WO2018226622A1 - Compounds for treating huntington's disease - Google Patents

Compounds for treating huntington's disease Download PDF

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Publication number
WO2018226622A1
WO2018226622A1 PCT/US2018/035954 US2018035954W WO2018226622A1 WO 2018226622 A1 WO2018226622 A1 WO 2018226622A1 US 2018035954 W US2018035954 W US 2018035954W WO 2018226622 A1 WO2018226622 A1 WO 2018226622A1
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Prior art keywords
fluoro
alkyl
piperidin
amino
pyridazin
Prior art date
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Ceased
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PCT/US2018/035954
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English (en)
French (fr)
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WO2018226622A8 (en
Inventor
Matthew G. WOLL
Lukiana AMEDZO
Suresh Babu
Scott J. BARRAZA
Anuradha Bhattacharyya
Gary Mitchell Karp
Anthony R. MAZZOTTI
Jana Narasimhan
Jigar Patel
Anthony Turpoff
Zhenrong Xu
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PTC Therapeutics Inc
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PTC Therapeutics Inc
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Priority to KR1020207000124A priority Critical patent/KR20200033249A/ko
Priority to JP2020516795A priority patent/JP7376471B2/ja
Priority to EA201992878A priority patent/EA201992878A1/ru
Priority to IL300875A priority patent/IL300875B2/en
Priority to EP22203869.7A priority patent/EP4151627A1/en
Priority to SG11201911615WA priority patent/SG11201911615WA/en
Priority to EP18813494.4A priority patent/EP3634953B1/en
Priority to BR112019025740-3A priority patent/BR112019025740A2/pt
Priority to US16/617,450 priority patent/US11407753B2/en
Priority to CN201880050893.7A priority patent/CN111065626B/zh
Priority to AU2018282154A priority patent/AU2018282154B2/en
Application filed by PTC Therapeutics Inc filed Critical PTC Therapeutics Inc
Priority to MX2019014514A priority patent/MX2019014514A/es
Priority to CA3066224A priority patent/CA3066224A1/en
Priority to NZ759824A priority patent/NZ759824B2/en
Publication of WO2018226622A1 publication Critical patent/WO2018226622A1/en
Priority to IL271046A priority patent/IL271046B2/en
Anticipated expiration legal-status Critical
Publication of WO2018226622A8 publication Critical patent/WO2018226622A8/en
Priority to AU2022201299A priority patent/AU2022201299A1/en
Priority to US17/723,163 priority patent/US12384789B2/en
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Definitions

  • An aspect of the present description relates to compounds, forms, and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof useful for treating or ameliorating Huntington's disease.
  • another aspect of the present description relates to substituted bicyclic heteroaryl compounds, forms and
  • compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease.
  • Huntington's disease 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.
  • Htt huntingtin
  • polyQ poly-glutamine
  • An aspect of the present description includes compounds comprising, a compound of Formula (I):
  • An aspect of the present description includes a method 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) or a form thereof.
  • An aspect of the present description includes a method for use of a compound of Formula (I) or a form or composition thereof for treating or ameliorating HD in a subject in need thereof comprising, administering to the subject an effective amount of the compound of Formula (I) or a form or composition thereof.
  • An aspect of the present description includes a use for a compound of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof comprising,
  • An aspect of the present description includes a use for 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 to the subject an effective amount of the medicament.
  • An aspect of the present description includes a use for a compound of Formula (I) or a form thereof in a combination product with one or more therapeutic agents for treating or ameliorating HD in a subject in need thereof comprising, administering to the subject an effective amount of the compound of Formula (I) or a form thereof in combination with an effective amount of the one or more agents.
  • An aspect of the present description relates to compounds comprising, a compound of Formula (I):
  • Wi, W 2 , W 3 , W 4 , W 5 and W 6 are independently C-R a , C-R b or N, wherein, when one, two or three of Wi, W5 and W 6 are N, then W 2 , W 3 and W 4 are C-R a or C-Rb, and
  • Ri is aryl, heterocyclyl, heterocyclyl-amino, (heterocyclyl)(Ci_ 8 alkyl)amino or heteroaryl, wherein, each instance of heterocyclyl is optionally substituted with one, two or three R 3
  • each instance of heterocyclyl is optionally substituted with one, two, three or four R 3 substituents;
  • R 2 is aryl, heteroaryl, heteroaryl-amino or (heteroaryl)(Ci_ 8 alkyl)amino,
  • each instance of aryl and heteroaryl is optionally substituted with one, two or three R 6 substituents and optionally, with one additional R 7 substituent;
  • R a is, in each instance, independently selected from hydrogen, halogen or Ci_ 8 alkyl
  • R b is, in each instance, independently selected from hydrogen, halogen or Ci_ 8 alkyl
  • R 3 is, in each instance, independently selected from cyano, halogen, hydroxy, Ci_ 8 alkyl,
  • halo-Ci_ 8 alkyl Ci_ 8 alkyl-carbonyl, Ci_ 8 alkoxy, halo-Ci_ 8 alkoxy, Ci_ 8 alkoxy-Ci_ 8 alkyl, Ci_ 8 alkoxy-carbonyl, amino, Ci_ 8 alkyl-amino, (Ci_ 8 alkyl) 2 -amino, amino-Ci_ 8 alkyl, Ci- 8 alkyl-amino-Ci_ 8 alkyl, (Ci_ 8 alkyl) 2 -amino-Ci- 8 alkyl, amino-Ci_ 8 alkyl-amino,
  • Ci_ 8 alkyl-carbonyl-amino Ci_ 8 alkoxy-carbonyl-amino, hydroxy-Ci_ 8 alkyl,
  • hydroxy-Ci_ 8 alkoxy-Ci_ 8 alkyl hydroxy-Ci_ 8 alkyl-amino, (hydroxy-Ci_ 8 alkyl) 2 -amino or (hydroxy-C i_ 8 alkyl)(C i_ 8 alkyl)amino;
  • R 4 is C 3 _i 4 cycloalkyl, C 3 _i 4 cycloalkyl-Ci_ 8 alkyl, C 3 _i 4 cycloalkyl-amino, aryl-Ci_ 8 alkyl,
  • R 6 is, in each instance, independently selected from halogen, hydroxy, cyano, nitro, Ci-galkyl, d-galkenyl, cyano-Ci-galkyl, halo-Ci-galkyl, hydroxy-Ci-galkyl, Ci-galkoxy,
  • Ci-galkoxy-Ci-galkyl Ci-galkoxy-Ci-galkoxy, amino, Ci-galkyl-amino, (Ci_ 8 alkyl) 2 -amino, Ci-galkoxy-Ci-galkyl-amino, (Ci-galkoxy-Ci-galkyl, Ci_ 8 alkyl)amino or Ci_ 8 alkyl-thio; and,
  • R 7 is C 3 _i 4 cycloalkyl, C 3 _i 4 cycloalkyl-oxy, aryl, heterocyclyl, heteroaryl or heteroaryl-Ci-galkoxy; 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 includes a compound of Formula (I) comprising, a compound of Formula (1.1):
  • Wi, W 2 , W 3 , W 4 , W 5 and W 6 are independently C-R a , C-R b or N,
  • W 2 , W3 and W4 are C-R a or C-R b , and
  • Ri is Ci-galkyl, amino, Ci-galkyl-amino, (Ci_ 8 alkyl) 2 -amino, Ci-salkoxy-Ci-salkyl-amino,
  • aryl-Ci- 8 alkyl (Ci- 8 alkyl)amino-Ci- 8 alkyl, heterocyclyl, heterocyclyl-C i_ 8 alkyl, heterocyclyl-C i_ 8 alkoxy, heterocyclyl-amino, (heterocyclyl)(Ci_ 8 alkyl)amino, heterocyclyl-amino-Ci_ 8 alkyl, heterocyclyl-C i_ 8 alkyl-amino,
  • heterocyclyl-C i- 8 alkyl-amino-Ci_ 8 alkyl (heterocyclyl-C i_ 8 alkyl) 2 -amino-Ci_ 8 alkyl, (heterocyclyl-C i_ 8 alkyl)(Ci_ 8 alkyl)amino-Ci_ 8 alkyl, heterocyclyl-oxy,
  • heterocyclyl-carbonyl heterocyclyl-carbonyl, heterocyclyl-carbonyl-oxy, heteroaryl, heteroaryl-C i_ 8 alkyl, heteroaryl-C i- 8 alkoxy, heteroaryl-amino, heteroaryl-C i_ 8 alkyl-amino,
  • heteroaryl-C i_ 8 alkyl 2 -amino, (heteroaryl-C i_ 8 alkyl)(Ci_ 8 alkyl)amino, heteroaryl-Ci-galkyl-amino-Ci-galkyl, (heteroaryl-Ci- 8 alkyl) 2 -amino-Ci- 8 alkyl or (heteroaryl-Ci- 8 alkyl)(Ci- 8 alkyl)amino-Ci- 8 alkyl,
  • R 2 is aryl, heteroaryl, heteroaryl-amino or (heterocyclyl)(Ci_ 8 alkyl)amino,
  • each instance of aryl and heteroaryl is optionally substituted with one, two or three R 6 substituents and optionally, with one additional R 7 substituent;
  • R a is, in each instance, independently selected from hydrogen, or Ci_ 8 alkyl
  • R is, in each instance, independently selected from hydrogen, or halogen
  • R 3 is, in each instance, independently selected from cyano, halogen, hydroxy, Ci-salkyl,
  • Ci_ 8 alkyl-carbonyl Ci_ 8 alkoxy, halo-Ci_ 8 alkoxy, Ci- 8 alkoxy-Ci_ 8 alkyl, Ci-galkoxy-carbonyl, amino, Ci_ 8 alkyl-amino, (Ci_ 8 alkyl) 2 -amino, amino-Ci_ 8 alkyl, Ci-galkyl-amino-Ci-galkyl, (Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl, amino-Ci_ 8 alkyl-amino,
  • Ci-salkyl-carbonyl-amino Ci_ 8 alkoxy-carbonyl-amino, hydroxy-C i_ 8 alkyl,
  • hydroxy-Ci_ 8 alkoxy-Ci_ 8 alkyl hydroxy-Ci_ 8 alkyl-amino, (hydroxy-Ci_ 8 alkyl) 2 -amino or (hydroxy-C i_ 8 alkyl)(C i_ 8 alkyl)amino;
  • R 4 is C 3 _i 4 cycloalkyl, C 3 _i 4 cycloalkyl-Ci_ 8 alkyl, C 3 _i 4 cycloalkyl-amino, aryl-Ci_ 8 alkyl,
  • R5 is, in each instance, independently selected from halogen, hydroxy, cyano, nitro, Ci_ 8 alkyl, halo-Ci_ 8 alkyl, Ci_ 8 alkoxy, halo-Ci_ 8 alkoxy, hydroxy-C i_ 8 alkyl, amino, Ci_ 8 alkyl-amino, (Ci_ 8 alkyl) 2 -amino, (Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl, Ci_ 8 alkyl-thio or heteroaryl-Ci_ 8 alkyl;
  • R 6 is, in each instance, independently selected from halogen, hydroxy, cyano, nitro, Ci_ 8 alkyl, d-galkenyl, cyano-Ci_ 8 alkyl, halo-Ci_ 8 alkyl, hydroxy-Ci_ 8 alkyl, Ci_ 8 alkoxy,
  • Ci- 8 alkoxy-Ci- 8 alkyl-amino (Ci_ 8 alkoxy-Ci_ 8 alkyl, Ci_ 8 alkyl)amino or Ci_ 8 alkyl-thio;
  • R 7 is C 3 _i 4 cycloalkyl, C 3 _i 4 cycloalkyl-oxy, aryl, heterocyclyl, heteroaryl or heteroaryl-Ci_ 8 alkoxy.
  • One aspect includes a compound of Formula (I), wherein Wi is N.
  • Another aspect includes a compound of Formula (I), wherein Wi is N, W4 is C-R b and W 2 , W3,
  • W 5 and W 6 are C-R a .
