US 12,577,226 B2Granted

Compounds for treating Huntington's disease

AssigneePTC Therapeutics, Inc.

InventorsNadiya Sydorenko, Rauful Alam, Lukiana Amedzo, Michael A. Arnold, Suresh Babu, Anuradha Bhattacharyya, Gary Mitchell Karp, Nathaniel T. Kenton, Tom Tuan Luong, Anthony R. Mazzotti, Young-Choon Moon, Christie Morrill, Nicholas Walter Mszar, Jana Narasimhan, Jigar S. Patel, Hongyu Ren, Anthony Turpoff, Gang Wang, Matthew G. Woll, Nanjing Zhang, Xiaoyan Zhang

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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), Formula (II), or Formula (III), forms and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease.

Claims16

Dependent claims

A compound comprising, a compound of Formula (I) or Formula (III):

or a form thereof, wherein:
X is selected from the group consisting of O, NRx, and a bond;
Rx is selected from the group consisting of hydrogen and C1-4alkyl;
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, optionally substituted where allowed by available valences with 1, 2, 3, 4, or 5 Rb substituents;
Rb is independently selected from the group consisting of halogen, C1-4alkyl, amino, C1-4alkyl-amino, (C1-4alkyl)2-amino, and C3-6cycloalkyl;
R1 is selected from the group consisting of heteroaryl, heterocyclyl, phenyl, heteroaryl-C1-4alkyl, heteroaryl-C2-4alkenyl, heteroaryl-amino, and heteroaryl-C1-4alkyl-amino,
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, and
wherein each instance of phenyl, heteroaryl or heterocyclyl is optionally substituted where allowed by available valences with 1 or 2 R1a substituents;
and
R1a is independently selected from the group consisting of halogen, hydroxyl, cyano, C1-4alkyl, deutero-C1-4alkyl, halo-C1-4alkyl, amino, C1-4alkyl-amino, (C1-4alkyl)2-amino, C1-4alkoxy, deutero-C1-4alkoxy, and halo-C1-4alkoxy;
wherein a form of the compound is selected from the group consisting of a salt, hydrate, solvate, racemate, enantiomer, diastereomer, tautomer, and mixtures thereof.

10 more elements

A compound selected from the group consisting of:

