METHODS FOR TREATING HUNTINGTON'S DISEASE

Description

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

BACKGROUND

Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder of the brain, having symptoms characterized by involuntary movements, cognitive impairment, and mental deterioration. Death, typically caused by pneumonia or coronary artery disease, usually occurs 13 to 15 years after the onset of symptoms. The prevalence of HD is between three and seven individuals per 100,000 in populations of western European descent. In North America, an estimated 30,000 people have HD, while an additional 200,000 people are at risk of inheriting the disease from an affected parent. The disease is caused by an expansion of uninterrupted trinucleotide CAG repeats in the “mutant” huntingtin (Htt) gene, leading to production of HTT (Htt protein) with an expanded poly-glutamine (polyQ) stretch, also known as a “CAG repeat” sequence. There are no current small molecule therapies targeting the underlying cause of the disease, leaving a high unmet need for medications that can be used for treating or ameliorating HD. Consequently, there remains a need to identify and provide small molecule compounds for treating or ameliorating HD.

All other documents referred to herein are incorporated by reference into the present application as though fully set forth herein.

SUMMARY

The present description relates to methods for treating or ameliorating HD in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula (I):

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wherein W, X, A and B are as defined herein, or forms and compositions thereof.

In particular, the present description relates to a use of a compound of Formula (I) or a form or composition thereof in a method for treating or ameliorating HD in a subject in need thereof comprising, administering an effective amount of the compound or a form or composition thereof, to the subject.

The present description further relates to the use of a compound of Formula (I) or a form thereof in combination with agents having additive or synergistic activity, thus providing a combination product for the treatment of HD.

DETAILED DESCRIPTION

The present description relates to a method or use of a compound for treating or ameliorating HD in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula (I):

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or a form thereof, wherein

W is CH═CH or S;

X is CH₂, CH(C_1-4alkyl), C(C_1-4alkyl)₂, CH═CH, O, NR₅, or a bond;

A is aryl, heteroaryl, heterocyclyl, or C_9-10cycloalkyl,

wherein aryl is selected from phenyl and naphthyl, each optionally substituted with 1, 2, 3, or 4 substituents each selected from R₁,

wherein heteroaryl is a saturated monocyclic, bicyclic or tricyclic 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 R₁,

wherein heterocyclyl is a saturated or partially unsaturated monocyclic, bicyclic or tricyclic 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 R₂, and

wherein C_9-10cycloalkyl is a saturated or partially unsaturated bicyclic ring system optionally substituted with 1, 2, 3, 4, or 5 substituents each selected from R₂;

B is heterocyclyl,

wherein heterocyclyl is a saturated or partially unsaturated monocyclic, bicyclic or 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 R₄;

R₁is halogen, hydroxyl, cyano, C_1-4alkyl, halo-C_1-4alkyl, amino, C_1-4alkyl-amino, (C_1-4alkyl)₂-amino, amino-C_1-4alkyl, C_1-4alkyl-amino-C_1-4alkyl, (C_1-4alkyl)₂-amino-C_1-4alkyl, amino-carbonyl, C_1-4alkyl-amino-carbonyl, (C_1-4alkyl)₂-amino-carbonyl, C_1-4alkyl-amino-carbonyl-C_1-4alkyl, (C_1-4alkyl)₂-amino-carbonyl-C_1-4alkyl, C_1-4alkyl-carbonyl-amino, C_1-4alkyl-carbonyl-amino-C_1-4alkyl, hydroxyl-C_1-4alkyl, C_1-4alkyl-carbonyl, C_1-4alkoxy, halo-C_1-4alkoxy, amino-C_1-4alkoxy, hydroxyl-C_1-4alkoxy, C_1-4alkyl-C_1-4alkoxy, C_1-4alkyl-amino-C_1-4alkoxy, (C_1-4alkyl)₂-amino-C_1-4alkoxy, C_1-4alkyl-carbonyl-amino-C_1-4alkoxy, C_1-4alkoxy-C_1-4alkoxy, C_1-4alkoxy-carbonyl, C_1-4alkoxy-carbonyl-amino, C_1-4alkoxy-carbonyl-amino-C_1-4alkoxy, C_2-4alkenyl, C_2-4alkenyl-amino-carbonyl, C_3-7cycloalkyl, C_3-7cycloalkyl-C_1-4alkoxy, C_3-7cycloalkenyl, heteroaryl, heteroaryl-C_1-4alkyl, heteroaryl-C_1-4alkyl-amino, heteroaryl-C_1-4alkyl-amino-carbonyl, heteroaryl-C_1-4alkyl-carbonyl-amino, heteroaryl-C_1-4alkyl-amino-carbonyl-C_1-4alkyl, heteroaryl-C_1-4alkyl-carbonyl-amino-C_1-4alkyl, heterocyclyl, heterocyclyl-C_1-4alkyl, heterocyclyl-C_1-4alkoxy, phenyl, or phenyl-C_1-4alkoxy,

wherein heteroaryl is a saturated monocyclic or bicyclic ring system having 1, 2, or 3 heteroatom ring members selected from N, O, and S,

wherein heterocyclyl is a saturated or partially unsaturated monocyclic or 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 R₃;

R₂is halogen, hydroxyl, cyano, oxo, hydroxyl-imino, C_1-4alkyl, halo-C_1-4alkyl, amino, C_1-4alkyl-amino, (C_1-4alkyl)₂-amino, amino-C_1-4alkyl, C_1-4alkyl-amino-C_1-4alkyl, (C_1-4alkyl)₂-amino-C_1-4alkyl, amino-carbonyl, hydroxyl-C_1-4alkyl, C_1-4alkoxy, C_1-4alkoxy-carbonyl, C_2-4alkenyl, C_3-7cycloalkyl, or heterocyclyl-C_1-4alkyl,

wherein heterocyclyl is a saturated or partially unsaturated monocyclic or bicyclic ring system having 1, 2, or 3 heteroatom ring members selected from N, O, and S, and

wherein each instance of heterocyclyl is optionally substituted with 1, or 2 substituents each selected from R₃;

R₃is halogen, hydroxyl, nitro, oxo, hydroxyl-imino, C_1-4alkyl, halo-C_1-4alkyl, amino, C_1-4alkyl-amino, (C_1-4alkyl)₂-amino, amino-C_1-4alkyl, C_1-4alkyl-amino-C_1-4alkyl, (C_1-4alkyl)₂-amino-C_1-4alkyl, amino-carbonyl, C_1-4alkyl-amino-carbonyl, (C_1-4alkyl)₂-amino-carbonyl, C_1-4alkyl-amino-carbonyl-C_1-4alkyl, (C_1-4alkyl)₂-amino-carbonyl-C_1-4alkyl, C_1-4alkyl-carbonyl-amino, C_1-4alkyl-carbonyl-amino-C_1-4alkyl, hydroxyl-C_1-4alkyl, C_1-4alkyl-carbonyl, C_1-4alkoxy, halo-C_1-4alkoxy, amino-C_1-4alkoxy, hydroxyl-C_1-4alkoxy, C_1-4alkyl-C_1-4alkoxy, C_1-4alkyl-amino-C_1-4alkoxy, (C_1-4alkyl)₂-amino-C_1-4alkoxy, C_1-4alkyl-carbonyl-amino-C_1-4alkoxy, C_1-4alkoxy-C_1-4alkoxy, C_1-4alkoxy-carbonyl, C_1-4alkoxy-carbonyl-amino, C_1-4alkoxy-carbonyl-amino-C_1-4alkoxy, C_2-4alkenyl, C_2-4alkenyl-amino-carbonyl, C_3-7cycloalkyl, C_3-7cycloalkyl-C_1-4alkoxy, C_3-7cycloalkenyl, heteroaryl, heteroaryl-C_1-4alkyl, heteroaryl-C_1-4alkyl-amino, heteroaryl-C_1-4alkyl-amino-carbonyl, heteroaryl-C_1-4alkyl-carbonyl-amino, heteroaryl-C_1-4alkyl-amino-carbonyl-C_1-4alkyl, heteroaryl-C_1-4alkyl-carbonyl-amino-C_1-4alkyl, heterocyclyl, heterocyclyl-C_1-4alkyl, phenyl, or phenyl-C_1-4alkoxy;

R₄is independently selected from halogen, C_1-4alkyl, hydroxyl-C_1-4alkyl, amino, C_1-4alkyl-amino, (C_1-4alkyl)₂-amino or hydroxyl-C_1-4alkyl-amino; and

R₅is hydrogen, C_1-4alkyl, or hydroxyl-C_1-4alkyl;

wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

An embodiment of the present description further relates to a method or use of a compound for treating or ameliorating HD in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula (I) selected from a compound of Formula (Ia) and Formula (Ib):

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or a form thereof, wherein

X is CH₂, CH(C_1-4alkyl), C(C_1-4alkyl)₂, CH═CH, O, NR₅, or a bond;

A is aryl, heteroaryl, heterocyclyl, or C_9-10cycloalkyl,

wherein aryl is selected from phenyl and naphthyl, each optionally substituted with 1, 2, 3, or 4 substituents each selected from R₁,

wherein heteroaryl is a saturated monocyclic, bicyclic or tricyclic 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 R₁,

wherein heterocyclyl is a saturated or partially unsaturated monocyclic, bicyclic or tricyclic 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 R₂, and

wherein C_9-10cycloalkyl is a saturated or partially unsaturated bicyclic ring system optionally substituted with 1, 2, 3, 4, or 5 substituents each selected from R₂;

B is heterocyclyl,

wherein heterocyclyl is a saturated or partially unsaturated monocyclic, bicyclic or 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 R₄;

R₁is halogen, hydroxyl, cyano, C_1-4alkyl, halo-C_1-4alkyl, amino, C_1-4alkyl-amino, (C_1-4alkyl)₂-amino, amino-C_1-4alkyl, C_1-4alkyl-amino-C_1-4alkyl, (C_1-4alkyl)₂-amino-C_1-4alkyl, amino-carbonyl, C_1-4alkyl-amino-carbonyl, C_1-4alkyl-amino-carbonyl-C_1-4alkyl, C_1-4alkyl-carbonyl-amino, C_1-4alkyl-carbonyl-amino-C_1-4alkyl, hydroxyl-C_1-4alkyl, C_1-4alkyl-carbonyl, C_1-4alkoxy, halo-C_1-4alkoxy, amino-C_1-4alkoxy, hydroxyl-C_1-4alkoxy, C_1-4alkyl-C_1-4alkoxy, C_1-4alkyl-amino-C_1-4alkoxy, (C_1-4alkyl)₂-amino-C_1-4alkoxy, C_1-4alkyl-carbonyl-amino-C_1-4alkoxy, C_1-4alkoxy-C_1-4alkoxy, C_1-4alkoxy-carbonyl, C_1-4alkoxy-carbonyl-amino, C_1-4alkoxy-carbonyl-amino-C_1-4alkoxy, C_2-4alkenyl, C_2-4alkenyl-amino-carbonyl, C_3-7cycloalkyl, C_3-7cycloalkyl-C_1-4alkoxy, C_3-7cycloalkenyl, heteroaryl, heteroaryl-C_1-4alkyl, heteroaryl-C_1-4alkyl-amino, heteroaryl-C_1-4alkyl-amino-carbonyl, heteroaryl-C_1-4alkyl-carbonyl-amino, heteroaryl-C_1-4alkyl-amino-carbonyl-C_1-4alkyl, heteroaryl-C_1-4alkyl-carbonyl-amino-C_1-4alkyl, heterocyclyl, heterocyclyl-C_1-4alkyl, heterocyclyl-C_1-4alkoxy, phenyl, or phenyl-C_1-4alkoxy,

wherein heteroaryl is a saturated monocyclic or bicyclic ring system having 1, 2, or 3 heteroatom ring members selected from N, O, and S,

wherein heterocyclyl is a saturated or partially unsaturated monocyclic or 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 R₃;

R₂is halogen, hydroxyl, cyano, oxo, hydroxyl-imino, C_1-4alkyl, halo-C_1-4alkyl, amino, C_1-4alkyl-amino, (C_1-4alkyl)₂-amino, amino-C_1-4alkyl, amino-carbonyl, hydroxyl-C_1-4alkyl, C_1-4alkoxy, C_1-4alkoxy-carbonyl, C_2-4alkenyl, C_3-7cycloalkyl, or heterocyclyl-C_1-4alkyl;

R₃is halogen, hydroxyl, nitro, oxo, hydroxyl-imino, C_1-4alkyl, amino, C_1-4alkyl-amino, (C_1-4alkyl)₂-amino, amino-C_1-4alkyl, C_1-4alkyl-amino-C_1-4alkyl, (C_1-4alkyl)₂-amino-C_1-4alkyl, amino-carbonyl, C_1-4alkyl-amino-carbonyl, C_1-4alkyl-amino-carbonyl-C_1-4alkyl, C_1-4alkyl-carbonyl-amino, C_1-4alkyl-carbonyl-amino-C_1-4alkyl, hydroxyl-C_1-4alkyl, C_1-4alkyl-carbonyl, C_1-4alkoxy, halo-C_1-4alkoxy, amino-C_1-4alkoxy, hydroxyl-C_1-4alkoxy, C_1-4alkyl-C_1-4alkoxy, C_1-4alkyl-amino-C_1-4alkoxy, (C_1-4alkyl)₂-amino-C_1-4alkoxy, C_1-4alkyl-carbonyl-amino-C_1-4alkoxy, C_1-4alkoxy-C_1-4alkoxy, C_1-4alkoxy-carbonyl, C_1-4alkoxy-carbonyl-amino, C_1-4alkoxy-carbonyl-amino-C_1-4alkoxy, C_2-4alkenyl, C_2-4alkenyl-amino-carbonyl, C_3-7cycloalkyl, C_3-7cycloalkyl-C_1-4alkoxy, C_3-7cycloalkenyl, heteroaryl, heteroaryl-C_1-4alkyl, heteroaryl-C_1-4alkyl-amino, heteroaryl-C_1-4alkyl-amino-carbonyl, heteroaryl-C_1-4alkyl-carbonyl-amino, heteroaryl-C_1-4alkyl-amino-carbonyl-C_1-4alkyl, heteroaryl-C_1-4alkyl-carbonyl-amino-C_1-4alkyl, heterocyclyl, heterocyclyl-C_1-4alkyl, phenyl, or phenyl-C_1-4alkoxy;

R₄is independently selected from halogen, C_1-4alkyl, hydroxyl-C_1-4alkyl, amino, C_1-4alkyl-amino, (C_1-4alkyl)₂-amino or hydroxyl-C_1-4alkyl-amino; and

R₅is hydrogen, C_1-4alkyl, or hydroxyl-C_1-4alkyl;

wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

Another embodiment of the present description further relates to methods for treating or ameliorating HD in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula (I) selected from a compound of Formula (Ia) and Formula (Ib):

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or a form thereof, wherein

X is O, NH, N(CH₃) or a bond;

A is aryl, heteroaryl or heterocyclyl,

wherein aryl is selected from the group consisting of

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wherein heteroaryl is selected from the group consisting of

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wherein heterocyclyl is selected from the group consisting of

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B is heterocyclyl selected from the group consisting of

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R_1a, R_1band R_1care each, where allowed by available valences, one or more substituents each selected from halogen, hydroxyl, cyano, C_1-4alkyl, halo-C_1-4alkyl, amino, C_1-4alkyl-amino, (C_1-4alkyl)₂-amino, amino-C_1-4alkyl, C_1-4alkyl-amino-C_1-4alkyl, (C_1-4alkyl)₂-amino-C_1-4alkyl, amino-carbonyl, C_1-4alkyl-amino-carbonyl, (C_1-4alkyl)₂-amino-carbonyl, C_1-4alkyl-amino-carbonyl-C_1-4alkyl, (C_1-4alkyl)₂-amino-carbonyl-C_1-4alkyl, C_1-4alkyl-carbonyl-amino, C_1-4alkyl-carbonyl-amino-C_1-4alkyl, hydroxyl-C_1-4alkyl, C_1-4alkyl-carbonyl, C_1-4alkoxy, halo-C_1-4alkoxy, amino-C_1-4alkoxy, hydroxyl-C_1-4alkoxy, C_1-4alkyl-C_1-4alkoxy, C_1-4alkyl-amino-C_1-4alkoxy, (C_1-4alkyl)₂-amino-C_1-4alkoxy, C_1-4alkyl-carbonyl-amino-C_1-4alkoxy, C_1-4alkoxy-C_1-4alkoxy, C_1-4alkoxy-carbonyl, C_1-4alkoxy-carbonyl-amino, C_1-4alkoxy-carbonyl-amino-C_1-4alkoxy, C_2-4alkenyl, C_2-4alkenyl-amino-carbonyl, C_3-7cycloalkyl, C_3-7cycloalkyl-C_1-4alkoxy, C_3-7cycloalkenyl, heteroaryl, heteroaryl-C_1-4alkyl, heteroaryl-C_1-4alkyl-amino, heteroaryl-C_1-4alkyl-amino-carbonyl, heteroaryl-C_1-4alkyl-carbonyl-amino, heteroaryl-C_1-4alkyl-amino-carbonyl-C_1-4alkyl, heteroaryl-C_1-4alkyl-carbonyl-amino-C_1-4alkyl, heterocyclyl, heterocyclyl-C_1-4alkyl, heterocyclyl-C_1-4alkoxy, phenyl, or phenyl-C_1-4alkoxy,

wherein heteroaryl is a saturated monocyclic or bicyclic ring system having 1, 2, or 3 heteroatom ring members selected from N, O, and S,

wherein heterocyclyl is a saturated or partially unsaturated monocyclic or 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 R₃;

R_2a, R_2band R_2care each, where allowed by available valences, one or more substituents each selected from halogen, hydroxyl, cyano, oxo, hydroxyl-imino, C_1-4alkyl, halo-C_1-4alkyl, amino, C_1-4alkyl-amino, (C_1-4alkyl)₂-amino, amino-C_1-4alkyl, C_1-4alkyl-amino-C_1-4alkyl, (C_1-4alkyl)₂-amino-C_1-4alkyl, amino-carbonyl, hydroxyl-C_1-4alkyl, C_1-4alkoxy, C_1-4alkoxy-carbonyl, C_2-4alkenyl, C_3-7cycloalkyl, or heterocyclyl-C_1-4alkyl,

wherein heterocyclyl is a saturated or partially unsaturated monocyclic or bicyclic ring system having 1, 2, or 3 heteroatom ring members selected from N, O, and S, and

wherein each instance of heterocyclyl is optionally substituted with 1, or 2 substituents each selected from R₃;

R₃is halogen, hydroxyl, nitro, oxo, hydroxyl-imino, C_1-4alkyl, amino, C_1-4alkyl-amino, (C_1-4alkyl)₂-amino, amino-C_1-4alkyl, C_1-4alkyl-amino-C_1-4alkyl, (C_1-4alkyl)₂-amino-C_1-4alkyl, amino-carbonyl, C_1-4alkyl-amino-carbonyl, (C_1-4alkyl)₂-amino-carbonyl, C_1-4alkyl-amino-carbonyl-C_1-4alkyl, (C_1-4alkyl)₂-amino-carbonyl-C_1-4alkyl, C_1-4alkyl-carbonyl-amino, C_1-4alkyl-carbonyl-amino-C_1-4alkyl, hydroxyl-C_1-4alkyl, C_1-4alkyl-carbonyl, C_1-4alkoxy, halo-C_1-4alkoxy, amino-C_1-4alkoxy, hydroxyl-C_1-4alkoxy, C_1-4alkyl-C_1-4alkoxy, C_1-4alkyl-amino-C_1-4alkoxy, (C_1-4alkyl)₂-amino-C_1-4alkoxy, C_1-4alkyl-carbonyl-amino-C_1-4alkoxy, C_1-4alkoxy-C_1-4alkoxy, C_1-4alkoxy-carbonyl, C_1-4alkoxy-carbonyl-amino, C_1-4alkoxy-carbonyl-amino-C_1-4alkoxy, C_2-4alkenyl, C_2-4alkenyl-amino-carbonyl, C_3-7cycloalkyl, C_3-7cycloalkyl-C_1-4alkoxy, C_3-7cycloalkenyl, heteroaryl, heteroaryl-C_1-4alkyl, heteroaryl-C_1-4alkyl-amino, heteroaryl-C_1-4alkyl-amino-carbonyl, heteroaryl-C_1-4alkyl-carbonyl-amino, heteroaryl-C_1-4alkyl-amino-carbonyl-C_1-4alkyl, heteroaryl-C_1-4alkyl-carbonyl-amino-C_1-4alkyl, heterocyclyl, heterocyclyl-C_1-4alkyl, phenyl, or phenyl-C_1-4alkoxy; and

R_4a, R_4b, R_4c, R_4d, R_4e, R_4fand R_4gare independently selected from halogen, C_1-4alkyl, hydroxyl-C_1-4alkyl, amino, C_1-4alkyl-amino, (C_1-4alkyl)₂-amino or hydroxyl-C_1-4alkyl-amino;

wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

Another aspect of the present description relates to a compound of Formula (I) selected from a compound of Formula (Ia11), Formula (Ia15), Formula (Ia18) or Formula (Ib1):

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or a form thereof, wherein (when present),

X is selected from O, NR₅, or a bond;

A is selected from phenyl, thiophenyl, indazolyl, pyridinyl, pyrimidinyl or phenoxy,

wherein phenyl and phenoxy are each optionally substituted with 1, 2 or 3 substituents each selected from R_1a,

wherein thiophenyl, indazolyl, pyridinyl, pyrimidinyl are each optionally substituted with 1 or 2 substituents each selected from R_1a,

B is selected from 1H-pyrazolyl, piperidinyl, 1,2,3,6-tetrahydropyridinyl, (1R,5S)-8-azabicyclo[3.2.1]octyl, 8-azabicyclo[3.2.1]oct-2-enyl, 2,6-diazaspiro[3.4]octyl or 2,7-diazaspiro[3.5]nonyl, each optionally substituted with 1 or 2 substituents each selected from R_4a;

R_1ais selected from halogen, hydroxyl, C_1-4alkyl, halo-C_1-4alkyl, amino, C_1-4alkoxy, or heteroaryl,

wherein heteroaryl is a saturated monocyclic or bicyclic ring system having 1, 2, or 3 heteroatom ring members selected from N, O, and S optionally substituted with 1 or 2 substituents each selected from R_3a;

R_3ais selected from nitro or C_1-4alkyl; and,

R_4ais C_1-4alkyl;

R_5ais hydrogen, C_1-4alkyl, or hydroxyl-C_1-4alkyl;

wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

Another aspect of the present description relates to a compound of Formula (I) selected from a compound of Formula (Ia11), Formula (Ia15), Formula (Ia18) or Formula (Ib1):

or a form thereof, wherein (when present),
R_1ais selected from fluoro, chloro, hydroxyl, methyl, difluoromethyl, amino, methoxy or 1H-pyrazolyl or 1H-imidazol-1-yl,
wherein 1H-pyrazolyl is optionally substituted with 1 or 2 substituents each selected from R_3a;
R_3ais selected from nitro or methyl or amino; and,
R_4ais methyl or ethyl;
R_5ais hydrogen or methyl;
wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia1) or a form thereof, wherein substituents R_1a, R_1b, and X, when present, are indicated in the table below with multiple substituents separated by a comma; and, “-” indicates that one or more R_1a, R_1b, and X substituents are not present:

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Cpd
R_1a
R_1b
X

1
—
—
NH

8
2-OH
—
N(CH₃)

40
1-CH₂CH═CH₂,
—
N(CH₃)

2-OH

106
1-Br,
7-OH
N(CH₃)

2-OH

107
1-Cl,
7-OH
N(CH₃)

2-OH

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia2) or a form thereof, wherein substituents R_1a, R_1b, and R_4a, when present, are indicated in the table below with multiple substituents separated by a comma; and, “-” indicates that one or more R_1a, R_1b, and R_4asubstituents are not present:

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Cpd
R_1a
R_1b
R_4a

13
—
—
—

207
—
7-OH
—

208
—
7-OH
CH₃

210
2-CH₃
7-OH
—

222
3-Cl
7-OH
—

223
3-Br
7-OH
—

224
3-CN
7-OH
—

225
3-(1-CH₃-1H-imidazol-4-yl)
7-OH
—

226
3-(1H-imidazol-1-yl)
7-OH
—

227
3-OH
7-OH
—

228
3-CH₂CH₃
7-OH
—

229
3-CH(CH₃)₂
7-OH
—

232
2-CH₃,
7-OH
—

4-OCH₃,

233
2-CH₃,
7-OH
—

4-(pyrrolidin-1-yl)

234
2-CH₃,
7-OH
—

4-(morpholin-4-yl)

235
2-CH₃,
7-OH
—

4-N(CH₃)₂

236
2-CH₃,
7-OH
—

4-OCH₂CH₃

237
2-CH₃,
7-OH
—

4-(1-CH₃-1H-pyrazol-4-yl)

240
3-(tetrahydro-2H-pyran-4-yl)
7-OH
—

249
4-OCH₃
7-OH
—

250
2-CH₃,
7-OH
—

4-(azetidin-1-yl)

251
2-CH₃,
7-OH
—

4-CN

252
2-CH₃,
7-OH
—

4-cyclopropyl

253
2-CH₃,
7-OH
—

4-(3,6-dihydro-2H-pyran-4-yl)

254
2-CH₃,
7-OH
—

4-(tetrahydro-2H-pyran-4-yl)

255
2-CH₃,
7-OH
—

4-(oxetan-3-yl)

256
4-N(CH₃)₂
7-OH
—

262
2-CN
7-OH
—

265
2-C(O)NH₂
7-OH
—

293
3-Cl
7-OH
—

294
3-CH(CH₃)₂
7-OH
—

296
2-CH₃,
7-OH
—

4-Cl

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia3) or a form thereof, wherein substituents R_1a, R_1band X, when present, are indicated in the table below with multiple substituents separated by a comma; and, “-” indicates that one or more R_1a, R_1band X substituents are not present:

embedded image

Cpd
R_1a
R_1b
X

11
—
—
O

15
—
—
N(CH₃)

218
—
7-OH
N(CH₃)

261
1-CN
7-OH
N(CH₃)

272
1-CH₃
7-OH
N(CH₃)

275
1-CN,
7-OH
N(CH₃)

3-CH₃

292
3-(OCH₂-phenyl)
—
N(CH₃)

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia4) or a form thereof, wherein substituents X, R_1a, R_1band R_4a, when present, are indicated in the table below; and, “-” indicates that one or more X, R_1a, R_1band R_4asubstituents are not present:

embedded image

Cpd
R_1a
R_1b
X
R_4a

10
—
—
O
—

14
—
—
N(CH₃)
—

159
1-(OCH₂-phenyl)
—
N(CH₃)
—

211
—
6-OH
N(CH₃)
CH₃

212
—
6-OH
N(CH₃)
—

213
—
6-OH
O
—

215
1-cyclopropyl
6-OH
N(CH₃)
—

216
1-OH
6-OH
N(CH₃)
—

217
1-CN
6-OH
N(CH₃)
—

264
1-C(O)NH₂
6-OH
N(CH₃)
—

273
1-CH₃
6-OH
N(CH₃)
—

274
1,3-(CH₃)₂
6-OH
N(CH₃)
—

276
1-NH₂
6-OH
N(CH₃)
—

283
1-OCH₂CH₃
6-OH
N(CH₃)
—

284
1-OH
6-OH
O
—

285
3-phenyl
6-OH
N(CH₃)
—

286
3-CH₃
6-OH
N(CH₃)
—

287
3-cyclopropyl
6-OH
N(CH₃)
—

288
3-CH(CH₃)₂
6-OH
N(CH₃)
—

289
3-(CH₂)₂CH₃
6-OH
N(CH₃)
—

290
3-CH(CH₃)₂
6-OH
O
—

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia5) or a form thereof, wherein substituents R_1aand R_1b, when present, are indicated in the table below with multiple substituents separated by a comma; and, “-” indicates that one or more R_1aand R_1bsubstituents are not present:

embedded image

Cpd
R_1a
R_1b

12
—
—

220
—
6-OH

221
2-CH₃
6-OH

238
4-OCH₃
6-OH

241
3-Cl
6-OH

242
3-Br
6-OH

243
3-CH₃
6-OH

244
3-CH₃
5-Br,

6-OH

263
2-CN
6-OH

266
2-C(O)NH₂
6-OH

267
2-CO₂CH₃
6-OH

297
4-Cl
6-OH

300
—
6-OH

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia6) or a form thereof, wherein substituents R_1a, when present, are indicated in the table below; and, “-” indicates that one or more R_1asubstituents are not present:

embedded image

Cpd
R_1a

239
—

246
2,3-(CH₃)₂

247
2-CH₃

248
3-CH₃

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia7) or a form thereof, wherein substituents R_1a, when present, are indicated in the table below; and, “-” indicates that one or more R_1asubstituents are not present:

embedded image

Cpd
R_1a

258
—

260
2-CH₃

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia8) or a form thereof, wherein substituents R_1aand B, when present, are indicated in the table below; and, “-” indicates that one or more R_1aand B substituents are not present:

embedded image

Cpd
R_1a
B

209
—
6-((3aR,6aS)-5-CH₃-hexahydropyrrolo[3,4-

c]pyrrol-2(1H)-yl)

269
2-CN
piperazin-1-yl

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia9) or a form thereof, wherein substituents R_1aand B, when present, are indicated in the table below; and, “-” indicates that one or more R_1aand B substituents are not present:

embedded image

Cpd
R_1a
B

214
—
6-((3aR,6aS)-5-CH₃-hexahydropyrrolo[3,4-

c]pyrrol-2(1H)-yl)