  • One aspect includes a compound of Formula (I), wherein W 2 is N.
  • Another aspect includes a compound of Formula (I), wherein W 2 is N, W4 is C-R b and Wi, W3,
  • W 5 and W 6 are C-R a .
  • One aspect includes a compound of Formula (I), wherein W3 is N.
  • Another aspect includes a compound of Formula (I), wherein W3 is N, W4 is C-R b and Wi, W 2 ,
  • W 5 and W 6 are C-R a .
  • One aspect includes a compound of Formula (I), wherein W4 is N.
  • Another aspect includes a compound of Formula (I), wherein W4 is N and Wi, W 2 , W3, W5 and
  • W 6 are independently C-R a .
  • One aspect includes a compound of Formula (I), wherein W5 is N.
  • Another aspect includes a compound of Formula (I), wherein W5 is N, W4 is C-R b and Wi, W 2 ,
  • W 3 and W 6 are C-R a .
  • One aspect includes a compound of Formula (I), wherein W 6 is N.
  • Another aspect includes a compound of Formula (I), wherein W 6 is N, W4 is C-R b and Wi, W 2 , W 3 and W 5 are C-R a .
  • Another aspect includes a compound of Formula (I), wherein Ri is aryl, heterocyclyl,
  • heterocyclyl-amino (heterocyclyl)(Ci_ 8 alkyl)amino, or heteroaryl.
  • Another aspect includes a compound of Formula (I), wherein Ri is aryl or heteroaryl.
  • Another aspect includes a compound of Formula (I), wherein Ri is aryl.
  • Another aspect includes a compound of Formula (I), wherein Ri is heteroaryl.
  • Another aspect includes a compound of Formula (I), wherein Ri is heterocyclyl,
  • heterocyclyl-amino or (heterocyclyl)(Ci_ 8 alkyl)amino.
  • Another aspect includes a compound of Formula (I), wherein Ri is heterocyclyl.
  • Another aspect includes a compound of Formula (I), wherein Ri is heterocyclyl-amino.
  • Another aspect includes a compound of Formula (I), wherein Ri is
  • Another aspect includes a compound of Formula (I), wherein R a is hydrogen or Ci_ 8 alkyl.
  • Another aspect includes a compound of Formula (I), wherein R b is hydrogen or halogen.
  • Another aspect includes a compound of Formula (I), wherein R 4 is heterocyclyl-Ci_ 8 alkyl or heteroaryl-C i_ 8 alkyl.
  • Another aspect includes a compound of Formula (I), wherein R5 is hydroxy-Ci_ 8 alkyl,
  • Another aspect includes a compound of Formula (I), wherein R 6 is halogen, hydroxy, cyano,
  • Ci_ 8 alkoxy-Ci 8 alkyl-amino Another aspect includes a compound of Formula (I), wherein R 7 is C3_i 4 cycloalkyl, heterocyclyl, or heteroaryl-C i_ 8 alkoxy.
  • One aspect includes a compound of Formula (I), wherein Wi and W5 are N.
  • Another aspect includes a compound of Formula (I), wherein Wi and W5 are N, W 4 is C-R b and
  • W 2 , W 3 and W 6 are C-R a .
  • One aspect includes a compound of Formula (I), wherein Wi and W 6 are N.
  • Another aspect includes a compound of Formula (I), wherein Wi and W 6 are N, W 4 is C-R b and
  • W 2 , W 3 and W 5 are C-R a .
  • One aspect includes a compound of Formula (I), wherein W 2 and W 3 are N.
  • Another aspect includes a compound of Formula (I), wherein W 2 and W 3 are N, W 4 is C-R b and
  • Wi, W 5 and W 6 are C-R a .
  • One aspect includes a compound of Formula (I), wherein W 2 and W 4 are N.
  • Another aspect includes a compound of Formula (I), wherein W 2 and W 4 are N, and Wi, W 3 , W5 and W 6 are independently C-R a .
  • One aspect includes a compound of Formula (I), wherein W 3 and W 4 are N.
  • Another aspect includes a compound of Formula (I), wherein W 3 and W 4 are N, and Wi, W 2 , W5 and W 6 are independently C-R a .
  • One aspect includes a compound of Formula (I), wherein W5 and W 6 are N.
  • Another aspect includes a compound of Formula (I), wherein W5 and W 6 are N, W 4 is C-R b and
  • Wi, W 2 and W 3 are C-R a .
  • Another aspect includes a compound of Formula (I), wherein W5 and W 6 are N, W 2 is C-R b and
  • Wi, W 3 and W 4 are C-R a .
  • Another aspect includes a compound of Formula (I), wherein W5 and W 6 are N, W 3 is C-R b and
  • Wi, W 2 and W 4 are C-R a .
  • One aspect includes a compound of Formula (I), wherein Wi, W5 and W 6 are N.
  • Another aspect includes a compound of Formula (I), wherein Wi, W5 and W 6 are N, W 4 is C-R b and W 2 and W 3 are C-R a .
  • One aspect includes a compound of Formula (I), wherein W 2 , W 3 and W 4 are N.
  • Another aspect includes a compound of Formula (I), wherein W 2 , W 3 and W 4 are N, and Wi, W5 and W 6 are independently C-R a .
  • One aspect includes a compound of Formula (I), wherein Ri is heterocyclyl selected from
  • Another aspect includes a compound of Formula (I), wherein Ri is heterocyclyl selected from azetidin- l-yl, tetrahydrofuran-3-yl, pyrrolidin- l-yl, pyrrolidin-3-yl, piperidin-l-yl, piperidin-4-yl, piperazin- l-yl, azepan-4-yl, 1,4-diazepan-l-yl,
  • Another aspect includes a compound of Formula (I), wherein Ri is heterocyclyl selected from pyrrolidinyl, piperidinyl, piperazinyl, azepanyl, 1 ,2,5,6-tetrahydropyridinyl,
  • Another aspect includes a compound of Formula (I), wherein Ri is heterocyclyl selected from pyrrolidin-3-yl, piperidin-4-yl, piperazin- l-yl, azepan-4-yl, l,2,5,6-tetrahydropyridin-5-yl, l,2,3,6-tetrahydropyridin-4-yl, 3-azabicyclo[3.1.0]hexan-3-yl,
  • Another aspect includes a compound of Formula (I), wherein Ri is substituted heterocyclyl selected from N,N-dimethylpyrrolidin-3-amine, N,N-dimethylpiperidin-4-amine, N,N-4-trimethylpiperidin-4-amine, 1 -methylpiperidin-4-yl, 1 -ethylpiperidin-4-yl,
  • Another aspect includes a compound of Formula (I), wherein Ri is substituted heterocyclyl
  • One aspect includes a compound of Formula (I), wherein Ri is heterocyclyl-amino, wherein
  • heterocyclyl is selected from azetidinyl, pyrrolidinyl, piperidinyl, 9-azabicyclo[3.3.1]nonyl or (1 ?,5S)-9-azabicyclo[3.3.1]nonyl; and, wherein, each instance of heterocyclyl is optionally substituted with R 3 and R 4 substituents.
  • Another aspect includes a compound of Formula (I), wherein Ri is heterocyclyl-amino selected from azetidin-3-yl-amino, pyrrolidin-3-yl-amino, piperidin-4-yl-amino,
  • One aspect includes a compound of Formula (I), wherein Ri is (heterocyclyl)(Ci_ 8 alkyl)amino, wherein heterocyclyl is selected from pyrrolidinyl or piperidinyl; and, wherein, each instance of heterocyclyl is optionally substituted with R 3 and R 4 substituents.
  • Another aspect includes a compound of Formula (I), wherein Ri is (heterocyclyl)(Ci_ 8 alkyl)amino wherein heterocyclyl is piperidinyl.
  • Another aspect includes a compound of Formula (I), wherein Ri is (heterocyclyl)(Ci_ 8 alkyl)amino selected from (pyrrolidin-3-yl)(methyl)amino or (piperidin-4-yl)(methyl)amino; wherein, each instance of heterocyclyl is optionally substituted with R 3 and R4 substituents.
  • Ri is (heterocyclyl)(Ci_ 8 alkyl)amino selected from (pyrrolidin-3-yl)(methyl)amino or (piperidin-4-yl)(methyl)amino; wherein, each instance of heterocyclyl is optionally substituted with R 3 and R4 substituents.
  • R 3 is selected from cyano, halogen, hydroxy, oxo, Ci_ 8 alkyl, halo-Ci_ 8 alkyl, Ci_ 8 alkyl-carbonyl, Ci_ 8 alkoxy, halo-Ci_ 8 alkoxy, Ci_ 8 alkoxy-Ci_ 8 alkyl, Ci_ 8 alkoxy-carbonyl, amino, Ci_ 8 alkyl-amino, (Ci_ 8 alkyl)2-amino, amino-Ci_ 8 alkyl, Ci_ 8 alkyl-amino-Ci_ 8 alkyl, (Ci- 8 alkyl)2-amino-Ci_ 8 alkyl,
  • Ci_ 8 alkyl-carbonyl-amino Ci_ 8 alkoxy-carbonyl-amino, hydroxy-Ci_ 8 alkyl,
  • hydroxy-Ci- 8 alkoxy-Ci_ 8 alkyl hydroxy-Ci_ 8 alkyl-amino, (hydroxy-Ci_ 8 alkyl)2-amino or (hydroxy-C i_ 8 alkyl)(C i_ 8 alkyl)amino.
  • Another aspect includes a compound of Formula (I), wherein R 3 is selected from cyano, halogen, hydroxy, oxo, Ci_ 8 alkyl, halo-Ci_ 8 alkyl, Ci_ 8 alkoxy, Ci_ 8 alkoxy-Ci_ 8 alkyl,
  • Ci- 8 alkoxy-carbonyl amino, Ci_ 8 alkyl-amino, (Ci_ 8 alkyl)2-amino, amino-Ci_ 8 alkyl, Ci- 8 alkyl-amino-Ci_ 8 alkyl, (Ci- 8 alkyl)2-amino-Ci_ 8 alkyl, Ci- 8 alkyl-amino-Ci_ 8 alkyl-amino, Ci_ 8 alkoxy-Ci_ 8 alkyl-amino, Ci_ 8 alkoxy-carbonyl-amino, hydroxy-C i_ 8 alkyl, hydroxy-Ci-galkoxy-Ci-galkyl, hydroxy-Ci_ 8 alkyl-amino, (hydroxy-Ci_ 8 alkyl) 2 -amino or
  • Another aspect includes a compound of Formula (I), wherein R 3 is Ci_ 8 alkyl selected from
  • R 3 is Ci_ 8 alkyl selected from methyl, ethyl, propyl, isopropyl or tert-butyl.
  • Another aspect includes a compound of Formula (I), wherein R 3 is halo-Ci_ 8 alkyl selected from trihalo-methyl, dihalo-methyl, halo-methyl, trihalo-ethyl, dihalo-ethyl, halo-ethyl, trihalo-propyl, dihalo-propyl or halo-propyl; wherein, halo is selected from fluoro, chloro, bromo or iodo.
  • Another aspect includes a compound of Formula (I), wherein R 3 is halo-Ci_ 8 alkyl selected from trihalo-methyl, dihalo-methyl, halo-methyl, trihalo-ethyl, dihalo-ethyl, trihalo-propyl or dihalo-propyl; wherein, halo is selected from fluoro, chloro, bromo or iodo.
  • Another aspect includes a compound of Formula (I), wherein R 3 is hydroxy-Ci_ 8 alkyl selected from hydroxy-methyl, hydroxy-ethyl, hydroxy-propyl, dihydroxy-propyl, hydroxy-butyl or dihydroxy-butyl.
  • Another aspect includes a compound of Formula (I), wherein R 3 is hydroxy-Ci_ 8 alkyl selected from hydroxy-methyl, hydroxy-ethyl, dihydroxy-propyl, hydroxy-butyl or
  • Another aspect includes a compound of Formula (I), wherein R 3 is Ci_ 8 alkoxy selected from
  • Another aspect includes a compound of Formula (I), wherein R 3 is halo-Ci_ 8 alkoxy selected from trihalo-methoxy, dihalo-methoxy, halo-methoxy, trihalo-ethoxy, dihalo-ethoxy, halo-ethoxy, trihalo-propoxy, dihalo-propoxy or halo-propoxy; wherein, halo is selected from fluoro, chloro, bromo or iodo.
