C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-carbonyl, amino, C1-6alkyl-amino, amino-C1-6alkyl, and hydroxy-C1-6alkyl;
R4 is selected from the group consisting of C3-10cycloalkyl, phenyl, heterocyclyl, and heteroaryl;
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 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, and
wherein each instance of C3-10cycloalkyl, phenyl, heterocyclyl, and heteroaryl is optionally substituted with one, two or three R7 substituents;
R5 is, in each instance, independently selected from the group consisting of cyano, halogen, hydroxy, C1-6alkyl, halo-C1-6alkyl, C1-6alkyl-carbonyl, C1-6alkoxy, halo-C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-carbonyl, C1-6alkoxy-carbonyl-C1-6alkyl, carboxyl, C1-6alkyl-carboxyl, amino, C1-6alkyl-amino, (C1-6alkyl)2-amino, amino-C1-6alkyl, amino-carbonyl, and hydroxy-C1-6alkyl;
R6 is selected from the group consisting of C3-10cycloalkyl, phenyl, phenyl-C1-6alkoxy, phenyl-oxy, heterocyclyl, and heteroaryl;
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 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, and
wherein, each instance of C3-10cycloalkyl, phenyl, heterocyclyl, and heteroaryl is optionally substituted with one, two or three R7 substituents; and
R7 is, in each instance, independently selected from the group consisting of cyano, halogen, hydroxy, C1-6alkyl, halo-C1-6alkyl, C1-6alkyl-carbonyl, C1-6alkoxy, halo-C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-carbonyl, amino, C1-6alkyl-amino, (C1-6alkyl)2-amino, amino-C1-6alkyl, and hydroxy-C1-6alkyl;
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.