US 12,103,926 B2
Compounds for treating huntington's disease
Nadiya Sydorenko, Princeton, NJ (US); Suresh Babu, Pennington, NJ (US); Anuradha Bhattacharyya, Edison, NJ (US); Young-Choon Moon, Belle Mead, NJ (US); Jana Narasimhan, Scotch Plains, NJ (US); and Jigar S. Patel, Jersey City, NJ (US)
Assigned to PTC Therapeutics, Inc., Warren, NJ (US)
Appl. No. 17/040,751
Filed by PTC THERAPEUTICS, INC., Warren, NJ (US)
PCT Filed Mar. 26, 2019, PCT No. PCT/US2019/024068
§ 371(c)(1), (2) Date Sep. 23, 2020,
PCT Pub. No. WO2019/191092, PCT Pub. Date Oct. 3, 2019.
Claims priority of provisional application 62/648,699, filed on Mar. 27, 2018.
Prior Publication US 2021/0009590 A1, Jan. 14, 2021
Int. Cl. C07D 401/14 (2006.01); A61P 25/28 (2006.01); C07D 401/12 (2006.01); C07D 403/14 (2006.01); C07D 405/14 (2006.01); C07D 409/14 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01); C07D 471/08 (2006.01); C07D 471/10 (2006.01); C07D 487/04 (2006.01); C07D 491/107 (2006.01); C07D 493/08 (2006.01); C07D 498/04 (2006.01)
CPC C07D 471/08 (2013.01) [A61P 25/28 (2018.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 405/14 (2013.01); C07D 409/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 471/10 (2013.01); C07D 487/04 (2013.01); C07D 491/107 (2013.01); C07D 493/08 (2013.01); C07D 498/04 (2013.01)] 4 Claims
 
1. A compound, or a form thereof, selected from the group consisting of:
4-(3-hydroxy-4-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenyl)pyridin-2-ol;
5-(1H-pyrazol-4-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyrazin-2-yl}phenol;
2-{5-[(7-azadispiro[5.1.58.36]hexadecan-15-yl)(methyl)amino]pyrazin-2-yl}-5-(1H-pyrazol-4-yl)phenol;
5-[2,5-dichloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrazin-2-amine;
5-(1H-imidazol-1-yl)-2-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
2-[5-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyrazin-2-yl]-5-(1H-pyrazol-4-yl)phenol;
2-{5-[(piperidin-4-yl)oxy]pyrazin-2-yl}-5-(1H-pyrazol-4-yl)phenol;
2-{5-[(piperidin-4-yl)amino]pyrazin-2-yl}-5-(1H-pyrazol-4-yl)phenol;
2-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}-5-(trifluoromethyl)-1H-pyrazol-4-yl]phenol;
2[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-5-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyrazine;
5-[2-fluoro-5-methyl-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrazin-2-amine;
5-(5-methyl-1H-pyrazol-4-yl)-2-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrazin-2-amine;
5-(3-amino-1H-pyrazol-1-yl)-2-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrazin-2-amine;
5-[3-fluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrazin-2-amine;
5-[3,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrazin-2-amine;
4-(3-hydroxy-4-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenyl)-1-methylpyridin-2(1H)-one;
2-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}-5-(1H-pyrazol-1-yl)phenol;
2-{5-[methyl(piperidin-4-yl)amino]pyrazin-2-yl}-5-(1H-pyrazol-4-yl)phenol;
2-[5-(2,6-diazaspiro[3.4]octan-2-yl)pyrazin-2-yl]-5-(1H-pyrazol-4-yl)phenol;
4-fluoro-2-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}-5-(1H-pyrazol-4-yl)phenol;
5-[5-chloro-2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrazin-2-amine;
4-fluoro-5-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}-2-(1H-pyrazol-4-yl)benzonitrile;
2-[5-(8-azabicyclo[3.2.1]oct-3-yloxy)pyrazin-2-yl]-5-(1H-pyrazol-4-yl)phenol;
2-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}-5-(1H-pyrazol-4-yl)phenol;
5-(1-methyl-1H-pyrazol-4-yl)-2-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-[1-(2H3)methyl-1H-pyrazol-4-yl]-2-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
(5-(2-hydroxy-4-(1H-pyrazol-4-yl)phenyl)pyrazin-2-yl)(2,2,6,6-tetramethylpiperidin-4-yl)methanone;
2-(5-(2-hydroxy-4-(1H-pyrazol-4-yl)phenyl)pyrazin-2-yl)-2-(2,2,6,6-tetramethylpiperidin-4-yl)acetonitrile;
2-(5-(amino(2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyrazin-2-yl)-5-(1H-pyrazol-4-yl)phenol;
2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyrazin-2-yl)-5-(1,3,5-triazin-2-yl)phenol;
4-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyrazin-2-yl)phenyl)-1,3,5-triazin-2-ol;
5-(4-amino-1,3,5-triazin-2-yl)-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyrazin-2-yl)phenol;
5-(4-chloro-1,3,5-triazin-2-yl)-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyrazin-2-yl)phenol;
5-(5-chloro-1H-pyrazol-4-yl)-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyrazin-2-yl)phenol;
4-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyrazin-2-yl)phenyl)-1H-pyrazole-5-carbonitrile;
5-(1,5-dimethyl-1H-pyrazol-4-yl)-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyrazin-2-yl)phenol;
5-(5-chloro-1-methyl-1H-pyrazol-4-yl)-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyrazin-2-yl)phenol;
5-[2,3-difluoro-4-(4-methyl-1H-imidazol-1-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrazin-2-amine;
5-[2,5-difluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyrazin-2-amine;
5-(3-fluoro-1H-pyrazol-4-yl)-2-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(pyridin-4-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(pyridin-3-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(1H-pyrazol-4-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(pyrimidin-2-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(pyridin-2-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(6-methoxypyrimidin-4-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(1H-imidazol-1-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}-5-(2H-1,2,3-triazol-2-yl)phenol;
2-{5-[3-(tert-butylamino)pyrrolidin-1-yl]pyrazin-2-yl}-5-(1H-pyrazol-4-yl)phenol;
5-(imidazo[1,2-a]pyrazin-6-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(1-methyl-1H-pyrazol-4-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(1-methyl-1H-pyrazol-3-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(imidazo[1,2-b]pyridazin-6-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(5-fluoro-1H-pyrazol-4-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(1H-pyrazol-3-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
5-(4-fluoro-1H-pyrazol-1-yl)-2-{5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}phenol;
2-{5-[3-(tert-butylamino)pyrrolidin-1-yl]pyrazin-2-yl}-5-[1-(2H3)methyl-1H-pyrazol-4-yl]phenol;
2-{5-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrazin-2-yl}-5-(2H-1,2,3-triazol-2-yl)phenol;
2-{5-[(tert-butylamino)pyrrolidin-1-yl]pyrazin-2-yl}-5-(1-methyl-1H-pyrazol-4-yl)phenol;
N-tert-butyl-1-{5-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]pyrazin-2-yl pyrrolidin-3-amine;
N-tert-butyl-1-{5-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]pyrazin-2-yl pyrrolidin-3-amine; and
2-{5-[3-(tert-butylamino)pyrrolidin-1-yl]pyrazin-2-yl}-5-(3-fluoro-1H-pyrazol-4-yl)phenol,
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.