  • Another aspect includes a compound of Formula (I), wherein R 3 is Ci_ 8 alkoxy-carbonyl-amino selected from methoxy-carbonyl- amino, ethoxy-carbonyl-amino,
  • propoxy-carbonyl-amino isopropoxy-carbonyl-amino, tert-butoxy-carbonyl-amino.
  • Another aspect includes a compound of Formula (I), wherein R 4 is C 3 _i 4 cycloalkyl,
  • Another aspect includes a compound of Formula (I), wherein R5 is, in each instance,
  • Ci_ 8 alkyl-amino independently selected from halogen, hydroxy, cyano, nitro, Ci_ 8 alkyl, halo-Ci_ 8 alkyl, Ci- 8 alkoxy, halo-Ci_ 8 alkoxy, hydroxy-Ci_ 8 alkyl, amino, Ci_ 8 alkyl-amino,
  • One aspect includes a compound of Formula (I), wherein R 2 is aryl, heteroaryl, heteroaryl- amino, (heteroaryl)(Ci_ 8 alkyl)amino or (heterocyclyl)(Ci_ 8 alkyl)amino.
  • Another aspect includes a compound of Formula (I), wherein R 2 is aryl, heteroaryl,
  • heteroaryl-amino or (heteroaryl)(Ci_ 8 alkyl)amino.
  • Another aspect includes a compound of Formula (I), wherein R 2 is aryl.
  • Another aspect includes a compound of Formula (I), wherein R 2 is heteroaryl.
  • Another aspect includes a compound of Formula (I), wherein R 2 is heteroaryl-amino.
  • Another aspect includes a compound of Formula (I), wherein R 2 is (heteroaryl)(Ci_ 8 alkyl)amino.
  • Another aspect includes a compound of Formula (I), wherein R 2 is
  • R 2 is heteroaryl selected from thienyl, lH-pyrazolyl, lH-imidazolyl, 1,3-thiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, pyridinyl, pyrimidinyl, IH-indolyl, 2H-indolyl, IH-indazolyl, 2H-indazolyl, indolizinyl, benzofuranyl, benzothienyl, lH-benzimidazolyl, 1,3-benzothiazolyl, 1,3-benzoxazolyl, 9H-purinyl, furo[3,2- ]pyridinyl, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl,
  • Another aspect includes a compound of Formula (I), wherein R 2 is heteroaryl selected from thien-2-yl, thien-3-yl, lH-pyrazol-3-yl, lH-pyrazol-4-yl, lH-pyrazol-5-yl,
  • imidazo[ 1 ,2- ]pyridazin-6-yl imidazo[ 1 ,2- ⁇ 3]pyrazin-2-yl, imidazo[ 1 ,2- ⁇ 3]pyrazin-6-yl, 3H-imidazo[4,5-b]pyridin-5-yl, imidazo[2,l- ][l,3]thiazol-6-yl,
  • One aspect includes a compound of Formula (I), wherein R 6 is selected from halogen, hydroxy, cyano, nitro, Ci-galkyl, halo-Ci-galkyl, hydroxy-Ci-galkyl, Ci-galkoxy, halo-Ci- 8 alkoxy, Ci- 8 alkoxy-Ci- 8 alkyl, Ci_ 8 alkoxy-Ci_ 8 alkoxy, (Ci_ 8 alkyl) 2 -amino-Ci- 8 alkoxy, heteroaryl- Ci_ 8 alkoxy, aryl-oxy, (Ci_ 8 alkyl) 2 -amino, Ci_ 8 alkoxy-Ci_ 8 alkyl-amino, Ci_ 8 alkyl-thio, C3_i 4 cycloalkyl; wherein, halogen and halo is selected from fluoro, chloro, bromo or iodo.
  • Another aspect includes a compound of Formula (I), wherein R 6 is Ci_ 8 alkyl selected from
  • Another aspect includes a compound of Formula (I), wherein R 6 is Ci_ 8 alkyl selected from methyl, ethyl, propyl, isopropyl or tert-butyl.
  • Another aspect includes a compound of Formula (I), wherein R 6 is halo-Ci_ 8 alkyl selected from trihalo-methyl, dihalo-methyl, halo-methyl, trihalo-ethyl, dihalo-ethyl, halo-ethyl, trihalo-propyl, dihalo-propyl or halo-propyl; wherein, halo is selected from fluoro, chloro, bromo or iodo.
  • Another aspect includes a compound of Formula (I), wherein R 7 is C 3 _i 4 cycloalkyl,
  • One aspect includes a compound of Formula (I), wherein R a is hydrogen or Ci_ 8 alkyl.
  • One aspect includes a compound of Formula (I), wherein R b is hydrogen or Ci_ 8 alkyl.
  • Another aspect includes a compound of Formula (I), wherein R is halo.
  • One aspect of the compound of Formula (I) includes a compound selected from Formula (la),
  • Another aspect of the compound of Formula (I) includes the compound selected from Formula (lb), Formula (Ic), Formula (Ie), Formula (If), Formula (Ig), Formula (Ii), Formula (Ij), Formula (Ik), Formula (Im) or Formula (In):
  • Another aspect of the compound of Formula (I) includes the compound selected from of Formula (lal), Formula (Ibl), Formula (Icl), Formula (Idl), Formula (lel), Formula (Ifl), Formula (Igl), Formula (Ihl), Formula (Iil), Formula (Ij l), Formula (Ikl), Formula (111), Formula (Iml) or Formula (Inl), respectively:
  • Another aspect of the compound of of Formula (I) includes the compound selected from
  • Another aspect of the compound of Formula (I) includes the compound of Formula (Ibl):
  • Another aspect of the compound of Formula (I) includes the compound of Formula (Icl):
  • Another aspect of the compound of Formula (I) includes the compound of Formula (Idl):
  • Another aspect of the compound of Formula (I) includes the compound of Formula (lel):
  • Another aspect of the compound of Formula (I) includes the compound of Formula (Igl):
  • Another aspect of the compound of Formula (I) includes the compound of Formula (Ihl):
  • Another aspect of the compound of Formula (I) includes the compound of Formula (Iil):
  • Another aspect of the compound of Formula (I) includes the compound of Formula (Ij 1):
  • Another aspect of the compound of Formula (I) includes the compound of Formula (Ikl):
  • Another aspect of the compound of Formula (I) includes the compound of Formula ( ⁇ 1):
  • Another aspect of the compound of Formula (I) includes the compound of Formula (Iml):
  • Another aspect of the compound of Formula (I) includes the compound of Formula (Inl):
  • One aspect of the compound of Formula (I) or a form thereof includes a compound selected from the group consisting of:
  • the form of the compound is selected from the group consisting of a salt, prodrug, hydrate, solvate, clathrate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, polymorph and tautomer form thereof.
  • An aspect the compound of Formula (I) or a form thereof includes a compound selected from the group consisting of:
  • Another aspect of the compound of Formula (I) or a form thereof is a compound salt selected from the group consisting of:
  • An aspect of the present description includes a method for preventing, treating or ameliorating HD in a subject in need thereof comprising, administering to the subject an effective amount of a compound of Formula (I) or a form thereof.
  • An aspect of the present description includes a method 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) or a form thereof.
  • Another aspect of the present description includes a method for treating or ameliorating HD in a subject in need thereof comprising, administering to the subject an effective amount of a compound salt of Formula (I) or a form thereof.
  • An aspect of the present description includes a method for use of a compound of Formula (I) or a form or composition thereof for treating or ameliorating HD in a subject in need thereof comprising, administering to the subject an effective amount of the compound of Formula (I) or a form or composition thereof.
  • Another aspect of the present description includes a method for use of a compound salt of Formula (I) or a form or composition thereof for treating or ameliorating HD in a subject in need thereof comprising, administering to the subject an effective amount of the compound salt of Formula (I) or a form thereof.
  • An aspect of the present description includes a use for a compound of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof comprising,
  • Another aspect of the present description includes a use for a compound salt of Formula (I) or a form thereof for treating or ameliorating HD in a subject in need thereof comprising, administering to the subject an effective amount of the compound salt of Formula (I) or a form thereof.
  • An aspect of the present description includes a use for 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 to the subject an effective amount of the medicament.
  • Another aspect of the present description includes a use for a compound salt 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 to the subject an effective amount of the medicament.
  • An aspect of the present description includes a use for a compound of Formula (I) or a form thereof in a combination product with one or more therapeutic agents for treating or ameliorating HD in a subject in need thereof comprising, administering to the subject an effective amount of the compound of Formula (I) or a form thereof in combination with an effective amount of the one or more agents.
  • Another aspect of the present description includes a use for a compound salt of Formula (I) or a form thereof in a combination product with one or more therapeutic agents for treating or ameliorating HD in a subject in need thereof comprising, administering to the subject an effective amount of the compound salt of Formula (I) or a form thereof in combination with an effective amount of the one or more agents.
  • Ci_ 8 alkyl generally refers to saturated hydrocarbon radicals having from one to eight carbon atoms in a straight or branched chain configuration, including, but not limited to, methyl, ethyl, n-propyl (also referred to as propyl or propanyl), isopropyl, n-butyl (also referred to as butyl or butanyl), isobutyl, sec -butyl, tert-butyl, n-pentyl (also referred to as pentyl or pentanyl), n-hexyl (also referred to as hexyl or hexanyl), n-heptyl (also referred to as heptyl or heptanyl), n-octyl and the like.
  • Ci_ 8 alkyl includes, but is not limited to, Ci_ 6 alkyl, Ci_ 4 alkyl and the like.
  • a Ci_ 8 alkyl radical is optionally substituted with substituent species as described herein where allowed by available valences.
  • C 2 _ 8 alkenyl generally refers to partially unsaturated
  • C 2 - 8 alkenyl includes, but is not limited to, C 2 _ 6 alkenyl, C 2 - 4 alkenyl and the like.
  • a C 2 _ 8 alkenyl radical is optionally substituted with substituent species as described herein where allowed by available valences.
  • C 2 _ 8 alkynyl generally refers to partially unsaturated
  • C 2 _ 8 alkynyl includes, but is not limited to, C 2 _ 6 alkynyl, C 2 _ 4 alkynyl and the like.
  • a C 2 _ 8 alkynyl radical is optionally substituted with substituent species as described herein where allowed by available valences.
  • Ci_ 8 alkoxy generally refers to saturated hydrocarbon radicals having from one to eight carbon atoms in a straight or branched chain configuration of the formula: -0-Ci_ 8 alkyl, including, but not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, n-hexoxy and the like.
  • Ci_ 8 alkoxy includes, but is not limited to, Ci_ 6 alkoxy, Ci- 4 alkoxy and the like.
  • a Ci-galkoxy radical is optionally substituted with substituent species as described herein where allowed by available valences.
  • C 3 _i 4 cycloalkyl generally refers to a saturated or partially unsaturated monocyclic, bicyclic or polycyclic hydrocarbon radical, including, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, lH-indanyl, indenyl, tetrahydro-naphthalenyl and the like.
  • C 3 _i 4 cycloalkyl includes, but is not limited to, C 3 _ 8 cycloalkyl, C5_ 8 cycloalkyl, C 3 _iocycloalkyl and the like.
  • a C 3 _i 4 cycloalkyl radical is optionally substituted with substituent species as described herein where allowed by available valences.
  • aryl generally refers to a monocyclic, bicyclic or polycyclic aromatic carbon atom ring structure radical, including, but not limited to, phenyl, naphthyl, anthracenyl, fluorenyl, azulenyl, phenanthrenyl and the like.
  • An aryl radical is optionally substituted with substituent species as described herein where allowed by available valences.