270
—
piperazin-1-yl

291
3-CH₃
piperazin-1-yl

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia10) or a form thereof, wherein substituents R_1aand B, when present, are indicated in the table below; and, “-” indicates that one or more R_1aand B substituents are not present:

embedded image

Cpd
R_1a
B

268
2-CN
piperazin-1-yl

271
—
1,2,3,6-tetrahydropyridin-4-yl

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia11) or a form thereof, wherein substituents A, X and R_4a, when present, are indicated in the table below; and, “-” indicates that one or more A, X and R_4asubstituents are not present:

embedded image

Cpd
A
X
R_4a

2
benzo[b]thiophen-2-yl
N(CH₃)
—

4
5-CN-benzo[b]thiophen-2-yl
N(CH₃)
—

5
quinolin-3-yl
NH
—

6
benzo[b]thiophen-2-yl
O
—

9
benzo[b]thiophen-2-yl
NH
—

16
imidazo[1,2-a]pyridin-6-yl
N(CH₃)
—

17
6-phenyl-pyridin-3-yl
N(CH₃)
—

18
6-(1H-pyrrol-1-yl)-pyridin-3-yl
N(CH₃)
—

19
6-(1H-pyrazol-1-yl)-pyridin-3-yl
N(CH₃)
—

20
quinoxalin-2-yl
N(CH₃)
—

21
quinolin-3-yl
N(CH₃)
—

22
phthalazin-6-yl
N(CH₃)
—

23
benzo[c][1,2,5]oxadiazol-5-yl
NH
—

24
benzo[d]thiazol-5-yl
NH
—

25
2-CH₃-benzo[d]oxazol-6-yl
NH
—

30
2-(4-CN-phenol)
N(CH₃)
—

32
2-(4-CF₃-phenol)
N(CH₃)
—

33
6-(2-F-phenol)
N(CH₃)
—

34
2-[3,5-(OCH₃)₂-phenol]
N(CH₃)
—

35
2-[4,5-(OCH₃)₂-phenol]
N(CH₃)
—

37
2-(4,5-F₂-phenol)
N(CH₃)
—

41
benzo[b]thiophen-2-yl
NH
CH₃

53
2-[4-(1H-pyrazol-1-yl)-phenol]
N(CH₃)
—

115
2-[3-OH-5-(1H-pyrazol-4-yl)-phenol]
N(CH₃)
—

116
2-[3-OCH₃-5-(1H-pyrazol-4-yl)-phenol]
N(CH₃)
—

117
2-[5-(1H-pyrazol-4-yl)-3-OCF₃-phenol]
NH
—

118
2-[5-(1-CH₃-1H-pyrazol-4-yl)-3-OCF₃-phenol]
N(CH₃)
—

119
2-[5-(1H-pyrazol-4-yl)-3-OCF₃-phenol]
N(CH₃)
—

120
2-[5-(1-CH₃-pyridin-2(1H)-one)-3-OCF₃-phenol]
N(CH₃)
—

121
2-[3-OCH₃-5-(1-CH₃-1H-pyrazol-4-yl)-phenol]
N(CH₃)
—

122
2-[3-OCH₃-5-(5,6,7,8-tetrahydroimidazo-[1,2-
N(CH₃)
—

a]pyridin-3-yl)-phenol]

123
2-[3-OCH₃-5-(pyridin-3-yl)-phenol]
N(CH₃)
—

124
2-[3-OCH₃-5-(1-cyclopentyl-1H-pyrazol-4-yl)-
N(CH₃)
—

phenol]

125
2-[5-(3-OCH₃-phenyl)-3-OCH₃-phenol]
N(CH₃)
—

126
2-[3-benzyloxy-5-(5-CH₃-oxazol-2-yl)-phenol]
N(CH₃)
—

127
2-[3-OCH₂CH₃-5-(5-CH₃-oxazol-2-yl)-phenol]
N(CH₃)
—

128
2-[3-(OCH₂-cyclopropyl)-5-(5-CH₃-oxazol-2-yl)-
N(CH₃)
—

phenol]

129
5-(2-CH₃-1H-benzo[d]imidazol-6-ol)
N(CH₃)
—

134
2-[4-(1H-pyrazol-4-yl)-phenol]
N(CH₃)
—

135
2-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-
N(CH₃)
—

yl)-phenol]

136
2-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-
N(CH₃)
—

yl)-phenol]

137
2-[4-(1H-indol-2-yl)-phenol]
N(CH₃)
—

138
2-[4-(cyclopent-1-en-1-yl)-phenol]
N(CH₃)
—

139
2-[4-(1H-pyrazol-3-yl)-phenol]
N(CH₃)
—

140
2-[4-(2-OH-pyridin-4-yl)-phenol]
N(CH₃)
—

141
2[4-(1-CH₃-pyridin-2(1H)-one)-phenol]
O
—

142
2-[4-(2-OH-pyridin-4-yl)-phenol]
O
—

144
2-[4-Cl-5-(1H-pyrazol-4-yl)-phenol]
N(CH₃)
—

145
2-[4-F-5-(1H-pyrazol-4-yl)-phenol]
N(CH₃)
—

146
2-[5-F-4-(1H-imidazol-4-yl)-phenol]
N(CH₃)
—

147
2-[5-F-4-(1H-pyrazol-4-yl)-phenol]
N(CH₃)
—

148
2-[5-F-(1H-pyrazol-5-yl)-phenol]
N(CH₃)
—

149
6-OH-1-oxo-2,3-dihydro-1H-inden-5-yl
N(CH₃)
—

150
6-(1,4-dihydroindeno[1,2-c]-1H-pyrazol-7-ol)
N(CH₃)
—

151
6-OH-1-OH-imino-2,3-dihydro-1H-inden-5-yl
N(CH₃)
—

152
6-OH-1-OH-2,3-dihydro-1H-inden-5-yl
N(CH₃)
—

153
6-(2-NH₂-8H-indeno[1,2-d]thiazol-5-ol)
N(CH₃)
—

154
9-(5,6-dihydroimidazo[5,1-a]isoquinolin-8-ol)
N(CH₃)
—

155
2-{4-[C(O)NHCH₂-(1-CH₃-1H-pyrazol-4-yl)]-
N(CH₃)
—

phenol}

156
2-[4-(4-CH₂OH-1H-pyrazol-1-yl)-phenol]
N(CH₃)
—

158
3-(OCH₂-phenyl)-isoquinolin-6-yl
N(CH₃)
—

160
2-[3-F-5-(2-OCH₃-pyridin-4-yl)-phenol]
N(CH₃)
—

161
4-[1-(4-pyridin-2(1H)-one)-3-F-5-OH-phenyl]
N(CH₃)
—

162
4-{1-[4-(1-CH₃-pyridin-2(1H)-one)]-3-F-5-OH-
N(CH₃)
—

phenyl}

163
4-{1-[5-(1-CH₃-pyridin-2(1H)-one)]-3-F-5-OH-
N(CH₃)
—

phenyl}

164
2-[3-F-5-(1H-pyrazol-4-yl)-phenol]
O
—

165
2-(5-Cl-3-F-phenol)
N(CH₃)
—

166
2-[3-F-5-(1H-pyrazol-4-yl)-phenol]
N(CH₃)
—

167
2-[3-F-5-(1-CH₃-1H-pyrazol-4-yl)-phenol]
N(CH₃)
—

219
8-(quinolin-7-ol)
N(CH₃)
—

230
6-(7-OH-quinolin-2(1H)-one)
N(CH₃)
—

231
6-(7-OH-1-CH₃-quinolin-2(1H)-one)
N(CH₃)
—

245
7-(6-OH-1-CH₃-quinolin-4(1H)-one)
N(CH₃)
—

257
6-(7-OH-quinazolin-4(1H)-one)
N(CH₃)
—

259
6-(7-OH-1-CH₃-3,4-dihydroquinolin-2(1H)-one)
N(CH₃)
—

277
7-OH-1,3-(CH₃)₂-quinazolin-6-yl-2,4(1H,3H)-
N(CH₃)
—

dione

278
6-OH-benzo[d]oxazol-5-yl-2(3H)-one
N(CH₃)
—

279
2-CH₃-6-OH-2H-indazol-5-yl
N(CH₃)
—

280
1-CH₃-6-OH-1H-indazol-5-yl
N(CH₃)
—

281
7-(6-OH-2-CH₃-isoquinolin-1(2H)-one)
N(CH₃)
—

282
7-(6-OH-2-CH₂CH₃-isoquinolin-1(2H)-one)
O
—

Another embodiment of the present description includes a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia11) or a form thereof, wherein substituents A, X and R_4a, when present, are indicated in the table below; and, “-” indicates that one or more A, X and R_4asubstituents are not present:

embedded image

Cpd
A
X

420
2-OCH₃-4-(4-NO₂-1H-pyrazol-1-yl)phenyl
N(CH₃)

428
2,5-F₂-4-(1H-pyrazol-4-yl)phenyl
N(CH₃)

430
2,3-F₂-4-(1H-pyrazol-4-yl)phenyl
N(CH₃)

431
2,5-F₂-4-(1H-pyrazol-4-yl)phenyl
O

434
2-OCH₃-4-(1H-pyrazol-4-yl)phenyl
N(CH₃)

435
4-(1H-pyrazol-4-yl)phenyl
O

437
2-F-4-(1H-pyrazol-4-yl)phenyl
O

438
4-(1-CH₃-1H-pyrazol-4-yl)thiophen-2-yl
O

440
2-F-4-OH-phenyl
N(CH₃)

442
2-CH₃-2H-indazol-5-yl
N(CH₃)

443
2-CH₃-2H-indazol-5-yl
O

444
4-Cl-2-OCH₃-phenyl
O

445
2-CH₃-pyrazolo[1,5-a]pyridin-3-yl
N(CH₃)

446
imidazo[1,2-a]pyridin-6-yl
O

447
2-OCH₃-4-(1H-pyrazol-1-yl)phenyl
O

448
5-(1H-pyrazol-4-yl)thiophen-2-yl
O

449
5-(1-CH₃-1H-pyrazol-4-yl)thiophen-2-yl
O

450
4-(1H-pyrazol-4-yl)thiophen-2-yl
O

451
2-OH-4-[3,5-(CH₃)₂-1H-pyrazol-4-yl]phenyl
O

452
2-F-4-(1H-pyrazol-4-yl)phenyl
N(CH₃)

453
2-OCH₃-4-OH-phenyl
O

454
2-OCH₃-4-(4-NO₂-1H-pyrazol-1-yl)phenyl
O

455
2,4-(OH)₂-phenyl
O

456
2-Cl-4-(1H-pyrazol-4-yl)phenyl
N(CH₃)

457
5-amino-2-(1H-pyrazol-4-yl)pyrimidin-4-yl
O

458
2,6-F₂-4-(1H-pyrazol-4-yl)phenyl
O

464
2-(CHF₂)-4-(1H-pyrazol-4-yl)phenyl
O

465
2-(CHF₂)-4-(1H-pyrazol-4-yl)phenyl
N(CH₃)

embedded image

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia12) or a form thereof, wherein substituents X, R_1aand B, when present, are indicated in the table below; and, “-” indicates that one or more X, R_1aand B substituents are not present:

embedded image

Cpd
R_1a
X
B

66
H
NH
azetidin-3-yl

82
OH
—
piperazin-1-yl

85
H
—
1,2,3,6-tetrahydropyridin-4-yl

86
OH
—
1,2,3,6-tetrahydropyridin-4-yl

87
OH
—
2,2,6,6-tetramethyl-(1,2,3,6-

tetrahydropyridin-4-yl)

88
OH
—
1-CH₃-(1,2,3,6-tetrahydropyridin-4-yl)

89
OH
—
piperidin-4-yl

99
H
CH₂
piperidin-4-yl

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia13) or a form thereof, wherein substituents X, R_1aand R_4a, when present, are indicated in the table below; and, “-” indicates that one or more X, R_1aand R_4asubstituents are not present:

embedded image

Cpd
X
R_1a
R_4a

26
N(CH₃)
H
—

28
NH
H
—

31
O
H
—

90
O
OH
—

91
N(CH₃)
OH
—

92
NH
OH
—

93
N(CH₃)
O(CH₂)₃NHCO₂C(CH₃)₃
—

94
N(CH₃)
O(CH₂)₃NH₂
—

95
N(CH₃)
O(CH₂)₃NHCO₂CH₃
—

96
N(CH₃)
O(CH₂)₃OH
—

97
N(CH₃)
O(CH₂)₃OCH₃
—

98
O
O(CH₂)₃-morpholin-4-yl
—

103
N(CH₃)
CN
—

104
N(CH₃)
CH₂-1-piperidinyl
—

105
N(CH₃)
CH₂-pyrrolidin-1-yl
—

108
N(CH₃)
OCH₃
—

109
N(CH₃)
OCH₃
CH₃

110
N(CH₃)
3,6-dihydro-2H-pyran-4-yl
—

111
N(CH₃)
tetrahydro-2H-pyran-4-yl
—

112
N(CH₃)
CHF₂
—

113
N(CH₃)
OC(CH₃)₂(CH₂)₂OH
—

114
N(CH₃)
O(CH₂)₂C(CH₃)₂OH
—

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia14) or a form thereof, wherein substituents X and B, when present, are indicated in the table below; and, “-” indicates that one or more X and B substituents are not present:

embedded image

Cpd
X
B

55
O
piperidin-4-yl

56
O
(2S,4R,6R)-2,6-(CH₃)₂-piperidin-4-yl

57
O
2,6-(CH₃)₂-piperidin-4-yl

58
O
pyrrolidin-3-yl

59
O
2-CH₃-piperidin-4-yl

60
OCH₂
1H-pyrrolidin-3-yl

61
O
3-F-piperidin-4-yl

65
—
piperazin-1-yl

67
NH
azetidin-3-yl

68
—
3,5-(CH₃)₂-piperazin-1-yl

69
—
7-CH₃-2,7-diazaspiro[4.4]non-2-yl

70
—
[1,4]diazepan-1-yl

71
—
4-CH₂CH₂OH-piperazin-1-yl

72
—
2,7-diazaspiro[3.5]non-7-yl

73
—
2,7-diazaspiro[3.5]non-7-yl

74
—
3-CH₂OH-piperazin-1-yl

75
—
1,7-diazaspiro[4.4]non-7-yl

76
—
4-NH₂-4-CH₃-piperidin-1-yl

77
—
3-N(CH₃)₂-piperidin-1-yl

79
—
3,3-(CH₃)₂-piperazin-1-yl

80
—
7-CH₂CH₂OH-2,7-diazaspiro[4.4]-nonan-2-yl

83
—
1,2,3,6-tetrahydropyridin-4-yl

84
—
piperidin-4-yl

102
O
(6S)-6-[(S)—CH(OH)CH₃]-2,2-(CH₃)₂-piperidin-4-yl

133
O
2,2-(CH₃)₂-piperidin-4-yl

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia15) or a form thereof, wherein substituents X, R_1aand R_4a, when present, are indicated in the table below; and, “-” indicates that one or more X, R_1aand R_4asubstituents are not present:

embedded image

Cpd
X
R_1a
R_4a

3
NH
H
—

7
N(CH₃)
H
—

27
N(CH₃)
Cl
CH₃

29
NH
Cl
CH₃

36
N(CH₃)
OCH₃
—

38
N(CH₃)
F
—

39
N(CH₃)
CN
—

42
N(CH₃)
C(O)NHCH₂CH═CH₂
—

43
N(CH₃)
1H-pyrazol-1-yl
—

44
N(CH₃)
5-CH₃-oxazol-2-yl
—

45
N(CH₃)
4-CH₂OH-1H-pyrazole-1-yl
—

46
N(CH₃)
1H-imidazole-1-yl
—

47
N(CH₃)
4-NH₂-1H-pyrazol-1-yl
—

48
N(CH₃)
1H-pyrazol-4-yl
—

49
N(CH₃)
3-NH₂-1H-pyrazol-1-yl
—

50
N(CH₃)
1-(CH₂CH₂-morpholin-4-yl)-1H-
—

pyrazol-4-yl

51
N(CH₃)
1-CH₃-1H-pyrazol-4-yl
—

52
N(CH₃)
5-NH₂-1H-pyrazol-1-yl
—

54
N(CH₂CH₂OH)
1H-pyrazol-1-yl
—

62
O
1H-pyrazol-1-yl
CH₃

63
O
1H-pyrazol-1-yl
—

64
O
1H-pyrazol-4-yl
—

78
NH
1H-pyrazol-1-yl
CH₃

100
CH₂
1H-pyrazol-1-yl
—

130
N(CH₃)
Cl
—

131
NH
1H-pyrazol-1-yl
—

132
NH
CN
—

143
N(CH₃)
1H-indazol-7-yl
—

157
CH₂
1H-pyrazol-4-yl
—

168
N(CH₃)
5-OCH₃-pyridin-3-yl
—

169
N(CH₃)
5-pyridin-2-ol
—

170
N(CH₃)
4-pyridin-2-ol
—

171
N(CH₃)
6-OCH₃-pyridin-3-yl
—

172
N(CH₃)
5-(3-CF₃-pyridin-2-ol)
—

173
N(CH₃)
5-(1-CH₃-pyridin-2(1H)-one)
—

174
N(CH₃)
4-(1-CH₃-pyridin-2(1H)-one)
—

175
N(CH₃)
2-OCH₃-pyridin-4-yl
—

176
O
4-pyridin-2-ol
—

177
N(CH₃)
6-N(CH₃)₂-pyridin-3-yl
—

178
O
4-(1-CH₃-pyridin-2(1H)-one)
—

179
N(CH₃)
pyrimidin-5-yl
—

180
N(CH₃)
5-pyridin-3-ol
—

181
N(CH₃)
4-(1-cyclopropyl-pyridin-2(1H)-
—

one)

182
N(CH₃)
1,2,3,6-tetrahydropyridin-4-yl
—

183
N(CH₃)
cyclopent-1-en-1-yl
—

184
N(CH₃)
3,6-dihydro-2H-pyran-4-yl
—

185
N(CH₃)
imidazo[1,5-a]pyridin-7-yl
—

186
N(CH₃)
imidazo[1,2-a]pyridin-7-yl
—

187
N(CH₃)
2-CH₃-pyridin-4-yl
—

188
N(CH₃)
1H-imidazol-2-yl
—

189
N(CH₃)
1H-imidazol-4-yl
—

190
N(CH₃)
imidazo[1,2-a]pyrazin-3-yl
—

191
N(CH₃)
5,6,7,8-tetrahydroimidazo[1,2-
—

a]pyrazin-3-yl

192
N(CH₃)
4-CH₃-1H-imidazol-2-yl
—

193
N(CH₃)
1-CH₃-1H-imidazol-4-yl
—

194
N(CH₃)
1-CH₃-1H-imidazol-5-yl
—

195
N(CH₃)
4-NO₂-1H-imidazol-2-yl
—

196
N(CH₃)
2-CH₃-1H-imidazol-4-yl
—

197
N(CH₃)
1,2-(CH₃)₂-1H-imidazol-4-yl
—

198
N(CH₃)
4-C(O)NH₂-1H-pyrazol-1-yl
—

206
N(CH₃)
H
—

Another embodiment of the present description includes a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia15) or a form thereof, wherein substituents X, R_1aand R_4a, when present, are indicated in the table below; and, “-” indicates that one or more X, R_1aand R_4asubstituents are not present:

embedded image

Cpd
X
R_1a
R_4a

413
NH
1H-pyrazol-4-yl
—

414
O
1-CH₃-1H-pyrazol-4-yl
—

416
N(CH₃)
5-CH₃-1H-pyrazol-4-yl
—

417
O
1H-imidazol-1-yl
—

418
O
5-CH₃-1H-pyrazol-4-yl
—

419
N(CH₃)
4-NO₂-1H-pyrazol-1-yl
—

421
O
4-NH₂-1H-pyrazol-1-yl
—

423
O
4-NO₂-1H-pyrazol-1-yl
—

460
N(CH₃)
1H-pyrazol-4-yl
—

461
O
1H-pyrazol-4-yl
—

embedded image

Cpd
X
R_1a

413
NH
1H-pyrazol-4-yl

414
O
1-CH₃-1H-pyrazol-4-yl

416
N(CH₃)
5-CH₃-1H-pyrazol-4-yl

417
O
1H-imidazol-1-yl

418
O
5-CH₃-1H-pyrazol-4-yl

419
N(CH₃)
4-NO₂-1H-pyrazol-1-yl

421
O
4-NH₂-1H-pyrazol-1-yl

423
O
4-NO₂-1H-pyrazol-1-yl

460
N(CH₃)
1H-pyrazol-4-yl

461
O
1H-pyrazol-4-yl

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia16) or a form thereof, wherein substituents R_1aand R_4a, when present, are indicated in the table below; and, “-” indicates that one or more R_1aand R_4asubstituents are not present:

embedded image

Cpd
R_1a
R_4a

81
1H-pyrazol-1-yl
—

199
1H-pyrazol-4-yl
(CH₂)₂OH

200
1H-pyrazol-4-yl
—

201
1H-pyrazol-4-yl
CH₃

202
4-(1-CH₃-pyridin-2(1H)-one)
CH₃

203
4-(1-CH₃-pyridin-2(1H)-one)
CH₃

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia17) or a form thereof, wherein substituent R_1a, when present, is indicated in the table below; and, “-” indicates that one or more R_1asubstituents are not present:

embedded image

Cpd
R_1a

204
1H-pyrazol-4-yl

205
4-(1-CH₃-pyridin-2(1H)-one)

Another embodiment of the present description includes a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia18) or a form thereof, wherein substituents X and B, when present, are indicated in the table below; and, “-” indicates that one or more X and B substituents are not present:

embedded image

Cpd
X
B

411
N(CH₃)
(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl

412
NH
(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl

415
O
(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl

422
—
1-CH₃-(1,2,3,6-tetrahydropyridin-4-yl)

424
—
1,2,3,6-tetrahydropyridin-4-yl

425
—
1-CH₃CH₂-(1,2,3,6-tetrahydropyridin-4-yl)

426
N(CH₃)
piperidin-4-yl

427
NH
piperidin-4-yl

429
—
8-azabicyclo[3.2.1]oct-2-en-3-yl

432
O
piperidin-4-yl

433
NH
(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl

436
O
2,6-(CH₃)₂-piperidin-4-yl

439
—
2,7-diazaspiro[3.5]non-2-yl

441
O
2,6-(CH₃)₂-piperidin-4-yl

459
—
2,6-diazaspiro[3.4]oct-2-yl

Another embodiment of the method of the present description includes the use of a compound of Formula (Ia) or a form thereof selected from a compound of Formula (Ia18) or a form thereof, wherein substituents X, R_1aand B, when present, are indicated in the table below; and, “-” indicates that one or more X, R_1aand B substituents are not present:

embedded image

Another embodiment of the method of the present description includes the use of a compound of Formula (Ib) or a form thereof selected from a compound of Formula (Ib1) or a form thereof, wherein substituent A is indicated in the table below:

embedded image

Cpd
A

302
6-(naphthalen-2-ol)

320
6-(naphthalen-2,7-diol)

331
7-OCH₃-quinolin-6-yl

332
7-OH-quinolin-6-yl

337
2-CN-7-OCH₃-quinolin-6-yl

355
3-F-5-(1H-pyrazol-4-yl)-pyridin-2-yl

364
2-(6-OCH₃-3,4-dihydroisoquinolin-1(2H)-one)

392
6-OH-1-oxo-2,3-dihydro-1H-inden-5-yl

401
3-(4-OCH₃-1-CH₃-quinolin-2(1H)-one)

402
3-(4-OH-1-CH₃-quinolin-2(1H)-one)

403
3-(quinolin-2(1H)-one)

404
3-(1-OCH₃-quinolin-2(1H)-one)

408
5-CN-benzo[b]thiophen-2-yl

409
3-Cl-benzo[b]thiophen-2-yl

Another embodiment of the present description includes a compound of Formula (Ib) or a form thereof selected from a compound of Formula (Ib1) or a form thereof, wherein substituent A is indicated in the table below:

Cpd
A

462
3-(1H-pyrazol-4-yl)phenoxy

463
4-(1H-pyrazol-4-yl)phenoxy

embedded image

Cpd
A

462
3-(1H-pyrazol-4-yl)phenoxy

463
4-(1H-pyrazol-4-yl)phenoxy

Another embodiment of the method of the present description includes the use of a compound of Formula (Ib) or a form thereof selected from a compound of Formula (Ib2) or a form thereof, wherein substituent A is indicated in the table below:

embedded image

Cpd
A

321
6-naphthalen-2,7-diol

Another embodiment of the method of the present description includes the use of a compound of Formula (Ib) or a form thereof selected from a compound of Formula (Ib3) or a form thereof, wherein substituents R_1a, R_1band B, when present, are indicated in the table below; and, “-” indicates that one or more R_1a, R_1band B substituents are not present:

embedded image

Cpd
R_1a
R_1b
B

329
1H-pyrazol-1-yl
OCH₃
1,2,3,6-tetrahydropyridin-4-yl

330
1H-pyrazol-1-yl
OH
piperazin-1-yl

381
1H-pyrazol-1-yl
Cl
5-((3aR,6aR)-1-CH₃-hexahydropyrrolo[3,4-

b]pyrrol-5(1H)-yl)

382
1H-pyrazol-1-yl
Cl
2-NHCH(CH₃)₂-morpholin-4-yl

383
1H-pyrazol-1-yl
Cl
2-OCH₃-2,7-diazaspiro[4.5]decan-7-yl

385
1-CH₃-1H-pyrazol-4-yl
OCH₃
5-((3aR,6aS)-5-CH₃-hexahydropyrrolo[3,4-

c]pyrrol-2(1H)-yl)

394
1-CH₃-1H-pyrazol-4-yl
OH
5-((3aR,6aS)-5-CH₃-hexahydropyrrolo[3,4-

c]pyrrol-2(1H)-yl)

406
1H-pyrazol-1-yl
Cl
2,7-diazaspiro[4.5]decan-2-yl

407
1H-pyrazol-1-yl
Cl
(3R)-(3-(R)—CH₂OH)-piperazin-1-yl

Another embodiment of the ccpresent description includes the use of a compound of Formula (Ib) or a form thereof selected from a compound of Formula (Ib4) or a form thereof, wherein substituents R_1a, R_1b, R_1c, R_1d(each representative of the scope of R₁) and X, when present, are indicated in the table below; and, “-” indicates that one or more R_1a, R_1b, R_1c, R_1dand X substituents are not present:

embedded image

Cpd
R_1a
R_1b
R_1c
R_1d
X

301
1H-pyrazol-1-yl
OCH₃
H
H
N(CH₃)

305
1H-pyrazol-1-yl
OCH₃
H
H
N(CH₃)

306
1-CH₃-1H-pyrazol-4-yl
OCH₃
H
H
N(CH₃)

307
1H-pyrazol-4-yl
OCH₃
H
H
N(CH₃)

308
4-(1-CH₃-pyridin-2(1H)-one)
OCH₃
H
H
N(CH₃)

309
5-pyridin-2-ol
OCH₃
H
H
N(CH₃)

310
5-(1-CH₃-pyridin-2(1H)-one)
OCH₃
H
H
N(CH₃)

311
1-CH₃-1H-pyrazol-4-yl
CH₃
H
H
N(CH₃)

312
4-(1-CH₃-pyridin-2(1H)-one)
OCF₃
H
H
N(CH₃)

313
3,5-(CH₃)₂-1H-pyrazol-4-yl
OCH₃
H
H
N(CH₃)

314
1-CH₃-1H-pyrazol-4-yl
CF₃
H
H
N(CH₃)

315
1-CH₃-1H-pyrazol-4-yl
OH
H
H
N(CH₃)

316
1H-pyrazol-1-yl
OH
H
H
N(CH₃)

317
5-(1-CH₃-pyridin-2(1H)-one)
OH
H
H
N(CH₃)

318
4-(1-CH₃-pyridin-2(1H)-one)
OH
H
H
N(CH₃)

319
5-pyridin-2-ol
OH
H
H
N(CH₃)

324
H
OH
1H-pyrazol-1-yl
H
N(CH₃)

325
1-CH₃-1H-pyrazol-4-yl
H
H
Cl
N(CH₃)

326
1-CH₃-1H-pyrazol-4-yl
OH
H
Cl
N(CH₃)

327
1-CH₃-1H-pyrazol-4-yl
H
H
Cl
N(CH₃)

328
5-CH₃-oxazol-2-yl
OH
H
OCH₃
N(CH₃)

333
CN
OCH₃
H
H
N(CH₃)

334
CN
F
H
H
N(CH₃)

335
CO₂CH₃
F
H
H
N(CH₃)

336
3-NHCH₃-1H-pyrazol-1-yl
OCH₃
H
H
N(CH₃)

338
4-(1-CH₃-pyridin-2(1H)-one)
OCH₃
H
H
N(CH₃)

339
4-(1-CH₃-pyridin-2(1H)-one)
Cl
H
H
N(CH₃)

340
1H-pyrazol-4-yl
Cl
H
H
N(CH₃)

341
4,5,6,7-
Cl
H
H
N(CH₃)

tetrahydropyrazolo[1,5-a]pyridin-

3-yl

343
1-CH₃-1H-pyrazol-4-yl
Cl
H
H
O

344
6-OCH₃-pyridin-3-yl
Cl
H
H
N(CH₃)

345
6-NH₂-pyridin-3-yl
F
H
H
N(CH₃)

346
3-CH₃-1H-pyrazol-5-yl
F
H
H
N(CH₃)

347
1H-pyrazol-5-yl
F
H
H
N(CH₃)

348
1H-pyrazol-4-yl
H
F
F
N(CH₃)

349
1H-pyrazol-5-yl
H
F
F
N(CH₃)

350
1H-pyrazol-4-yl
F
F
H
N(CH₃)

351
1H-pyrazol-5-yl
F
F
H
N(CH₃)

352
1H-pyrazol-4-yl
F
H
F
N(CH₃)

354
1H-pyrazol-4-yl
Cl
F
H
N(CH₃)

356
2-NH₂-pyrimidin-4-yl
Cl
H
H
N(CH₃)

357
H
Cl
2-NH₂-pyrimidin-
H
N(CH₃)

4-yl

358
2,4-(CH₃)₂-thiazol-5-yl
F
F
H
N(CH₃)

359
2,4-(CH₃)₂-thiazol-5-yl
H
F
F
N(CH₃)

360
4-(1-CH₃-pyridin-2(1H)-one)
OH
H
OCF₃
N(CH₃)

361
1H-pyrazol-4-yl
OCH₃
H
F
N(CH₃)

363
1H-pyrazol-4-yl
OCH₃
F
F
N(CH₃)

365
1H-pyrazol-1-yl
Cl
H
H
N(CH₃)

366
1H-1,2,3-triazol-1-yl
Cl
H
H
N(CH₃)

367
2H-1,2,3-triazol-2-yl
Cl
H
H
N(CH₃)

368
1H-1,2,4-triazol-1-yl
Cl
H
H
N(CH₃)

369
3-NH₂-1H-pyrazol-1-yl
Cl
H
H
N(CH₃)

371
1H-imidazol-1-yl
Cl
H
H
N(CH₃)

372
1H-imidazol-1-yl
F
H
H
N(CH₃)

373
1H-pyrazol-5-yl
OCH₃
H
H
N(CH₃)

374
2,4-(CH₃)₂-thiazol-5-yl
OCH₃
H
H
N(CH₃)

375
pyridin-3-yl
OCH₃
H
H
N(CH₃)

376
1H-pyrazol-4-yl
F
H
H
N(CH₃)

377
2-OCH₃-pyridin-4-yl
OCH₃
H
H
N(CH₃)

378
6-OCH₃-pyridin-3-yl
OCH₃
H
H
N(CH₃)

387
1H-pyrazol-1-yl
OH
H
H
N(CH₃)

388
5-(pyridin-2(1H)-one)
Cl
H
H
N(CH₃)

389
3-NHCH₃-1H-pyrazol-1-yl
OH
H
H
N(CH₃)