5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-3-ol;
2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)pyridin-3-ol;
5-[1-(2H3)methyl-1H-pyrazol-4-yl]-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-3-ol;
5-(1-methyl-1H-pyrazol-3-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-3-ol;
5-(1H-imidazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(1-methyl-1H-pyrazol-3-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(1-methyl-1H-pyrazol-3-yl)pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]amino}pyridazin-3-yl)-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(1H-imidazol-1-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(1H-imidazol-1-yl)pyridin-3-ol;
5-(1,3-oxazol-2-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl}oxy]pyridazin-3-yl)pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(2H-1,2,3-triazol-2-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(2H-1,2,3-triazol-2-yl)pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(1,3-oxazol-2-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(1,3-oxazol-2-yl)pyridin-3-ol;
5-(1-methyl-1H-pyrazol-3-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}pyridin-3-ol;
2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(1,3-oxazol-2-yl)pyridin-3-ol;
5-(1H-imidazol-1-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}pyridin-3-ol;
2-(6-{[(3S,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]amino}pyridazin-3-yl)-5-(1H-pyrazol-3-yl)pyridin-3-ol;
2-(6-{[(3R,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]amino}pyridazin-3-yl)-5-(1H-pyrazol-3-yl)pyridin-3-ol;
2-{6-[(3R)-(tert-butylamino)pyrrolidin-1-yl]pyridazin-3-yl}-5-(1-methyl-1H-pyrazol-3-yl)pyridin-3-ol;
2-{6-[(3S)-(tert-butylamino)pyrrolidin-1-yl]pyridazin-3-yl}-5-(1-methyl-1H-pyrazol-3-yl)pyridin-3-ol;
2-{6-[(3R)-(tert-butylamino)pyrrolidin-1-yl]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-{6-[(3S)-(tert-butylamino)pyrrolidin-1-yl]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-(6-{[(3R,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]amino}pyridazin-3-yl)-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
2-(6-{[(3S,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]amino}pyridazin-3-yl)-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(2H-1,2,3-triazol-2-yl)pyridin-3-ol;
2-{6-[(5,5-dimethyl-4-azaspiro[2.5]octan-7-yl)oxy]pyridazin-3-yl}-5-(2H-1,2,3-triazol-2-yl)pyridin-3-ol;
5-(5-fluoro-1H-pyrazol-4-yl)-2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
5-(5-fluoro-1H-pyrazol-4-yl)-2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
2-{6-[(3R)-3-(tert-butylamino)pyrrolidin-1-yl]pyridazin-3-yl}-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
2-{6-[(3R)-3-(tert-butylamino)pyrrolidin-1-yl]pyridazin-3-yl}-5-(2H-1,2,3-triazol-2-yl)pyridin-3-ol;
2-(6-{[(3R,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]amino}pyridazin-3-yl)-5-{6-[(2H3)methyloxy]pyrimidin-4-yl}pyridin-3-ol;
2-{6-[(5,5-dimethyl-4-azaspiro[2.5]octan-7-yl)oxy]pyridazin-3-yl}-5-(5-fluoro-1H-pyrazol-4-yl)pyridin-3-ol;
2-{6-[(5,5-dimethyl-4-azaspiro[2.5]octan-7-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-{6-[(5,5-dimethyl-4-azaspiro[2.5]octan-7-yl)oxy]pyridazin-3-yl}-5-(1,3-oxazol-2-yl)pyridin-3-ol;
2-{6-[3-(tert-butylamino)pyrrolidin-1-yl]pyridazin-3-yl}-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
2-{6-[(3R)-3-(tert-butylamino)pyrrolidin-1-yl]pyridazin-3-yl}-5-(6-methoxypyrimidin-4-yl)pyridin-3-ol;
2-{6-[(4-azadispiro[2.1.25.33]decan-9-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-(6-{[(1R,3s,5S)-1,5-dimethyl-8-azabicyclo[3.2.1]octan-3-yl]oxy}pyridazin-3-yl)-5-(2H-1,2,3-triazol-2-yl)pyridin-3-ol;
2-(6-{[(1S,3r,5R)-1,5-dimethyl-8-azabicyclo[3.2.1]octan-3-yl]oxy}pyridazin-3-yl)-5-(2H-1,2,3-triazol-2-yl)pyridin-3-ol;
2-(6-{[(1R,3s,5S)-1,5-dimethyl-8-azabicyclo[3.2.1]octan-3-yl]oxy}pyridazin-3-yl)-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
2-(6-{[(1S,3r,5R)-1,5-dimethyl-8-azabicyclo[3.2.1]octan-3-yl]oxy}pyridazin-3-yl)-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
5-[6-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-hydroxypyridin-3-yl]-2-methyl-2H-indazole-7-carbonitrile;
5-[6-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-hydroxypyridin-3-yl]-2-methyl-2H-indazole-7-carbonitrile;
5-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
5-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
2-(6-{[(1R,3s,5S)-1,5-dimethyl-8-azabicyclo[3.2.1]octan-3-yl]oxy}pyridazin-3-yl)-5-(pyrimidin-5-yl)pyridin-3-ol;
2-(6-{[(1S,3r,5R)-1,5-dimethyl-8-azabicyclo[3.2.1]octan-3-yl]oxy}pyridazin-3-yl)-5-(pyrimidin-5-yl)pyridin-3-ol;
6-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-hydroxy-1′-methyl[3,4′-bipyridin]-2′(1′H)-one;
6-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-hydroxy-1′-methyl[3,4′-bipyridin]-2′(1′H)-one;