  • 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, but not limited to, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxazolyl, 1,3-thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, indolyl, indazolyl, indolizinyl, isoindolyl, benzofuranyl, benzothienyl, benzoimidazolyl, 1,3-benzothiazolyl,
  • 1,3-benzoxazolyl purinyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, 1,3-diazinyl, 1,2-diazinyl, 1,2-diazolyl, 1,4-diazanaphthalenyl, acridinyl, furo[3,2- ]pyridinyl,
  • a heteroaryl radical is optionally substituted on a carbon or nitrogen atom ring member with substituent species as described herein where allowed by available valences.
  • heteroaryl radical may differ, such as in non- limiting examples where furanyl may also be referred to as furyl, thienyl may also be referred to as thiophenyl, pyridinyl may also be referred to as pyridyl, benzothienyl may also be referred to as benzothiophenyl and 1,3-benzoxazolyl may also be referred to as 1,3-benzooxazolyl.
  • the term for a heteroaryl radical may also include other regioisomers, such as in non-limiting examples where the term pyrrolyl may also include 2H-pyrrolyl, 3H-pyrrolyl and the like, the term pyrazolyl may also include IH-pyrazolyl and the like, the term imidazolyl may also include IH-imidazolyl and the like, the term triazolyl may also include lH-l,2,3-triazolyl and the like, the term oxadiazolyl may also include 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl and the like, the term tetrazolyl may also include lH-tetrazolyl, 2H-tetrazolyl and the like, the term indolyl may also include lH-indolyl and the like, the term indazolyl may also include lH-indazolyl and the like, the term indazolyl may also
  • 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, but not limited to, oxiranyl, oxetanyl, azetidinyl, tetrahydrofuranyl, pyrrolinyl, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, isoxazolinyl, isoxazolidinyl, isothiazolinyl, isothiazolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, triazolinyl, triazolidinyl, triazolidinyl,
  • a heterocyclyl radical is optionally substituted on a carbon or nitrogen atom ring member with substituent species as described herein where allowed by available valences.
  • heterocyclyl radical may differ, such as in non- limiting examples where 1,3-benzodioxolyl may also be referred to as benzo[ ⁇ i][l,3]dioxolyl and 2,3-dihydro- l,4-benzodioxinyl may also be referred to as 2,3-dihydrobenzo[ ] [l,4]dioxinyl.
  • heteroaryl-Ci-salkyl refers to a radical of the
  • Ci-salkoxy-Ci-galkyl refers to a radical of the
  • ''Ci_ 8 alkoxy-Ci_ 8 alkyl-amino refers to a radical of the formula: -NH-Ci_ 8 alkyl-0-Ci_ 8 alkyl.
  • (Ci- 8 alkoxy-Ci_ 8 alkyl)2-amino refers to a radical of the formula: -N(Ci- 8 alkyl-0-Ci_ 8 alkyl) 2 .
  • Ci_ 8 alkoxy-Ci_ 8 alkyl-amino-Ci_ 8 alkoxy refers to a radical of the formula: -0-Ci_ 8 alkyl-NH-Ci_ 8 alkyl-0-Ci_ 8 alkyl.
  • (Ci- 8 alkoxy-Ci- 8 alkyl) 2 -amino-Ci- 8 alkoxy refers to a radical of the formula: -0-Ci- 8 alkyl-N(Ci_ 8 alkyl-0-Ci- 8 alkyl) 2 .
  • (Ci- 8 alkoxy-Ci- 8 alkyl)(Ci- 8 alkyl)amino-Ci_ 8 alkoxy refers to a radical of the formula: -0-Ci- 8 alkyl-N(Ci-8alkyl)(Ci-8alkyl-0-Ci- 8 alkyl).
  • Ci_ 8 alkoxy-Ci_ 8 alkyl-amino-Ci_ 8 alky ' refers to a radical of the formula: -Ci_ 8 alkyl-NH-Ci_ 8 alkyl-0-Ci_ 8 alkyl.
  • (Ci- 8 alkoxy-Ci- 8 alkyl) 2 -amino-Ci- 8 alky ' refers to a radical of the formula: -Ci- 8 alkyl-N(Ci-8alkyl-0-Ci-8alkyl) 2 .
  • (Ci_ 8 alkoxy-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino-Ci_ 8 alkyl refers to a radical of the formula: -Ci_ 8 alkyl-N(Ci_ 8 alkyl)(Ci_ 8 alkyl-0-Ci_ 8 alkyl).
  • Ci- 8 alkoxy-carbonyl refers to a radical of the
  • Ci_ 8 alkoxy-carbonyl-C 2 _ 8 alkeny ' refers to a radical of the formula: -C 2 _ 8 alkenyl-C(0)-0-Ci_ 8 alkyl.
  • Ci_ 8 alkoxy-carbonyl-amino refers to a radical of the formula: -NH-C(0)-0-Ci_ 8 alkyl.
  • heteroaryl-C i_ 8 alkoxy refers to a radical of the
  • Ci_ 8 alkyl-amino refers to a radical of the
  • (Ci_ 8 alkyl) 2 -amino refers to a radical of the
  • Ci- 8 alkyl-amino-C 2 - 8 alkenyl refers to a radical of the formula: -C 2 - 8 alkenyl-NH-Ci_ 8 alkyl.
  • (Ci_ 8 alkyl) 2 -amino-C 2 _ 8 alkenyl refers to a radical of the formula: -C 2 _ 8 alkenyl-N(Ci_ 8 alkyl) 2 .
  • Ci- 8 alkyl-amino-Ci_ 8 alkoxy refers to a radical of the formula: -0-Ci_ 8 alkyl-NH-Ci_ 8 alkyl.
  • (Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkoxy refers to a radical of the formula: -0-Ci_ 8 alkyl-N(Ci_ 8 alkyl) 2 .
  • Ci- 8 alkyl-amino-Ci- 8 alkyl refers to a radical of the formula: -Ci- 8 alkyl-NH-Ci_ 8 alkyl.
  • (Ci-salkyl ⁇ -amino-Ci-salkyl” refers to a radical of the formula: -Ci_ 8 alkyl-N(Ci- 8 alkyl) 2 .
  • ''Ci_ 8 alkyl-amino-Ci_ 8 alkyl-amino refers to a radical of the formula: -NH-Ci_ 8 alkyl-NH-Ci_ 8 alkyl.
  • (Ci- 8 alkyl)2-amino-Ci_ 8 alkyl-amino refers to a radical of the formula: -NH-Ci- 8 alkyl-N(Ci_ 8 alkyl) 2 .
  • (Ci_ 8 alkyl-amino-Ci_ 8 alkyl) 2 -amino refers to a radical of the formula: -N(Ci_ 8 alkyl-NH-Ci_ 8 alkyl) 2 .
  • [(Ci- 8 alkyl)2-amino-Ci- 8 alkyl] 2 -amino refers to a radical of the formula: -N[Ci- 8 alkyl-N(Ci- 8 alkyl) 2 ] 2 -
  • (Ci_ 8 alkyl-amino-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino refers to a radical of the formula: -N(Ci_ 8 alkyl)(Ci_ 8 alkyl-NH-Ci_ 8 alkyl).
  • Ci_ 8 alkyl-amino-C 2 - 8 alkynyl refers to a radical of the formula: -C 2 - 8 alkynyl-NH-Ci_ 8 alkyl.
  • (Ci- 8 alkyl)2-amino-C2- 8 alkynyl refers to a radical of the formula: -C 2 - 8 alkynyl-N(Ci_ 8 alkyl) 2 .
  • Ci_ 8 alkyl-carbonyl refers to a radical of the
  • Ci_ 8 alkyl-carbonyl-amino refers to a radical of the
  • Ci_ 8 alkyl-thio refers to a radical of the formula: -S-Ci_ 8 alkyl.
  • amino-C 2 - 8 alkenyl refers to a radical of the
  • amino-Ci_ 8 alkoxy refers to a radical of the
  • amino-Ci_ 8 alkyl refers to a radical of the
  • amino-Ci_ 8 alkyl-amino refers to a radical of the
  • (amino-Ci_ 8 alkyl) 2 -amino refers to a radical of the formula: -N(Ci- 8 alkyl-NH 2 ) 2 -
  • (amino-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino refers to a radical of the formula: -N(Ci_ 8 alkyl)(Ci_ 8 alkyl-NH 2 ).
  • amino-C 2 - 8 alkynyl refers to a radical of the
  • aryl-Ci-salkoxy-carbonyl refers to a radical of the
  • aryl-Ci- 8 alkyl refers to a radical of the formula: -Ci- 8 alkyl-aryl.
  • aryl-Ci_ 8 alkyl-amino refers to a radical of the
  • (aryl-Ci_ 8 alkyl) 2 -amino refers to a radical of the
  • (aryl-Ci- 8 alkyl)(Ci_ 8 alkyl)amino refers to a radical of the formula: -N(Ci_ 8 alkyl)(Ci_ 8 alkyl-aryl).
  • aryl-Ci_ 8 alkyl-amino-Ci_ 8 alkyl refers to a radical of the formula: -Ci_ 8 alkyl-NH-Ci_ 8 alkyl-aryl.
  • (aryl-Ci- 8 alkyl) 2 -amino-Ci- 8 alkyl refers to a radical of the formula: -Ci_ 8 alkyl-N(Ci_ 8 alkyl-aryl) 2 .
  • (aryl-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino-Ci_ 8 alkyl refers to a radical of the formula: -Ci- 8 alkyl-N(Ci- 8 alkyl)(Ci_ 8 alkyl-aryl).
  • aryl-amino refers to a radical of the formula: -NH-aryl.
  • aryl-amino-carbonyl refers to a radical of the
  • aryl-sulfonyloxy-Ci_ 8 alkyl refers to a radical of the
  • benzoxy-carbonyl refers to a radical of the
  • C 3 -i 4 cycloalkyl-Ci_ 8 alkyl refers to a radical of the
  • C 3 _i 4 cycloalkyl-amino refers to a radical of the
  • C 3 _i 4 cycloalkyl-oxy refers to a radical of the
  • aryl-oxy refers to a radical of the formula: -O-aryl.
  • halo or halogen generally refers to a halogen atom radical, including fluoro, chloro, bromo and iodo.
  • halo-Ci_ 8 alkoxy refers to a radical of the
  • Ci_ 8 alkyl is partially or completely substituted with one or more halogen atoms where allowed by available valences.
  • halo-Ci_ 8 alkyl refers to a radical of the
  • Ci_ 8 alkyl-halo wherein Ci_ 8 alkyl is partially or completely substituted with one or more halogen atoms where allowed by available valences.
  • halo-Ci_ 8 alkyl-amino refers to a radical of the
  • halo-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino refers to a radical of the formula: -N(Ci_ 8 alkyl)(Ci_ 8 alkyl-halo).
  • halo-Ci_ 8 alkyl) 2 -amino refers to a radical of the
  • heteroaryl-Ci_ 8 alkoxy refers to a radical of the
  • heteroaryl-Ci- 8 alkyl refers to a radical of the
  • heteroaryl-Ci_ 8 alkyl-amino refers to a radical of the formula: -NH-Ci_ 8 alkyl-heteroaryl.
  • heteroaryl-Ci_ 8 alkyl) 2 -amino refers to a radical of the formula: -N(Ci_ 8 alkyl-heteroaryl) 2 .
  • heteroaryl-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino refers to a radical of the formula: -N(Ci- 8 alkyl)(Ci_ 8 alkyl-heteroaryl).
  • heteroaryl-Ci- 8 alkyl-amino-Ci- 8 alkyl refers to a radical of the formula: -Ci_ 8 alkyl-NH-Ci_ 8 alkyl-heteroaryl.
  • (heteroaryl-Ci-salkyl ⁇ -amino-Ci-galkyl) refers to a radical of the formula: -Ci-8alkyl-N(Ci_8alkyl-heteroaryl)2.
  • heteroaryl-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino-Ci_ 8 alkyl refers to a radical of the formula: -Ci_ 8 alkyl-N(Ci_ 8 alkyl)(Ci_ 8 alkyl-heteroaryl).