390
1H-pyrazol-4-yl
OH
H
F
N(CH₃)

391
1H-pyrazol-4-yl
OH
F
F
N(CH₃)

393
1H-pyrazol-4-yl
OH
H
H
N(CH₃)

397
1H-pyrazol-4-yl
OH
H
Cl
N(CH₃)

398
1H-pyrazol-1-yl
OCH₃
H
H
CH₂

410
1H-pyrazol-4-yl
OCH₃
H
H
N(CH₃)

Another embodiment of the method of the present description includes the use of a compound of Formula (Ib) or a form thereof selected from a compound of Formula (Ib5) or a form thereof, wherein substituents R_1a, R_1b, R_1c, R_1d(each representative of the scope of R₁) and R_4a, when present, are indicated in the table below; and, “-” indicates that one or more R_1a, R_1b, R_1c, R_1dand R_4asubstituents are not present:

embedded image

Cpd
R_1a
R_1b
R_1c
R_1d
R_4a

353
1H-pyrazol-4-yl
F
F
H
—

362
1H-pyrazol-4-yl
OCH₃
H
F
CH₃

370
1H-imidazol-1-yl
Cl
H
H
CH₃

379
1-CH₃-1H-pyrazol-4-yl
Cl
H
H
CH₃

380
1H-pyrazol-4-yl
Cl
H
H
CH₃

384
1H-pyrazol-4-yl
F
H
H
CH₃

396
1H-pyrazol-4-yl
F
H
OH
—

405
1H-pyrazol-4-yl
Cl
H
H
—

Another embodiment of the method of the present description includes the use of a compound of Formula (Ib) or a form thereof selected from a compound of Formula (Ib6) or a form thereof, wherein substituents R_1a, R_1b, R_1cand R_1d(each representative of the scope of R₁), when present, are indicated in the table below; and, “-” indicates that one or more R_1a, R_1b, R_1cand R_1dsubstituents are not present:

embedded image

Cpd
R_1a
R_1b
R_1c
R_1d

386
1-CH₃-1H-pyrazol-4-yl
OCH₃
H
H

395
1-CH₃-1H-pyrazol-4-yl
OH
H
H

399
1H-pyrazol-4-yl
H
F
F

400
1H-pyrazol-4-yl
OH
H
F

Another embodiment of the method of the present description includes the use of a compound of Formula (Ib) or a form thereof selected from a compound of Formula (Ib7) or a form thereof, wherein substituent R_1b, when present, is indicated in the table below:

embedded image

Cpd
R_1b

304
OCH₃

322
OH

Another embodiment of the method of the present description includes the use of a compound of Formula (Ib) or a form thereof selected from a compound of Formula (Ib8) or a form thereof, wherein substituent R_1b, when present, is indicated in the table below:

embedded image

Cpd
R_1b

303
OCH₃

323
OH

An embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use of a compound of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject, selected from the group consisting of:

embedded image

embedded image

wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

In another aspect, the compound of Formula (I) or a form thereof includes a compound selected from the group consisting of:

embedded image

Another embodiment of the use of a compound of Formula (I) or a form thereof includes a method of use of a compound of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof (wherein compound number (#¹) indicates that the salt form was isolated) to the subject, selected from the group consisting of:

Cpd
Name

1
6-(naphthalen-2-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

2
6-(benzo[b]thiophen-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-

amine

3
2-(6-(2,2,6,6-tetramethylpiperidin-4-yl-amino)-pyridazin-3-yl)phenol

4
2-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzo[b]-

thiophene-5-carbonitrile

5
6-(quinolin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

6
3-(benzo[b]-thiophen-2-yl)-6-(2,2,6,6-tetramethylpiperidin-4-yl-oxy)pyridazine

7
2-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)-pyridazin-3-yl)phenol

8
6-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)-pyridazin-3-yl)naphthalen-2-ol

9
6-(benzo[b]-thiophen-2-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

10
7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinoline

11
6-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinoline

12
N-methyl-6-(quinolin-7-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

13
N-methyl-6-(quinolin-6-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

14
6-(isoquinolin-7-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

15
6-(isoquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

16
6-(imidazo[1,2-a]pyridin-6-yl-pyridazin-3-yl)-methyl-(2,2,6,6-tetramethylpiperidin-4-

yl)-amine

17
N-methyl-6-(6-phenylpyridin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-

amine

18
6-(6-(1H-pyrrol-1-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine

19
6-(6-(1H-pyrazol-1-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine

20
methyl-(6-quinoxalin-2-yl-pyridazin-3-yl)-(2,2,6,6-tetramethylpiperidin-4-yl)-amine

21
methyl-(6-quinolin-3-yl-pyridazin-3-yl)-(2,2,6,6-tetramethylpiperidin-4-yl)-amine

22
N-methyl-6-(phthalazin-6-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

23
6-(benzo[c][1,2,5]oxa-diazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-

amine

24
6-(benzo[d]thiazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

25
6-(2-methylbenzo-[d]oxazol-6-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-

amine

26
3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol

27
5-chloro-2-(6-(methyl(1,2,2,6,6-pentamethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol

28
3-(6-(2,2,6,6-tetramethylpiperidin-4-yl-amino)pyridazin-3-yl)naphthalen-2-ol

29
5-chloro-2-(6-(1,2,2,6,6-pentamethylpiperidin-4-ylamino)pyridazin-3-yl)phenol

30
4-hydroxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)benzonitrile

31
3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)naphthalen-2-ol

32¹
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-

(trifluoromethyl)phenol

33
2-fluoro-6-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)phenol

34
3,5-dimethoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenol

35
4,5-dimethoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenol

36
5-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol

37
4,5-difluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenol

38
5-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol

39
3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)benzonitrile

40
1-allyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)naphthalen-2-ol

41
6-(benzo[b]thiophen-2-yl)-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyridazin-3-amine

42
N-allyl-3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)benzamide

43
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-1-

yl)phenol

44
5-(5-methyl-oxazol-2-yl)-2-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-

pyridazin-3-yl)phenol

45
5-(4-hydroxymethyl)-1H-pyrazole-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

46
5-(1H-imidazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-

3-yl)phenol

47
5-(4-amino-1H-pyrazole-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

48
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-

yl)phenol

49
5-(3-amino-1H-pyrazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

50
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-(2-

morpholino-ethyl)-1H-pyrazol-4-yl)phenol

51
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-

pyrazol-4-yl)phenol

52
5-(5-amino-1H-pyrazol-1-yl)-2-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

53¹
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-1-

yl)phenol

54
2-((6-((2-hydroxy-ethyl)-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)-5-

pyrazol-1-yl)phenol

55
2-(6-(piperidin-4-yloxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

56
2-(6-(((2S,4R,6R)-2,6-dimethylpiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-

yl)phenol

57
2-(6-((-2,6-dimethylpiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

58
5-(1H-pyrazol-1-yl)-2-(6-(pyrrolidin-3-yl-oxy)pyridazin-3-yl)phenol

59
2-(6-(((2S,4S)-2-methylpiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

60
(5-(1H-pyrazol-1-yl)-2-(6-(pyrrolidin-3-ylmethoxy)pyridazin-3-yl)phenol

61
2-(6-((3-fluoropiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

62
2-(6-(1,2,2,6,6-pentamethyl-piperidin-4-yl-oxy)-pyridazin-3-yl)-5-(1H-pyrazol-1-

yl)phenol

63
5-1H-pyrazol-1-yl-2-(6-(2,2,6,6-tetramethylpiperidin-4-yl-oxy)-pyridazin-3-yl)phenol

64
5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenol

65¹
2-(6-piperazin-1-yl-pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

66
3-(6-(azetidin-3-ylamino)-pyridazin-3-yl)naphthalen-2-ol

67
2-(6-(azetidin-3-ylamino)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

68
2-(6-(3,5-dimethylpiperazin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

69
2-(6-(7-methyl-2,7-diazaspiro[4.4]nonan-2-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-

yl)phenol

70
2-(6-(1,4-diazepan-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

71
2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

72
2-(6-(3,6-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

73
2-(6-(2,7-diazaspiro[3.5]nonan-7-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

74
2-(6-(3-(hydroxymethyl)piperazin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

75
2-(6-(1,7-diazaspiro[4.4]nonan-7-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

76
2-(6-(4-amino-4-methylpiperidin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

77
2-(6-(3-(dimethylamino)piperidin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

78
2-(6-(1,2,2,6,6-pentamethylpiperidin-4-ylamino)-pyridazin-3-yl)-5-1H-pyrazol-1-yl-

phenol

79
2-(6-(3,3-dimethylpiperazin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

80
2-(6-(7-(2-hydroxyethyl)-2,7-diazaspiro[4.4]-nonan-2-yl)pyridazin-3-yl)-5-(1H-pyrazol-

1-yl)phenol

81
2-(6-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-

pyrazol-1-yl)phenol

82¹
3-(6-(piperazin-1-yl)pyridazin-3-yl)naphthalene-2,7-diol

83
5-(1H-pyrazol-1-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol

84
2-(6-piperidin-4-yl-pyridazin-3-yl)-5-1H-pyrazol-1-yl-phenol

85
3-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalen-2-ol

86¹
3-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol

87
3-(6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-

diol

88¹
3-(6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol

89¹
3-(6-(piperidin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol

90
3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)naphthalene-2,7-diol

91
3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalene-2,7-

diol

92
3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalene-2,7-diol

93
tert-butyl (3-((7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)naphthalen-2-yl)oxy)propyl)carbamate

94
7-(3-amino-propoxy)-3-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-

pyridazin-3-yl)naphthalen-2-ol

95
N-(3-((7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)naphthalen-2-yl)oxy)propyl)acetamide

96
7-(3-hydroxypropoxy)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-

3-yl)naphthalen-2-ol

97
7-(3-methoxypropoxy)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-

3-yl)naphthalen-2-ol

98
7-(2-morpholinoethoxy)-3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-

yl)naphthalen-2-ol

99
3-(6-(piperidin-4-ylmethyl)pyridazin-3-yl)naphthalen-2-ol

100
5-(1H-pyrazol-1-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyridazin-3-

yl)phenol

101
3-methoxy-2-(6-(methyl(2,2,6-trimethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5-

methyloxazol-2-yl)phenol

102
2-(6-((6S)-6-((S)-1-hydroxyethyl)-2,2-dimethylpiperidin-4-yloxy)pyridazin-3-yl)-5-

(1H-pyrazol-1-yl)phenol

103
7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2-

naphthonitrile

104
3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-7-

(piperidinylmethyl)naphthalen-2-ol

105
3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-7-

(pyrrolidinylmethyl)naphthalen-2-ol

106
1-bromo-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)naphthalene-2,7-diol

107
1-chloro-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)naphthalene-2,7-diol

108
7-methoxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)naphthalene-2-ol

109
7-methoxy-3-(6-(methyl(1,2,2,6,6-pentamethylpiperidin-4-yl)amino)pyridazin-3-

yl)naphthalen-2-ol

110
7-(3,6-dihydro-2H-pyran-4-yl)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)naphthalen-2-ol

111
3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-7-(tetrahydro-2H-

pyran-4-yl)naphthalene-2-ol

112
7-(difluoromethyl)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)naphthalen-2-ol

113
7-((4-hydroxy-2-methylbutan-2-yl)oxy)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)naphthalen-2-ol

114
7-(3-hydroxy-3-methylbutoxy)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)naphthalen-2-ol

115
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-

yl)benzene-1,3-diol

116
3-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-

(1H-pyrazol-4-yl)phenol

117
5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3-

(trifluoromethoxy)phenol

118
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-

pyrazol-4-yl)-3-(trifluoromethoxy)phenol

119
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-

yl)-3-(trifluoromethoxy)phenol

120
4-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-

(trifluoromethoxy)phenyl)-1-methylpyridin-2(1H)-one

121
3-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-

methyl-1H-pyrazol-4-yl)phenol

122
3-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-

(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-3-yl)phenol

123
3-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-

(pyridine-3-yl)phenol

124
5-(1-cyclopentyl-1H-pyrazol-4-yl)-3-methoxy-2-(6-(methyl(2,2,6,6-

tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol

125
3′,5-dimethoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-

(1,1′-biphenyl)-3-ol

126
3-(benzyloxy)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-

(5-methyloxazol-2-yl)phenol

127
3-ethoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5-

methyloxazol-2-yl)phenol

128
3-(cyclopropylmethoxy)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-

pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol

129
2-methyl-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-1H-

benzo[d]imidazol-6-ol

130
5-chloro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol

131
5-(1H-pyrazol-1-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenol

132
3-hydroxy-4-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzonitrile

133
2-(6-((2,2-dimethylpiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

134
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-4-

yl)phenol

135
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridin-3-yl)-4-(4,5,6,7-

tetrahydropyrazolo[1,5-a]pyridin-3-yl)phenol

136
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(4,5,6,7-

tetrahydropyrazolo[1,5-a]pyrazin-3-yl)phenol

137
4-(1H-indol-2-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenol

138
4-(cyclopent-1-en-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

139
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-3-

yl)phenol

140
4-(4-hydroxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenyl)pyridin-2-ol

141
4-(4-hydroxy-3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenyl)-1-

methylpyridin-2(1H)-one

142
4-(4-hydroxy-3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-

yl)phenyl)pyridin-2-ol

143
5-(1H-indazol-7-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenol

144
4-chloro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-

pyrazol-4-yl)phenol

145
4-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-

pyrazol-4-yl)phenol

146
5-fluoro-4-(1H-imidazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

147
5-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-

pyrazol-4-yl)phenol

148
5-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-

pyrazol-5-yl)phenol

149
6-hydroxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-

dihydro-1H-inden-1-one

150
6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-1,4-

dihydroindeno[1,2-c]-1H-pyrazol-7-ol

151¹
6-hydroxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-

dihydro-1H-inden-1-oneoxime

152
5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-dihydro-1H-

indene-1,6-diol

153¹
2-amino-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-8H-

indeno[1,2-d]thiazol-5-ol

154¹
9-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5,6-

dihydroimidazo[5,1-a]isoquinolin-8-ol

155
4-hydroxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-N-((1-

methyl-1H-pyrazol-4-yl)methyl)benzamide

156
4-(4-(hydroxymethyl)-1H-pyrazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

157
5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyridazin-3-

yl)phenol

158
6-(3-(benzyloxy)isoquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine

159
6-(1-(benzyloxy)isoquinolin-7-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine

160¹
3-fluoro-5-(2-methoxypyridin-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

161¹
4-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-

3-yl)phenyl)pyridin-2(1H)-one

162¹
4-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-

3-yl)phenyl)-1-methylpyridin-2(1H)-one

163¹
5-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-

3-yl)phenyl)-1-methylpyridin-2(1H)-one

164¹
3-fluoro-5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-

yl)phenol

165¹
5-chloro-3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenol

166¹
3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-

pyrazol-4-yl)phenol

167¹
3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-

methyl-1H-pyrazol-4-yl)phenol

168
5-(5-methoxypyridin-3-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

169
5-(3-hydroxy-4-(6-methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenyl)pyridin-2-ol

170
4-(3-hydroxy-4-(6-methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenyl)pyridin-2-ol

171
5-(6-methoxypyridin-3-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

172
5-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenyl)-3-(trifluoromethyl)pyridin-2-ol

173
5-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenyl)-1-methylpyridin-2(1H)-one

174
4-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenyl)-1-methylpyridin-2(1H)-one

175
5-(2-methoxypyridin-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

176
4-(3-hydroxy-4-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-

yl)phenyl)pyridin-2-ol

177
5-(6-(dimethylamino)pyridin-3-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

178
4-(3-hydroxy-4-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenyl)-1-

methylpyridin-2(1H)-one

179
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(pyrimidin-5-

yl)phenol

180
5-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenyl)pyridin-3-ol

181
1-cyclopropyl-4-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenyl)pyridin-2(1H)-one

182
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1,2,3,6-

tetrahydropyridin-4-yl)phenol

183
5-(cyclopent-1-en-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

184
5-(3,6-dihydro-2H-pyran-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

185
5-(imidazo[1,5-a]pyridin-7-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

186
5-(imidazo[1,2-a]pyridin-7-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

187
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(2-

methylpyridin-4-yl)phenol

188
5-(1H-imidazol-2-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-

3-yl)phenol

189
5-(1H-imidazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-

3-yl)phenol

190
5-(imidazo[1,2-a]pyrazin-3-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

191
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5,6,7,8-

tetrahydroimidazo[1,2-a]pyrazin-3-yl)phenol

192
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(4-methyl-1H-

imidazol-2-yl)phenol

193
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-

imidazol-4-yl)phenol

194
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-

imidazol-5-yl)phenol

195
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(4-nitro-1H-

imidazol-2-yl)phenol

196
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(2-methyl-1H-

imidazol-4-yl)phenol

197
5-(1,2-dimethyl-1H-imidazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol

198
1-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenyl)-1H-pyrazole-4-carboxamide

199
2-(6-((3aR,6aS)-5-(2-hydroxyethyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-

3-yl)-5-(1H-pyrazol-4-yl)phenol

200
2-(6-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-

pyrazol-4-yl)phenol

201
2-(6-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-

(1H-pyrazol-4-yl)phenol

202
4-(3-hydroxy-4-(6-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-

yl)phenyl)-1-methylpyridin-2(1H)-one

203
4-(3-hydroxy-4-(6-((3aR,6aR)-1-methylhexahydropyrrolo[3,4-b]pyrrol-5(1H)-

yl)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one

204
2-(6-(2,7-diazaspiro[4.5]decan-2-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol

205
4-(4-(6-(2,7-diazaspiro[4.5]decan-2-yl)pyridazin-3-yl)-3-hydroxyphenyl)-1-

methylpyridin-2(1H)-one

206
2-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)phenol

207
6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol

208
6-(6-(methyl(1,2,2,6,6-pentamethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol

209
6-(6-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-

yl)quinolin-7-ol

210
2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-

7-ol

211
7-(6-(methyl(1,2,2,6,6-pentamethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol

212
7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol

213
7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinoline-6-ol

214
7-(6-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-

yl)isoquinolin-6-ol

215
1-cyclopropyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinolin-6-ol

216
7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinoline-1,6-

diol

217
6-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinoline-1-carbonitrile

218
6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-7-ol

219
8-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol

220
6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol

221
2-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-

6-ol

222
3-chloro-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-

7-ol

223
3-bromo-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-

7-ol

224
7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinoline-3-carbonitrile

225
6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3-(1-methyl-1H-

imidazol-4-yl)quinolin-7-ol

226¹
3-(1H-imidazol-1-yl)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-

3-yl)quinolin-7-ol

227
6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-3,7-diol

228
3-ethyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-

7-ol

229
3-isopropyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-7-ol

230
7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-2(1H)-one

231¹
7-hydroxy-1-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-2(1H)-one

232
4-methoxy-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-7-ol

233
2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-

(pyrrolidin-1-yl)quinolin-7-ol

234
2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-

morpholinoquinolin-7-ol

235
4-(dimethylamino)-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)quinolin-7-ol

236
4-ethoxy-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-7-ol

237
2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1-

methyl-1H-pyrazol-4-yl)quinolin-7-ol

238¹
4-methoxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-6-ol

239¹
7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoxalin-6-ol

240
6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3-(tetrahydro-2H-

pyran-4-yl)quinolin-7-ol

241
3-chloro-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-

6-ol

242
3-bromo-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-

6-ol

243
3-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-

6-ol

244
5-bromo-3-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-6-ol

245
6-hydroxy-1-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-4(1H)-one

246
2,3-dimethyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-6-ol

247
2-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinoxalin-6-ol

248
3-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinoxalin-6-ol

249
4-methoxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-7-ol

250
4-(azetidin-1-yl)-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)quinolin-7-ol

251
7-hydroxy-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolone-4-carbonitrile

252
4-cyclopropyl-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)-quinolin-7-ol

253
4-(3,6-dihydro-2H-pyran-4-yl)-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)quinolin-7-ol

254¹
2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-

(tetrahydro-2H-pyran-4-yl)quinolin-7-ol

255
2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-

(oxetan-3-yl)quinolin-7-ol

256¹
4-(dimethylamino)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)-quinolin-7-ol

257
7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinazolin-4(1H)-one

258
6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinazolin-7-ol

259
7-hydroxy-1-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)-3,4-dihydroquinolin-2(1H)-one

260
2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinazolin-7-ol

261
7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinoline-1-carbonitrile

262
7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinoline-2-carbonitrile

263
6-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-2-carbonitrile

264
6-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinoline-1-carboxamide

265
7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-2-carboxamide

266
6-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinoline-2-carboxamide

267
methyl 6-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinoline-2-carboxylate

268
6-hydroxy-7-(6-(piperazin-1-yl)pyridazin-3-yl)quinoline-2-carbonitrile

269
7-hydroxy-6-(6-(piperazin-1-yl)pyridazin-3-yl)quinoline-2-carbonitrile

270
7-(6-(piperazin-1-yl)pyridazin-3-yl)isoquinolin-6-ol

271
7-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)quinolin-6-ol

272
1-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinolin-7-ol

273
1-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinolin-6-ol

274
1,3-dimethyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinolin-6-ol

275
7-hydroxy-3-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinoline-1-carbonitrile

276
1-amino-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinolin-6-ol

277
7-hydroxy-1,3-dimethyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)quinazoline-2,4(1H,3H)-dione

278
6-hydroxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)benzo[d]oxazol-2(3H)-one

279
2-methyl-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2H-

indazol-6-ol

280
1-methyl-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-1H-

indazol-6-ol

281¹
6-hydroxy-2-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinolin-1(2H)-one

282
2-ethyl-6-hydroxy-7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-

yl)isoquinolin-1(2H)-one

283
1-ethoxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinolin-6-ol

284
7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinoline-1,6-diol

285
7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-pyridazin-3-yl)-3-

phenylisoquinolin-6-ol

286
3-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinolin-6-ol

287
3-cyclopropyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinolin-6-ol

288
3-isopropyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinolin-6-ol

289
3-propyl-7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)-pyridazin-3-yl)isoquinolin-6-ol

290
3-isopropyl-7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)-pyridazin-3-yl)isoquinolin-6-

ol

291
3-methyl-7-(6-(piperazin-1-yl)pyridazin-3-yl)isoquinolin-6-ol

292
6-(3-(benzyloxy)isoquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine

293
3-chloro-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-

7-ol

294
3-isopropyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-7-ol

295
3-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinoxalin-6-ol

296
4-chloro-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-7-ol

297
4-chloro-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-

6-ol

300
7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol

301
5-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)-1,3,4-thiadiazol-2-amine

302
6-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)naphthalen-

2-ol

303
5-(2-methoxyquinolin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-

thiadiazol-2-amine

304
5-(3-methoxy-naphthalen-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-

thiadiazol-2-amine

305
5-(2-methoxy-4-(1H-pyrazol-1yl)phenyl)-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-

1,3,4-thiadiazol-2-amine

306
5-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

307
5-(2-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)-1,3,4-thiadiazol-2-amine

308
4-(3-methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)phenyl)-1-methylpyridin-2(1H)-one

309
5-(3-methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)phenyl)pyridin-2-ol

310
5-(3-methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)phenyl)-1-methylpyridin-2(1H)-one

311
N-methyl-5-(2-methyl-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

312
1-methyl-4-(4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)-3-(trifluoromethoxy)phenyl)pyridin-2(1H)-one

313
5-(4-(3,5-dimethyl-1H-pyrazol-4-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

314
5-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

315
2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4,-thiadiozol-2-yl-5-(1-

methyl-1H-pyrazol-4-yl)phenol

316
2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4,-thiadiozol-2-yl-5-(1H-

pyrazol-1-yl)phenol

317
5-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)phenyl)-1-methylpyridin-2(1H)-one

318
4-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)phenyl)-1-methylpyridin-2(1H)-one

319
5-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)phenyl)pyridin-2-ol

320
3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)naphthalene-2,7-diol

321
3-(5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazol-2-

yl)naphthalene-2,7-diol

322¹
3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)naphthalen-

2-ol

323
3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-2-

ol

324
2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-4-(1H-

pyrazol-1-yl)phenol

325
5-(2-chloro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

326
3-chloro-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-

5-(1-methyl-1H-pyrazol-4-yl)phenol

327
5-(2-chloro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)-

1,3,4-thiadiazol-2-amine

328
3-methoxy-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)-5-methyloxazol-2-yl)phenol

329
2-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1,3,4-

thiadiazole

330
2-(5-(piperazin-1-yl)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-1-yl)phenol

331
5-(7-methoxyquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-

thiadiazole-2-amine

332
6-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-7-

ol

333
3-methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)benzonitrile

334
3-fluoro-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)benzonitrile

335
methyl-3-fluoro-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-

2-yl)benzoate

336
5-(2-methoxy-4-(3-(methylamino)-1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

337
7-methoxy-6-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)quinoline-2-carbonitrile

338
4-(3-methoxy-4-(5-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)-1,3,4-thiadiazol-2-

yl)phenyl)-1-methylpyridin-2(1H)-one

339
4-(3-chloro-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)phenyl)-1-methylpyridin-2(1H)-one

340
5-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)-1,3,4-thiadiazol-2-amine

341
5-(2-chloro-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)phenyl)-N-methyl-N-

(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

342¹
N-methyl-5-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

343
2-(2-chloro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-((2,2,6,6-tetramethylpiperidin-4-

yl)oxy-1,3,4-thiadiazole

344
5-(2-chloro-4-(6-methoxypyridin-3-yl)phenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

345
5-(4-(6-aminopyridin-3-yl)-2-fluorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)-1,3,4-thiadiazol-2-amine

346
5-(2-fluoro-4-(3-methyl-1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

347
5-(2-fluoro-4-(1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)-1,3,4-thiadiazol-2-amine

348
5-(2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)-1,3,4-thiadiazol-2-amine

349
5-(2,3-difluoro-4-(1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)-1,3,4-thiadiazol-2-amine

350
5-(2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)-1,3,4-thiadiazol-2-amine

351
5-(2,5-difluoro-4-(1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)-1,3,4-thiadiazol-2-amine

352
5-(2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)-1,3,4-thiadiazol-2-amine

353
2-(2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-hexahydropyrrolo[3,4-

c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole

354
5-(2-chloro-5-fluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

355
5-(3-fluoro-5-(1H-pyrazol-4-yl)pyridin-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)-1,3,4-thiadiazol-2-amine

356
5-(4-(2-aminopyrimidin-4-yl)-2-chlorophenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

357
5-(5-(2-aminopyrimidin-4-yl)-2-chlorophenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

358
5-(4-(2,4-dimethylthiazol-5-yl)-2,5-difluorophenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

359
5-(4-(2,4-dimethylthiazol-5-yl)-2,3-difluorophenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

360
4-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)-5-(trifluoromethoxy)phenyl)-1-methylpyridin-2(1H)-one

361
5-(2-fluoro-6-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

362
2-(2-fluoro-6-methoxy-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-5-

methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole

363
5-(2,3-difluoro-6-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

364
6-methoxy-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)-3,4-dihydroisoquinolin-1-(2H)-one

365
5-(2-chloro-4-(1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)-1,3,4-thiadiazol-2-amine

366
5-(2-chloro-4-(1H-1,2,3-triazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)-1,3,4-thiadiazol-2-amine

367
5-(2-chloro-4-(2H-1,2,3-triazol-2-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)-1,3,4-thiadiazol-2-amine

368
5-(2-chloro-4-(1H-1,2,4-triazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)-1,3,4-thiadiazol-2-amine

369
5-(4-(3-amino-1H-pyrazol-1-yl)-2-chlorophenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

370
2-(2-chloro-4-(1H-imidazol-1-yl)phenyl)-5-((3aR,6aS)-5-

methylhexahydropyrrolo[3,4c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole

371
5-(2-chloro-4-(1H-imidazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)-1,3,4-thiadiazol-2-amine

372
5-(2-fluoro-4-(1H-imidazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)-1,3,4-thiadiazol-2-amine

373
5-(2-methoxy-4-(1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)-1,3,4-thiadiazol-2-amine

374
5-(4-(2,4-dimethylthiazol-5-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

375
5-(2-methoxy-4-(pyridin-3-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-

1,3,4-thiadiazol-2-amine

376
5-(2-fluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)-1,3,4-thiadiazol-2-amine

377
5-(2-methoxy-4-(2-methoxypyridin-4-yl)phenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

378
5-(2-methoxy-4-(6-methoxypyridin-3-yl)phenyl)-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

379
2-(2-chloro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-5-

methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole

380
2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-

c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole

381
2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aR)-1-methylhexahydropyrrolo[3,4-

b]pyrrol-5(1H)-yl)-1,3,4-thiadiazole

382
1-(4-(5-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-yl)morpholin-2-yl)-

N,N-dimethylmethanamine

383
2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-(2-methyl-2,7-diazaspiro[4.5]decan-7-yl)-

1,3,4-thiadiazole

384
2-(2-fluoro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-

c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole

385
2-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-(2,6-diazaspiro[3.5]nonan-2-yl)-

1,3,4-thiadiazole

386
2-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-(2,7-diazaspiro[3.5]nonan-2-yl)-

1,3,4-thiadiazole

387
2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-

pyrazol-1-yl)phenol

388
5-(3-chloro-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)phenyl)pyridin-2(1H)-one

389
2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(3-

(methylamino)-1H-pyrazol-1-yl)phenol

390
3-fluoro-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-

(1H-pyrazol-4-yl)phenol

391
3,4-difluoro-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)-5-(1H-pyrazol-4-yl)phenol

392
6-hydroxy-5-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)-2,3-dihydro-1H-inden-1-one

393
2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-

pyrazol-4-yl)phenol

394
2-(5-(2,6-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazol-2-yl)-5-(1-methyl-1H-pyrazol-4-

yl)phenol

395
2-(5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazol-2-yl)-5-(1-methyl-1H-pyrazol-4-

yl)phenol

396¹
3-fluoro-2-(5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazol-2-

yl)-5-(1H-pyrazol-4-yl)phenol

397
3-chloro-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-

5-(1H-pyrazol-4-yl)phenol

398
2-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-5-((2,2,6,6-tetramethylpiperidin-4-

yl)methyl)-1,3,4-thiadiazole

399
2-(2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl)-5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,3,4-

thiadiazole

400
2-(5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazol-2-yl)-3-fluoro-5-(1H-pyrazol-4-

yl)phenol

401
4-methoxy-1-methyl-3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-

thiadiazol-2-yl)quinolin-2(1H)-one

402
4-hydroxy-1-methyl-3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-

thiadiazol-2-yl)quinolin-2(1H)-one

403
3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-

2(1H)-one

404
1-methyl-3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)quinolin-2(1H)-one