5-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
5-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
2-(6-{[(3R,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-(6-{[(3S,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(4-methyl-1H-imidazol-1-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(4-methyl-1H-imidazol-1-yl)pyridin-3-ol;
6-[6-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-hydroxypyridin-3-yl]-3-methylpyrimidin-4(3H)-one;
6-[6-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-hydroxypyridin-3-yl]-3-methylpyrimidin-4(3H)-one;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(2-methylimidazo[1,2-a]pyridin-6-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(2-methylimidazo[1,2-a]pyridin-6-yl)pyridin-3-ol;
5-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
5-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
5-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)-2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
5-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)-2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-[2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl]pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-[2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl]pyridin-3-ol;
5-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-2-(6-{[(3R,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
5-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-2-(6-{[(3S,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(2-methylimidazo[1,2-b]pyridazin-6-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(2-methylimidazo[1,2-b]pyridazin-6-yl)pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(imidazo[1,2-b]pyridazin-6-yl)pyridin-3-ol;
5-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-3-ol;
2-(6-{[(3R,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-(6-{[(3S,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(1H-pyrazol-4-yl)pyridin-3-ol;
5-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-3-ol;
2-{6-[(5,5-dimethyl-4-azaspiro[2.5]octan-7-yl)(methyl)amino]pyridazin-3-yl}-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(2-methylimidazo[1,2-a]pyrimidin-6-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(2-methylimidazo[1,2-a]pyrimidin-6-yl)pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(2-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(2-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyridin-3-ol;
5-(2,4-dimethyl-1,3-benzoxazol-6-yl)-2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
5-(2,4-dimethyl-1,3-benzoxazol-6-yl)-2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(8-methoxy-2-methylimidazo[1,2-b]pyridazin-6-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(8-methoxy-2-methylimidazo[1,2-b]pyridazin-6-yl)pyridin-3-ol;
5-(7-fluoro-2-methyl-2H-indazol-4-yl)-2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
5-(7-fluoro-2-methyl-2H-indazol-4-yl)-2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
6-[6-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-hydroxypyridin-3-yl]-2-methylimidazo[1,2-a]pyridine-8-carbonitrile;
6-[6-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-hydroxypyridin-3-yl]-2-methylimidazo[1,2-a]pyridine-8-carbonitrile;
5-(8-ethyl-2-methylimidazo[1,2-b]pyridazin-6-yl)-2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
5-(8-ethyl-2-methylimidazo[1,2-b]pyridazin-6-yl)-2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-1,2,4-triazol-1-yl)pyridin-3-ol;
5-[6-(6-{[2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-hydroxypyridin-3-yl]-2-methyl-2H-indazole-7-carbonitrile;
2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-1,2,3-triazol-1-yl)pyridin-3-ol;
2-{6-[(5,5-dimethyl-4-azaspiro[2.5]octan-7-yl)(methyl)amino]pyridazin-3-yl}-5-(7-fluoro-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
5-(imidazo[1,2-b]pyridazin-6-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(imidazo[1,2-a]pyrazin-6-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-(imidazo[1,2-a]pyrazin-6-yl)pyridin-3-ol;
5-(1,3-dimethylpyrrolo[1,2-a]pyrazin-7-yl)-2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
5-(1,3-dimethylpyrrolo[1,2-a]pyrazin-7-yl)-2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)pyridin-3-ol;
6-[6-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-hydroxypyridin-3-yl]-2-methylimidazo[1,2-b]pyridazine-8-carbonitrile;
6-[6-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-hydroxypyridin-3-yl]-2-methylimidazo[1,2-b]pyridazine-8-carbonitrile;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(7-fluoro-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
2-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(7-fluoro-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
5-(6-methoxypyrimidin-4-yl)-2-{6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyridazin-3-yl}pyridin-3-ol;