  • heteroaryl- amino refers to a radical of the
  • heterocyclyl-Ci-salkoxy refers to a radical of the
  • heterocyclyl-Ci-galkyl refers to a radical of the
  • heterocyclyl-Ci-galkyl-amino refers to a radical of the formula: -NH-Ci-galkyl-heterocyclyl.
  • heterocyclyl-Ci_ 8 alkyl 2 -amino refers to a radical of the formula: -N(Ci_8alkyl-heterocyclyl)2.
  • heterocyclyl-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino refers to a radical of the formula: -N(Ci_ 8 alkyl)(Ci_ 8 alkyl-heterocyclyl).
  • heterocyclyl-Ci-salkyl-amino-Ci-salkyl refers to a radical of the formula: -Ci-galkyl-NH-Ci-galkyl-heterocyclyl.
  • heterocyclyl-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl refers to a radical of the formula: -Ci_8alkyl-N(Ci_8alkyl-heterocyclyl) 2 .
  • heterocyclyl-Ci- 8 alkyl)(Ci- 8 alkyl)amino-Ci_ 8 alkyl refers to a radical of the formula: -Ci- 8 alkyl-N(Ci- 8 alkyl)(Ci_ 8 alkyl-heterocyclyl).
  • heterocyclyl-amino refers to a radical of the
  • (heterocyclyl)(Ci_ 8 alkyl)amino refers to a radical of the formula: -N(Ci_ 8 alkyl)(heterocyclyl).
  • heterocyclyl-amino-Ci-salkyl refers to a radical of the formula: -Ci-galkyl-NH-heterocyclyl.
  • heterocyclyl-carbonyl refers to a radical of the
  • heterocyclyl-carbonyl-oxy refers to a radical of the formula: -0-C(0)-heterocyclyl.
  • heterocyclyl-oxy refers to a radical of the
  • hydroxy refers to a radical of the formula: -OH.
  • hydroxy-Ci-galkoxy-Ci-galkyl refers to a radical of the formula: -Ci_ 8 alkyl-0-Ci_ 8 alkyl-OH.
  • hydroxy-Ci_ 8 alkyl refers to a radical of the
  • Ci_ 8 alkyl-OH formula: -Ci_ 8 alkyl-OH, wherein Ci_ 8 alkyl is partially or completely substituted with one or more hydroxy radicals where allowed by available valences.
  • hydroxy-Ci_ 8 alkyl-amino refers to a radical of the
  • (hydroxy-Ci_ 8 alkyl)2-amino refers to a radical of the formula: -N(Ci_ 8 alkyl-OH) 2 .
  • hydroxy-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino refers to a radical of the formula: -N(Ci_ 8 alkyl)(Ci_ 8 alkyl-OH).
  • hydroxy-Ci- 8 alkyl-amino-Ci_ 8 alkyl refers to a radical of the formula: -Ci- 8 alkyl-NH-Ci_ 8 alkyl-OH.
  • (hydroxy-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alky ' refers to a radical of the formula: -Ci_ 8 alkyl-N(Ci_ 8 alkyl-OH) 2 .
  • hydroxy-Ci- 8 alkyl)(Ci- 8 alkyl)amino-Ci_ 8 alkyl refers to a radical of the formula: -Ci_ 8 alkyl-N(Ci- 8 alkyl)(Ci_ 8 alkyl-OH).
  • hydroxy-Ci_ 8 alkyl-amino-Ci_ 8 alkoxy refers to a radical of the formula: -0-Ci_ 8 alkyl-NH-Ci_ 8 alkyl-OH.
  • (hydroxy-Ci- 8 alkyl) 2 -amino-Ci- 8 alkoxy refers to a radical of the formula: -0-Ci- 8 alkyl-N(Ci_ 8 alkyl-OH) 2 .
  • hydroxy-Ci_ 8 alkyl)(Ci_ 8 alkyl)amino-Ci_ 8 alkoxy refers to a radical of the formula: -0-Ci_ 8 alkyl-N(Ci_ 8 alkyl)(Ci_ 8 alkyl-OH).
  • hydroxy-Ci- 8 alkyl-amino-Ci_ 8 alkyl-amino refers to a radical of the formula: -NH-Ci- 8 alkyl-NH-Ci_ 8 alkyl-OH.
  • (hydroxy-Ci- 8 alkyl-amino-Ci_ 8 alkyl) 2 -amino refers to a radical of the formula: -N(Ci_ 8 alkyl-NH-Ci- 8 alkyl-OH) 2 .
  • (hydroxy-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl-amino refers to a radical of the formula: -NH-Ci_ 8 alkyl-N(Ci_ 8 alkyl-OH) 2 .
  • hydroxy-Ci- 8 alkyl-amino-Ci- 8 alkyl)(Ci_ 8 alkyl)amino refers to a radical of the formula: -N(Ci- 8 alkyl)(Ci- 8 alkyl-NH-Ci_ 8 alkyl-OH).
  • the term "[(hydroxy-Ci_ 8 alkyl) 2 -amino-Ci_ 8 alkyl](Ci_ 8 alkyl)amino" refers to a radical of the formula: -N(Ci_ 8 alkyl)[Ci_ 8 alkyl-N(Ci_ 8 alkyl-OH) 2 ].
  • hydroxy-Ci- 8 alkyl)(Ci- 8 alkyl)amino-Ci_ 8 alkyl-amino refers to a radical of the formula: -NH-Ci_ 8 alkyl-N(Ci- 8 alkyl,Ci_ 8 alkyl-OH).
  • substituted 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.
  • 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.
  • 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.
  • each functionality appearing at any location within the disclosed compound may be independently selected, and as appropriate, independently and/or optionally substituted.
  • 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.
  • 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.
  • each instance of or “in each instance, when present,” when used preceding a phrase such as "...C 3 _i 4 cycloalkyl, C 3 -i 4 cycloalkyl-Ci- 4 alkyl, aryl, aryl-Ci- 4 alkyl, heteroaryl, heteroaryl-Ci- 4 alkyl, heterocyclyl and heterocyclyl-Ci- 4 alkyl,” are intended to refer to the C 3 _i 4 cycloalkyl, aryl, heteroaryl and heterocyclyl ring systems when each are present either alone or as a substituent.

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AU2018282154A AU2018282154B2 (en) 2017-06-05 2018-06-05 Compounds for treating huntington's disease
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IL300875A IL300875B2 (en) 2017-06-05 2018-06-05 Compounds for the treatment of Huntington's disease
EP22203869.7A EP4151627A1 (en) 2017-06-05 2018-06-05 Compounds for treating huntington's disease
SG11201911615WA SG11201911615WA (en) 2017-06-05 2018-06-05 Compounds for treating huntington's disease
EP18813494.4A EP3634953B1 (en) 2017-06-05 2018-06-05 Compounds for treating huntington's disease
BR112019025740-3A BR112019025740A2 (pt) 2017-06-05 2018-06-05 Compostos para tratar a doença de huntington
US16/617,450 US11407753B2 (en) 2017-06-05 2018-06-05 Compounds for treating Huntington's disease
MX2019014514A MX2019014514A (es) 2017-06-05 2018-06-05 Compuestos para tratar la enfermedad de huntington.
KR1020207000124A KR20200033249A (ko) 2017-06-05 2018-06-05 헌팅턴병 치료 화합물
JP2020516795A JP7376471B2 (ja) 2017-06-05 2018-06-05 ハンチントン病を処置するための化合物
CN201880050893.7A CN111065626B (zh) 2017-06-05 2018-06-05 用于治疗亨廷顿氏舞蹈病的化合物
CA3066224A CA3066224A1 (en) 2017-06-05 2018-06-05 Compounds for treating huntington's disease
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IL271046A IL271046B2 (en) 2017-06-05 2019-11-28 Compounds for the treatment of Huntington's disease
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Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10874672B2 (en) 2015-12-10 2020-12-29 Ptc Therapeutics, Inc. Methods for treating Huntington's disease
WO2021014428A1 (en) 2019-07-25 2021-01-28 Novartis Ag Regulatable expression systems
WO2021084495A1 (en) 2019-11-01 2021-05-06 Novartis Ag The use of a splicing modulator for a treatment slowing progression of huntington's disease
WO2022006550A1 (en) 2020-07-02 2022-01-06 Remix Therapeutics Inc. 2-(indazol-5-yl)-6-(piperidin-4-yl)-1,7-naphthyridine derivatives and related compounds as modulators for splicing nucleic acids and for the treatment of proliferative diseases
WO2022006543A1 (en) 2020-07-02 2022-01-06 Remix Therapeutics Inc. 5-[5-(piperidin-4-yl)thieno[3,2-c]pyrazol-2-yl]indazole derivatives and related compounds as modulators for splicing nucleic acids and for the treatment of proliferative diseases
WO2022103980A1 (en) 2020-11-12 2022-05-19 Ptc Therapeutics Inc. Novel rna transcript
US20220151938A1 (en) * 2022-01-28 2022-05-19 Ptc Therapeutics, Inc. Tablet for use in treating huntington's disease and method of making the same
US11382918B2 (en) 2017-06-28 2022-07-12 Ptc Therapeutics, Inc. Methods for treating Huntington's Disease
US11395822B2 (en) 2017-06-28 2022-07-26 Ptc Therapeutics, Inc. Methods for treating Huntington's disease
US11407753B2 (en) 2017-06-05 2022-08-09 Ptc Therapeutics, Inc. Compounds for treating Huntington's disease
US11685746B2 (en) 2018-06-27 2023-06-27 Ptc Therapeutics, Inc. Heteroaryl compounds for treating Huntington's disease
WO2023133225A1 (en) * 2022-01-05 2023-07-13 Remix Therapeutics Inc. Compounds and methods for modulating splicing
WO2023170115A1 (en) * 2022-03-10 2023-09-14 F. Hoffmann-La Roche Ag Pyrido[1,2-a]pyrimidin-4-one derivatives
US11780839B2 (en) 2018-03-27 2023-10-10 Ptc Therapeutics, Inc. Compounds for treating Huntington's disease
US11806346B2 (en) 2020-05-13 2023-11-07 Chdi Foundation, Inc. HTT modulators for treating Huntington's disease
WO2023225244A1 (en) * 2022-05-20 2023-11-23 Biogen Ma Inc. Heterocyclic compounds for treating huntington's disease
US11858941B2 (en) 2018-06-27 2024-01-02 Ptc Therapeutics, Inc. Heterocyclic and heteroaryl compounds for treating Huntington's disease