405¹
2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-

2(1H)-yl)-1,3,4-thiadiazole

406¹
2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-(2,7-diazaspiro[4.5]decan-2-yl)-1,3,4-

thiadiazole

407¹
(R)-(4-(5-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-yl)piperazin-2-

yl)methanol

408
2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-

yl)benzo[b]thiophene-5-carbonitrile

409
5-(3-chlorobenzo[b]thiophen-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-

1,3,4-thiadiazol-2-amine

410
5-(2-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)-1,3,4-thiadiazol-2-amine

411¹
2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-

pyrazol-4-yl)phenol

412¹
2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-

yl)phenol

413¹
5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-

yl}phenol

414
5-(1-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}phenol

415¹
2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-

yl)phenol

416
5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino]pyridazin-3-yl}phenol

417
5-(1H-imidazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}phenol

418
5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}phenol

419¹
2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-

pyrazol-1-yl)phenol

420
6-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)pyridazin-3-amine

421
5-(4-amino-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}phenol

422¹
2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-

yl)phenol

423
5-(4-nitro-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}phenol

424¹
5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol

425¹
2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

426¹
2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol

427¹
2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

428¹
6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)pyridazin-3-amine

429¹
2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

430¹
6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)pyridazin-3-amine

431¹
3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

432
2-[6-(piperidin-4-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

433¹
2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-

yl)phenol

434¹
6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)pyridazin-3-amine

435
3-[4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine

436¹
2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol

437¹
3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

438
3-[4-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

439¹
2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

440
3-fluoro-4-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol

441
2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-1-yl)phenol

442
N-methyl-6-(2-methyl-2H-indazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-

3-amine

443
2-methyl-5-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}-2H-indazole

444
3-(4-chloro-2-methoxyphenyl)-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine

445
N-methyl-6-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine

446
6-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}imidazo[1,2-a]pyridine

447
3-[2-methoxy-4-(1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

448¹
3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

449
3-[5-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

450¹
3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

451
5-(3,5-dimethyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazin-3-yl}phenol

452
6-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine

453
3-methoxy-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol

454
3-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

455
4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}benzene-1,3-diol

456¹
6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine

457
2-(1H-pyrazol-4-yl)-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}pyrimidin-5-amine

458¹
3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

459
2-[6-(2,6-diazaspiro[3.4]oct-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

460¹
3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-

yl)pyridin-2-ol

461
6-(1H-pyrazol-4-yl)-3-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}pyridin-2-ol

462¹
N,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-

yl}piperidin-4-amine

463¹
N,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-

yl}piperidin-4-amine

464¹
3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine and

465¹
6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)pyridazin-3-amine

In one aspect, the compound of Formula (I) or a form thereof includes a compound selected from the group consisting of:

411¹
2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-

pyrazol-4-yl)phenol

412¹
2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-

yl)phenol

413¹
5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-

yl}phenol

414
5-(1-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}phenol

415¹
2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-

yl)phenol

416
5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino]pyridazin-3-yl}phenol

417
5-(1H-imidazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}phenol

418
5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}phenol

419¹
2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-

pyrazol-1-yl)phenol

420
6-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)pyridazin-3-amine

421
5-(4-amino-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}phenol

422¹
2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-

yl)phenol

423
5-(4-nitro-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}phenol

424¹
5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol

425¹
2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

426¹
2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol

427¹
2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

428¹
6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)pyridazin-3-amine

429¹
2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

430¹
6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-

4-yl)pyridazin-3-amine

431¹
3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

432
2-[6-(piperidin-4-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

433¹
2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-

yl)phenol

434¹
6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)pyridazin-3-amine

435
3-[4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine

436¹
2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol

437¹
3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

438
3-[4-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

439¹
2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

440
3-fluoro-4-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol

441
2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-1-yl)phenol

442
N-methyl-6-(2-methyl-2H-indazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-

3-amine

443
2-methyl-5-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}-2H-indazole

444
3-(4-chloro-2-methoxyphenyl)-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine

445
N-methyl-6-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine

446
6-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}imidazo[1,2-a]pyridine

447
3-[2-methoxy-4-(1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

448¹
3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

449
3-[5-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

450¹
3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

451
5-(3,5-dimethyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazin-3-yl}phenol

452
6-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine

453
3-methoxy-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol

454
3-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

455
4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}benzene-1,3-diol

456¹
6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine

457
2-(1H-pyrazol-4-yl)-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}pyrimidin-5-amine

458¹
3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine

459
2-[6-(2,6-diazaspiro[3.4]oct-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

460¹
3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-

yl)pyridin-2-ol

461
6-(1H-pyrazol-4-yl)-3-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-

yl}pyridin-2-ol

462¹
N,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-

yl}piperidin-4-amine

463¹
N,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-

yl}piperidin-4-amine

464¹
3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine and

465¹
6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)pyridazin-3-amine

Another embodiment of the use of a compound salt of Formula (I) or a form thereof includes a method of use of a compound salt of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the compound salt of Formula (I) or a form thereof to the subject, selected from the group consisting of:

Cpd
Name

32
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-

(trifluoromethyl)phenol hydrochloride

53
2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-1-

yl)phenol hydrochloride

65
2-(6-piperazin-1-yl-pyridazin-3-yl)-5-1H-pyrazol-1-yl-phenol hydrochloride

82
3-(6-(piperazin-1-yl)pyridazin-3-yl)naphthalene-2,7-diol trifluoroacetate

86
3-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol trifluoroacetate

88
3-(6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol

trifluoroacetate

89
3-(6-(piperidin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol trifluoroacetate

151
6-hydroxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-

dihydro-1H-inden-1-one oxime hydrochloride

153
2-amino-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-8H-

indeno[1,2-d]thiazol-5-ol hydrochloride

154
9-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5,6-

dihydroimidazo[5,1-a]isoquinolin-8-ol hydrochloride

160
3-fluoro-5-(2-methoxypyridin-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-

yl)amino)pyridazin-3-yl)phenol hydrochloride

161
4-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenyl)pyridin-2(1H)-one hydrochloride

162
4-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenyl)-1-methylpyridin-2(1H)-one hydrochloride

163
5-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenyl)-1-methylpyridin-2(1H)-one hydrochloride

164
3-fluoro-5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-

yl)phenol hydrochloride

165
5-chloro-3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)phenol hydrochloride

166
3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-

pyrazol-4-yl)phenol hydrochloride

167
3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-

methyl-1H-pyrazol-4-yl)phenol hydrochloride

226
3-(1H-imidazol-1-yl)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-7-ol hydrochloride

227
6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-3,7-diol

formate

231
7-hydroxy-1-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)quinolin-2(1H)-one hydrochloride

238
4-methoxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-

6-ol formate

239
7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoxalin-6-ol

hydrochloride

254
2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-

(tetrahydro-2H-pyran-4-yl)quinolin-7-ol formate

256
4-(dimethylamino)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-

quinolin-7-ol formate

281
6-hydroxy-2-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-

yl)isoquinolin-1(2H)-one hydrochloride

322
3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)naphthalen-

2-ol hydrobromide

342
N-methyl-5-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-N-(2,2,6,6-tetramethylpiperidin-

4-yl)-1,3,4-thiadiazol-2-amine hydrochloride

396
3-fluoro-2-(5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazol-2-yl)-

5-(1H-pyrazol-4-yl)phenol dihydrochloride

405
2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-

2(1H)-yl)-1,3,4-thiadiazole hydrochloride

406
2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-(2,7-diazaspiro[4.5]decan-2-yl)-1,3,4-

thiadiazole hydrochloride

407
(R)-(4-(5-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-yl)piperazin-2-

yl)methanol hydrochloride

411
2-{6-[8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-

yl)phenol hydrochloride

412
2-[6-(8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

hydrochloride

413
5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-

yl}phenol hydrochloride

415
2-[6-(8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

hydrochloride

419
2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-

pyrazol-1-yl)phenol dihydrochloride

422
2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

trihydrochloride

424
5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol

trihydrochloride

425
2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

trihydrochloride

426
2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol

tetrahydrochloride

427
2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride

428
6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine tetrahydrochloride

429
2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

hydrochloride

430
6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine hydrochloride

431
3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine trihydrochloride

433
2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-

yl)phenol hydrochloride

434
6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride

436
2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol

trihydrochloride

437
3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine hydrochloride

439
2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

tetrahydrochloride

448
3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine hydrochloride

450
3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine hydrochloride

456
6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine trihydrochloride

458
3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine trihydrochloride

460
3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-

yl)pyridin-2-ol hydrochloride

462
N,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-

yl}piperidin-4-amine hydrochloride

463
N,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-

yl}piperidin-4-amine hydrochloride

464
3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine hydrochloride and

465
6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride

wherein a form of the compound salt is selected from the group consisting of a prodrug, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

In one aspect, the compound salt of Formula (I) or a form thereof includes a compound salt selected from the group consisting of:

411
2-{6-[8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-

yl)phenol hydrochloride

412
2-[6-(8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

hydrochloride

413
5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-

yl}phenol hydrochloride

415
2-[6-(8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

hydrochloride

419
2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-

pyrazol-1-yl)phenol dihydrochloride

422
2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

trihydrochloride

424
5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol

trihydrochloride

425
2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

trihydrochloride

426
2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol

tetrahydrochloride

427
2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride

428
6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine tetrahydrochloride

429
2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

hydrochloride

430
6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine hydrochloride

431
3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine trihydrochloride

433
2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-

yl)phenol hydrochloride

434
6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride

436
2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol

trihydrochloride

437
3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine hydrochloride

439
2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol

tetrahydrochloride

448
3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine hydrochloride

450
3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine hydrochloride

456
6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-

yl)pyridazin-3-amine trihydrochloride

458
3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine trihydrochloride

460
3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-

yl)pyridin-2-ol hydrochloride

462
N,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-

yl}piperidin-4-amine hydrochloride

463
N,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-

yl}piperidin-4-amine hydrochloride

464
3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-

yl)oxy]pyridazine hydrochloride and

465
6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-

tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride

Another embodiment of the present description includes a method of use of a compound of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

Another embodiment of the present description includes a use of the compound of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

Another embodiment of the present description includes a use of the compound salt of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the compound salt of Formula (I) or a form thereof to the subject.

Chemical Definitions

As used herein, the term “C_1-4alkyl” generally refers to saturated hydrocarbon radicals having from one to four carbon atoms in a straight or branched chain configuration, including, without limitation, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, and the like. In some embodiments, C_1-4alkyl includes C_1-3alkyl, C_1-2alkyl, and the like. A C_1-4alkyl radical may be optionally substituted where allowed by available valences.

As used herein, the term “C_2-6alkenyl” generally refers to partially unsaturated hydrocarbon radicals having from two to five carbon atoms in a straight or branched chain configuration and one or more carbon-carbon double bonds therein, including, without limitation, ethenyl, allyl, propenyl and the like. In some embodiments, C_2-6alkenyl includes C_2-4alkenyl, C_2-3alkenyl, and the like. A C_2-6alkenyl radical may be optionally substituted where allowed by available valences.

As used herein, the term “C_1-4alkoxy” generally refers to saturated hydrocarbon radicals having from one to four carbon atoms in a straight or branched chain configuration of the formula: —O—C_1-4alkyl, including, without limitation, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, and the like. In some embodiments, C_1-4alkoxy includes C_1-3alkoxy, C_1-2alkoxy and the like. A C_1-4alkoxy radical may be optionally substituted where allowed by available valences.

As used herein, the term “C_3-14cycloalkyl” generally refers to a saturated monocyclic, bicyclic or polycyclic hydrocarbon radical, including, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 1H-indanyl, indenyl, tetrahydro-naphthalenyl and the like. In some embodiments, C_3-14cycloalkyl includes C_3-10cycloalkyl, C_3-8cycloalkyl, C_3-7cycloalkyl, C_5-8cycloalkyl, C_9-10cycloalkyl and the like. A C_3-14cycloalkyl radical may be optionally substituted where allowed by available valences.

As used herein, the term “C_3-14cycloalkenyl” generally refers to a partially unsaturated monocyclic, bicyclic or polycyclic hydrocarbon radical having one or more chemically stable carbon-carbon double bonds therein, including, without limitation, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl and the like. In some embodiments, C_3-14cycloalkenyl includes C_3-7cycloalkenyl, C_3-8cycloalkenyl, C_5-8cycloalkenyl, C_3-10cycloalkenyl and the like. A C_3-14cycloalkenyl radical may be optionally substituted where allowed by available valences.

As used herein, the term “aryl” generally refers to a monocyclic, bicyclic or polycyclic aromatic carbon atom ring structure radical, including, without limitation, phenyl, naphthyl, anthracenyl, fluorenyl, azulenyl, phenanthrenyl and the like. An aryl radical may be optionally substituted where allowed by available valences.

As used herein, the term “heteroaryl” generally refers to a monocyclic, bicyclic or polycyclic aromatic carbon atom ring structure radical in which one or more carbon atom ring members have been replaced, where allowed by structural stability, with one or more heteroatoms, such as an O, S or N atom, including, without limitation, furanyl, thienyl (also referred to as thiophenyl), pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyranyl, thiopyranyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, indolyl, indazolyl, indolizinyl, benzofuranyl, benzothienyl, benzimidazolyl, benzothiazolyl, benzooxazolyl, 9H-purinyl, quinoxalinyl, isoindolyl, quinolinyl, isoquinolinyl, quinazolinyl, acridinyl, phthalazinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, imidazo[5,1-a]isoquinolinyl, 1,4-dihydroindeno[1,2-c]-1H-pyrazolyl, 2,3-dihydro-1H-inden-1-one, 2,3-dihydro-1H-indenyl, 3,4-dihydroquinolin-2(1H)-one, 5,6-dihydroimidazo[5,1-a]isoquinolinyl, 8H-indeno[1,2-d]thiazolyl, benzo[c][1,2,5]oxadiazolyl, benzo[d]oxazol-2(3H)-one, quinolin-2(1H)-one, quinazolin-4(1H)-one, quinazoline-2,4(1H,3H)-dione, benzo-[d]oxazolyl, pyrazolo[1,5-a]pyridinyl, and the like. A heteroaryl radical may be optionally substituted on a carbon or nitrogen atom ring member where allowed by available valences.

As used herein, the term “heterocyclyl” generally refers to a saturated or partially unsaturated monocyclic, bicyclic or polycyclic carbon atom ring structure radical in which one or more carbon atom ring members have been replaced, where allowed by structural stability, with a heteroatom, such as an O, S or N atom, including, without limitation, oxiranyl, oxetanyl, azetidinyl, dihydrofuranyl, tetrahydrofuranyl, dihydrothienyl, tetrahydrothienyl, pyrrolinyl, pyrrolidinyl, dihydropyrazolyl, pyrazolinyl, pyrazolidinyl, dihydroimidazolyl, imidazolinyl, imidazolidinyl, isoxazolinyl, isoxazolidinyl, isothiazolinyl, isothiazolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, triazolinyl, triazolidinyl, oxadiazolinyl, oxadiazolidinyl, thiadiazolinyl, thiadiazolidinyl, tetrazolinyl, tetrazolidinyl, dihydro-2H-pyranyl, dihydro-pyridinyl, tetrahydro-pyridinyl, 1,2,3,6-tetrahydropyridinyl, hexahydro-pyridinyl, dihydro-pyrimidinyl, tetrahydro-pyrimidinyl, 1,4,5,6-tetrahydropyrimidinyl, dihydro-pyrazinyl, tetrahydro-pyrazinyl, dihydro-pyridazinyl, tetrahydro-pyridazinyl, piperazinyl, piperidinyl, morpholinyl, thiomorpholinyl, dihydro-triazinyl, tetrahydro-triazinyl, hexahydro-triazinyl, 1,4-diazepanyl, dihydro-indolyl, indolinyl, tetrahydro-indolyl, dihydro-indazolyl, tetrahydro-indazolyl, dihydro-isoindolyl, dihydro-benzofuranyl, tetrahydro-benzofuranyl, dihydro-benzothienyl, tetrahydro-benzothienyl, dihydro-benzimidazolyl, tetrahydro-benzimidazolyl, dihydro-benzooxazolyl, 2,3-dihydrobenzo[d]oxazolyl, tetrahydro-benzooxazolyl, dihydro-benzooxazinyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, tetrahydro-benzooxazinyl, benzo[1,3]dioxolyl, benzo[1,4]dioxanyl, dihydro-purinyl, tetrahydro-purinyl, dihydro-quinolinyl, tetrahydro-quinolinyl, 1,2,3,4-tetrahydroquinolinyl, dihydro-isoquinolinyl, 3,4-dihydroisoquinolin-(1H)-yl, tetrahydro-isoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, dihydro-quinazolinyl, tetrahydro-quinazolinyl, dihydro-quinoxalinyl, tetrahydro-quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,3-dioxolanyl, 2,5-dihydro-1H-pyrrolyl, 4,5-dihydro-1H-imidazolyl, tetrahydro-2H-pyranyl, hexahydropyrrolo[3,4-b][1,4]oxazin-(2H)-yl, (4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-(4aH)-yl, 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl, (cis)-octahydrocyclopenta[c]pyrrolyl, hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl, (3aR,6aR)-hexahydropyrrolo[3,4-b]pyrrol-(1H)-yl, (3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-(1H)-yl, 5H-pyrrolo[3,4-b]pyridin-(7H)-yl, 5,7-dihydro-6H-pyrrolo[3,4-b]pyridinyl, tetrahydro-1H-pyrrolo[3,4-b]pyridin-(2H,7H,7aH)-yl, hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl, (4aR,7aR)-hexahydro-1H-pyrrolo[3,4-b]pyridin-(2H)-yl, octahydro-6H-pyrrolo[3,4-b]pyridinyl, 2,3,4,9-tetrahydro-1H-carbazolyl, 1,2,3,4-tetrahydropyrazino[1,2-a]indolyl, 2,3-dihydro-1H-pyrrolo[1,2-a]indolyl, (3aR,6aR)-hexahydrocyclopenta[c]pyrrol-(1H)-yl, (3aR,4R,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl, (3aR,4S,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl, (3aR,5r,6aS)-hexahydrocyclopenta[c]pyrrol-(1H)-yl, 1,3-dihydro-2H-isoindolyl, octahydro-2H-isoindolyl, (3aS)-1,3,3a,4,5,6-hexahydro-2H-isoindolyl, (3aR,4R,7aS)-1H-isoindol-(3H,3aH,4H,5H,6H,7H,7aH)-yl, (3aR,7aS)-octahydro-2H-isoindolyl, (3aR,4R,7aS)-octahydro-2H-isoindolyl, (3aR,4S,7aS)-octahydro-2H-isoindolyl, 2,5-diazabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]heptenyl, 3-azabicyclo[3.1.0]hexanyl, 3,6-diazabicyclo[3.1.0]hexanyl, (1R,5S)-3-azabicyclo[3.1.0]hexanyl, (1S,5R)-3-azabicyclo[3.2.0]heptanyl, 5-azaspiro[2.4]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 2,5-diazaspiro[3.4]octanyl, 2,6-diazaspiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2-azaspiro[4.5]decanyl, 2,8-diazaspiro[4.5]decanyl, 3,6-diazabicyclo[3.2.1]octyl, 1,4-dihydroindeno[1,2-c]pyrazolyl, dihydropyranyl, dihydropyridinyl, dihydroquinolinyl, 8H-indeno[1,2-d]thiazolyl, tetrahydroimidazo[1,2-a]pyridinyl, pyridin-2(1H)-one, (1R,5S)-8-azabicyclo[3.2.1]octyl, 8-azabicyclo[3.2.1]oct-2-enyl and the like. A heterocyclyl radical may be optionally substituted on a carbon or nitrogen atom ring member where allowed by available valences.

As used herein, the term “C_2-4alkenyl-amino-carbonyl” refers to a radical of the formula: —C(═O)—NH—C_2-4alkenyl.

As used herein, the term “C_1-4alkoxy-C_1-4alkoxy” refers to a radical of the formula: —O—C_1-4alkyl-O—C_1-4alkyl.

As used herein, the term “C_1-4alkoxy-carbonyl” refers to a radical of the formula: —C(═O)—O—C_1-4alkyl.

As used herein, the term “C_1-4alkoxy-carbonyl-amino” refers to a radical of the formula: —NH—C(═O)—O—C_1-4alkyl.

As used herein, the term “C_1-4alkoxy-carbonyl-amino-C_1-4alkoxy” refers to a radical of the formula: —O—C_1-4alkyl-NH—C(═O)—O—C_1-4alkyl.

As used herein, the term “C_1-4alkyl-C_1-4alkoxy” refers to a radical of the formula: —O—C_1-4alkyl-C_1-4alkyl.

As used herein, the term “C_1-4alkyl-amino” refers to a radical of the formula: —NH—C_1-4alkyl.

As used herein, the term “(C_1-4alkyl)₂-amino” refers to a radical of the formula: —N(C_1-4alkyl)₂.

As used herein, the term “C_1-4alkyl-amino-C_1-4alkoxy” refers to a radical of the formula: —O—C_1-4alkyl-NH—C_1-4alkyl.

As used herein, the term “(C_1-4alkyl)₂-amino-C_1-4alkoxy” refers to a radical of the formula: —O—C_1-4alkyl-N(C_1-4alkyl)₂.

As used herein, the term “C_1-4alkyl-amino-C_1-4alkyl” refers to a radical of the formula: —C_1-4alkyl-NH—C_1-4alkyl.

As used herein, the term “(C_1-4alkyl)₂-amino-C_1-4alkyl” refers to a radical of the formula: —C_1-4alkyl-N(C_1-4alkyl)₂.

As used herein, the term “C_1-4alkyl-amino-carbonyl” refers to a radical of the formula: —C(═O)—NH—C_1-4alkyl.

As used herein, the term “(C_1-4alkyl)₂-amino-carbonyl” refers to a radical of the formula: —C(═O)—N(C_1-4alkyl)₂.

As used herein, the term “C_1-4alkyl-amino-carbonyl-C_1-4alkyl” refers to a radical of the formula: —C_1-4alkyl-C(═O)—NH—C_1-4alkyl.

As used herein, the term “(C_1-4alkyl)₂-amino-carbonyl-C_1-4alkyl” refers to a radical of the formula: —C_1-4alkyl-C(═O)—N(C_1-4alkyl)₂.

As used herein, the term “C_1-4alkyl-carbonyl” refers to a radical of the formula: —C(═O)—C_1-4alkyl.

As used herein, the term “C_1-4alkyl-carbonyl-amino” refers to a radical of the formula: —NH—C(═O)—C_1-4alkyl.

As used herein, the term “C_1-4alkyl-carbonyl-amino-C_1-4alkoxy” refers to a radical of the formula: —O—C_1-4alkyl-NH—C(═O)—C_1-4alkyl.

As used herein, the term “C_1-4alkyl-carbonyl-amino-C_1-4alkyl” refers to a radical of the formula: —C_1-4alkyl-NH—C(═O)—C_1-4alkyl.

As used herein, the term “amino” refers to a radical of the formula: —NH₂.

As used herein, the term “amino-C_1-4alkoxy” refers to a radical of the formula: —O—C_1-4alkyl-NH₂.

As used herein, the term “amino-C_1-4alkyl” refers to a radical of the formula: —C_1-4alkyl-NH₂.

As used herein, the term “amino-carbonyl” refers to a radical of the formula: —C(═O)—NH₂.

As used herein, the term “cyano” refers to a radical of the formula: —CN.

As used herein, the term “C_3-7cycloalkyl-C_1-4alkoxy” refers to a radical of the formula: —O—C_1-4alkyl-C_3-7cycloalkyl.

As used herein, the term “halo-C_1-4alkoxy” refers to a radical of the formula: —O—C_1-4alkyl-halo, wherein C_1-4alkyl may be partially or completely substituted where allowed by available valences with one or more halogen atoms. In some embodiments, halo-C_1-4alkoxy includes halo-C_1-6alkoxy, halo-C_1-4alkoxy and the like.

As used herein, the term “halo-C_1-4alkyl” refers to a radical of the formula: —C_1-4alkyl-halo, wherein C_1-4alkyl may be partially or completely substituted where allowed by available valences with one or more halogen atoms. In some embodiments, halo-C_1-4alkyl includes halo-C_1-6alkyl, halo-C_1-4alkyl and the like.

As used herein, the term “heteroaryl-C_1-4alkyl” refers to a radical of the formula: —C_1-4alkyl-heteroaryl.

As used herein, the term “heteroaryl-C_1-4alkyl-amino” refers to a radical of the formula: —NH—C_1-4alkyl-heteroaryl.

As used herein, the term “heteroaryl-C_1-4alkyl-amino-carbonyl” refers to a radical of the formula: —C(═O)—NH—C_1-4alkyl-heteroaryl.

As used herein, the term “heteroaryl-C_1-4alkyl-amino-carbonyl-C_1-4alkyl” refers to a radical of the formula: —C_1-4alkyl-C(═O)—NH—C_1-4alkyl-heteroaryl.

As used herein, the term “heteroaryl-C_1-4alkyl-carbonyl-amino” refers to a radical of the formula: —NH—C(═O)—C_1-4alkyl-heteroaryl.

As used herein, the term “heteroaryl-C_1-4alkyl-carbonyl-amino-C_1-4alkyl” refers to a radical of the formula: —C_1-4alkyl-NH—C(═O)—C_1-4alkyl-heteroaryl.

As used herein, the term “heterocyclyl-C_1-4alkoxy” refers to a radical of the formula: —C_1-4alkoxy-heterocyclyl.

As used herein, the term “heterocyclyl-C_1-4alkyl” refers to a radical of the formula: —C_1-4alkyl-heterocyclyl.

As used herein, the term “hydroxyl” refers to a radical of the formula: —OH.

As used herein, the term “hydroxyl-C_1-4alkoxy” refers to a radical of the formula: —O—C_1-4alkyl-OH, wherein C_1-4alkyl may be partially or completely substituted where allowed by available valences with one or more hydroxy radicals.

As used herein, the term “hydroxyl-C_1-4alkyl” refers to a radical of the formula: —C_1-4alkyl-OH, wherein C_1-4alkyl may be partially or completely substituted where allowed by available valences with one or more hydroxy radicals.

As used herein, the term “hydroxyl-C_1-4alkyl-amino” refers to a radical of the formula: —NH—C_1-4alkyl-OH, wherein C_1-4alkyl may be partially or completely substituted where allowed by available valences with one or more hydroxyl radicals.

As used herein, the term “hydroxyl-imino” refers to the ═NOH radical of the formula: C(═NOH).

As used herein, the term “oxo” refers to the radical of the formula: C═O.

As used herein, the term “phenyl-C_1-4alkoxy” refers to a radical of the formula: —C_1-4alkoxy-phenyl.

As used herein, the term “substituent” means positional variables on the atoms of a core molecule that are substituted at a designated atom position, replacing one or more hydrogens on the designated atom, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds. A person of ordinary skill in the art should note that any carbon as well as heteroatom with valences that appear to be unsatisfied as described or shown herein is assumed to have a sufficient number of hydrogen atom(s) to satisfy the valences described or shown. In certain instances one or more substituents having a double bond (e.g., “oxo” or “═O”) as the point of attachment may be described, shown or listed herein within a substituent group, wherein the structure may only show a single bond as the point of attachment to the core structure of Formula (I). A person of ordinary skill in the art would understand that, while only a single bond is shown, a double bond is intended for those substituents.

As used herein, the term “and the like,” with reference to the definitions of chemical terms provided herein, means that variations in chemical structures that could be expected by one skilled in the art include, without limitation, isomers (including chain, branching or positional structural isomers), hydration of ring systems (including saturation or partial unsaturation of monocyclic, bicyclic or polycyclic ring structures) and all other variations where allowed by available valences which result in a stable compound.

For the purposes of this description, where one or more substituent variables for a compound of Formula (I) or a form thereof encompass functionalities incorporated into a compound of Formula (I), each functionality appearing at any location within the disclosed compound may be independently selected, and as appropriate, independently and/or optionally substituted.

As used herein, the terms “independently selected,” or “each selected” refer to functional variables in a substituent list that may occur more than once on the structure of Formula (I), the pattern of substitution at each occurrence is independent of the pattern at any other occurrence. Further, the use of a generic substituent variable on any formula or structure for a compound described herein is understood to include the replacement of the generic substituent with species substituents that are included within the particular genus, e.g., aryl may be replaced with phenyl or naphthalenyl and the like, and that the resulting compound is to be included within the scope of the compounds described herein.

As used herein, the terms “each instance of” or “in each instance, when present,” when used preceding a phrase such as “ . . . C_3-14cycloalkyl, C_3-14cycloalkyl-C_1-4alkyl, aryl, aryl-C_1-4alkyl, heteroaryl, heteroaryl-C_1-4alkyl, heterocyclyl and heterocyclyl-C_1-4alkyl,” are intended to refer to the C_3-14cycloalkyl, aryl, heteroaryl and heterocyclyl ring systems when each are present either alone or as a substituent.

As used herein, the term “optionally substituted” means optional substitution with the specified substituent variables, groups, radicals or moieties.

Compound Forms

As used herein, the term “form” means a compound of Formula (I) having a form selected from the group consisting of a free acid, free base, prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.

In certain embodiments described herein, the form of the compound of Formula (I) is a free acid, free base or salt thereof.

In certain embodiments described herein, the form of the compound of Formula (I) is a salt thereof.

In certain embodiments described herein, the form of the compound of Formula (I) is an isotopologue thereof.

In certain embodiments described herein, the form of the compound of Formula (I) is a stereoisomer, racemate, enantiomer or diastereomer thereof.

In certain embodiments described herein, the form of the compound of Formula (I) is a tautomer thereof.

In certain embodiments described herein, the form of the compound of Formula (I) is a pharmaceutically acceptable form.

In certain embodiments described herein, the compound of Formula (I) or a form thereof is isolated for use.

As used herein, the term “isolated” means the physical state of a compound of Formula (I) or a form thereof after being isolated and/or purified from a synthetic process (e.g., from a reaction mixture) or natural source or combination thereof according to an isolation or purification process or processes described herein or which are well known to the skilled artisan (e.g., chromatography, recrystallization and the like) in sufficient purity to be characterized by standard analytical techniques described herein or well known to the skilled artisan.