2-(6-{[(1R,3s,5S)-1,5-dimethyl-8-azabicyclo[3.2.1]octan-3-yl]oxy}pyridazin-3-yl)-5-(1H-1,2,3-triazol-1-yl)pyridin-3-ol;
2-(6-{[(1S,3r,5S)-1,5-dimethyl-8-azabicyclo[3.2.1]octan-3-yl]oxy}pyridazin-3-yl)-5-(1H-1,2,3-triazol-1-yl)pyridin-3-ol;
2-(6-{[(3R,4S)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-([1,2,4]triazolo[1,5-a]pyrazin-2-yl)pyridin-3-ol;
2-(6-{[(3S,4R)-3-fluoro-2,2,6,6-tetramethylpiperidin-4-yl]oxy}pyridazin-3-yl)-5-([1,2,4]triazolo[1,5-a]pyrazin-2-yl)pyridin-3-ol;
2-{6-[(4-azadispiro[2.1.25.33]decan-9-yl)oxy]pyridazin-3-yl}-5-(2H-1,2,3-triazol-2-yl)pyridin-3-ol;
5-(6-methoxypyrimidin-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-3-ol;
2-{6-[(5,5-dimethyl-4-azaspiro[2.5]octan-7-yl)oxy]pyridazin-3-yl}-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
2-{6-[(3R)-3-(tert-butylamino)pyrrolidin-1-yl]pyridazin-3-yl}-5-(2-methyl-1,3-oxazol-5-yl)pyridin-3-ol;
2-{6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyridazin-3-yl}-5-(2-methyl-1,3-oxazol-5-yl)pyridin-3-ol;
5-(6-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-hydroxypyridin-3-yl)-2-methyl-2H-indazole-7-carbonitrile;
5-(6-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-hydroxypyridin-3-yl)-2-methyl-2H-indazole-7-carbonitrile;
2-{6-[(5,5-dimethyl-4-azaspiro[2.5]octan-7-yl)oxy]pyridazin-3-yl}-5-(1,3-thiazol-2-yl)pyridin-3-ol;
2-{6-[(3R)-3-(methylamino)pyrrolidin-1-yl]pyridazin-3-yl}-5-(1,3-oxazol-2-yl)pyridin-3-ol;
5-(8-methoxy-2-methylimidazo[1,2-b]pyridazin-6-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-3-ol;
2-(6-{[(5R,7S)-5-methyl-4-azaspiro[2.5]octan-7-yl]oxy}pyridazin-3-yl)-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
2-(6-{[(5S,7R)-5-methyl-4-azaspiro[2.5]octan-7-yl]oxy}pyridazin-3-yl)-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
2-(6-{[(5S,7S)-5-methyl-4-azaspiro[2.5]octan-7-yl]oxy}pyridazin-3-yl)-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
2-(6-{[(5R,7R)-5-methyl-4-azaspiro[2.5]octan-7-yl]oxy}pyridazin-3-yl)-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(7-methoxy-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
2-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(7-methoxy-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
5-(1H-pyrazol-4-yl)-2-[6-(3,3,5,5-tetramethylpiperazin-1-yl)pyridazin-3-yl]pyridin-3-ol;
5-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-[6-(3,3,5,5-tetramethylpiperazin-1-yl)pyridazin-3-yl]pyridin-3-ol;
5-(1H-pyrazol-4-yl)-2-{6-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
5-(1H-pyrazol-4-yl)-2-{6-[(3S,5R)-3,4,5-trimethylpiperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
5-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-{6-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
5-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-{6-[(3S,5R)-3,4,5-trimethylpiperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(2-methylimidazo[1,2-a]pyridin-6-yl)pyridin-3-ol;
2-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(2-methylimidazo[1,2-a]pyridin-6-yl)pyridin-3-ol;
5-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-[6-(piperazin-1-yl)pyridazin-3-yl]pyridin-3-ol;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyridin-3-ol;
2-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyridin-3-ol;
5-(7-methoxy-2-methyl-2H-indazol-5-yl)-2-[6-(3-methylpiperazin-1-yl)pyridazin-3-yl]pyridin-3-ol;
6-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-2′-methoxy[3,4′-bipyridin]-5-ol;
6-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-2′-methoxy[3,4′-bipyridin]-5-ol;
5-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-[6-(3-methylpiperazin-1-yl)pyridazin-3-yl]pyridin-3-ol;
2-[6-(4,7-diazaspiro[2.5]octan-7-yl)pyridazin-3-yl]-5-(7-fluoro-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(2-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyridin-3-ol;
2-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(2-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)pyridin-3-ol;
2-[6-(4-cyclopropylpiperazin-1-yl)pyridazin-3-yl]-5-(7-fluoro-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
5-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-[6-(4-methylpiperazin-1-yl)pyridazin-3-yl]pyridin-3-ol;
[(3R,4S)-3-fluoro-4-({6-[3-hydroxy-5-(1H-pyrazol-4-yl)pyridin-2-yl]pyridazin-3-yl}oxy)-2,2,6,6-tetramethylpiperidin-1-yl]oxidanyl;
5-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-{6-[(3S)-3-methylpiperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
5-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-{6-[(3R)-3-methylpiperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
2-[6-(2,5-diazabicyclo[2.2.1]heptan-2-yl)pyridazin-3-yl]-5-(7-fluoro-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
2-{6-[(3R,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(7-fluoro-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