US20240226098A1 (en) * 2020-02-28 2024-07-11 Remix Therapeutics Inc. Compounds and methods for modulating splicing
US12139499B2 (en) 2018-06-27 2024-11-12 Ptc Therapeutics, Inc. Heteroaryl compounds for treating Huntington's disease
US12281116B2 (en) 2021-11-17 2025-04-22 Chdi Foundation, Inc. HTT modulators for treating Huntington's disease
US12577226B2 (en) 2019-05-13 2026-03-17 Ptc Therapeutics, Inc. Compounds for treating Huntington's disease

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW202237119A (zh) 2020-12-10 2022-10-01 美商住友製藥腫瘤公司 Ａｌｋ﹘５抑制劑和彼之用途
WO2022194802A1 (en) * 2021-03-17 2022-09-22 F. Hoffmann-La Roche Ag New thiadiazolopyrimidone derivatives
BR112023018466A2 (pt) * 2021-03-17 2023-10-10 Hoffmann La Roche Derivados de tiazolopirimidinona
WO2025217430A1 (en) * 2024-04-11 2025-10-16 Board Of Regents, The University Of Texas System Heterocyclic compounds as nras inhibitors

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5916916A (en) * 1996-10-10 1999-06-29 Eli Lilly And Company 1-aryloxy-2-arylnaphthyl compounds, intermediates, compositions, and methods
US6468607B1 (en) * 1998-04-22 2002-10-22 Dainippon Ink And Chemicals, Inc. Naphthalene derivative and liquid crystal composition comprising the same
WO2005019215A1 (en) 2003-08-22 2005-03-03 Warner-Lambert Company Llc [1,8]naphthyridin-2-ones and related compounds for the treatment of schizophrenia
US20070191374A1 (en) * 2004-04-08 2007-08-16 Neurogen Coroperation Substituted cinnolin-4-ylamines
US20110118289A1 (en) * 2008-06-20 2011-05-19 Rottapharm S.P.A. 6-1h-imidazo-quinazoline and quinolines derivatives, new mao inhibitors and imidazoline receptor ligands
WO2012104823A2 (en) 2011-02-04 2012-08-09 Novartis Ag Pyridopyrimidinone compounds in the treatment of neurodegenerative diseases
US20150057218A1 (en) * 2010-05-24 2015-02-26 Presidio Pharmaceuticals, Inc. Inhibitors of hcv ns5a
US20170096411A1 (en) * 2015-10-02 2017-04-06 Incyte Corporation Heterocyclic compounds useful as pim kinase inhibitors

Family Cites Families (208)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL297170A (https=) 1963-04-04 1900-01-01
US3558618A (en) 1968-04-01 1971-01-26 Dow Chemical Co Novel 4h-pyrazino(1,2-a)pyrimidine-4-ones
GB1383409A (en) 1972-09-09 1974-02-12 Pfizer Ltd Derivatives of 2-amino- and 4-amino-quinazoline and pharmaceutical compositions containing them
US4122274A (en) 1977-05-25 1978-10-24 Bristol-Myers Company 3-Tetrazolo-5,6,7,8-substituted-pyrido[1,2-a]pyrimidin-4-ones
US4342870A (en) 1980-03-28 1982-08-03 Janssen Pharmaceutica N.V. Novel 3-(1-piperidinylalkyl)-4H-pyrido[1,2-a]pyrimidin-4-one derivatives
JPS56150091A (en) 1980-03-28 1981-11-20 Janssen Pharmaceutica Nv 3-(1-piperidinylalkyl)-4h-pyrido(1,2-a)pyrimidine- 4-one derivative and its manufacture
JPS5852307A (ja) 1981-09-22 1983-03-28 Hitachi Chem Co Ltd 水分散樹脂組成物
FR2567518B1 (fr) 1984-07-11 1987-11-13 Sanofi Sa Nouveaux composes a noyau heterocyclique azote, leur preparation et les medicaments qui en contiennent
US5089633A (en) 1987-04-28 1992-02-18 Georgia Tech Research Corporation Substituted isocoumarins
US4902695A (en) 1989-02-13 1990-02-20 Eli Lilly And Company Excitatory amino acid receptor antagonists
US5599816A (en) 1990-05-02 1997-02-04 Abbott Laboratories Quinolizinone type compounds
EP0640083A1 (en) 1992-05-13 1995-03-01 E.I. Du Pont De Nemours And Company Substituted pyrido 1,2-a]pyrimidinone derivatives as fungicides
DE69435005T2 (de) 1993-05-11 2008-04-17 The University Of North Carolina At Chapel Hill Antisense Oligonukleotide die anomales Splicing verhindern und deren Verwendung
WO1994026877A1 (en) 1993-05-17 1994-11-24 The Regents Of The University Of California Ribozyme gene therapy for hiv infection and aids
KR19990022524A (ko) 1995-06-06 1999-03-25 웨인스톡 스티븐 에프. 퀴놀리지논형화합물
US5869500A (en) 1996-12-13 1999-02-09 Hoffmann-La Roche Inc. Pyridone compounds useful in treating Alzheimer's disease
AU5991699A (en) 1998-09-21 2000-04-10 Biochem Pharma Inc. Quinolizinones as integrin inhibitors
US6172216B1 (en) 1998-10-07 2001-01-09 Isis Pharmaceuticals Inc. Antisense modulation of BCL-X expression
US6214986B1 (en) 1998-10-07 2001-04-10 Isis Pharmaceuticals, Inc. Antisense modulation of bcl-x expression
US6210892B1 (en) 1998-10-07 2001-04-03 Isis Pharmaceuticals, Inc. Alteration of cellular behavior by antisense modulation of mRNA processing
WO2001030757A1 (en) 1999-10-28 2001-05-03 Microcide Pharmaceuticals, Inc. Drug discharge pump inhibitors
CN1891693A (zh) 2000-01-24 2007-01-10 基纳西亚股份有限公司 用于治疗的吗啉代基取代的化合物
CA2437942C (en) 2000-11-09 2013-06-11 Cold Spring Harbor Laboratory Chimeric molecules to modulate gene expression
US6774134B2 (en) 2000-12-20 2004-08-10 Bristol-Myers Squibb Company Heterocyclic substituted 2-methyl-benzimidazole antiviral agents
US6989385B2 (en) 2000-12-21 2006-01-24 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
US20050009843A1 (en) 2001-04-26 2005-01-13 Kiyoshi Nakayama Medicine for inhibiting drug elimination pump
ATE466581T1 (de) 2001-12-07 2010-05-15 Vertex Pharma Verbindungen auf pyrimidin-basis als gsk-3-hemmer
GB0205281D0 (en) 2002-03-06 2002-04-17 Novartis Ag Organic compounds
AU2003256755A1 (en) 2002-07-24 2004-02-09 Ptc Therapeutics, Inc. Ureido substituted benzoic acid compounds, their use for nonsense suppression and the treatment of diseases caused by such mutations
AU2003262833A1 (en) 2002-08-23 2004-03-11 The Board Of Trustees Of The Leland Stanford Junior University Fluorescent glycosides and methods for their use
EP1785425B1 (en) 2002-09-30 2009-03-25 NeuroSearch A/S 1,4-Diazabicycloalkane derivatives, their preparation and use
AU2003291329A1 (en) * 2002-11-12 2004-06-03 Abbott Laboratories Bicyclic-substituted amines as histamine-3 receptor ligands
US20070078144A1 (en) 2003-01-29 2007-04-05 Stockwell Brent R Agents for treating neurodegenerative diseases
US20040224952A1 (en) 2003-05-07 2004-11-11 Cowart Marlon D. Fused bicyclic-substituted amines as histamine-3 receptor ligands
CN1809563A (zh) 2003-06-20 2006-07-26 希龙公司 吡啶并[1,2－a]嘧啶－4－酮化合物用作抗癌药
GB0315494D0 (en) 2003-07-02 2003-08-06 Biofocus Plc Compounds which bind to the active site of protein kinase enzymes
JP2007501189A (ja) * 2003-08-01 2007-01-25 ジェネラブス テクノロジーズ，インコーポレイテッド フラビウイルス科に対する二環式イミダゾール誘導体
US20050074801A1 (en) 2003-09-09 2005-04-07 Monia Brett P. Chimeric oligomeric compounds comprising alternating regions of northern and southern conformational geometry
US20050245531A1 (en) 2003-12-22 2005-11-03 Abbott Laboratories Fused bicycloheterocycle substituted quinuclidine derivatives
US7655657B2 (en) 2003-12-22 2010-02-02 Abbott Laboratories Fused bicycloheterocycle substituted quinuclidine derivatives
US7309699B2 (en) 2003-12-22 2007-12-18 Abbott Laboratories 3-Quinuclidinyl amino-substituted biaryl derivatives
US20050137203A1 (en) 2003-12-22 2005-06-23 Jianguo Ji 3-quinuclidinyl amino-substituted biaryl derivatives
NZ551468A (en) 2003-12-24 2010-05-28 Biota Scient Management Polycyclic agents for the treatment of respiratory syncytial virus infections
SE0400184D0 (sv) 2004-01-30 2004-01-30 Fyrkloevern Scandinavia Ab New therapeutical use
TW200536830A (en) 2004-02-06 2005-11-16 Chugai Pharmaceutical Co Ltd 1-(2H)-isoquinolone derivative
ZA200609267B (en) * 2004-04-08 2009-02-25 Targegen Inc Benzotriazine inhibitors of kinases
ATE373659T1 (de) 2004-05-04 2007-10-15 Warner Lambert Co Pyrrolylsubstituierte pyrido(2,3-d)pyrimidin-7- one und derivate davon als therapeutische mittel
AU2006206446A1 (en) 2005-01-21 2006-07-27 Janssen Pharmaceutica N.V. Novel heterocyclic benzo[c]chromene derivatives useful as modulators of the estrogen receptors
US7879992B2 (en) 2005-01-31 2011-02-01 Isis Pharmaceuticals, Inc. Modification of MyD88 splicing using modified oligonucleotides
GB0501999D0 (en) * 2005-02-01 2005-03-09 Sentinel Oncology Ltd Pharmaceutical compounds
JP2006219453A (ja) * 2005-02-14 2006-08-24 Tokyo Univ Of Pharmacy & Life Science キノリン環を母核とする金属識別型二波長性蛍光分子
US7563601B1 (en) 2005-06-01 2009-07-21 City Of Hope Artificial riboswitch for controlling pre-mRNA splicing
WO2006138418A2 (en) * 2005-06-14 2006-12-28 President And Fellows Of Harvard College Improvement of cognitive performance with sirtuin activators
MX2007015675A (es) 2005-07-04 2008-02-20 Novo Nordisk As Antagonistas del receptor de histamina h3.