As used herein, the term “protected” means that a functional group in a compound of Formula (I) or a form thereof is in a form modified to preclude undesired side reactions at the protected site when the compound is subjected to a reaction. Suitable protecting groups will be recognized by those with ordinary skill in the art as well as by reference to standard textbooks such as, for example, T. W. Greene et al, Protective Groups in organic Synthesis (1991), Wiley, New York. Such functional groups include hydroxy, phenol, amino and carboxylic acid. Suitable protecting groups for hydroxy or phenol include trialkylsilyl or diarylalkylsilyl (e.g., t-butyldimethylsilyl, t-butyldiphenylsilyl or trimethylsilyl), tetrahydropyranyl, benzyl, substituted benzyl, methyl, methoxymethanol, and the like. Suitable protecting groups for amino, amidino and guanidino include t-butoxycarbonyl, benzyloxycarbonyl, and the like. Suitable protecting groups for carboxylic acid include alkyl, aryl or arylalkyl esters. In certain instances, the protecting group may also be a polymer resin, such as a Wang resin or a 2-chlorotrityl-chloride resin. Protecting groups may be added or removed in accordance with standard techniques, which are well-known to those skilled in the art and as described herein. It will also be appreciated by those skilled in the art, although such protected derivatives of compounds described herein may not possess pharmacological activity as such, they may be administered to a subject and thereafter metabolized in the body to form compounds described herein which are pharmacologically active. Such derivatives may therefore be described as “prodrugs”. All prodrugs of compounds described herein are included within the scope of the use described herein.

As used herein, the term “prodrug” means a form of an instant compound (e.g., a drug precursor) that is transformed in vivo to yield an active compound of Formula (I) or a form thereof. The transformation may occur by various mechanisms (e.g., by metabolic and/or non-metabolic chemical processes), such as, for example, by hydrolysis and/or metabolism in blood, liver and/or other organs and tissues. A discussion of the use of prodrugs is provided by T. Higuchi and W. Stella, “Pro-drugs as Novel Delivery Systems,” Vol. 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987.

In one example, when a compound of Formula (I) or a form thereof contains a carboxylic acid functional group, a prodrug can comprise an ester formed by the replacement of the hydrogen atom of the acid group with a functional group such as alkyl and the like. In another example, when a compound of Formula (I) or a form thereof contains a hydroxyl functional group, a prodrug form can be prepared by replacing the hydrogen atom of the hydroxyl with another functional group such as alkyl, alkylcarbonyl or a phosphonate ester and the like. In another example, when a compound of Formula (I) or a form thereof contains an amine functional group, a prodrug form can be prepared by replacing one or more amine hydrogen atoms with a functional group such as alkyl or substituted carbonyl. Pharmaceutically acceptable prodrugs of compounds of Formula (I) or a form thereof include those compounds substituted with one or more of the following groups: carboxylic acid esters, sulfonate esters, amino acid esters, phosphonate esters and mono-, di- or triphosphate esters or alkyl substituents, where appropriate. As described herein, it is understood by a person of ordinary skill in the art that one or more of such substituents may be used to provide a compound of Formula (I) or a form thereof as a prodrug.

One or more compounds described herein may exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like, and the description herein is intended to embrace both solvated and unsolvated forms.

As used herein, the term “solvate” means a physical association of a compound described herein with one or more solvent molecules. This physical association involves varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain instances the solvate will be capable of isolation, for example when one or more solvent molecules are incorporated in the crystal lattice of the crystalline solid. As used herein, “solvate” encompasses both solution-phase and isolatable solvates. Non-limiting examples of suitable solvates include ethanolates, methanolates, and the like.

As used herein, the term “hydrate” means a solvate wherein the solvent molecule is water.

The compounds of Formula (I) can form salts, which are intended to be included within the scope of this description. Reference to a compound of Formula (I) or a form thereof herein is understood to include reference to salt forms thereof, unless otherwise indicated. The term “salt(s)”, as employed herein, denotes acidic salts formed with inorganic and/or organic acids, as well as basic salts formed with inorganic and/or organic bases. In addition, when a compound of Formula (I) or a form thereof contains both a basic moiety, such as, without limitation an amine moiety, and an acidic moiety, such as, but not limited to a carboxylic acid, zwitterions (“inner salts”) may be formed and are included within the term “salt(s)” as used herein.

The term “pharmaceutically acceptable salt(s)”, as used herein, means those salts of compounds described herein that are safe and effective (i.e., non-toxic, physiologically acceptable) for use in mammals and that possess biological activity, although other salts are also useful. Salts of the compounds of the Formula (I) may be formed, for example, by reacting a compound of Formula (I) or a form thereof with an amount of acid or base, such as an equivalent amount, in a medium such as one in which the salt precipitates or in an aqueous medium followed by lyophilization.

Pharmaceutically acceptable salts include one or more salts of acidic or basic groups present in compounds described herein. Embodiments of acid addition salts include, and are not limited to, acetate, ascorbate, benzoate, benzenesulfonate, bisulfate, bitartrate, borate, bromide, butyrate, chloride, citrate, camphorate, camphorsulfonate, ethanesulfonate, formate, fumarate, gentisinate, gluconate, glucaronate, glutamate, iodide, isonicotinate, lactate, maleate, methanesulfonate, naphthalenesulfonate, nitrate, oxalate, pamoate, pantothenate, phosphate, propionate, saccharate, salicylate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate (also known as tosylate), trifluoroacetate salts and the like. Certain embodiments of acid addition salts include chloride, dichloride, trichloride, bromide, acetate, formate or trifluoroacetate salts.

Additionally, acids which are generally considered suitable for the formation of pharmaceutically useful salts from basic pharmaceutical compounds are discussed, for example, by P. Stahl et al, Camille G. (eds.) Handbook of Pharmaceutical Salts. Properties, Selection and Use. (2002) Zurich: Wiley-VCH; S. Berge et al, Journal of Pharmaceutical Sciences (1977) 66(1) 1-19; P. Gould, International J. of Pharmaceutics (1986) 33, 201-217; Anderson et al, The Practice of Medicinal Chemistry (1996), Academic Press, New York; and in The Orange Book (Food & Drug Administration, Washington, D.C. on their website). These disclosures are incorporated herein by reference thereto.

Suitable basic salts include, but are not limited to, aluminum, ammonium, calcium, lithium, magnesium, potassium, sodium and zinc salts.

All such acid salts and base salts are intended to be included within the scope of pharmaceutically acceptable salts as described herein. In addition, all such acid and base salts are considered equivalent to the free forms of the corresponding compounds for purposes of this description.

Compounds of Formula (I) and forms thereof, may further exist in a tautomeric form. All such tautomeric forms are contemplated and intended to be included within the scope of the compounds of Formula (I) or a form thereof as described herein.

The compounds of Formula (I) or a form thereof may contain asymmetric or chiral centers, and, therefore, exist in different stereoisomeric forms. The present description is intended to include all stereoisomeric forms of the compounds of Formula (I) as well as mixtures thereof, including racemic mixtures.

The compounds described herein may include one or more chiral centers, and as such may exist as racemic mixtures (R/S) or as substantially pure enantiomers and diastereomers. The compounds may also exist as substantially pure (R) or (S) enantiomers (when one chiral center is present). In one embodiment, the compounds described herein are (S) isomers and may exist as enantiomerically pure compositions substantially comprising only the (S) isomer. In another embodiment, the compounds described herein are (R) isomers and may exist as enantiomerically pure compositions substantially comprising only the (R) isomer. As one of skill in the art will recognize, when more than one chiral center is present, the compounds described herein may also exist as a (R,R), (R,S), (S,R) or (S,S) isomer, as defined by IUPAC Nomenclature Recommendations.

As used herein, the term “substantially pure” refers to compounds consisting substantially of a single isomer in an amount greater than or equal to 90%, in an amount greater than or equal to 92%, in an amount greater than or equal to 95%, in an amount greater than or equal to 98%, in an amount greater than or equal to 99%, or in an amount equal to 100% of the single isomer.

In one aspect of the description, a compound of Formula (I) or a form thereof is a substantially pure (S) enantiomer form present in an amount greater than or equal to 90%, in an amount greater than or equal to 92%, in an amount greater than or equal to 95%, in an amount greater than or equal to 98%, in an amount greater than or equal to 99%, or in an amount equal to 100%.

In one aspect of the description, a compound of Formula (I) or a form thereof is a substantially pure (R) enantiomer form present in an amount greater than or equal to 90%, in an amount greater than or equal to 92%, in an amount greater than or equal to 95%, in an amount greater than or equal to 98%, in an amount greater than or equal to 99%, or in an amount equal to 100%.

As used herein, a “racemate” is any mixture of isometric forms that are not “enantiomerically pure”, including mixtures such as, without limitation, in a ratio of about 50/50, about 60/40, about 70/30, or about 80/20.

In addition, the present description embraces all geometric and positional isomers. For example, if a compound of Formula (I) or a form thereof incorporates a double bond or a fused ring, both the cis- and trans-forms, as well as mixtures, are embraced within the scope of the description. Diastereomeric mixtures can be separated into their individual diastereomers on the basis of their physical chemical differences by methods well known to those skilled in the art, such as, for example, by chromatography and/or fractional crystallization. Enantiomers can be separated by use of chiral HPLC column or other chromatographic methods known to those skilled in the art. Enantiomers can also be separated by converting the enantiomeric mixture into a diastereomeric mixture by reaction with an appropriate optically active compound (e.g., chiral auxiliary such as a chiral alcohol or Mosher's acid chloride), separating the diastereomers and converting (e.g., hydrolyzing) the individual diastereomers to the corresponding pure enantiomers. Also, some of the compounds of Formula (I) may be atropisomers (e.g., substituted biaryls) and are considered as part of this description.

All stereoisomers (for example, geometric isomers, optical isomers and the like) of the present compounds (including those of the salts, solvates, esters and prodrugs of the compounds as well as the salts, solvates and esters of the prodrugs), such as those which may exist due to asymmetric carbons on various substituents, including enantiomeric forms (which may exist even in the absence of asymmetric carbons), rotameric forms, atropisomers, and diastereomeric forms, are contemplated within the scope of this description, as are positional isomers (such as, for example, 4-pyridyl and 3-pyridyl). Individual stereoisomers of the compounds described herein may, for example, be substantially free of other isomers, or may be present in a racemic mixture, as described supra.

The use of the terms “salt”, “solvate”, “ester”, “prodrug” and the like, is intended to equally apply to the salt, solvate, ester and prodrug of enantiomers, stereoisomers, rotamers, tautomers, positional isomers, racemates or isotopologues of the instant compounds.

The term “isotopologue” refers to isotopically-enriched compounds described herein which are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into compounds described herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, such as ²H, ³H, ¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷O, ³¹P, ³²P, ³⁵S, ¹⁸F, ³⁵Cl and ³⁶Cl, respectively, each of which are also within the scope of this description.

Certain isotopically-enriched compounds described herein (e.g., those labeled with ³H and ¹⁴C) are useful in compound and/or substrate tissue distribution assays. Tritiated (i.e., ³H) and carbon-14 (i.e., ¹⁴C) isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium (i.e., ²H) may afford certain therapeutic advantages resulting from greater metabolic stability (e.g., increased in vivo half-life or reduced dosage requirements) and hence may be preferred in some circumstances.

Polymorphic crystalline and amorphous forms of the compounds of Formula (I) and of the salts, solvates, hydrates, esters and prodrugs of the compounds of Formula (I) are further intended to be included in the present description.

Compound Uses

The present description relates to a method of use of a compound of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the compound or a form thereof to the subject.

The present description further relates to use of the compound of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof.

The present description further relates to use of the compound of Formula (I) or a form thereof having activity toward HD.

The present description further relates to use of the compound of Formula (I) or a form thereof in a combination therapy to provide additive or synergistic activity, thus enabling the development of a combination product for treating or ameliorating HD.

In addition to monotherapeutic use, the instant compounds are useful in a combination therapy with current standard of agents, having additive or synergistic activity with one or more known agents.

A combination therapy comprising compounds described herein in combination with one or more known drugs may be used to treat HD regardless of whether HD is responsive to the known drug.

Embodiments of the present description include the use of a compound of Formula (I) or a form thereof in a combination therapy for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof and an effective amount of one or more agent(s).

In an embodiment of a use or method provided herein, compounds of Formula (I) or a form thereof used in combination with one or more additional agents can be administered to a subject or contacted with a subject or patient cell(s) prior to, concurrently with, or subsequent to administering to the subject or patient or contacting the cell with an additional agent(s). A compound(s) of Formula (I) or a form thereof and an additional agent(s) can be administered to a subject or contacted with a cell in single composition or different compositions. In a specific embodiments, a compound(s) of Formula (I) or a form thereof is used in combination with gene therapy to inhibit HTT expression (using, e.g., viral delivery vectors) or the administration of another small molecule HTT inhibitor. In another specific embodiment, a compound(s) of Formula (I) or a form thereof are used in combination with cell replacement using differentiated non-mutant HTT stem cells. In another specific embodiment, a compound(s) of Formula (I) or a form thereof are used in combination with cell replacement using differentiated HTT stem cells.

In one embodiment, provided herein is the use of compounds of Formula (I) or a form thereof in combination with supportive standard of care therapies, including palliative care.

An embodiment of the present description includes the use of a compound of Formula (I) or a form thereof in the preparation of a kit comprising the compound of Formula (I) or a form thereof and instructions for administering an effective amount of the compound of Formula (I) or a form thereof and an effective amount of one or more agent(s) in a combination therapy for treating or ameliorating HD in a subject in need thereof.

Accordingly, the present description relates to use of a compound of Formula (I) or a form thereof for treating or ameliorating HD. In accordance with the use of the present description, compounds that are useful in selectively treating or ameliorating HD, have been identified and use of these compounds for treating or ameliorating HD has been provided.

One embodiment of the use of the present description relates to use of a compound of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof to the subject.

One embodiment of the use of the present description relates to a method of use of a compound of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the compound to the subject.

An embodiment of the use of the present description relates to a method of use of a compound of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the compound to the subject.

An embodiment of the use of the present description relates to use of a compound of Formula (I) or a form thereof in the manufacture of a medicament for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the medicament to the subject.

An embodiment of the use of the present description relates to use of a compound of Formula (I) or a form thereof in the preparation of a kit comprising the compound of Formula (I) or a form thereof and instructions for administering the compound for treating or ameliorating HD in a subject in need thereof.

In one respect, for each of such embodiments, the subject is treatment naive. In another respect, for each of such embodiments, the subject is not treatment naive.

As used herein, the term “treating” refers to: (i) preventing a disease, disorder or condition from occurring in a subject that may be predisposed to the disease, disorder and/or condition but has not yet been diagnosed as having the disease, disorder and/or condition; (ii) inhibiting a disease, disorder or condition, i.e., arresting the development thereof; and/or (iii) relieving a disease, disorder or condition, i.e., causing regression of the disease, disorder and/or condition.

As used herein, the term “subject” refers to an animal or any living organism having sensation and the power of voluntary movement, and which requires oxygen and organic food. Nonlimiting examples include members of the human, primate, equine, porcine, bovine, murine, rattus, canine and feline specie. In some embodiments, the subject is a mammal or a warm-blooded vertebrate animal. In other embodiments, the subject is a human. As used herein, the term “patient” may be used interchangeably with “subject” and “human”.

As used herein, the terms “effective amount” or “therapeutically effective amount” mean an amount of compound of Formula (I) or a form, composition or medicament thereof effective in inhibiting the above-noted diseases and thus producing the desired therapeutic, ameliorative, inhibitory or preventative effect in a subject in need thereof.

The dose administered to achieve an effective target plasma concentration may also be administered based upon the weight of the subject or patient. Doses administered on a weight basis may be in the range of about 0.001 mg/kg/day to about 3500 mg/kg/day, or about 0.001 mg/kg/day to about 3000 mg/kg/day, or about 0.001 mg/kg/day to about 2500 mg/kg/day, or about 0.001 mg/kg/day to about 2000 mg/kg/day, or about 0.001 mg/kg/day to about 1500 mg/kg/day, or about 0.001 mg/kg/day to about 1000 mg/kg/day, or about 0.001 mg/kg/day to about 500 mg/kg/day, or about 0.001 mg/kg/day to about 250 mg/kg/day, or about 0.001 mg/kg/day to about 100 mg/kg/day, or about 0.001 mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day to about 50 mg/kg/day, or about 0.001 mg/kg/day to about 40 mg/kg/day, or about 0.001 mg/kg/day to about 30 mg/kg/day, or about 0.001 mg/kg/day to about 20 mg/kg/day, or about 0.001 mg/kg/day to about 10 mg/kg/day, or about 0.01 mg/kg/day to about 2000 mg/kg/day, or about 0.01 mg/kg/day to about 1500 mg/kg/day, or about 0.01 mg/kg/day to about 1000 mg/kg/day, or about 0.01 mg/kg/day to about 600 mg/kg/day, or about 0.01 mg/kg/day to about 500 mg/kg/day, or about 0.01 mg/kg/day to about 300 mg/kg/day, or about 0.015 mg/kg/day to about 200 mg/kg/day, or about 0.02 mg/kg/day to about 100 mg/kg/day, or about 0.025 mg/kg/day to about 100 mg/kg/day, or about 0.03 mg/kg/day to about 100 mg/kg/day, wherein said amount is orally administered once (once in approximately a 24 hour period), twice (once in approximately a 12 hour period) or thrice (once in approximately an 8 hour period) daily according to subject weight.

In certain embodiments, the effective amount will be in a range of from about 0.001 mg/kg/day to about 500 mg/kg/day, or about 0.01 mg/kg/day to about 500 mg/kg/day, or about 0.1 mg to about 500 mg/kg/day, or about 1.0 mg/day to about 500 mg/kg/day, in single, divided, or a continuous dose for a patient or subject having a weight in a range of between about 40 to about 200 kg (which dose may be adjusted for patients or subjects above or below this range, particularly children under 40 kg). The typical adult subject is expected to have a median weight in a range of about 70 kg.

In another embodiment, where daily doses are adjusted based upon the weight of the subject or patient, compounds described herein may be formulated for delivery at about 0.02, 0.025, 0.03, 0.05, 0.06, 0.075, 0.08, 0.09, 0.10, 0.20, 0.25, 0.30, 0.50, 0.60, 0.75, 0.80, 0.90, 1.0, 1.10, 1.20, 1.25, 1.50, 1.75, 2.0, 3.0, 5.0, 10, 20, 30, 40, 50, 100, 150, 200, 250, 300, 400 or 500 mg/kg/day. Daily doses adjusted based upon the weight of the subject or patient may be administered as a single, divided, or continuous dose. In embodiments where a dose of compound is given more than once per day, the dose may be administered twice, thrice, or more times per day.

Within the scope of the present description, the “effective amount” of a compound of Formula (I) or a form thereof for use in the manufacture of a medicament, for use in the preparation of a pharmaceutical kit or in a method of use for treating or ameliorating HD in a subject in need thereof is intended to include an amount in a range of from about 0.001 mg/kg/day to about 3500 mg/kg/day, or about 0.001 mg/kg/day to about 3000 mg/kg/day, or about 0.001 mg/kg/day to about 2500 mg/kg/day, or about 0.001 mg/kg/day to about 2000 mg/kg/day, or about 0.001 mg/kg/day to about 1500 mg/kg/day, or about 0.001 mg/kg/day to about 1000 mg/kg/day, or about 0.001 mg/kg/day to about 500 mg/kg/day, or about 0.001 mg/kg/day to about 250 mg/kg/day, or about 0.001 mg/kg/day to about 100 mg/kg/day, or about 0.001 mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day to about 50 mg/kg/day, or about 0.001 mg/kg/day to about 40 mg/kg/day, or about 0.001 mg/kg/day to about 30 mg/kg/day, or about 0.001 mg/kg/day to about 20 mg/kg/day, or about 0.001 mg/kg/day to about 10 mg/kg/day, or about 0.01 mg/kg/day to about 2000 mg/kg/day, or about 0.01 mg/kg/day to about 1500 mg/kg/day, or about 0.01 mg/kg/day to about 1000 mg/kg/day, or about 0.01 mg/kg/day to about 600 mg/kg/day, or about 0.01 mg/kg/day to about 500 mg/kg/day, or about 0.01 mg/kg/day to about 300 mg/kg/day, or about 0.015 mg/kg/day to about 200 mg/kg/day, or about 0.02 mg/kg/day to about 100 mg/kg/day, or about 0.025 mg/kg/day to about 100 mg/kg/day, or about 0.03 mg/kg/day to about 100 mg/kg/day, wherein said amount is administered once (once in approximately a 24 hour period; i.e., “q.d.”), twice (once in approximately a 12 hour period; i.e., “b.i.d.” or “q.12 h”), thrice (once in approximately an 8 hour period; i.e., “t.i.d.” or “q.8 h”), or four times (once in approximately a 6 hour period; i.e., “q.d.s.”, “q.i.d.” or “q.6 h”) daily according to subject weight.

Such amounts may further include an amount in a range of from about 0.001 mg to about 3500 mg administered daily; 0.001 mg to about 3000 mg administered daily; 0.001 mg to about 2500 mg administered daily; 0.001 mg to about 2000 mg administered daily; 0.001 mg to about 1500 mg administered daily; 0.001 mg to about 1000 mg administered daily; 0.001 mg to about 500 mg administered daily; 0.001 mg to about 250 mg administered daily; 1.0 mg to about 3500 mg administered daily; 1.0 mg to about 1500 mg administered daily; 1.0 mg to about 1000 mg administered daily; 10.0 mg to about 600 mg administered daily; 0.5 mg to about 2000 mg administered daily; or, an amount in a range of from about 5.0 mg to about 300 mg administered daily.

For example, the effective amount may be the amount required to treat HD in a subject or, more specifically, in a human. The effective amount for a subject will depend upon various factors, including the subject's body weight, size and health. Effective amounts for a given patient can be determined by routine experimentation that is within the skill and judgment of the clinician.

For any compound, the effective amount can be estimated initially either in cell culture assays or in relevant animal models, such as a mouse, chimpanzee, marmoset or tamarin animal model. Relevant animal models may also be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans. Therapeutic efficacy and toxicity may be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., ED₅₀(the dose therapeutically effective in 50% of the population) and LD₅₀(the dose lethal to 50% of the population). The dose ratio between therapeutic and toxic effects is therapeutic index, and can be expressed as the ratio, LD₅₀/ED₅₀. In some embodiments, the effective amount is such that a large therapeutic index is achieved. In further embodiments, the dosage is within a range of circulating concentrations that include an ED₅₀with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed, sensitivity of the patient, and the route of administration.

More specifically, the concentration-biological effect relationships observed with regard to a compound of Formula (I) or a form thereof indicate a target plasma concentration ranging from approximately 0.001 μg/mL to approximately 50 μg/mL, from approximately 0.01 μg/mL to approximately 20 μg/mL, from approximately 0.05 μg/mL to approximately 10 μg/mL, or from approximately 0.1 μg/mL to approximately 5 μg/mL. To achieve such plasma concentrations, the compounds described herein may be administered at doses that vary, such as, for example, without limitation, from 0.1 ng to 10,000 mg, depending upon the route of administration in single, divided, or continuous doses for a patient weighing between about 10 to about 100 kg (which dose may be adjusted for patients within this weight range, particularly for children under 40 kg).

The exact dosage will be determined by the practitioner, in light of factors related to the subject. Dosage and administration may be adjusted to provide sufficient levels of the active agent(s) or to maintain the desired effect. Factors which may be taken into account include the severity of the disease state, general health of the subject, ethnicity, age, weight, gender, diet, time of day and frequency of administration, drug combination(s), reaction sensitivities, experience with other therapies, and tolerance/response to therapy. Long-acting pharmaceutical compositions may be administered every 2, 3 or 4 days, once every week, or once every two weeks depending on half-life and clearance rate of the particular formulation.

The compounds and compositions described herein may be administered to the subject via any drug delivery route known in the art. Nonlimiting examples include oral, ocular, rectal, buccal, topical, nasal, sublingual, transdermal, subcutaneous, intramuscular, intraveneous (bolus and infusion), intracerebral, and pulmonary routes of administration.

In one aspect, provided herein are methods for modulating the amount of HTT (huntingtin protein), comprising contacting a human cell with a compound of Formula (I) or a form thereof. In a specific embodiment, provided herein are methods for modulating the amount of HTT, comprising contacting a human cell with a compound of Formula (I) or a form thereof that modulates the expression of HTT. The human cell can be contacted with a compound of Formula (I) or a form thereof in vitro, or in vivo, e.g., in a non-human animal or in a human. In a specific embodiment, the human cell is from or in a human. In another specific embodiment, the human cell is from or in a human with HD. In another specific embodiment, the human cell is from or in a human with HD, caused by a CAG repeat in the Htt gene, resulting in a loss of HTT expression and/or function. In another embodiment, the human cell is from a human with HD. In another embodiment, the human cell is in a human with HD. In one embodiment, the compound is a form of the compound of Formula (I).

In a specific embodiment, provided herein is a method for enhancing the inhibition of mutant HTT transcribed from the Htt gene, comprising contacting a human cell with a compound of Formula (I) or a form thereof. The human cell can be contacted with a compound of Formula (I) or a form thereof in vitro, or in vivo, e.g., in a non-human animal or in a human. In a specific embodiment, the human cell is from or in a human. In another specific embodiment, the human cell is from or in a human with HD. In another specific embodiment, the human cell is from or in a human with HD, caused by a CAG repeat in the Htt gene, resulting in a loss of wild-type “normal” HTT expression and/or function. In another embodiment, the human cell is from a human with HD. In another embodiment, the human cell is in a human with HD. In one embodiment, the compound is a form of the compound of Formula (I).

In another aspect, provided herein is a method for modulating the inhibition of mutant HTT transcribed from the Htt gene, comprising administering to a non-human animal model for HD a compound of Formula (I) or a form thereof. In a specific embodiment, provided herein is a method for modulating the inhibition of mutant HTT transcribed from the Htt gene, comprising administering to a non-human animal model for HD a compound of Formula (I) or a form thereof. In a specific embodiment, the compound is a form of the compound of Formula (I).

In another aspect, provided herein is a method for decreasing the amount of mutant HTT, comprising contacting a human cell with a compound of Formula (I) or a form thereof. In a specific embodiment, provided herein is a method for decreasing the amount of mutant HTT, comprising contacting a human cell with a compound of Formula (I) that inhibits the transcription of mutant HTT (huntingtin mRNA) from the Htt gene. In another specific embodiment, provided herein is a method for decreasing the amount of HTT, comprising contacting a human cell with a compound of Formula (I) that inhibits the expression of mutant HTT transcribed from the Htt gene. The human cell can be contacted with a compound of Formula (I) or a form thereof in vitro, or in vivo, e.g., in a non-human animal or in a human. In a specific embodiment, the human cell is from or in a human. In another specific embodiment, the human cell is from or in a human with HD. In another specific embodiment, the human cell is from or in a human with HD, caused by a CAG repeat in the Htt gene, resulting in a loss of HTT expression and/or function. In another embodiment, the human cell is from a human with HD. In another embodiment, the human cell is in a human with HD. In one embodiment, the compound is a form of the compound of Formula (I).

In certain embodiments, treating or ameliorating HD with a compound of Formula (I) or a form thereof (alone or in combination with an additional agent) has a therapeutic effect and/or beneficial effect. In a specific embodiment, treating HD with a compound of Formula (I) or a form thereof (alone or in combination with an additional agent) results in one, two or more of the following effects: (i) reduces or ameliorates the severity of HD; (ii) delays onset of HD; (iii) inhibits the progression of HD; (iv) reduces hospitalization of a subject; (v) reduces hospitalization length for a subject; (vi) increases the survival of a subject; (vii) improves the quality of life for a subject; (viii) reduces the number of symptoms associated with HD; (ix) reduces or ameliorates the severity of a symptom(s) associated with HD; (x) reduces the duration of a symptom associated with HD; (xi) prevents the recurrence of a symptom associated with HD; (xii) inhibits the development or onset of a symptom of HD; and/or (xiii) inhibits of the progression of a symptom associated with HD.

Metabolites of the Compounds

Also included within the scope of the present description are the use of in vivo metabolic products of the compounds described herein. Such products may result, for example, from the oxidation, reduction, hydrolysis, amidation, esterification and the like of the administered compound, primarily due to enzymatic processes. Accordingly, the description includes the use of compounds produced by a process comprising contacting a compound described herein with a mammalian tissue or a mammal for a period of time sufficient to yield a metabolic product thereof.

Such products typically are identified by preparing a radio-labeled isotopologue (e.g., ¹⁴C or ³H) of a compound described herein, administering the radio-labeled compound in a detectable dose (e.g., greater than about 0.5 mg/kg) to a mammal such as a rat, mouse, guinea pig, dog, monkey or human, allowing sufficient time for metabolism to occur (typically about 30 seconds to about 30 hours), and identifying the metabolic conversion products from urine, bile, blood or other biological samples. The conversion products are easily isolated since they are “radiolabeled” by virtue of being isotopically-enriched (others are isolated by the use of antibodies capable of binding epitopes surviving in the metabolite). The metabolite structures are determined in conventional fashion, e.g., by MS or NMR analysis. In general, analysis of metabolites may be done in the same way as conventional drug metabolism studies well-known to those skilled in the art. The conversion products, so long as they are not otherwise found in vivo, are useful in diagnostic assays for therapeutic dosing of the compounds described herein even if they possess no biological activity of their own.

Pharmaceutical Compositions

Embodiments of the present description include the use of a compound of Formula (I) or a form thereof in a pharmaceutical composition for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the compound of Formula (I) or a form thereof in admixture with one or more pharmaceutically acceptable excipient(s).

An embodiment of the present description includes the use of a pharmaceutical composition of the compound of Formula (I) or a form thereof in the preparation of a kit comprising the pharmaceutical composition of the compound of Formula (I) or a form thereof and instructions for administering the compound for treating or ameliorating HD in a subject in need thereof.

As used herein, the term “composition” means a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts.

The pharmaceutical composition may be formulated to achieve a physiologically compatible pH, ranging from about pH 3 to about pH 11. In some embodiments, the pharmaceutical composition is formulated to achieve a pH of from about pH 3 to about pH 7. In other embodiments, the pharmaceutical composition is formulated to achieve a pH of from about pH 5 to about pH 8.

The term “pharmaceutically acceptable excipient” refers to an excipient for administration of a pharmaceutical agent, such as the compounds described herein. The term refers to any pharmaceutical excipient that may be administered without undue toxicity. Pharmaceutically acceptable excipients may be determined in part by the particular composition being administered, as well as by the particular mode of administration and/or dosage form. Nonlimiting examples of pharmaceutically acceptable excipients include carriers, solvents, stabilizers, adjuvants, diluents, etc. Accordingly, there exists a wide variety of suitable formulations of pharmaceutical compositions for the instant compounds described herein (see, e.g., Remington's Pharmaceutical Sciences).

Suitable excipients may be carrier molecules that include large, slowly metabolized macromolecules such as proteins, polysaccharides, polylactic acids, polyglycolic acids, polymeric amino acids, amino acid copolymers, and inactive antibodies. Other exemplary excipients include antioxidants such as ascorbic acid; chelating agents such as EDTA; carbohydrates such as dextrin, hydroxyalkylcellulose, hydroxyalkylmethylcellulose (e.g., hydroxypropylmethylcellulose, also known as HPMC), stearic acid; liquids such as oils, water, saline, glycerol and ethanol; wetting or emulsifying agents; pH buffering substances; and the like. Liposomes are also included within the definition of pharmaceutically acceptable excipients.