2-{6-[(3S,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(7-fluoro-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
2-[6-(1,6-diazaspiro[3.4]octan-6-yl)pyridazin-3-yl]-5-(2-methylimidazo[1,2-a]pyridin-6-yl)pyridin-3-ol;
2-[6-(3-methylpiperazin-1-yl)pyridazin-3-yl]-5-{[(3-methyl-1H-pyrazol-4-yl)methyl]amino}pyridin-3-ol;
2-[6-(3-methylpiperazin-1-yl)pyridazin-3-yl]-5-{[(pyridin-2-yl)methyl]amino}pyridin-3-ol;
2-[6-(3-methylpiperazin-1-yl)pyridazin-3-yl]-5-{[(pyridin-3-yl)methyl]amino}pyridin-3-ol;
2-[6-(3-methylpiperazin-1-yl)pyridazin-3-yl]-5-{[(pyridin-4-yl)methyl]amino}pyridin-3-ol;
2-[6-(3-methylpiperazin-1-yl)pyridazin-3-yl]-5-{[(quinolin-3-yl)methyl]amino}pyridin-3-ol;
2-[6-(3-methylpiperazin-1-yl)pyridazin-3-yl]-5-{[(quinolin-8-yl)methyl]amino}pyridin-3-ol;
2-{6-[(6,6-dimethyl-2-oxa-5-azaspiro[3.5]nonan-8-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(2-methylimidazo[1,2-a]pyrimidin-6-yl)pyridin-3-ol;
2-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(2-methylimidazo[1,2-a]pyrimidin-6-yl)pyridin-3-ol;
2-[6-(2,5-diazabicyclo[2.2.1]heptan-2-yl)pyridazin-3-yl]-5-(2-methylimidazo[1,2-a]pyrimidin-6-yl)pyridin-3-ol;
2-[6-(3-methylpiperazin-1-yl)pyridazin-3-yl]-5-[(pyridin-3-yl)amino]pyridin-3-ol;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-[(E)-2-(1-methyl-1H-pyrazol-4-yl)ethenyl]pyridin-3-ol;
2-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-[(E)-2-(1-methyl-1H-pyrazol-4-yl)ethenyl]pyridin-3-ol;
2-[6-(3-ethylpiperazin-1-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-[6-(3-ethylpiperazin-1-yl)pyridazin-3-yl]-5-(7-fluoro-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
2-{6-[(3S)-3-(propan-2-yl)piperazin-1-yl]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-{6-[(3R)-3-(propan-2-yl)piperazin-1-yl]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)pyridin-3-ol;
5-(7-fluoro-2-methyl-2H-indazol-5-yl)-2-{6-[(3S)-3-(propan-2-yl)piperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
2-[6-(3-cyclopropylpiperazin-1-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(2-methyl-2H-indazol-5-yl)pyridin-3-ol;
2-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(2-methyl-2H-indazol-5-yl)pyridin-3-ol;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-[(6-methylpyridin-3-yl)amino]pyridin-3-ol;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(1-methyl-1H-indazol-5-yl)pyridin-3-ol;
2-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(1-methyl-1H-indazol-5-yl)pyridin-3-ol;
5-[(6-methylpyridin-3-yl)amino]-2-{6-[(3R)-3-(propan-2-yl)piperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
5-[(6-methylpyridin-3-yl)amino]-2-{6-[(3S)-3-(propan-2-yl)piperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
2-{6-[(3S)-3-cyclopropylpiperazin-1-yl]pyridazin-3-yl}-5-(2H-1,2,3-triazol-2-yl)pyridin-3-ol;
2-{6-[(3S)-3-cyclopropylpiperazin-1-yl]pyridazin-3-yl}-5-[1-(2H3)methyl-1H-pyrazol-4-yl]pyridin-3-ol;
2-{6-[3-(propan-2-yl)piperazin-1-yl]pyridazin-3-yl}-5-[(E)-2-(1H-pyrazol-4-yl)ethenyl]pyridin-3-ol;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(2H-indazol-5-yl)pyridin-3-ol;
2-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyridazin-3-yl}-5-(2H-indazol-5-yl)pyridin-3-ol;
2-{6-[(3S)-3-ethylpiperazin-1-yl]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)pyridin-3-ol;
5-[(5-methylpyrazin-2-yl)amino]-2-{6-[(3R)-3-(propan-2-yl)piperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
5-[(5-methylpyrazin-2-yl)amino]-2-{6-[(3S)-3-(propan-2-yl)piperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
5-[(2-methylpyrimidin-5-yl)amino]-2-{6-[(3R)-3-(propan-2-yl)piperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
5-[(2-methylpyrimidin-5-yl)amino]-2-{6-[(3S)-3-(propan-2-yl)piperazin-1-yl]pyridazin-3-yl}pyridin-3-ol;
2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-3-yl}-5-(2H-1,2,3-triazol-2-yl)pyridin-3-ol;
2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-3-yl}-5-(1H-pyrazol-4-yl)pyridin-3-ol;
2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,2,4-triazin-3-yl}-5-(2H-1,2,3-triazol-2-yl)pyridin-3-ol;
2-{6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-1,2,4-triazin-3-yl}-5-(7-fluoro-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
and
2-{6-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-1,2,4-triazin-3-yl}-5-(7-fluoro-2-methyl-2H-indazol-5-yl)pyridin-3-ol;
or a salt, hydrate, solvate, racemate, enantiomer, diastereomer, tautomer, or mixtures thereof.

197 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/610,617Filed 12 May 2020 · us provisional application
Priority: 13 May 2019
Published: US 2022/0204478 A130 Jun 2022
Granted: 17 Mar 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…
C07D 413/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms:…
C07D 417/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms,…