US7473784B2 (en) 2005-08-01 2009-01-06 Bristol-Myers Squibb Company Benzothiazole and azabenzothiazole compounds useful as kinase inhibitors
US7576110B2 (en) 2005-09-22 2009-08-18 Abbott Laboratories Benzothiazole cyclobutyl amine derivatives
WO2007047913A2 (en) 2005-10-20 2007-04-26 Isis Pharmaceuticals, Inc Compositions and methods for modulation of lmna expression
US20070179123A1 (en) * 2005-11-08 2007-08-02 Chiang Peter K Methods and compositions for treating diseases associated with pathogenic proteins
WO2007058894A2 (en) 2005-11-10 2007-05-24 The University Of North Carolina At Chapel Hill Splice switching oligomers for tnf superfamily receptors and their use in treatment of disease
ATE473978T1 (de) 2005-12-06 2010-07-15 Neurosearch As Neue diazabicyclische arylderivate und medizinische verwendung dafür
KR20080089416A (ko) * 2005-12-21 2008-10-06 페인셉터 파마 코포레이션 개폐 이온 통로를 조절하기 위한 조성물 및 방법
EP1991677A2 (en) 2006-01-26 2008-11-19 Isis Pharmaceuticals, Inc. Compositions and their uses directed to huntingtin
AU2007211082B2 (en) 2006-01-27 2012-09-27 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of microRNAs
AR059339A1 (es) 2006-02-09 2008-03-26 Chugai Pharmaceutical Co Ltd Derivados de la cumarina para trastornos proliferativos de celulas, composicion farmaceutica y agente terapeutico que los contiene
US8110681B2 (en) 2006-03-17 2012-02-07 The United States Of America As Represented By The Secretary, Department Of Health And Human Services Compounds for the treatment of spinal muscular atrophy and other uses
CN101410385B (zh) 2006-03-28 2011-08-24 高点制药有限责任公司 具有组胺h3受体活性的苯并噻唑类
WO2007130383A2 (en) 2006-04-28 2007-11-15 Northwestern University Compositions and treatments using pyridazine compounds and secretases
US20080247964A1 (en) 2006-05-08 2008-10-09 Yuelian Xu Substituted azaspiro derivatives
TW200812588A (en) 2006-05-15 2008-03-16 Neurogen Corp CRF1 receptor ligands comprising heteroaryl fused bicycles
WO2007135121A1 (en) 2006-05-23 2007-11-29 Neurosearch A/S Novel 8,10-diaza-bicyclo[4.3.1]decane derivatives and their medical use
DE602007006835D1 (de) * 2006-07-20 2010-07-08 Amgen Inc Substituierte pyridonverbindungen und anwendungsverfahren
US8337941B2 (en) 2006-07-27 2012-12-25 The Trustees Of Columbia University In The City Of New York Fluorescent substrates for monoamine transporters as optical false neurotransmitters
EP2066653B1 (en) * 2006-08-03 2012-09-12 Rottapharm S.p.A. 6-1h-imidazo-quinazoline and quinolines derivatives, new potent analgesics and anti-inflammatory agents
WO2008020302A2 (en) * 2006-08-17 2008-02-21 Pfizer Products Inc. Heteroaromatic quinoline-based compounds as phosphodiesterase (pde) inhibitors
WO2008049864A1 (en) 2006-10-25 2008-05-02 Neurosearch A/S Oxadiazole and thiadiazole compounds and their use as nicotinic acetylcholine receptor modulators
US8314119B2 (en) 2006-11-06 2012-11-20 Abbvie Inc. Azaadamantane derivatives and methods of use
JP5208962B2 (ja) 2006-12-22 2013-06-12 アベキサ・リミテッド 二環式ピリミジノンおよびその使用
US20080171792A1 (en) 2006-12-28 2008-07-17 Jobdevairakkam Christopher New Use of highly concentrated formulations of 4-phenylbutyrate for treatment of certain disorders
FR2914188B1 (fr) 2007-03-28 2012-06-22 Trophos Nouvelle composition a base d'oxime de cholest-4-en-3-one
EP2014656A3 (en) 2007-06-11 2011-08-24 High Point Pharmaceuticals, LLC New heteocyclic h3 antagonists
HUE025976T2 (en) 2007-09-27 2016-05-30 Fund Centro Nac De Investig Oncologicas Carlos Iii Imidazolothiadiazoles for use as protein kinase inhibitors
EP2215074B1 (en) 2007-09-27 2014-02-19 The United States of America, as Represented by the Secretary, Department of Health and Human Services Isoindoline compounds for the treatment of spinal muscular atrophy and other uses
US8153813B2 (en) 2007-12-20 2012-04-10 Abbott Laboratories Benzothiazole and benzooxazole derivatives and methods of use
US8993580B2 (en) 2008-03-14 2015-03-31 Intellikine Llc Benzothiazole kinase inhibitors and methods of use
WO2009126635A1 (en) 2008-04-09 2009-10-15 Abbott Laboratories 2-amino-benzothiazole derivates useful as inhibitors of rock kinases
US20090264433A1 (en) 2008-04-21 2009-10-22 Institute For Oneworld Health Compounds, Compositions and Methods Comprising Triazine Derivatives
WO2009151546A2 (en) 2008-05-27 2009-12-17 Ptc Therapeutics, Inc. Methods for treating spinal muscular atrophy
EP2138493A1 (en) 2008-06-26 2009-12-30 Sanofi-Aventis Substituted pyrimidone derivatives
PL2212324T3 (pl) 2008-07-02 2014-11-28 Avexa Ltd Związki posiadające właściwości przeciwwirusowe
WO2010019243A1 (en) 2008-08-13 2010-02-18 Ptc Therapeutics, Inc. Methods for treating viral infections
EP2337609B1 (en) 2008-08-14 2016-08-17 Cardiac Pacemakers, Inc. Performance assessment and adaptation of an acoustic communication link
WO2010024903A1 (en) 2008-08-29 2010-03-04 Yangbo Feng BENZO[d]OXAZOLES AND BENZO[d]THIAZOLES AS KINASE INHIBITORS
AU2009303441A1 (en) 2008-10-16 2010-04-22 Schering Corporation Pyrrolidine, piperidine and piperazine derivatives and methods of use thereof
GB2465405A (en) 2008-11-10 2010-05-19 Univ Basel Triazine, pyrimidine and pyridine analogues and their use in therapy
WO2010071819A1 (en) 2008-12-19 2010-06-24 Schering Corporation Bicyclic heterocyclic derivatives and methods of use thereof
BRPI1008020A2 (pt) 2009-02-11 2016-03-15 Sunovion Pharmaceuticals Inc antagonistas e agonistas inversos h3 da histamina e métodos de uso dos mesmos
FR2945289A1 (fr) 2009-05-11 2010-11-12 Sanofi Aventis Derives de 2-cycloamino-5-(pyridin-4-yl)imidazo°2,1-b! °1,3,4!thiadiazole, leur preparation et leur application en therapeutique
US8765747B2 (en) 2009-06-12 2014-07-01 Dana-Farber Cancer Institute, Inc. Fused 2-aminothiazole compounds
AU2010262643B2 (en) 2009-06-19 2015-02-19 Abbvie Inc. Diazahomoadamantane derivatives and methods of use thereof
NZ714887A (en) 2009-09-11 2019-07-26 Ionis Pharmaceuticals Inc Modulation of huntingtin expression
WO2011050245A1 (en) 2009-10-23 2011-04-28 Yangbo Feng Bicyclic heteroaryls as kinase inhibitors
WO2011057204A2 (en) 2009-11-06 2011-05-12 The Johns Hopkins University Lrrk2-mediated neuronal toxicity
EP2501231B1 (en) 2009-11-20 2016-12-21 Merck Sharp & Dohme Corp. Quinolizidinone carboxamide m1 receptor positive allosteric modulators
CN102812023A (zh) 2010-01-13 2012-12-05 韩国巴斯德研究所 抗感染吡啶并(1,2-a)嘧啶类
CA2789038A1 (en) 2010-02-08 2011-08-11 Isis Pharmaceuticals, Inc. Selective reduction of allelic variants
JP2013518603A (ja) 2010-02-08 2013-05-23 アイシス ファーマシューティカルズ， インコーポレーテッド 反復伸張に関連する疾患または病態の治療に有用な方法および組成物
US8957040B2 (en) 2010-02-08 2015-02-17 Isis Pharmaceuticals, Inc. Selective reduction of allelic variants
US8940716B2 (en) 2010-05-06 2015-01-27 Bristol-Myers Squibb Company Bicyclic heteroaryl compounds as GPR119 modulators
EP2595663A4 (en) 2010-07-19 2014-03-05 Isis Pharmaceuticals Inc MODULATION OF DYSTROPHIA MYOTONICA PROTEIN KINASE (DMPK) EXPRESSION
WO2012019106A2 (en) * 2010-08-06 2012-02-09 Board Of Regents Of The University Of Nebraska Positive and negative modulators of nmda receptors
WO2012075393A2 (en) 2010-12-02 2012-06-07 President And Fellows Of Harvard College Activators of proteasomal degradation and uses thereof
CN102617548A (zh) 2011-01-31 2012-08-01 北京赛林泰医药技术有限公司 作为gpr受体激动剂的双环杂芳基化合物及其组合物和应用
EA034451B1 (ru) * 2011-02-07 2020-02-10 Байоджен Ма Инк. Модуляторы s1p
EP2673361B1 (en) 2011-02-08 2016-04-13 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
US8703763B2 (en) 2011-03-02 2014-04-22 Hoffmann-La Roche Inc. Bridged piperidine derivatives
US9447075B2 (en) 2011-08-02 2016-09-20 The Brigham And Women's Hospital, Inc. Pyridazine derivatives as EAAT2 activators
US8871756B2 (en) 2011-08-11 2014-10-28 Hoffmann-La Roche Inc. Compounds for the treatment and prophylaxis of Respiratory Syncytial Virus disease
US10202599B2 (en) 2011-08-11 2019-02-12 Ionis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
US20130046093A1 (en) 2011-08-18 2013-02-21 Korea Institute Of Science And Technology Pharmaceutical compositions for preventing or treating degenerative brain disease and method of screening the same
WO2013033223A1 (en) 2011-08-29 2013-03-07 Isis Pharmaceuticals, Inc. Methods and compounds useful in conditions related to repeat expansion
US9662314B2 (en) 2011-10-21 2017-05-30 Tufts Medical Center, Inc. Compounds and methods for the treatment of muscular disease, and related screening methods
GB201119538D0 (en) 2011-11-10 2011-12-21 Viral Ltd Pharmaceutical compounds
BR112014012815A8 (pt) 2011-11-28 2017-06-20 Novartis Ag derivados de trifluormetil-oxadiazol e uso dos mesmos no tratamento de doença
KR102057351B1 (ko) 2011-12-30 2019-12-18 피티씨 테라퓨틱스, 인크. 척수성 근위축증을 치료하기 위한 화합물
PL2809322T3 (pl) 2012-01-26 2019-11-29 Ptc Therapeutics Inc Związki do leczenia zaniku mięśni pochodzenia rdzeniowego
DK2812004T3 (en) 2012-02-10 2018-10-15 Ptc Therapeutics Inc COMPOUNDS FOR TREATMENT OF SPINAL MUSCLE DROPHY
CN104302181B (zh) 2012-03-01 2017-09-15 Ptc医疗公司 用于治疗脊髓性肌萎缩的化合物
KR102109992B1 (ko) 2012-03-23 2020-05-13 피티씨 테라퓨틱스, 인크. 척수성 근위축증을 치료하기 위한 화합물
EP2844643B1 (en) 2012-04-03 2016-11-30 Bristol-Myers Squibb Company Pyrimidinedione carboxamide inhibitors of endothelial lipase
MX371331B (es) 2012-04-24 2020-01-27 Vertex Pharma Inhibidores de la proteina cinasa dependiente de acido desoxirribonucleico(adn-pk).
WO2013171642A1 (en) 2012-05-15 2013-11-21 Novartis Ag Benzamide derivatives for inhibiting the activity of abl1, abl2 and bcr-abl1
US9212209B2 (en) 2012-07-13 2015-12-15 Indiana University Research And Technology Corporation Screening methods for spinal muscular atrophy
US8729263B2 (en) 2012-08-13 2014-05-20 Novartis Ag 1,4-disubstituted pyridazine analogs there of and methods for treating SMN-deficiency-related conditions
EP3459549B1 (en) 2012-10-12 2022-04-06 Ionis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
EP2906255B1 (en) 2012-10-12 2023-02-22 Ionis Pharmaceuticals, Inc. Antisense compounds and uses thereof
HUE039970T2 (hu) 2012-10-25 2019-02-28 Usher Iii Initiative Inc Pirazolopiridazinok és eljárás degeneratív retina betegségek és Usher-szindrómával összefüggõ hallásvesztés kezelésére
US9227976B2 (en) 2012-10-25 2016-01-05 Usher Iii Initiative, Inc. Pyrazolopyridazines and methods for treating retinal-degenerative diseases and hearing loss associated with usher syndrome
JP6255711B2 (ja) * 2012-11-01 2018-01-10 株式会社リコー エレクトロクロミック化合物、エレクトロクロミック組成物及び表示素子
US9040712B2 (en) 2013-01-23 2015-05-26 Novartis Ag Thiadiazole analogs thereof and methods for treating SMN-deficiency-related-conditions
WO2014121287A2 (en) 2013-02-04 2014-08-07 Isis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
AU2014224975B2 (en) 2013-03-05 2017-09-14 Merck Patent Gmbh Triazolo(4,5-d)pyrimidine derivatives for the treatment of diseases such as cancer
EP2997028A1 (en) 2013-05-14 2016-03-23 F.Hoffmann-La Roche Ag Aza-oxo-indoles for the treatment and prophylaxis of respiratory syncytial virus infection
WO2014209841A2 (en) 2013-06-25 2014-12-31 F. Hoffmann-La Roche Ag Compounds for treating spinal muscular atrophy
KR20210130843A (ko) 2013-07-31 2021-11-01 노파르티스 아게 1,4-이치환된 피리다진 유사체 및 smn-결핍-관련 상태를 치료하기 위한 그의 용도
WO2015024876A2 (en) 2013-08-19 2015-02-26 F. Hoffmann-La Roche Ag Screening method
WO2015095449A1 (en) 2013-12-19 2015-06-25 Ptc Therapeutics, Inc. Methods for modulating the amount rna transcripts
WO2015095446A1 (en) 2013-12-19 2015-06-25 Ptc Therapeutics, Inc. Methods for modulating the amount of rna transcripts
EP3082820B1 (en) 2013-12-19 2022-07-20 PTC Therapeutics, Inc. Methods for modulating the amount of rna transcripts
BR112016016400A2 (pt) 2014-01-16 2017-10-03 Wave Life Sciences Ltd Composições de oligonucleotídeos quiralmente controlados, seu uso, sua composição farmacêutica, e métodos
WO2015107494A1 (en) 2014-01-17 2015-07-23 Novartis Ag 1 -(triazin-3-yi_/pyridazin-3-yl)-piper(-azine)idine derivatives and compositions thereof for inhibiting the activity of shp2
AR099134A1 (es) 2014-01-24 2016-06-29 Hoffmann La Roche Procedimiento para la preparación de n-[(3-aminooxetán-3-il)metil]-2-(1,1-dioxo-3,5-dihidro-1,4-benzotiazepín-4-il)-6-metil-quinazolín-4-amina
TWI674257B (zh) 2014-03-14 2019-10-11 日商拉夸里亞創藥股份有限公司 作為ｔｒｐｍ８拮抗劑之氮雜螺衍生物
AU2015231239B2 (en) * 2014-03-19 2018-11-29 Amydis, Inc. Amyloid targeting agents and methods of using the same
SI3143025T1 (sl) 2014-05-15 2020-01-31 F. Hoffmann-La Roche Ag Spojine za zdravljenje spinalne mišične atrofije
GB201410693D0 (en) 2014-06-16 2014-07-30 Univ Southampton Splicing modulation
US20170121197A1 (en) 2014-06-17 2017-05-04 Novozymes A/S Biological Phosphorus Removal from Wastewater
BR112016026951B1 (pt) 2014-06-25 2022-09-20 F. Hoffmann-La Roche Ag Imidazo[1,2-a]pirazin-1-il-benzamida, seu uso, e composições farmacêuticas
MX381224B (es) 2014-10-31 2025-03-12 Massachusetts Gen Hospital Potentes moduladores de gamma-secretasa.