The pharmaceutical compositions described herein may be formulated in any form suitable for the intended use described herein. Suitable formulations for oral administration include solids, liquid solutions, emulsions and suspensions, while suitable inhalable formulations for pulmonary administration include liquids and powders. Alternative formulations include syrups, creams, ointments, tablets, and lyophilized solids which can be reconstituted with a physiologically compatible solvent prior to administration.

When intended for oral use for example, tablets, troches, lozenges, aqueous or oil suspensions, non-aqueous solutions, dispersible powders or granules (including micronized particles or nanoparticles), emulsions, hard or soft capsules, syrups or elixirs may be prepared. Compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions, and such compositions may contain one or more agents including sweetening agents, flavoring agents, coloring agents, and preserving agents, in order to provide a palatable preparation.

Pharmaceutically acceptable excipients suitable for use in conjunction with tablets include, for example, inert diluents, such as celluloses, calcium or sodium carbonate, lactose, calcium or sodium phosphate; disintegrating agents, such as croscarmellose sodium, cross-linked povidone, maize starch, or alginic acid; binding agents, such as povidone, starch, gelatin or acacia; and lubricating agents, such as magnesium stearate, stearic acid, or talc. Tablets may be uncoated or may be coated by known techniques including microencapsulation to delay disintegration and adsorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate alone or with a wax may be employed.

Formulations for oral use may be also presented as hard gelatin capsules where the active ingredient is mixed with an inert solid diluent, for example celluloses, lactose, calcium phosphate, or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with non-aqueous or oil medium, such as glycerin, propylene glycol, polyethylene glycol, peanut oil, liquid paraffin, or olive oil.

In other embodiments, pharmaceutical compositions described herein may be formulated as suspensions comprising a compound of Formula (I) or a form thereof in admixture with one or more pharmaceutically acceptable excipient(s) suitable for the manufacture of a suspension. In yet other embodiments, pharmaceutical compositions described herein may be formulated as dispersible powders and granules suitable for preparation of a suspension by the addition of one or more excipient(s).

Excipients suitable for use in connection with suspensions include suspending agents, such as sodium carboxymethylcellulose, methylcellulose, hydroxypropyl methylcelluose, sodium alginate, polyvinylpyrrolidone, gum tragacanth, gum acacia, dispersing or wetting agents such as a naturally occurring phosphatide (e.g., lecithin), a condensation product of an alkylene oxide with a fatty acid (e.g., polyoxyethylene stearate), a condensation product of ethylene oxide with a long chain aliphatic alcohol (e.g., heptadecaethyleneoxycethanol), a condensation product of ethylene oxide with a partial ester derived from a fatty acid and a hexitol anhydride (e.g., polyoxyethylene sorbitan monooleate); and thickening agents, such as carbomer, beeswax, hard paraffin, or cetyl alcohol. The suspensions may also contain one or more preservatives such as acetic acid, methyl and/or n-propyl p-hydroxy-benzoate; one or more coloring agents; one or more flavoring agents; and one or more sweetening agents such as sucrose or saccharin.

The pharmaceutical compositions described herein may also be in the form of oil-in-water emulsions. The oily phase may be a vegetable oil, such as olive oil or arachis oil, a mineral oil, such as liquid paraffin, or a mixture of these. Suitable emulsifying agents include naturally-occurring gums, such as gum acacia and gum tragacanth; naturally occurring phosphatides, such as soybean lecithin, esters or partial esters derived from fatty acids; hexitol anhydrides, such as sorbitan monooleate; and condensation products of these partial esters with ethylene oxide, such as polyoxyethylene sorbitan monooleate. The emulsion may also contain sweetening and flavoring agents. Syrups and elixirs may be formulated with sweetening agents, such as glycerol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative, a flavoring or a coloring agent.

Additionally, the pharmaceutical compositions described herein may be in the form of a sterile injectable preparation, such as a sterile injectable aqueous emulsion or oleaginous suspension. Such emulsion or suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents which have been mentioned above. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, such as a solution in 1,2-propanediol. The sterile injectable preparation may also be prepared as a lyophilized powder. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile fixed oils may be employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono- or di-glycerides. In addition, fatty acids such as oleic acid may likewise be used in the preparation of injectables.

The compounds described herein may be substantially insoluble in water and sparingly soluble in most pharmaceutically acceptable protic solvents and vegetable oils, but generally soluble in medium-chain fatty acids (e.g., caprylic and capric acids) or triglycerides and in propylene glycol esters of medium-chain fatty acids. Thus, contemplated in the description are compounds which have been modified by substitutions or additions of chemical or biochemical moieties which make them more suitable for delivery (e.g., increase solubility, bioactivity, palatability, decrease adverse reactions, etc.), for example by esterification, glycosylation, PEGylation, etc.

In some embodiments, the compound described herein is formulated for oral administration in a lipid-based composition suitable for low solubility compounds. Lipid-based formulations can generally enhance the oral bioavailability of such compounds. As such, pharmaceutical compositions described herein may comprise a effective amount of a compound of Formula (I) or a form thereof, together with at least one pharmaceutically acceptable excipient selected from medium chain fatty acids or propylene glycol esters thereof (e.g., propylene glycol esters of edible fatty acids such as caprylic and capric fatty acids) and pharmaceutically acceptable surfactants, such as polysorbate 20 or 80 (also referred to as Tween® 20 or Tween® 80, respectively) or polyoxyl 40 hydrogenated castor oil.

In other embodiments, the bioavailability of low solubility compounds may be enhanced using particle size optimization techniques including the preparation of nanoparticles or nanosuspensions using techniques known to those skilled in the art. The compound forms present in such preparations include amorphous, partially amorphous, partially crystalline or crystalline forms.

In alternative embodiments, the pharmaceutical composition may further comprise one or more aqueous solubility enhancer(s), such as a cyclodextrin. Nonlimiting examples of cyclodextrin include hydroxypropyl, hydroxyethyl, glucosyl, maltosyl and maltotriosyl derivatives of α-, β-, and γ-cyclodextrin, and hydroxypropyl-β-cyclodextrin (HPBC). In some embodiments, the pharmaceutical composition further comprises HPBC in a range of from about 0.1% to about 20%, from about 1% to about 15%, or from about 2.5% to about 10%. The amount of solubility enhancer employed may depend on the amount of the compound in the composition.

Preparation of Compounds

Compounds provided herein can be prepared by those skilled in the art, such as, by the synthetic methods set forth in International Application Publication Number WO2014/028459 A1, published Feb. 20, 2014, International Application Publication Number WO2014/116845 A1, published Jul. 31, 2014, and International Application Publication Number WO2015/017589 A1, published Feb. 5, 2015, each of which are herein incorporated by reference.

General Schemes

The following reaction schemes illustrate methods to make compounds described herein. It is understood that one skilled in the art would be able to make these compounds by similar methods or by methods known to one skilled in the art.

In general, starting components and reagents may be commercially obtained from various sources such as commercial vendors, synthesized according to methodology known to those skilled in the art, or prepared as described herein. It is understood that in the following description, combinations of substituents and/or variables of the depicted formulae are permissible only if such contributions result in stable compounds.

In general, compounds of Formula (I) described herein can be synthesized following the general procedure for Scheme 1.

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General Procedure for Scheme 1

The starting materials for the above reaction scheme are commercially available or can be prepared according to methods known to one skilled in the art or by methods disclosed herein. In general, the compounds described herein are prepared in the above reaction Scheme 1 as follows: a halogenated Compound 1a (wherein Hal is a halogen selected from bromine or chlorine) is reacted with a Compound 1b (wherein H is a reactive hydrogen atom in an amine or alcohol X functional group, wherein X and B for a compound of Formula (I) are as described herein) using a displacement or a metal-mediated cross coupling reaction, such as a Buchwald reaction, to provide an intermediate Compound 1c. Compound 1c is carried forward and reacted with a boronate acid or boronate ester Compound 1d (where B represents a boron atom, R represents a an acid or ester functional group or, when taken together with boron, form a ring system and A for a compound of Formula (I) is as described herein) using a transition metal-mediated cross coupling reaction, such as a Suzuki reaction, to provide a Compound of Formula (I).

In a complementary manner, compounds of Formula (I) may also be synthesized in reverse order wherein the boronate Compound 1d is reacted first with Compound 1a followed by reaction of the intermediate with amine Compound 1b. Other variations representing different combinations for substituting either or both boronate Compound 1d and amine Compound 1b on Compound 1a are intended to be included within the scope of the synthetic methodologies described herein.

SPECIFIC EXAMPLES

To assist in understanding the present description, the following specific examples are included. The experiments relating to this description should not, of course, be construed as specifically limiting the description and such variations of the description, now known or later developed, which would be within the purview of one skilled in the art are considered to fall within the scope of the description as described herein and hereinafter claimed.

Other than in the working examples, unless indicated to the contrary, all numbers expressing quantities of materials, reagents, reaction conditions, experimental data, and so forth used in the specification and claims are to be understood as being modified by the term “about”. Accordingly, all such numbers represent approximations that may vary depending upon the desired properties sought to be obtained by a reaction or as a result of variable experimental conditions. Therefore, within an expected range of experimental reproducibility, the term “about” in the context of the resulting data, refers to a range for data provided that may vary according to a standard deviation from the mean. As well, for experimental results provided, the resulting data may be rounded up or down to present data consistently, without loss of significant figures. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding techniques.

While the numerical ranges and parameters setting forth the broad scope of the description are approximations, the numerical values set forth in the working examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

The column chromatography system used for product purification was an ISCO CombiFlash™ brand chromatography system (manufactured by Teledyne Isco).

SYNTHETIC EXAMPLES

Greater details of the present description are provided with reference to the following non-limiting examples, which are offered to more fully illustrate the description, but are not to be construed as limiting the scope thereof. The examples illustrate the preparation of certain compounds described herein, and the testing of these compounds in vitro and/or in vivo. Those of skill in the art will understand that the techniques described in these examples represent techniques described by the inventors to function well in the practice of the description, and as such constitute preferred modes for the practice thereof. However, those of skill in the art should appreciate in light of the present disclosure that many changes can be made to the specific methods that are disclosed and still obtain a like or similar result without departing from the spirit and scope of the description.

As used above, and throughout this description, the following abbreviations, unless otherwise indicated, shall be understood to have the following meanings:

Abbreviation
Meaning

AcOH or HOAc
acetic acid

ACN or MeCN
acetonitrile

Bn
benzyl

BnBr
benzyl bromide

BnO or OBn
benzyloxy

Boc
tert-butoxycarbonyl

Boc₂O or (Boc)₂O
di-tert-butyl dicarbonate

tBuXPhos-Pd-G3
[(2-di-tert-butylphosphino-2′,4′,

6′-triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-

biphenyl)] palladium(II) methanesulfonate

Cbz
benzyloxycarbonyl

DCE
dichloroethane

DCM
dichloromethane (CH₂Cl₂)

DIBAL-H
diisobutylaluminium hydride

DIPEA
N,N-diisopropylethylamine

DMF
dimethyl formamide

DMA
dimethylacetamide

DMAP
4-dimethylaminopyridine

DMB
2,4-dimethoxybenzyl

DMSO
dimethylsulfoxide

EA or EtOAc
ethyl acetate

EtOH
ethanol

Et₂O
diethyl ether

HCl
hydrochloric acid

HPLC
high performance liquid chromatography

h/hr/hrs/min/s
hour(s) (h, hr or hrs)/minute(s) (min/mins)/

second(s)

K₂CO₃
potassium carbonate

KOAc
potassium acetate

K₃PO₄
potassium phosphate

LAH
lithium aluminium hydride

LC/MS, LCMS
liquid chromatographic mass spectroscopy

or LC-MS

LDA
lithium diisopropylamide

LiHMDS
lithium bis(trimethylsilyl)amide

Me₄tBu-XPhos
di-tert-butyl(2′,4′,6′-triisopropyl-

3,4,5,6-tetramethyl-[1,1′-biphenyl]-2-yl)phosphine

MeI
methyl iodide

MeOH
methanol

Me₂NH or NHMe₂
dimethyl amine

MS
mass spectroscopy

N₂
nitrogen

Na₂SO₄
sodium sulfate

NaBH(OAc)₃
sodium triacetoxyborohydride

NaHMDS
sodium bis(trimethylsilyl)amide

NBS
N-bromosuccinimide

NH₄OH
ammonium hydroxide

NMO
N-methylmorpholine-N-oxide

NMP
N-methyl-2-pyrrolidone

n-BuLi
n-butyl lithium

NMR
nuclear magnetic resonance

Pd/C
palladium on carbon

Pd₂(dba)₃
tris(dibenzylideneacetone)dipalladium(0)

Pd(dppf)Cl₂
[1,1′-bis(diphenylphosphino)ferrocene]

dichloropalladium(II)

Pd(PPh₃)₄
tetrakis(triphenylphosphine)palladium

Pin
pinacol

psi
pounds per square inch pressure

S-Phos
2-dicyclohexylphosphino-2′,

6′-dimethoxybiphenyl

TBDPSCl
tert-butyldiphenylchlorosilane

TBS
tert-butyldimethylsilyl

TBSCl
tert-butyldimethylsilyl chloride

t-BuOK
potassium tert-butoxide

TEA or NEt₃
triethylamine

TFA
trifluoroacetic acid

THF
tetrahydrofuran

THP
tetrahydro-2H-pyranyl

THPO or OTHP
tetrahydro-2H-pyran-2-yl-oxy

TIPS-H or TIPSH
triisopropyl silane

TLC
thin layer chromatography

TMP
2,2,6,6-tetramethylpiperidinyl

TMPMgCl—LiCl
2,2,6,6-tetramethylpiperidinylmagnesium

chloride lithium chloride

TMSI
trimethylsilyl iodide

TMSOK
potassium trimethylsilanolate

Example 1 (Compound 411)
2-{6-[8-Azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol hydrochloride
Step 1:

3,6-Dibromopyridazine (133.7 mg, 0.56 mmol), tert-butyl (1R,5S)-3-(methylamino)-8-azabicyclo[3.2.1]octane-8-carboxylate (85 mg, 0.28 mmol) and DIPEA (0.15 mL, 0.84 mmol) were mixed in 1 mL of ACN and heated to 100° C. for 1 h until LC-MS showed complete consumption of the starting material. The reaction mixture was concentrated and purified via column chromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 30% MeOH), column: silica 4 g to afford tert-butyl (1S,5R)-3-[(6-bromopyridazin-3-yl)-methyl-amino]-8-azabicyclo[3.2.1]octane-8-carboxylate (55 mg, 49.25% yield).

Step 2:

tert-Butyl 3-[(6-bromopyridazin-3-yl)-methyl-amino]-8-azabicyclo[3.2.1]octane-8-carboxylate (55 mg, 0.14 mmol), 4-[3-(methoxymethoxy)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-tetrahydropyran-2-yl-pyrazole (68.82 mg, 0.17 mmol), Pd(dppf)Cl₂(10.34 mg, 0.01 mmol), K₂CO₃(57.98 mg, 0.42 mmol) were mixed in a Schlenk tube. The reaction was degassed with N₂for 15 min and dioxane (2 mL) and water (0.5 mL) were added and the reaction was heated to 90° C. for 16 h. The reaction was cooled to room temperature, partitioned between EtOAc and water. The organic layers were dried over Na₂SO₄, concentrated under vacuum, purified via column chromatography: eluting with gradient CH₂Cl₂/EtOAc (0% to 80%), column: silica 4 g, to providetert-butyl (1S,5R)-3-[[6-[2-(methoxymethoxy)-4-(1-tetrahydropyran-2-ylpyrazol-4-yl)phenyl]pyridazin-3-yl]-methyl-amino]-8-azabicyclo[3.2.1]octane-8-carboxylate (52 mg, 62%) as a tan solid.

Step 3:

To a solution of tert-butyl (1S,5R)-3-[[6-[2-(methoxymethoxy)-4-(1-tetrahydropyran-2-ylpyrazol-4-yl)phenyl]pyridazin-3-yl]-methyl-amino]-8-azabicyclo[3.2.1]octane-8-carboxylate (52 mg, 0.086 mmol) in a 1 mL mixture of CH₂Cl₂and 0.5 mL of MeOH was added HCl (4 mol/L) in 1,4-dioxane (0.06 mL). The reaction was stirred overnight. The precipitate was filtered, then dried under vacuum to provide 2-[6-[8-azabicyclo[3.2.1]octan-3-yl(methyl)amino]pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol; hydrochloride (15 mg, 42.25% yield) as a yellow solid.

LC-MS: 377 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.37-9.51 (m, 1H), 8.87-8.96 (m, 1H), 8.31 (d, J=9.8 Hz, 1H), 8.12 (s, 2H), 7.74 (d, J=8.2 Hz, 2H), 7.19-7.27 (m, 2H), 4.80-4.92 (m, 1H), 4.08-4.14 (m, 3H), 3.07 (s, 3H), 2.30 (td, J=12.6, 2.8 Hz, 2H), 1.99-2.15 (m, 4H), 1.74-1.87 (m, 2H)

Using the procedure described for Example 1 above, additional compounds described herein may be prepared by substituting the appropriate starting materials reagents, and reaction conditions, obtaining compounds such as those selected from:

Cpd
Data

412
LC-MS: 363 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.24-9.34 (m, 1H),

9.09-9.21 (m, 1H), 8.30 (d, J = 9.8 Hz, 1H), 8.09 (s, 2H), 7.64-7.67 (m, 1H), 7.63 (d, J = 8.2 Hz,

1H), 7.25-7.27 (m, 1H), 7.24 (s, 1H), 5.42 (br s, 2H), 4.23-4.31 (m, 1H),

4.00-4.13 (m, 2H), 2.17 (s, 4H), 1.97-2.02 (m, 2H), 1.94 (td, J = 12.6, 2.5 Hz, 2H)

413
LC-MS: 393 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.34-9.49 (m, 1H),

8.43-8.56 (m, 1H), 8.30 (d, J = 9.8 Hz, 1H), 8.10 (s, 2H), 7.63 (s, 2H), 7.19-7.30 (m, 2H),

5.77 (br s, 2H), 4.41-4.62 (m, 1H), 2.08 (dd, J = 11.7, 2.8 Hz, 2H), 1.72 (td, J = 12.1,

2.8 Hz, 2H), 1.53 (s, 6H), 1.49 (s, 6H)

415
LC-MS: 364 [M + H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: 8.61 (d, J = 9.5 Hz, 1H),

8.24 (s, 2H), 7.85 (d, J = 8.2 Hz, 1H), 7.72 (d, J = 9.5 Hz, 1H), 7.38 (dd, J = 8.2, 1.6 Hz,

1H), 7.32 (d, J = 1.6 Hz, 1H), 5.65 (spt, J = 5.7 Hz, 1H), 4.25 (dd, J = 3.6, 2.8 Hz, 2H),

4.17-4.32 (m, 2H), 2.24 (s, 4H), 2.11 (tt, J = 11.2, 2.8 Hz, 2H) (3 hydrogens

corresponding to OH and NH unobserved)

433
LC-MS: 363 [M + H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: 8.42 (d, J = 9.5 Hz, 1H),

8.34 (s, 2H), 7.80 (d, J = 9.8 Hz, 1H), 7.74 (d, J = 8.5 Hz, 1H), 7.40 (dd, J = 8.2, 2.5 Hz,

1H), 7.32 (d, J = 1.6 Hz, 1H), 4.18 (td, J = 6.9, 0.9 Hz, 1H), 4.11-4.16 (m, 2H),

2.42-2.52 (m, 4H), 2.32-2.35 (m, 1H), 2.28-2.32 (m, 1H), 2.15-2.25 (m, 2H), (4

hydrogens corresponding to OH and NH unobserved)

Example 2 (Compound 416)
5-(5-Methyl-1H-pyrazol-4-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol
Step 1:

3-Methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl trifluoromethanesulfonate (80 mg, 0.16 mmol), (tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (59 mg, 0.19 mmol), Pd(dppf)Cl₂(7 mg, 0.01 mmol), K₂CO₃(66 mg, 0.48 mmol) were mixed in a Schlenk tube. The reaction was degassed with N₂for 15 min and dioxane (2 mL) and water (0.5 mL) were added and the reaction was heated to 90° C. for 16 h. The reaction was cooled to room temperature, partitioned between EtOAc and water. The organic layers were dried over Na₂SO₄, concentrated under vacuum, then purified via column chromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 30% MeOH), column: silica 4 g to provide tert-butyl 4-(3-methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-3-methyl-1H-pyrazole-1-carboxylate (46 mg, 54%) as light brown solid.

Step 2:

A solution of tert-butyl 4-(3-methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-3-methyl-1H-pyrazole-1-carboxylate (46 mg, 0.09 mmol) in 2 mL of dry CH₂Cl₂was cooled in ice-water bath. Boron tribromide 1.0 M in CH₂Cl₂(0.45 mL, 0.45 mmol) was added and the reaction mixture was stirred at room temperature for 16 hours. The reaction was quenched with 2 mL of MeOH, stirred for 30 min, then concentrated and purified via column chromatography: eluting with gradient CH₂Cl₂/MeOH (2.5% NH₄OH) (0% to 30% MeOH/NH₄OH), column: silica 4 g, to provide tert-butyl 2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(3-methyl-1H-pyrazol-4-yl)phenol (20 mg, 55%) as a yellow solid.

LC-MS: 421 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 13.74 (s, 1H), 12.63-12.71 (m, 1H), 8.20 (d, J=9.5 Hz, 1H), 8.03-8.04 (m, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.73-7.75 (m, 1H), 7.36 (d, J=9.5 Hz, 1H), 7.03-7.06 (m, 2H), 4.90-5.05 (m, 1H), 2.92 (s, 3H), 2.43 (s, 3H), 1.43-1.54 (m, 2H), 1.15-1.43 (m, 2H), 1.14 (s, 6H), 1.09 (s, 6H)

Using the procedure described for Example 2 above, additional compounds described herein may be prepared by substituting the appropriate starting materials reagents, and reaction conditions, obtaining compounds such as those selected from:

Cpd
Data

414
LC-MS: 408 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 13.84 (s, 1H),

8.10-8.29 (m, 2H), 7.92 (s, 1H), 7.84 (d, J = 8.2 Hz, 1H), 7.36 (d, J = 9.8 Hz, 1H), 7.08-7.19 (m,

2H), 4.87-5.03 (m, 1H), 3.87 (s, 3H), 2.96 (s, 3H), 1.48-1.59 (m, 2H), 1.38-1.48 (m,

2H), 1.26 (s, 6H), 1.09 (s, 6H)

418
LC-MS: 422 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 12.89 (s, 1H),

12.29-12.48 (m, 1H), 8.41 (dd, J = 8.8, 0.9 Hz, 1H), 7.95 (dd, J = 7.9, 0.9 Hz, 1H), 7.37 (dd, J = 9.1,

1.3 Hz, 1H), 6.85-6.94 (m, 2H), 5.61-5.70 (m, 1H), 2.25 (br s., 6H), 2.09 (dd,

J = 11.8, 3.9 Hz, 2H), 1.25-1.33 (m, 2H), 1.24 (s, 6H), 1.11 (s, 6H), (1 hydrogen

corresponding to OH or NH unobserved)

451
LC-MS: 408 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 13.00 (s, 1H),

12.59-12.80 (m, 1H), 8.42 (d, J = 9.5 Hz, 1H), 7.94 (d, J = 8.8 Hz, 1H), 7.38 (d, J = 9.5 Hz, 1H),

7.03-7.18 (m, 2H), 5.55-5.78 (m, 1H), 2.39 (br s., 3H), 2.03-2.13 (m, 2H),

1.26-1.41 (m, 2H), 1.24 (s, 6H), 1.11 (s, 6H), (1 hydrogen corresponding to OH or NH

unobserved)

Example 3 (Compound 419)
2-{6-[Methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-pyrazol-1-yl)phenol dihydrochloride
Step 1:

3-Methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl trifluoromethanesulfonate (335 mg, 0.67 mmol), 4-nitro-1H-pyrazole (340 mg, 4.5 mmol), Pd₂(dba)₃(67 mg, 0.07 mmol), Me₄tBu-XPhos (35 mg, 0.07 mmol), K₃PO₄(368 mg, 1.73 mmol) were mixed in a Schlenk tube. The reaction was degassed with N₂for 15 min and dioxane (8 mL) was added and the reaction was heated to 90° C. for 16 h. The reaction was cooled to room temperature, filtered through celite, concentrated, purified via column chromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 30% MeOH), column: silica 12 g, to provide 6-(2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (202 mg, 65%).

LC-MS: 466 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.81-9.85 (m, 1H), 8.61 (d, J=0.6 Hz, 1H), 7.91 (d, J=8.5 Hz, 1H), 7.81 (d, J=9.8 Hz, 1H), 7.73 (d, J=1.9 Hz, 1H), 7.68 (dd, J=8.2, 2.2 Hz, 1H), 7.10-7.21 (m, 1H), 5.08-5.26 (m, 1H), 3.96 (s, 3H), 2.95 (s, 3H), 1.59-1.75 (m, 4H), 1.40 (s, 6H), 1.33, (s, 6H), (1 hydrogen corresponding to OH or NH unobserved)

Step 2:

6-(2-Methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (150 mg, 0.32 mmol), benzenethiol (33 μL, 0.32 mmol) and K₂CO₃(44 mg, 0.32 mmol) were mixed in a microwave tube. The reaction was degassed with N₂for 15 min and dry NMP (1.5 mL) was added. The reaction was heated in a Biotage microwave at 190° C. for 20 min, then diluted with 10 mL EtOAc, and washed with water and brine. The product was dried over Na₂SO₄, concentrated under vacuum, then purified via column chromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 30% MeOH), column: silica 4 g, to provide 2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(4-nitro-1H-pyrazol-1-yl)phenol (60 mg, 42%) as a brown solid.

LC-MS: 452 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.77 (s, 1H), 8.68 (d, J=9.8 Hz, 1H), 8.62 (s, 1H), 8.27 (d, J=8.8 Hz, 1H), 7.87-7.94 (m, 1H), 7.66 (dd, J=8.5, 2.6 Hz, 1H), 7.64 (d, J=2.6 Hz, 1H), 5.03-5.22 (m, 1H), 3.01 (s, 3H), 1.84-1.94 (m, 2H), 1.70-1.77 (m, 2H), 1.53 (s, 6H), 1.43 (s, 6H), (2 hydrogens corresponding to OH and NH unobserved)

Using the procedure described for Example 3 above, additional compounds described herein may be prepared by substituting the appropriate starting materials reagents, and reaction conditions, obtaining compounds such as those selected from:

Cpd
Data

417
LC-MS: 394 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 13.49 (br s, 1H), 8.49 (d,

J = 9.8 Hz, 1H), 8.39 (s, 1H), 8.10 (d, J = 8.8 Hz, 1H), 7.79-7.92 (m, 1H), 7.43 (d,

J = 9.5 Hz, 1H), 7.34 (d, J = 2.5 Hz, 1H), 7.30 (dd, J = 8.5, 2.5 Hz, 1H), 7.12 (s, 1H),

5.61-5.71 (m, 1H), 2.09 (dd, J = 12.0, 3.8 Hz, 2H), 1.25-1.32 (m, 2H), 1.24 (s, 6H),

1.11 (s, 6H), (1 hydrogen corresponding to OH or NH unobserved)

421
LC-MS: 409 [M + H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: 8.31 (d, J = 9.5 Hz, 1H),

7.92 (d, J = 9.1 Hz, 1H), 7.79 (d, J = 0.6 Hz, 1H), 7.44 (d, J = 0.9 Hz, 1H),

7.24-7.33 (m, 3H), 5.77 (tt, J = 11.2, 4.1 Hz, 1H), 2.28 (dd, J = 12.3, 4.2 Hz, 2H), 1.49 (t, J = 12.3 Hz,

2H), 1.42 (s, 6H), 1.30 (s, 6H), (4 hydrogens corresponding to OH and NH

unobserved)

423
LC-MS: 439 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.71 (d, J = 0.6 Hz, 1H),

8.58 (d, J = 0.6 Hz, 1H), 8.47 (d, J = 9.5 Hz, 1H), 8.14 (d, J = 8.5 Hz, 1H),

7.59-7.64 (m, 2H), 7.44 (d, J = 9.5 Hz, 1H), 5.67-5.73 (m, 1H), 2.18-2.28 (m, 2H),

1.45-1.56 (m, 2H), 1.37 (s, 6H), 1.27 (s, 6H), ), (2 hydrogens corresponding to OH and NH

unobserved)

Example 4 (Compound 424)
5-(1H-Pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol trihydrochloride
Step 1:

3-Bromo-6-(2-methoxy-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)pyridazine (100 mg, 0.24 mmol), (1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)boronic acid (66 mg, 0.29 mmol), PddppfCl₂(8 mg, 0.012 mmol), K₂CO₃(99 mg, 0.72 mmol) were mixed in a Schlenk tube. The reaction was degassed with N₂for 15 min and dioxane (2 mL) and water (0.5 mL) were added and the reaction was heated to 90° C. for 16 h. The reaction was cooled to room temperature, and partitioned between EtOAc and water. The organic layers were dried over Na₂SO₄, then concentrated under vacuum, and purified via column chromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 20% MeOH), column: silica 4 g, to provide 5-(1H-pyrazol-4-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol (102 mg, 82%) as an off-white solid.

Step 2:

A solution of 5-(1H-pyrazol-4-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol (102 mg, 0.196 mmol) in 2 mL of dry CH₂Cl₂was cooled in ice-water bath. Boron tribromide 1.0 M in CH₂Cl₂(0.98 mL, 0.98 mmol) was added and the reaction mixture was stirred at room temperature for 16 hours. The reaction was quenched with 2 mL of MeOH, stirred for 30 min, then concentrated and purified using preparative HPLC to provide 5-(1H-pyrazol-4-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol (41 mg, 66%) as an off-white solid.

LC-MS: 320 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.19 (br S, 2H), 8.54 (d, J=9.6 Hz, 1H), 8.22, (d, J=9.6 Hz, 1H), 8.18 (s, 1H), 8.05 (d, J=8.8 Hz, 1H), 7.25-7.29 (m, 2H), 6.92 (s, 1H), 3.85-3.92 (m, 2H), 3.38-3.41 (m, 2H), 2.88-2.98 (m, 2H), (1 hydrogen corresponding to OH or NH unobserved)

Using the procedure described for Example 4 above, additional compounds described herein may be prepared by substituting the appropriate starting materials reagents, and reaction conditions, obtaining compounds such as those selected from:

Cpd
Data

422
LC-MS: 334 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 11.06 (br s, 1H), 8.56 (d,

J = 9.2 Hz, 1H), 8.25 (d, J = 9.2 Hz, 1H), 8.20 (s, 2H), 8.05 (d, J = 8.8 Hz, 1H),

7.22-7.31 (m, 2H), 6.92 (s, 1H), 4.06-4.12 (m, 1H), 3.87-3.94 (m, 1H), 3.62-3.70 (m, 1H),

3.21-3.30 (m, 1H), 3.07-3.12 (m, 2H), 3.03 (s, 3H), (1 hydrogen corresponding to

OH or NH unobserved)

425
LC-MS: 348 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 10.94 (br S, 1H), 8.56 (d,

J = 9.6 Hz, 1H), 8.26 (d, J = 9.6 Hz, 1H), 8.19-8.23 (m, 2H), 8.05 (d, J = 8.4 Hz, 1H),

7.26-7.31 (m, 2H), 6.93 (s, 1H), 4.07-4.13 (m, 1H), 3.85-3.91 (m, 1H),

3.70-3.74 (m, 1H), 3.22-3.30 (m, 3H), 3.08-3.14 (m, 2H), 1.33 (t, J = 7.2 Hz, 3H), (1 hydrogen

corresponding to OH or NH unobserved)

429
LC-MS: 346 [M + H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: 1.79-1.89 (m, 1H)

1.98-2.11 (m, 1H) 2.11-2.33 (m, 2H) 2.65-2.80 (m, 1H) 3.09-3.21 (m, 1H)

4.02-4.16 (m, 2H) 7.02-7.14 (m, 1H) 7.24 (s, 2 H) 7.85-7.97 (m, 1H) 8.04 (d, J = 9.46 Hz,

3H) 8.33 (d, J = 9.46 Hz, 1H)

Example 5 (Compound 427)
2-[6-(Piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride
Step 1:

3,6-Dibromopyridazine (500 mg, 2.1 mmol), 4-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (970 mg, 2.52 mmol), Pd(dppf)Cl₂(77 mg, 0.11 mmol), K₂CO₃(870 mg, 6.3 mmol) were mixed in a Schlenk tube. The reaction was degassed with N₂for 15 min and dioxane (8 mL) and water (1 mL) were added and the reaction was heated to 90° C. for 16 h. The reaction was cooled to room temperature, partitioned between EtOAc and water. The organic layers were dried over Na₂SO₄, concentrated under vacuum, purified via column chromatography: eluting with gradient hexanes/EtOAc (0% to 40% EtOAc), column: silica 4 g, to provide 3-bromo-6-(2-methoxy-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)pyridazine (690 mg, 79%) as an off-white fluffy solid.

Step 2:

3-Bromo-6-(2-methoxy-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)pyridazine (50 mg, 0.12 mmol), tert-butyl 4-aminopiperidine-1-carboxylate (36 mg, 0.18 mmol), potassium t-butoxide (41 mg, 0.36 mmol), tBuXPhos-Pd-G3 (10 mg, 0.012 mmol) were mixed in a Schlenk tube. The reaction was degassed with Ar then dry THF (2 mL) was added and the reaction was heated to 80° C. for 12 h. The reaction was cooled to room temperature, then partitioned between EtOAc and water. The organic layers were dried over Na₂SO₄, concentrated under vacuum, and purified via column chromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 15% MeOH), column: silica 4 g, to provide tert-butyl 4-((6-(2-methoxy-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)pyridazin-3-yl)amino)piperidine-1-carboxylate (45 mg, 70%) as a tan solid.

Step 3:

A solution of 4-(((6-(2-methoxy-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)pyridazin-3-yl)amino)piperidine-1-carboxylate (45 mg, 0.084 mmol) in 2 mL of dry CH₂Cl₂was cooled in an ice-water bath. Boron tribromide 1.0 M in CH₂Cl₂(0.42 mL, 0.42 mmol) was added and the reaction mixture was stirred at room temperature for 16 hours. The reaction was quenched with 2 mL of MeOH, stirred for 30 min, then concentrated and purified using preparative HPLC to provide 2-(6-(piperidin-4-ylamino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol (21 mg, 73%) as a yellowish solid.

LC-MS: 377 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 8.95 (s, 2H), 8.25 (d, J=9.6 Hz, 1H), 8.09 (s, 2H), 7.69 (d, J=8.8 Hz, 1H), 7.49-7.41 (m, 1H), 7.21-7.24 (m, 2H), 4.11-4.15 (m, 1H), 3.34-3.39 (m, 4H), 3.01-3.08 (m, 2H), 2.11-2.17 (m, 2H), 1.79 (q, J=9.2 Hz, 2H)

Using the procedure described for Example 5 above, additional compounds described herein may be prepared by substituting the appropriate starting materials reagents, and reaction conditions, obtaining compounds such as those selected from:

Cpd
Data

426
LC-MS: 351 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.22-9.28 (m, 2H),

8.34 (d, J = 9.6 Hz, 1H), 8.06-8.11 (m, 2H), 78.5-7.89 (m, 1H), 7.74 (d, J = 8.2 Hz, 1H),

7.20-7.27 (m, 2H), 4.67-4.75 (m, 2H), 3.35-3.39 (m, 2H), 3.07-3.09 (m, 2H),

3.05 (s, 3H), 2.21 (q, J = 10.2 Hz, 2H), 1.83-1.88 (m, 2H)

432
LC-MS: 338 [M + H]⁺. 1H NMR (500 MHz, methanol-d₄) δ: 8.72 (d, J = 9.6 Hz, 1H),

8.41-8.54 (m, 2H), 7.91-8.08 (m, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 8.2 Hz,

1H), 7.38 (s, 1H), 5.51 (quint, J = 2.8 Hz, 1H), 3.30-3.46 (m, 2H), 3.28-3.31 (m, 2H),

2.33-2.38 (m, 2H), 2.25-2.32 (m, 2H), (3 hydrogens corresponding to OH and NH

unobserved)

436
LC-MS: 366 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.17-9.30 (m, 1H),

8.81-8.95 (m, 1H), 8.49 (d, J = 9.8 Hz, 1H), 8.17 (s, 2H), 7.94 (d, J = 8.8 Hz, 1H), 7.46 (d,

J = 9.8 Hz, 1H), 7.18-7.29 (m, 2H), 5.47 (spt, J = 5.7 Hz, 1H), 3.31-3.52 (m, 2H),

2.41 (dd, J = 12.9, 5.7 Hz, 2H), 1.68 (q, J = 12.0 Hz, 2H), 1.34 (d, J = 6.3 Hz, 6H), (1

hydrogen corresponding to OH or NH unobserved)

439
LC-MS: 363 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.07 (s, 2H), 8.28 (d,

J = 10 Hz, 1H), 1.7 (s, 2H), 7.81 (d, J = 8.8 Hz, 1H), 7.73 (d, J = 9.6 Hz, 1H),

7.19-7.22 (m, 2H), 3.75-3.81 (m, 4H), 3.58-3.69 (m, 4H), 1.85-1.89 (m, 4H), (1 hydrogen

corresponding to OH or NH unobserved)

459
LC-MS: 349 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 10.53 (s, 1H), 10.40 (s,

1H), 9.79 (br s, 1H), 9.67 (br s, 1H), 8.28 (d, J = 9.6 Hz, 1H), 8.06 (s, 2H), 7.65 (d,

J = 9.6 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.21-7.25 (m, 1H), 4.53 (q, J = 14 Hz, 2H),

3.64 (d, J = 12.8 Hz, 1H), 3.52 (d, J = 12.8 Hz, 1H), 3.37-3.40 (m, 2H), 3.15-3.24 (m, 2H),

1.92-2.02 (m, 2H)

Example 6 (Compound 430)
6-[2,3-Difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride
Step 1:

To a RBF, equipped with a N₂inlet, were added: 6-bromo-N-methyl-N-(2,2,6,6-tetramethyl-4-piperidyl)pyridazin-3-amine (90 mg, 0.28 mmol),4-[2,3-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-tetrahydropyran-2-yl-pyrazole (128.8 mg, 0.33 mmol), Pd(PPh₃)₄(31.8 mg, 0.03 mmol), Na₂CO₃(87.43 mg, 0.83 mmol). The reaction was degassed with N₂for 15 min then dioxane (8 mL) and water (2 mL) were added. The reaction was heated to 90° C. for 16 h, then cooled to room temperature, and partitioned between EtOAc and water. The organic layers were dried over Na₂SO₄, concentrated on a rotavap, and purified via column chromatography: eluting with gradient CH₂Cl₂/MeOH (0% to 30%), column: silica 4 g to provide 6-(2,3-Difluoro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (88 mg, 63%) as a grey solid.

Step 2:

6-[2,3-Difluoro-4-(1-tetrahydropyran-2-ylpyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethyl-4-piperidyl)pyridazin-3-amine (88 mg, 0.17 mmol) was dissolved in MeOH (2 mL) and 4M HCl in dioxane (90 μL, 0.34 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 30 min until LC-MS showed complete consumption of starting material. The reaction mixture was concentrated under reduced pressure to provide 6-(2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride salt.

LC-MS: 427 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.21-9.33 (m, 1H), 8.27-8.43 (m, 1H), 8.20 (s, 2H), 8.01 (d, J=9.8 Hz, 1H), 7.60-7.79 (m, 3H), 5.01-5.14 (m, 1H), 3.05 (s, 3H), 2.10 (td, J=13.2, 1.6 Hz, 2H), 1.79 (dd, J=12.9, 4.1 Hz, 2H), 1.55 (s, 6H), 1.50 (s, 6H)

Using the procedure described for Example 6 above, additional compounds described herein may be prepared by substituting the appropriate starting materials reagents, and reaction conditions, obtaining compounds such as those selected from:

Cpd
Data

426
LC-MS: 427 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.22-9.38 (m, 1H),

8.33-8.45 (m, 1H), 8.21 (d, J = 1.9 Hz, 2H), 7.97 (dd, J = 10.4, 2.8 Hz, 1H), 7.86 (d, J = 5.7 Hz,

1H), 7.81 (dd, J = 11.7, 6.6 Hz, 1H), 7.54-7.63 (m, 1H), 5.09-5.16 (m, 1H),

3.03 (s, 3H), 2.09 (t, J = 12.9 Hz, 2H), 1.78 (dd, J = 12.9, 3.8 Hz, 2H), 1.55 (s, 6H), 1.51 (s,

6H)

431
LC-MS: 414 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.24-9.35 (m, 1H),

8.43-8.58 (m, 1H), 8.22 (d, J = 1.6 Hz, 2H), 8.06 (dd, J = 9.1, 1.9 Hz, 1H), 7.87 (dd, J = 12.1,

6.5 Hz, 1H), 7.83 (dd, J = 11.5, 6.5 Hz, 1H), 7.37 (d, J = 9.5 Hz, 1H), 5.77 (tt, J = 10.7,

4.1 Hz, 1H), 2.33 (dd, J = 13.1, 3.9 Hz, 2H), 1.84 (dd, J = 12.9, 11.3 Hz, 2H), 1.54 (s,

6H), 1.52 (s, 6H)

435
LC-MS: 378 [M + H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: 8.57-8.58 (m, 1H),

8.55 (d, J = 5.0 Hz, 1H), 8.45 (s, 2H), 8.05-8.10 (m, 1H), 7.95-7.99 (m, 1H), 7.86 (s, 1H),

7.82 (d, J = 9.5 Hz, 1H), 5.79 (tt, J = 10.4, 4.4 Hz, 1H), 2.53 (dd, J = 14.5, 4.5 Hz, 2H),

1.86-2.01 (m, 2H), 1.66 (s, 6H), 1.60 (s, 6H), (2 hydrogens corresponding to NH

unobserved)

437
LC-MS: 396 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.28-9.44 (m, 1H),

8.47-8.61 (m, 1H), 8.25 (s, 2H), 8.01 (dd, J = 9.3, 2.0 Hz, 1H), 7.92 (t, J = 8.2 Hz, 1H),

7.69 (dd, J = 12.8, 1.7 Hz, 1H), 7.65 (dd, J = 8.0, 1.7 Hz, 1H), 7.34 (d, J = 9.1 Hz, 1H),

5.76 (tt, J = 10.7, 4.1 Hz, 1H), 2.33 (dd, J = 13.2, 3.9 Hz, 2H), 1.85 (dd, J = 13.2, 10.1 Hz,

2H), 1.54 (s, 6H), 1.53 (s, 6H)

440
LC-MS: 359 [M + H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: .06 (d, J = 10.1 Hz, 1H),

7.78 (dd, J = 9.5, 6.3 Hz, 1H), 7.32 (d, J = 9.8 Hz, 1H), 6.58-6.76 (m, 2H), 5.11 (tt,

J = 12.0, 4.1 Hz, 1H), 3.02 (s, 3H), 1.73 (dd, J = 12.9, 3.5 Hz, 2H), 1.63 (t, J = 12.5 Hz,

2H), 1.43 (s, 6H), 1.27 (s, 6H), (1 hydrogen corresponding to NH unobserved)

441
LC-MS: 364 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 1.33 (d, J = 6.62 Hz, 6H)

1.65 (q, J = 12.40 Hz, 2H) 2.42 (d, J = 12.61 Hz, 2H) 3.38-3.50 (m, 2H) 5.48 (s, 1H)

6.51-6.63 (m, 1H) 7.42-7.57 (m, 3H) 7.80 (d, J = 1.58 Hz, 1H) 8.09 (d, J = 8.83 Hz,

1H) 8.50 (d, J = 9.46 Hz, 1H) 8.61 (d, J = 2.52 Hz, 1H) 8.76 (br s., 1H) 9.12 (br s., 1H)

13.18 (s, 1H)

442
LC-MS: 379 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 8.42 (s, 1H), 8.28 (dd,

J = 1.6, 0.9 Hz, 1H), 8.03 (dd, J = 9.1, 1.6 Hz, 1H), 7.95 (s, 1H), 7.67 (d, J = 9.1 Hz,

1H), 7.14 (d, J = 9.1 Hz, 1H), 5.03-5.17 (m, 1H), 4.19 (s, 3H), 2.94 (s, 3H),

1.49-1.58 (m, 2H), 1.37-1.48 (m, 2H), 1.27 (s, 6H), 1.10 (s, 6H), (1 hydrogen corresponding to

NH unobserved)

443
LC-MS: 366 [M + H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: 8.35 (s, 1H), 8.31 (dd,

J = 1.6, 0.9 Hz, 1H), 8.11 (d, J = 9.1 Hz, 1H), 7.99 (dd, J = 9.1, 1.9 Hz, 1H), 7.75 (dt,

J = 9.1, 0.9 Hz, 1H), 7.21 (d, J = 9.5 Hz, 1H), 5.81 (tt, J = 11.2, 4.1 Hz, 1H), 4.27 (s,

3H), 2.28 (dd, J = 12.6, 4.1 Hz, 2H), 1.48 (t, J = 12.3 Hz, 2H), 1.41 (s, 6H), 1.30 (s,

6H), (1 hydrogen corresponding to NH unobserved)

445
LC-MS: 379 [M + H]⁺. ¹H NMR (500 MHz, acetone-d₆) δ: 8.52 (dt, J = 7.0, 1.1 Hz,

1H), 8.13 (dt, J = 8.8, 1.3 Hz, 1H), 7.66 (d, J = 9.8 Hz, 1H), 7.28 (ddd, J = 9.0, 6.8, 1.3 Hz,

1H), 7.13 (d, J = 9.5 Hz, 1H), 6.89 (td, J = 6.9, 1.4 Hz, 1H), 5.22 (tt, J = 12.3, 3.5 Hz,

1H), 3.04 (s, 3H), 2.63 (s, 3H), 1.67 (dd, J = 12.3, 3.5 Hz, 2H), 1.56 (t, J = 12.3 Hz,

2H), 1.36 (s, 6H), 1.18 (s, 6H), (1 hydrogen corresponding to NH unobserved)

446
LC-MS: 352 [M + H]⁺. ¹H NMR (500 MHz, acetone-d₆) δ: 9.14 (dd, J = 1.6, 0.9 Hz,

1H), 7.98 (dd, J = 9.5, 1.9 Hz, 1H), 7.94 (t, J = 0.9 Hz, 1H), 7.89 (d, J = 9.5 Hz, 1H),

7.63 (dt, J = 9.5, 0.8 Hz, 1H), 7.60 (d, J = 1.3 Hz, 1H), 7.14 (d, J = 9.5 Hz, 1H), 5.34 (tt,

J = 12.6, 3.5 Hz, 1H), 1.67 (dd, J = 12.3, 3.8 Hz, 2H), 1.55 (t, J = 12.1 Hz, 2H), 1.36 (s,

6H), 1.17 (s, 6H), (1 hydrogen corresponding to NH unobserved)

447
LC-MS: 394 [M + H]⁺. ¹H NMR (500 MHz, acetone-d₆) δ: 8.47 (d, J = 2.5 Hz, 1H),

8.05 (d, J = 9.1 Hz, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.76 (d, J = 1.9 Hz, 1H), 7.70 (d,

J = 2.2 Hz, 1H), 7.59 (dd, J = 8.5, 2.2 Hz, 1H), 7.06 (d, J = 9.1 Hz, 1H), 6.57 (dd,

J = 2.4, 1.7 Hz, 1H), 5.85 (tt, J = 11.3, 4.1 Hz, 1H), 2.21 (dd, J = 12.1, 3.9 Hz, 2H),

2.04-2.08 (m, 2H), 1.35 (s, 6H), 1.18 (s, 6H), (2 hydrogens corresponding to OH

and NH unobserved)

452
LC-MS: 409 [M + H]⁺. ¹H NMR (500 MHz, acetone-d₆) δ: 7.59 (dd, J = 8.5, 6.0 Hz,

1H), 7.46 (s, 2H), 7.31 (dd, J = 10.1, 2.5 Hz, 1H), 7.15 (td, J = 8.5, 2.5 Hz, 1H),

7.04 (d, J = 9.5 Hz, 1H), 6.91 (d, J = 9.5 Hz, 1H), 5.23 (tt, J = 12.3, 2.8 Hz, 1H), 3.00 (s,

3H), 1.65 (dd, J = 12.3, 3.5 Hz, 2H), 1.51 (t, J = 12.1 Hz, 2H), 1.33 (s, 6H), 1.15 (s,

6H), (2 hydrogens corresponding to NH unobserved)

455
LC-MS: 344 [M + H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: 8.17 (d, J = 9.5 Hz, 1H),

7.66 (d, J = 8.8 Hz, 1H), 7.19 (d, J = 9.5 Hz, 1H), 6.44 (dd, J = 8.7, 2.4 Hz, 1H),

6.41 (d, J = 2.5 Hz, 1H), 5.71 (tt, J = 11.0, 3.8 Hz, 1H), 2.23 (dd, J = 12.6, 4.1 Hz, 2H),

1.40-1.47 (m, 2H), 1.39 (s, 6H), 1.27 (s, 6H), (3 hydrogens corresponding to OH and NH

unobserved)

456
LC-MS: 425 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 9.23-9.39 (m, 1H),

8.39-8.52 (m, 1H), 8.26 (s, 2H), 8.00-8.08 (m, 1H), 7.93 (s, 1H), 7.81-7.85 (m, 1H),

7.78 (d, J = 7.9 Hz, 1H), 7.63 (d, J = 8.2 Hz, 1H), 4.95-5.03 (m, 1H), 3.08 (s, 3H), 2.13 (t,

J = 12.9 Hz, 2H), 1.81 (dd, J = 12.9, 3.5 Hz, 2H), 1.56 (s, 6H), 1.52 (s, 6H)

458
LC-MS: 414 [M + H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 8.70-9.36 (m, 1H), 8.29 (s,

2H), 7.85 (d, J = 9.1 Hz, 1H), 7.60 (d, J = 9.5 Hz, 1H), 7.33-7.39 (m, 1H),

5.59-5.68 (m, 1H), 2.24-2.33 (m, 2H), 1.72-1.82 (m, 2H), 1.50 (s, 6H), 1.48 (s, 6H), (2

hydrogens corresponding to NH unobserved)

Example 7 (Compound 434)
6-[2-Methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride

6-(2-Methoxy-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (6 mg) was dissolved in 1 mL of 4N HCl/dioxane and the resulting mixture was stirred at RT for 20 minutes. The mixture was evaporated and triturated with ether to provide 6-(2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine 4 mg, 75%).

LC-MS: 422 [M+H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: 8.42-8.47 (m, 1H), 8.33-8.42 (m, 2H), 8.09-8.17 (m, 1H), 7.99-8.08 (m, 1H), 7.50-7.56 (m, 1H), 5.0 (m, 1H), 4.16 (s, 3H), 3.20 (s, 3H), 1.94-2.15 (m, 4H), 1.65 (s, 6H), 1.57 (s, 6H)

Example 8 (Compound 460)
3-{6-[Methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-yl)pyridin-2-ol hydrochloride
Step 1:

6-Chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (280 mg, 1.0 mmol) was dissolved in 10 mL, a mixture of dioxane and water (4:1). To the solution was added sodium carbonate (190 mg, 3 eq), (6-chloro-2-methoxypyridin-3-yl)boronic acid (190 mg, 1 eq) and Pd(Ph₃P)₄(70 mg, 0.1 eq). The reaction mixture was stirred at 90° C. for 16 h, then applied to a column and purified using DCM/MeOH to yield (133 mg, 55%) 6-(6-chloro-2-methoxypyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine.

LC-MS: 390 [M+H]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 8.25 (d, J=7.88 Hz, 1H), 7.83 (d, J=9.77 Hz, 1H), 7.24 (d, J=7.88 Hz, 1H), 7.11 (d, J=9.77 Hz, 1H), 5.00-5.24 (m, 1H), 3.93 (s, 3H), 2.87-2.96 (m, 3H), 1.40-1.57 (m, 4H), 1.21-1.29 (m, 7H), 1.10 (br s, 6H

Step 2:

6-(6-Chloro-2-methoxypyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (90 mg) was dissolved in a mixture of dioxane and water (4:1, 5 mL). To the solution was added sodium carbonate (100 mg, 3 eq), 1-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (70 mg, 1.1 eq) and Pd(Ph₃P)₄(27 mg, 0.1 eq). The reaction mixture was stirred at 90° C. for 16 h, then purified by column chromatography using DCM/MeOH to yield 80 mg (68%) of 6-(2-methoxy-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine.

Step 3:

6-(2-Methoxy-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (45 mg) was dissolved in 4 mL of 4N HCl/dioxane and the resulting mixture was heated for 2 hours at 60° C.F. The resulting mixture was evaporated and triturated with ether to provide 3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-6-(1H-pyrazol-4-yl)pyridin-2-ol (24 mg, 61%).

LC-MS: 408 [M+H]⁺; ¹H NMR (500 MHz, methanol-d₄) δ: 8.62-8.69 (m, 1H), 8.55-8.61 (m, 1H), 8.39 (s, 2H), 7.95-8.06 (m, 1H), 7.04-7.14 (m, 1H), 5.02-5.24 (m, 1H), 3.18 (s, 3H), 2.03 (s, 4H), 1.67 (s, 6H), 1.57 (s, 6H)

Using the procedure described for Example 8 above, an additional compound described herein may be prepared by substituting the appropriate starting materials reagents, and reaction conditions, obtaining compounds such as those selected from:

Cpd
Data

461
LC-MS: 395 [M + H]⁺. ¹H NMR (500 MHz, methanol-d₄) δ: 8.46

(d, J = 9.5 Hz, 1H), 8.33-8.42 (m, 1H), 8.29 (d, J = 7.6 Hz, 1H),

8.10-8.23 (m, 1H), 7.20 (d, J = 9.1 Hz, 1H), 6.86 (d, J = 7.3 Hz,

1H), 5.84 (tt, J = 10.4, 3.8 Hz, 1H), 2.49 (dd, J = 13.9, 4.1 Hz,

2H), 1.86 (dd, J = 13.9, 10.4 Hz, 2H), 1.65 (s, 6H), 1.56 (s, 6H),

(3 hydrogens corresponding to OH and NH unobserved)

BIOLOGICAL EXAMPLES

The following in vitro biological examples demonstrate the usefulness of the compounds of the present description for treating Huntington's disease.

To describe in more detail and assist in understanding the present description, the following non-limiting biological examples are offered to more fully illustrate the scope of the description and are not to be construed as specifically limiting the scope thereof. Such variations of the present description that may be now known or later developed, which would be within the purview of one skilled in the art to ascertain, are considered to fall within the scope of the present description and as hereinafter claimed.

Example 1
Development and Validation of Meso Scale Discovery (MSD) Assay to Quantify Mutant and Total Huntingtin Protein (HTT)—Best Pair Analysis for Endogenous HTT Detection

To identify orally bioavailable small molecules useful for HTT reduction, high throughput ELISA methods to detect and measure both total HTT (wild-type and mutant)(tHTT) and mutant HTT (mHTT) in cells and tissues from HD patients and animal models are needed. The method described herein permits relatively high throughput protein measurement of tHTT and mHTT levels in cells and tissues from HD patients and in HD animal models. The ELISA method described herein enables screening of molecules for their ability to decrease the level of HTT and to identify and optimize small molecules for use in treating HD.

To determine the combination of antibodies that detect HTT (wild type and mutant) in a sensitive, high throughput format, multiple commercially available antibodies (Table 1) were screened in capture/detection combinations.

Protocol for Best Pair Analysis for Antibody Comparison in Detecting Total and Mutant HTT in Cells

1. Cells were cultured in a cell culture-compatible 96-well plate.

2. The medium was removed and 50-100 μL of lysis buffer per well (composition described below) was added to cells to provide a “cell lysate”. The plate was placed on a shaker at 4° C. for 30 minutes, then stored at −20° C.

3. A Capture Antibody Diluent was prepared by diluting the capture antibody in PBS for standard plates as described in the plate layout, then 30 μL of the Capture Antibody Diluent was added per well. The plate was sealed and incubated at 4° C. overnight.

4. The plate was washed 3× with 200 μL of Wash Buffer. Blocking Buffer (150 μL per well) was added, then the plate was sealed and incubated on a plate shaker for 3-4 hours at room temperature (RT).

5. The Blocking Buffer was decanted and the plate was washed 3× with 200 μL of Wash Buffer. The cell lysate (25 μL per well) was then added. The plate was sealed and incubated at 4° C. overnight.

6. A First Detection Antibody Diluent was prepared by diluting a first detection antibody for pairing in an Assay Antibody Diluent. The plate was washed 3× with 200 μL of Wash Buffer, then 25 μL of the First Detection Antibody Diluent was added per well. The plate was sealed and incubated on a plate shaker for 1 hour at RT.

7. A Second Detection Antibody Diluent was prepared by diluting a second detection antibody for pairing in an Assay Antibody Diluent. The plate was washed 3× with 200 μL of Wash Buffer, then 25 μL of the Second Detection Antibody Diluent was added per well. The plate was sealed and incubated on a plate shaker for 1 hour at RT.

8. The Read Buffer was diluted 4×. The plate was washed 3× with 200 μL of Wash Buffer, then 150 μL of the Read Buffer was added per well. The plate were read immediately following.

The various commercially available antibodies screened in the Best Pair Analysis, providing different capture/detection combinations are shown in Table 1. The capture/detection antibody pairs evaluated are shown in Table 2. The two antibody pairs that gave the maximum spread of values (higher signal to noise ratio) were selected for polyglutamine-expanded (mHTT) and total human HTT detection.

TABLE 1

Species
ID
Antibody Epitope

monoclonal
MAB2166
Huntingtin fragment from aa 181-810 as a fusion protein

mouse

monoclonal rat
MAB2174
Huntingtin fusion protein 549-679, fused to Glutathione S-

tranferase

monoclonal
MAB5374
GST fusion protein from the first 256 amino acids from human

mouse

huntingtin with the deletion of the polyglutamine tract

goat polyclonal
sc-8767
Peptide mapping near the N-terminus of Huntingtin of human

origin (N18)

monoclonal
P1874
GST human Huntingtin (N-terminal fragment of 171 amino

mouse

acids containing 65Q)

monoclonal
MAB1574
Homopolymeric glutamine stretch

mouse

monoclonal
#5656S
Synthetic peptide corresponding to residues surrounding

rabbit

Pro1220 of human huntingtin protein

monoclonal
MW1
DRPLA-19Q

mouse

TABLE 2

Signal to

Pair
HTT MSD
ID
Noise ratio

Capture/Detection
Total
MAB2166/MAB2174
95

Capture/Detection
Total
MAB2166/sc-8767
6

Capture/Detection
Total
sc-8767/#5656
5

Capture/Detection
Total
MAB2166/#5656S
483

Capture/Detection
Mutant
MAB5374/#5656S
8

Capture/Detection
Mutant
MAB1574/#5656S
25

Capture/Detection
Mutant
P1874/#5656S
20

Capture/Detection
Mutant
MW1/#5656S
45

Characteristics for Best Pair capture/detection antibody pairs are those combinations that give minimum background and maximum signal. Such highly sensitive ELISA assays would be useful to detect HTT in the context of drug discovery for screening agents (small and large molecules and gene therapies) and for use in detecting HTT as a biomarker in clinical studies. Such capture/detection antibody pairs for quantifying total HTT are selected from MAB2166/MAB2174 and MAB2166/#5656S. Such capture/detection antibody pairs for quantifying mutant HTT are selected from MAB1574/#5656S, P1874/#5656S and MW1/#5656S. The antibody pair for mHTT (MW1/#5656S) and the other for total HTT (MAB2166/#5656S) from this analysis were further optimized and validated to provide high-throughput assays that enabled HTT detection in patient fibroblasts and lymphocytes.

The Endogenous Huntingtin Protein assay used in Example 2 was developed using the Best Pair antibodies identified in Table 2, providing highly sensitive, high-throughput detection assays for polyglutamine-expanded (mHTT) and total human HTT in multiple cell systems. The platform used for the assay is the ELISA-based Meso Scale Discovery (MSD) electrochemiluminescence assay platform.

Example 2
Endogenous Huntingtin Protein Assay

Meso Scale Discovery (MSD) 96-well or 384-well plates were coated overnight at 4° C. with MW1 (expanded polyglutamine) or MAB2166 monoclonal antibody (for capture) at a concentration of 1 μg/mL in PBS (30 μL per well). Plates were then washed three times with 300 μL wash buffer (0.05% Tween-20 in PBS) and blocked (100 μL blocking buffer; 5% BSA in PBS) for 4-5 hours at room temperature with rotational shaking and then washed three times with wash buffer.

Samples (25 μL) were transferred to the antibody-coated MSD plate and incubated overnight at 4° C. After removal of the lysates, the plate was washed three times with wash buffer, and 25 μL of #5656S (Cell signaling; rabbit monoclonal) secondary antibody (diluted to 0.25 μg/mL in 0.05% Tween-20 in blocking buffer) was added to each well and incubated with shaking for 1 Hour at room temperature. Following incubation with the secondary antibody, the wells were rinsed with wash buffer after which 25 μL of goat anti-rabbit SULFO TAG secondary detection antibody (required aspect of the MSD system) (diluted to 0.25 μg/mL in 0.05% Tween-20 in blocking buffer) was added to each well and incubated with shaking for 1 hour at room temperature. After rinsing three times with wash buffer, 150 μL of read buffer T with surfactant (MSD) were added to each empty well, and the plate was imaged on a SI 6000 imager (MSD) according to manufacturers' instructions provided for 96- or 384-well plates. The resulting IC₅₀values (μM) for compounds tested are shown in Table 3.

As shown in Table 3, test compounds described herein had the following IC₅₀values, an IC₅₀value between >3 μM and ≤9 μM is indicated by a single star (*), an IC₅₀value between >1 μM and ≤3 μM is indicated by two stars (**), an IC₅₀value between >0.5 μM and ≤1 μM is indicated by three stars (***), an IC₅₀value between >0.1 μM and ≤0.5 μM is indicated by four stars (****) and an IC₅₀value of ≤0.1 μM is indicated by five stars (*****).

TABLE 3

Cpd
IC₅₀

16
*

26
****

31
****

460
*

39
*

44
*****

46
*****

47
****

48
*****

51
*****

63
*****

64
*****

170
*****

176
*****

200
*****

207
****

212
*****

218
*****

258
****

307
****

315
*****

318
*****

348
*****

350
*****

352
****

393
*****

411
*****

412
*****

413
*****

414
*****

415
*****

416
*****

417
*****

418
*****

419
*****

420
*****

421
*****

422
*****

423
*****

424
****

425
****

426
****

427
****

428
****

429
****

430
****

431
****

432
****

433
****

434
***

435
***

436
***

437
**

438
**

439
**

440
*

441
*

442
*

443
*

444
*

445
*

446
*

447
*

448
*

449
*

450
*

451
*

451
*

452
*

454
*

455
*

456
*

456
*

456
*

457
*

458
*

459
*

460
*

461
*

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Without regard to whether a document cited herein was specifically and individually indicated as being incorporated by reference, all documents referred to herein are incorporated by reference into the present application for any and all purposes to the same extent as if each individual reference was fully set forth herein.

Having now fully described the subject matter of the claims, it will be understood by those having ordinary skill in the art that the same can be performed within a wide range of equivalents without affecting the scope of the subject matter or embodiments described herein. It is intended that the appended claims be interpreted to include all such equivalents.

Claims

1. A method of use of a compound for treating or ameliorating HD in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula (I):
2. The method of claim 1, wherein the compound of Formula (I) is selected from a compound of Formula (Ia) and Formula (Ib):
3. The method of claim 1, wherein: X is O, NH, N(CH3) or a bond;A is aryl, heteroaryl or heterocyclyl,wherein, aryl is selected from the group consisting of:
4. A compound selected from a compound of Formula (Ia11), Formula (Ia15), Formula (Ia18) or Formula (Ib1):
5. The compound of claim 4 wherein (when present): R1a is selected from fluoro, chloro, hydroxyl, methyl, difluoromethyl, amino, methoxy or 1H-pyrazolyl or 1H-imidazol-1-yl,wherein 1H-pyrazolyl is optionally substituted with 1 or 2 substituents each selected from R3a;R3a is selected from nitro or methyl or amino; and,R4a is methyl or ethyl;R5a is hydrogen or methyl;wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.
6. The method of claim 1, wherein the compound is selected from the group consisting of: 6-(naphthalen-2-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine6-(benzo[b]thiophen-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2-(6-(2,2,6,6-tetramethylpiperidin-4-yl-amino)-pyridazin-3-yl)phenol2-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzo[b]-thiophene-5-carbonitrile6-(quinolin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine3-(benzo[b]-thiophen-2-yl)-6-(2,2,6,6-tetramethylpiperidin-4-yl-oxy)pyridazine2-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)-pyridazin-3-yl)phenol6-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)-pyridazin-3-yl)naphthalen-2-ol6-(benzo[b]-thiophen-2-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinoline6-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinolineN-methyl-6-(quinolin-7-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amineN-methyl-6-(quinolin-6-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine6-(isoquinolin-7-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine6-(isoquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine6-(imidazo[1,2-a]pyridin-6-yl-pyridazin-3-yl)-methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amineN-methyl-6-(6-phenylpyridin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine6-(6-(1H-pyrrol-1-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine6-(6-(1H-pyrazol-1-yl)pyridin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-aminemethyl-(6-quinoxalin-2-yl-pyridazin-3-yl)-(2,2,6,6-tetramethylpiperidin-4-yl)-aminemethyl-(6-quinolin-3-yl-pyridazin-3-yl)-(2,2,6,6-tetramethylpiperidin-4-yl)-amineN-methyl-6-(phthalazin-6-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine6-(benzo[c][1,2,5]oxa-diazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine6-(benzo[d]thiazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine6-(2-methylbenzo-[d]oxazol-6-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol5-chloro-2-(6-(methyl(1,2,2,6,6-pentamethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol3-(6-(2,2,6,6-tetramethylpiperidin-4-yl-amino)pyridazin-3-yl)naphthalen-2-ol5-chloro-2-(6-(1,2,2,6,6-pentamethylpiperidin-4-ylamino)pyridazin-3-yl)phenol4-hydroxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzonitrile3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)naphthalen-2-ol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(trifluoromethyl)phenol2-fluoro-6-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)phenol3,5-dimethoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol4,5-dimethoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol4,5-difluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzonitrile1-allyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol6-(benzo[b]thiophen-2-yl)-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyridazin-3-amineN-allyl-3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzamide2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol5-(5-methyl-oxazol-2-yl)-2-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)phenol5-(4-hydroxymethyl)-1H-pyrazole-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-(1H-imidazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-(4-amino-1H-pyrazole-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol5-(3-amino-1H-pyrazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-(2-morpholino-ethyl)-1H-pyrazol-4-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol5-(5-amino-1H-pyrazol-1-yl)-2-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-1-yl)phenol2-((6-((2-hydroxy-ethyl)-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)-5-pyrazol-1-yl)phenol2-(6-(piperidin-4-yloxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(((2S,4R,6R)-2,6-dimethylpiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-((-2,6-dimethylpiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol5-(1H-pyrazol-1-yl)-2-(6-(pyrrolidin-3-yl-oxy)pyridazin-3-yl)phenol2-(6-(((2S,4S)-2-methylpiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol(5-(1H-pyrazol-1-yl)-2-(6-(pyrrolidin-3-ylmethoxy)pyridazin-3-yl)phenol2-(6-((3-fluoropiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(1,2,2,6,6-pentamethyl-piperidin-4-yl-oxy)-pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol5-1H-pyrazol-1-yl-2-(6-(2,2,6,6-tetramethylpiperidin-4-yl-oxy)-pyridazin-3-yl)phenol5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenol2-(6-piperazin-1-yl-pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol3-(6-(azetidin-3-ylamino)-pyridazin-3-yl)naphthalen-2-ol2-(6-(azetidin-3-ylamino)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(3,5-dimethylpiperazin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(7-methyl-2,7-diazaspiro[4.4]nonan-2-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(1,4-diazepan-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(3,6-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(2,7-diazaspiro[3.5]nonan-7-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(3-(hydroxymethyl)piperazin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(1,7-diazaspiro[4.4]nonan-7-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(4-amino-4-methylpiperidin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(3-(dimethylamino)piperidin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(1,2,2,6,6-pentamethylpiperidin-4-ylamino)-pyridazin-3-yl)-5-1H-pyrazol-1-yl-phenol2-(6-(3,3-dimethylpiperazin-1-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(7-(2-hydroxyethyl)-2,7-diazaspiro[4.4]-nonan-2-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-((3 aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol3-(6-(piperazin-1-yl)pyridazin-3-yl)naphthalene-2,7-diol5-(1H-pyrazol-1-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol2-(6-piperidin-4-yl-pyridazin-3-yl)-5-1H-pyrazol-1-yl-phenol3-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalen-2-ol3-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol3-(6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol3-(6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol3-(6-(piperidin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)naphthalene-2,7-diol3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalene-2,7-diol3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalene-2,7-dioltert-butyl (3-((7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-yl)oxy)propyl)carbamate7-(3-amino-propoxy)-3-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)naphthalen-2-olN-(3-((7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-yl)oxy)propyl)acetamide7-(3-hydroxypropoxy)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol7-(3-methoxypropoxy)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol7-(2-morpholinoethoxy)-3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)naphthalen-2-ol3-(6-(piperidin-4-ylmethyl)pyridazin-3-yl)naphthalen-2-ol5-(1H-pyrazol-1-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyridazin-3-yl)phenol3-methoxy-2-(6-(methyl(2,2,6-trimethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol2-(6-((6S)-6-((S)-1-hydroxyethyl)-2,2-dimethylpiperidin-4-yloxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2-naphthonitrile3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-7-(piperidinylmethyl)naphthalen-2-ol3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-7-(pyrrolidinylmethyl)naphthalen-2-ol1-bromo-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalene-2,7-diol1-chloro-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalene-2,7-diol7-methoxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalene-2-ol7-methoxy-3-(6-(methyl(1,2,2,6,6-pentamethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol7-(3,6-dihydro-2H-pyran-4-yl)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-7-(tetrahydro-2H-pyran-4-yl)naphthalene-2-ol7-(difluoromethyl)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol7-((4-hydroxy-2-methylbutan-2-yl)oxy)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol7-(3-hydroxy-3-methylbutoxy)-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-ol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)benzene-1,3-diol3-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3-(trifluoromethoxy)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-pyrazol-4-yl)-3-(trifluoromethoxy)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)-3-(trifluoromethoxy)phenol4-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(trifluoromethoxy)phenyl)-1-methylpyridin-2(1H)-one3-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol3-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-3-yl)phenol3-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(pyridine-3-yl)phenol5-(1-cyclopentyl-1H-pyrazol-4-yl)-3-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol3′,5-dimethoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-(1,1′-biphenyl)-3-ol3-(benzyloxy)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol3-ethoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol3-(cyclopropylmethoxy)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-pyridazin-3-yl)-5-(5-methyloxazol-2-yl)phenol2-methyl-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-1H-benzo[d]imidazol-6-ol5-chloro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-(1H-pyrazol-1-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol3-hydroxy-4-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzonitrile2-(6-((2,2-dimethylpiperidin-4-yl)oxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-4-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridin-3-yl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)phenol4-(1H-indol-2-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol4-(cyclopent-1-en-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-3-yl)phenol4-(4-hydroxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-2-ol4-(4-hydroxy-3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one4-(4-hydroxy-3-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenyl)pyridin-2-ol5-(1H-indazol-7-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol4-chloro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol4-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol5-fluoro-4-(1H-imidazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-4-yl)phenol5-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-5-yl)phenol6-hydroxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-dihydro-1H-inden-1-one6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-1,4-dihydroindeno[1,2-c]-1H-pyrazol-7-ol6-hydroxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-dihydro-1H-inden-1-one oxime5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-dihydro-1H-indene-1,6-diol2-amino-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-8H-indeno[1,2-d]thiazol-5-ol9-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5,6-dihydroimidazo[5,1-a]isoquinolin-8-ol4-hydroxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-N-((1-methyl-1H-pyrazol-4-yl)methyl)benzamide4-(4-(hydroxymethyl)-1H-pyrazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyridazin-3-yl)phenol6-(3-(benzyloxy)isoquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine6-(1-(benzyloxy)isoquinolin-7-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine3-fluoro-5-(2-methoxypyridin-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol4-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-2(1H)-one4-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one5-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one3-fluoro-5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenol5-chloro-3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol5-(5-methoxypyridin-3-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-(3-hydroxy-4-(6-methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-2-ol4-(3-hydroxy-4-(6-methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-2-ol5-(6-methoxypyridin-3-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-3-(trifluoromethyl)pyridin-2-ol5-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one4-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one5-(2-methoxypyridin-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol4-(3-hydroxy-4-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenyl)pyridin-2-ol5-(6-(dimethylamino)pyridin-3-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol4-(3-hydroxy-4-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(pyrimidin-5-yl)phenol5-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-3-ol1-cyclopropyl-4-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-2(1H)-one2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)phenol5-(cyclopent-1-en-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-(3,6-dihydro-2H-pyran-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-(imidazo[1,5-a]pyridin-7-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-(imidazo[1,2-a]pyridin-7-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(2-methylpyridin-4-yl)phenol5-(1H-imidazol-2-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-(1H-imidazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol5-(imidazo[1,2-a]pyrazin-3-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(4-methyl-1H-imidazol-2-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-imidazol-4-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-imidazol-5-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(4-nitro-1H-imidazol-2-yl)phenol2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(2-methyl-1H-imidazol-4-yl)phenol5-(1,2-dimethyl-1H-imidazol-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol1-(3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1H-pyrazole-4-carboxamide2-(6-((3aR,6aS)-5-(2-hydroxyethyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol2-(6-((3 aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol2-(6-((3 aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol4-(3-hydroxy-4-(6-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one4-(3-hydroxy-4-(6-((3aR,6aR)-1-methylhexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one2-(6-(2,7-diazaspiro[4.5]decan-2-yl)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol4-(4-(6-(2,7-diazaspiro[4.5]decan-2-yl)pyridazin-3-yl)-3-hydroxyphenyl)-1-methylpyridin-2(1H)-one2-(6-(methyl-(2,2,6,6-tetramethylpiperidin-4-yl)-amino)-pyridazin-3-yl)phenol6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol6-(6-(methyl(1,2,2,6,6-pentamethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol6-(6-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)quinolin-7-ol2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol7-(6-(methyl(1,2,2,6,6-pentamethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinoline-6-ol7-(6-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)isoquinolin-6-ol1-cyclopropyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinoline-1,6-diol6-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinoline-1-carbonitrile6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-7-ol8-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol2-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol3-chloro-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol3-bromo-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-3-carbonitrile6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3-(1-methyl-1H-imidazol-4-yl)quinolin-7-ol3-(1H-imidazol-1-yl)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-3,7-diol3-ethyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol3-isopropyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-2(1H)-one7-hydroxy-1-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-2(1H)-one4-methoxy-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(pyrrolidin-1-yl)quinolin-7-ol2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-morpholinoquinolin-7-ol4-(dimethylamino)-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol4-ethoxy-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1-methyl-1H-pyrazol-4-yl)quinolin-7-ol4-methoxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoxalin-6-ol6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3-(tetrahydro-2H-pyran-4-yl)quinolin-7-ol3-chloro-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol3-bromo-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol3-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol5-bromo-3-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol6-hydroxy-1-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-4(1H)-one2,3-dimethyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol2-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoxalin-6-ol3-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoxalin-6-ol4-methoxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol4-(azetidin-1-yl)-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol7-hydroxy-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolone-4-carbonitrile4-cyclopropyl-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-quinolin-7-ol4-(3,6-dihydro-2H-pyran-4-yl)-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(tetrahydro-2H-pyran-4-yl)quinolin-7-ol2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(oxetan-3-yl)quinolin-7-ol4-(dimethylamino)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-quinolin-7-ol7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinazolin-4(1H)-one6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinazolin-7-ol7-hydroxy-1-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3,4-dihydroquinolin-2(1H)-one2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinazolin-7-ol7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinoline-1-carbonitrile7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-2-carbonitrile6-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-2-carbonitrile6-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinoline-1-carboxamide7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-2-carboxamide6-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-2-carboxamidemethyl 6-hydroxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-2-carboxylate6-hydroxy-7-(6-(piperazin-1-yl)pyridazin-3-yl)quinoline-2-carbonitrile7-hydroxy-6-(6-(piperazin-1-yl)pyridazin-3-yl)quinoline-2-carbonitrile7-(6-(piperazin-1-yl)pyridazin-3-yl)isoquinolin-6-ol7-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)quinolin-6-ol1-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-7-ol1-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol1,3-dimethyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol7-hydroxy-3-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinoline-1-carbonitrile1-amino-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol7-hydroxy-1,3-dimethyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinazoline-2,4(1H,3H)-dione6-hydroxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)benzo[d]oxazol-2(3H)-one2-methyl-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2H-indazol-6-ol1-methyl-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-1H-indazol-6-ol6-hydroxy-2-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-1(2H)-one2-ethyl-6-hydroxy-7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinolin-1(2H)-one1-ethoxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)isoquinoline-1,6-diol7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-pyridazin-3-yl)-3-phenylisoquinolin-6-ol3-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol3-cyclopropyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol3-isopropyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-6-ol3-propyl-7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)-pyridazin-3-yl)isoquinolin-6-ol3-isopropyl-7-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)-pyridazin-3-yl)isoquinolin-6-ol3-methyl-7-(6-(piperazin-1-yl)pyridazin-3-yl)isoquinolin-6-ol6-(3-(benzyloxy)isoquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine3-chloro-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol3-isopropyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol3-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoxalin-6-ol4-chloro-2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol4-chloro-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol5-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine6-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)naphthalen-2-ol5-(2-methoxyquinolin-3-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(3-methoxy-naphthalen-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-methoxy-4-(1H-pyrazol-1yl)phenyl)-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine4-(3-methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)-1-methylpyridin-2(1H)-one5-(3-methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)pyridin-2-ol5-(3-methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)-1-methylpyridin-2(1H)-oneN-methyl-5-(2-methyl-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine1-methyl-4-(4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-3-(trifluoromethoxy)phenyl)pyridin-2(1H)-one5-(4-(3,5-dimethyl-1H-pyrazol-4-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4,-thiadiozol-2-yl-5-(1-methyl-1H-pyrazol-4-yl)phenol2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4,-thiadiozol-2-yl-5-(1H-pyrazol-1-yl)phenol5-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)-1-methylpyridin-2(1H)-one4-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)-1-methylpyridin-2(1H)-one5-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)pyridin-2-ol3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)naphthalene-2,7-diol3-(5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazol-2-yl)naphthalene-2,7-diol3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)naphthalen-2-ol3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-2-ol2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-4-(1H-pyrazol-1-yl)phenol5-(2-chloro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine3-chloro-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol5-(2-chloro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine3-methoxy-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-methyloxazol-2-yl)phenol2-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1,3,4-thiadiazole2-(5-(piperazin-1-yl)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-1-yl)phenol5-(7-methoxyquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazole-2-amine6-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-7-ol3-methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)benzonitrile3-fluoro-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)benzonitrilemethyl-3-fluoro-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)benzoate5-(2-methoxy-4-(3-(methylamino)-1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine7-methoxy-6-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinoline-2-carbonitrile4-(3-methoxy-4-(5-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)-1,3,4-thiadiazol-2-yl)phenyl)-1-methylpyridin-2(1H)-one4-(3-chloro-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)-1-methylpyridin-2(1H)-one5-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-chloro-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amineN-methyl-5-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine2-(2-chloro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-((2,2,6,6-tetramethylpiperidin-4-yl)oxy-1,3,4-thiadiazole5-(2-chloro-4-(6-methoxypyridin-3-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(4-(6-aminopyridin-3-yl)-2-fluorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-fluoro-4-(3-methyl-1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-fluoro-4-(1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2,3-difluoro-4-(1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2,5-difluoro-4-(1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine2-(2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl)-5-((3 aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole5-(2-chloro-5-fluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(3-fluoro-5-(1H-pyrazol-4-yl)pyridin-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(4-(2-aminopyrimidin-4-yl)-2-chlorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(5-(2-aminopyrimidin-4-yl)-2-chlorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(4-(2,4-dimethylthiazol-5-yl)-2,5-difluorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(4-(2,4-dimethylthiazol-5-yl)-2,3-difluorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine4-(3-hydroxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(trifluoromethoxy)phenyl)-1-methylpyridin-2(1H)-one5-(2-fluoro-6-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine2-(2-fluoro-6-methoxy-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole5-(2,3-difluoro-6-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine6-methoxy-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-3,4-dihydroisoquinolin-1-(2H)-one5-(2-chloro-4-(1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-chloro-4-(1H-1,2,3-triazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-chloro-4-(2H-1,2,3-triazol-2-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-chloro-4-(1H-1,2,4-triazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(4-(3-amino-1H-pyrazol-1-yl)-2-chlorophenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine2-(2-chloro-4-(1H-imidazol-1-yl)phenyl)-5-((3 aR,6aS)-5-methylhexahydropyrrolo[3,4c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole5-(2-chloro-4-(1H-imidazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-fluoro-4-(1H-imidazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-methoxy-4-(1H-pyrazol-5-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(4-(2,4-dimethylthiazol-5-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-methoxy-4-(pyridin-3-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-fluoro-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-methoxy-4-(2-methoxypyridin-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-methoxy-4-(6-methoxypyridin-3-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine2-(2-chloro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aR)-1-methylhexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl)-1,3,4-thiadiazole(R)-1-(4-(5-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-yl)morpholin-2-yl)-N,N-dimethylmethanamine2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-(2-methyl-2,7-diazaspiro[4.5]decan-7-yl)-1,3,4-thiadiazole2-(2-fluoro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole2-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-(2,6-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazole2-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazole2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-1-yl)phenol5-(3-chloro-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenyl)pyridin-2(1H)-one2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(3-(methylamino)-1H-pyrazol-1-yl)phenol3-fluoro-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-4-yl)phenol3,4-difluoro-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-4-yl)phenol6-hydroxy-5-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-one2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-4-yl)phenol2-(5-(2,6-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol2-(5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazol-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol3-fluoro-2-(5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-4-yl)phenol3-chloro-2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-4-yl)phenol2-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-5-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)-1,3,4-thiadiazole2-(2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl)-5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazole2-(5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,3,4-thiadiazol-2-yl)-3-fluoro-5-(1H-pyrazol-4-yl)phenol4-methoxy-1-methyl-3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-2(1H)-one4-hydroxy-1-methyl-3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-2(1H)-one3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-2(1H)-one1-methyl-3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)quinolin-2(1H)-one2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-(2,7-diazaspiro[4.5]decan-2-yl)-1,3,4-thiadiazole (R)-(4-(5-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-yl)piperazin-2-yl)methanol2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)benzo[b]thiophene-5-carbonitrile5-(3-chlorobenzo[b]thiophen-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine5-(2-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol5-(1-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol5-(1H-imidazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-pyrazol-1-yl)phenol6-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine5-(4-amino-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol5-(4-nitro-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine2-[6-(piperidin-4-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine3-[4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine3-[4-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol3-fluoro-4-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-1-yl)phenolN-methyl-6-(2-methyl-2H-indazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2-methyl-5-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}-2H-indazole3-(4-chloro-2-methoxyphenyl)-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazineN-methyl-6-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine6-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}imidazo[1,2-a]pyridine3-[2-methoxy-4-(1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine3-[5-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine5-(3,5-dimethyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol6-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine3-methoxy-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol3-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}benzene-1,3-diol6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2-(1H-pyrazol-4-yl)-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyrimidin-5-amine3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine2-[6-(2,6-diazaspiro[3.4]oct-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-yl)pyridin-2-ol6-(1H-pyrazol-4-yl)-3-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-2-olN,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amineN,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine and6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine;wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.
7. The compound of claim 4, wherein the compound is selected from the group consisting of: 2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol2-{6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol5-(1-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol5-(1H-imidazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-pyrazol-1-yl)phenol6-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine5-(4-amino-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol5-(4-nitro-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine2-[6-(piperidin-4-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine3-[4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine3-[4-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol3-fluoro-4-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-1-yl)phenolN-methyl-6-(2-methyl-2H-indazol-5-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2-methyl-5-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}-2H-indazole3-(4-chloro-2-methoxyphenyl)-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazineN-methyl-6-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine6-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}imidazo[1,2-a]pyridine3-[2-methoxy-4-(1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine3-[5-(1-methyl-1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine5-(3,5-dimethyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol6-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine3-methoxy-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol3-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}benzene-1,3-diol6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2-(1H-pyrazol-4-yl)-4-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyrimidin-5-amine3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine2-[6-(2,6-diazaspiro[3.4]oct-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-yl)pyridin-2-ol6-(1H-pyrazol-4-yl)-3-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}pyridin-2-olN,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amineN,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine and6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine;wherein a form of the compound is selected from the group consisting of a prodrug, salt, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.
8. The method of claim 6, wherein the compound is a compound salt selected from the group consisting of: 2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(trifluoromethyl)phenol hydrochloride2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(1H-pyrazol-1-yl)phenol hydrochloride2-(6-piperazin-1-yl-pyridazin-3-yl)-5-1H-pyrazol-1-yl-phenol hydrochloride3-(6-(piperazin-1-yl)pyridazin-3-yl)naphthalene-2,7-diol trifluoroacetate3-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol trifluoroacetate3-(6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol trifluoroacetate3-(6-(piperidin-4-yl)pyridazin-3-yl)naphthalene-2,7-diol trifluoroacetate6-hydroxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-dihydro-1H-inden-1-one oxime hydrochloride2-amino-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-8H-indeno[1,2-d]thiazol-5-ol hydrochloride9-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5,6-dihydroimidazo[5,1-a]isoquinolin-8-ol hydrochloride3-fluoro-5-(2-methoxypyridin-4-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol hydrochloride4-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)pyridin-2(1H)-one hydrochloride4-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one hydrochloride5-(3-fluoro-5-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1-methylpyridin-2(1H)-one hydrochloride3-fluoro-5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenol hydrochloride5-chloro-3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol hydrochloride3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1H-pyrazol-4-yl)phenol hydrochloride3-fluoro-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol hydrochloride3-(1H-imidazol-1-yl)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-7-ol hydrochloride6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoline-3,7-diol formate7-hydroxy-1-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-2(1H)-one hydrochloride4-methoxy-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinolin-6-ol formate7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)quinoxalin-6-ol hydrochloride2-methyl-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-4-(tetrahydro-2H-pyran-4-yl)quinolin-7-ol formate4-(dimethylamino)-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-quinolin-7-ol formate6-hydroxy-2-methyl-7-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)isoquinolin-1(2H)-one hydrochloride3-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)naphthalen-2-ol hydrobromideN-methyl-5-(5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine hydrochloride3-fluoro-2-(5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-4-yl)phenol dihydrochloride2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1,3,4-thiadiazole hydrochloride2-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-5-(2,7-diazaspiro[4.5]decan-2-yl)-1,3,4-thiadiazole hydrochloride(R)-(4-(5-(2-chloro-4-(1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-yl)piperazin-2-yl)methanol hydrochloride2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol hydrochloride2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol hydrochloride5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol hydrochloride2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol hydrochloride2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-pyrazol-1-yl)phenol dihydrochloride2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol trihydrochloride5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol trihydrochloride2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol trihydrochloride2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine tetrahydrochloride2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol hydrochloride6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine trihydrochloride2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol hydrochloride6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol trihydrochloride3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine hydrochloride2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine hydrochloride3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine hydrochloride6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine trihydrochloride3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine trihydrochloride3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-yl)pyridin-2-ol hydrochlorideN,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine hydrochlorideN,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine hydrochloride3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine hydrochloride and6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride;wherein a form of the compound salt is selected from the group consisting of a prodrug, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.
9. The compound of claim 7, wherein the compound is a compound salt selected from the group consisting of: 2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol hydrochloride2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol hydrochloride5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol hydrochloride2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol hydrochloride2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-pyrazol-1-yl)phenol dihydrochloride2-[6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol trihydrochloride5-(1H-pyrazol-4-yl)-2-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]phenol trihydrochloride2-[6-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol trihydrochloride2-{6-[methyl(piperidin-4-yl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride2-[6-(piperidin-4-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride6-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine tetrahydrochloride2-[6-(8-azabicyclo[3.2.1]oct-2-en-3-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol hydrochloride6-[2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride3-[2,5-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine trihydrochloride2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol hydrochloride6-[2-methoxy-6-(1H-pyrazol-4-yl)pyridin-3-yl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride2-{6-[(2,6-dimethylpiperidin-4-yl)oxy]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol trihydrochloride3-[2-fluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine hydrochloride2-[6-(2,7-diazaspiro[3.5]non-2-yl)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol tetrahydrochloride3-[5-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine hydrochloride3-[4-(1H-pyrazol-4-yl)thiophen-2-yl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine hydrochloride6-[2-chloro-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine trihydrochloride3-[2,6-difluoro-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine trihydrochloride3-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-6-(1H-pyrazol-4-yl)pyridin-2-ol hydrochlorideN,2,2,6,6-pentamethyl-N-{5-[3-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine hydrochlorideN,2,2,6,6-pentamethyl-N-{5-[4-(1H-pyrazol-4-yl)phenoxy]-1,3,4-thiadiazol-2-yl}piperidin-4-amine hydrochloride3-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazine hydrochloride and6-[2-(difluoromethyl)-4-(1H-pyrazol-4-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine hydrochloride;wherein a form of the compound salt is selected from the group consisting of a prodrug, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.
10. An assay for detecting HTT (Huntingtin protein) using capture/detection antibody pairs, wherein: (i) when HTT is total HTT, the capture/detection antibody pairs are selected from MAB2166/MAB2174 and MAB2166/#5656S; and, (ii) when HTT is mutant HTT, the capture/detection antibody pairs are selected from MAB1574/#5656S, P1874/#5656S and MW1/#5656S.
11. The assay of claim 10, wherein HTT is total HTT and the capture/detection antibody pair is MAB2166/#5656S; and, wherein HTT is mutant HTT and the capture/detection antibody pair is MW1/#5656S.
12. The method of claim 1, wherein the effective amount of the compound is in a range of from about 0.001 mg/kg/day to about 500 mg/kg/day.
13-14. (canceled)
15. A use of the compound of any of claim 1, in the manufacture of a medicament for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the medicament to the subject.
16. The use of claim 15, wherein the effective amount of the compound in the medicament is in a range of from about 0.001 mg/kg/day to about 500 mg/kg/day.
17. A use of the compound of claim 1, in admixture with one or more pharmaceutically acceptable excipient(s) in a pharmaceutical composition for treating or ameliorating HD in a subject in need thereof, comprising administering an effective amount of the pharmaceutical composition to the subject.
18. The use of claim 17, wherein the effective amount of the compound in the pharmaceutical composition is in a range of from about 0.001 mg/kg/day to about 500 mg/kg/day.

PCT Information

Filing Document	Filing Date	Country	Kind
PCT/US16/66042	12/11/2016	WO	00

Provisional Applications (1)

	Number	Date	Country
	62265652	Dec 2015	US

METHODS FOR TREATING HUNTINGTON'S DISEASE

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