GB201419579D0 (en) * 2014-11-03 2014-12-17 Iomet Pharma Ltd Pharmaceutical compound
BR112017011791A2 (pt) 2014-12-02 2018-02-27 Bayer Cropscience Aktiengesellschaft compostos bicíclicos como agentes de controle de pragas
HRP20190992T1 (hr) 2014-12-24 2019-09-20 Uniqure Ip B.V. Suprimiranje gena za huntingtin inducirano s rnai
CA2973949C (en) 2015-01-16 2023-07-11 The General Hospital Corporation Compounds for improving mrna splicing
WO2016128343A1 (en) 2015-02-09 2016-08-18 F. Hoffmann-La Roche Ag Compounds for the treatment of cancer
GB201502567D0 (en) 2015-02-16 2015-04-01 Sentinel Oncology Ltd Pharmaceutical compounds
CN112679467B (zh) 2015-03-11 2024-11-01 Fmc公司 杂环取代的二环唑杀有害生物剂
WO2016163190A1 (ja) 2015-04-07 2016-10-13 株式会社フジクラ ルースチューブ、ルースチューブ型光ファイバケーブル、ルースチューブの光ファイバテープの単心分離方法、ルースチューブの製造方法、及び、複数の光ファイバの集線方法
GB201506933D0 (en) * 2015-04-23 2015-06-10 Sentinel Oncology Ltd Pharmaceutical compounds
CN104897232B (zh) * 2015-04-30 2018-10-12 青岛海尔股份有限公司 冰箱与冰箱的使用容积检测方法
EP3298017B1 (en) 2015-05-20 2019-08-14 H. Hoffnabb-La Roche Ag Compounds for treating spinal muscular atrophy
EP4249472A3 (en) 2015-05-30 2023-12-13 PTC Therapeutics, Inc. Methods for modulating rna splicing
IL320434A (en) 2015-07-22 2025-06-01 Wave Life Sciences Ltd Oligonucleotide preparations and methods
WO2017023987A1 (en) 2015-08-03 2017-02-09 Samumed, Llc. 3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridines and therapeutic uses thereof
JP6659841B2 (ja) 2015-11-12 2020-03-04 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ 脊髄性筋萎縮症を処置するための組成物
WO2017081111A1 (en) 2015-11-12 2017-05-18 F. Hoffmann-La Roche Ag Compounds for treating amyotrophic lateral sclerosis
US10383867B2 (en) * 2015-11-28 2019-08-20 Russell Dahl Quinoline derivatives and their use for treating endoplasmic reticulum stress-related diseases and disorders
IL294124B2 (en) 2015-12-10 2024-02-01 Ptc Therapeutics Inc Methods for treating huntington's disease
WO2017097728A1 (en) 2015-12-10 2017-06-15 F. Hoffmann-La Roche Ag Bridged piperidine derivatives
BR112018068066B1 (pt) 2016-03-11 2023-11-28 Ac Immune Sa Compostos bicíclicos e seu uso, composição diagnóstica e farmacêutica, misturas, métodos de coleção de dados para diagnóstico, para determinar uma predisposição a, para monitorar transtorno residual e para prever a capacidade de resposta de um paciente sofrendo de transtorno ou anormalidade associado com agregados de alfa-sinucleína, métodos para determinar a quantidade de agregados de alfa-sinucleína e para preparar um composto, kit teste e kit para preparar uma preparação radio farmacêutica
JP6549785B2 (ja) 2016-04-01 2019-07-24 京セラ株式会社 ユーザ装置及び方法
US10526345B2 (en) 2016-04-08 2020-01-07 Mankind Pharma Ltd. Compounds as GPR119 agonists
AR108325A1 (es) 2016-04-27 2018-08-08 Samumed Llc Isoquinolin-3-il carboxamidas y preparación y uso de las mismas
EP3452596A4 (en) 2016-05-04 2020-03-18 Wave Life Sciences Ltd. OLIGONUCLEOTIDE COMPOSITIONS AND RELATED METHODS
WO2017210134A1 (en) 2016-05-31 2017-12-07 Board Of Regents, University Of Texas System Heterocyclic inhibitors of ptpn11
KR102494647B1 (ko) 2016-07-14 2023-01-31 브리스톨-마이어스 스큅 컴퍼니 비시클릭 헤테로아릴 치환된 화합물
WO2018022473A1 (en) 2016-07-25 2018-02-01 Wave Life Sciences Ltd. Phasing
TW202500565A (zh) 2016-10-24 2025-01-01 美商傳達治療有限公司 Shp2磷酸酶抑制劑及其使用方法
WO2018187209A1 (en) 2017-04-03 2018-10-11 Acceleron Pharma Inc. Compositions and methods for treating spinal muscular atrophy
EP3630770B1 (en) 2017-05-26 2024-08-28 Relay Therapeutics, Inc. Pyrazolo[3,4-b]pyrazine derivatives as shp2 phosphatase inhibitors
US11407753B2 (en) 2017-06-05 2022-08-09 Ptc Therapeutics, Inc. Compounds for treating Huntington's disease
WO2019005993A1 (en) 2017-06-28 2019-01-03 Ptc Therapeutics, Inc. METHODS OF TREATING HUNTINGTON'S DISEASE
US11382918B2 (en) 2017-06-28 2022-07-12 Ptc Therapeutics, Inc. Methods for treating Huntington's Disease
WO2019028440A1 (en) 2017-08-04 2019-02-07 Skyhawk Therapeutics, Inc. METHODS AND COMPOSITIONS FOR MODULATING SPLICING
WO2019165073A1 (en) 2018-02-21 2019-08-29 Relay Therapeutics, Inc. Shp2 phosphatase inhibitors and methods of use thereof
US12138263B2 (en) 2018-03-21 2024-11-12 Relay Therapeutics, Inc. Pyrazolo[3,4-b]pyrazine SHP2 phosphatase inhibitors and methods of use thereof
AU2019240299B2 (en) 2018-03-21 2023-06-22 D.E. Shaw Research, Llc SHP2 phosphatase inhibitors and methods of use thereof
MX2020009957A (es) 2018-03-27 2021-01-15 Ptc Therapeutics Inc Compuestos para el tratamiento de enfermedad de hungtinton.
EP3814345B8 (en) 2018-06-27 2024-10-30 PTC Therapeutics, Inc. Heteroaryl compounds for treating huntington's disease
EP3814360B8 (en) 2018-06-27 2024-11-06 PTC Therapeutics, Inc. Heteroaryl compounds for treating huntington's disease
PL3814357T3 (pl) 2018-06-27 2024-09-16 Ptc Therapeutics, Inc. Związki heterocykliczne i heteroarylowe do leczenia choroby huntingtona
JP2022525417A (ja) 2019-03-15 2022-05-13 スカイホーク・セラピューティクス・インコーポレーテッド 異常スプライシングを修正するための組成物および方法
WO2020231977A1 (en) 2019-05-13 2020-11-19 Ptc Therapeutics, Inc. Compounds for treating huntington's disease
WO2021007378A1 (en) 2019-07-11 2021-01-14 Ptc Therapeutics, Inc. Compounds for use in treating huntington's disease
AU2020377204A1 (en) 2019-11-01 2022-06-02 Novartis Ag The use of a splicing modulator for a treatment slowing progression of huntington's disease
JP7736700B2 (ja) 2020-02-28 2025-09-09 リミックス セラピューティクス インコーポレイテッド 複素環アミド及びスプライシングを調節するためのその使用
MX2022012575A (es) 2020-04-09 2023-01-24 Ptc Therapeutics Inc Compuestos para usarse para tratar la enfermedad de huntington.
WO2022103980A1 (en) 2020-11-12 2022-05-19 Ptc Therapeutics Inc. Novel rna transcript
WO2023009816A1 (en) 2021-07-30 2023-02-02 Ptc Therapeutics, Inc. Heteroaryl compounds for treating huntington's disease
JP2025522298A (ja) 2022-06-15 2025-07-15 ピーティーシー セラピューティクス， インコーポレイテッド ハンチントン病を処置するための複素環式及びヘテロアリール化合物

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5916916A (en) * 1996-10-10 1999-06-29 Eli Lilly And Company 1-aryloxy-2-arylnaphthyl compounds, intermediates, compositions, and methods
US6468607B1 (en) * 1998-04-22 2002-10-22 Dainippon Ink And Chemicals, Inc. Naphthalene derivative and liquid crystal composition comprising the same
WO2005019215A1 (en) 2003-08-22 2005-03-03 Warner-Lambert Company Llc [1,8]naphthyridin-2-ones and related compounds for the treatment of schizophrenia
US20070191374A1 (en) * 2004-04-08 2007-08-16 Neurogen Coroperation Substituted cinnolin-4-ylamines
US20110118289A1 (en) * 2008-06-20 2011-05-19 Rottapharm S.P.A. 6-1h-imidazo-quinazoline and quinolines derivatives, new mao inhibitors and imidazoline receptor ligands
US20150057218A1 (en) * 2010-05-24 2015-02-26 Presidio Pharmaceuticals, Inc. Inhibitors of hcv ns5a
WO2012104823A2 (en) 2011-02-04 2012-08-09 Novartis Ag Pyridopyrimidinone compounds in the treatment of neurodegenerative diseases
US20170096411A1 (en) * 2015-10-02 2017-04-06 Incyte Corporation Heterocyclic compounds useful as pim kinase inhibitors

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
"The Orange Book", FOOD & DRUG ADMINISTRATION
ANDERSON: "The Practice of Medicinal Chemistry", 1996, ACADEMIC PRESS
P. GOULD, INTERNATIONAL J. OF PHARMACEUTICS, vol. 33, 1986, pages 201 - 217
P. STAHL: "Handbook of P arnwceutical Salts. Properties, Selection and Use.", 2002, WILEY-VCH
S. BERGE, JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 66, no. 1, 1977, pages 1 - 19
T. HIGUCHIW. STELLA: "A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design", vol. 14, 1987, AMERICAN PHARMACEUTICAL ASSOCIATION, article "Pro-drugs as Novel Delivery Systems"
T.W. GREENE ET AL.: "Protective Groups in organic Synthesis", 1991, WILEY

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10881658B2 (en) 2015-12-10 2021-01-05 Ptc Therapeutics, Inc. Methods for treating Huntington's disease
US11638706B2 (en) 2015-12-10 2023-05-02 Ptc Therapeutics, Inc. Methods for treating Huntington's disease
US10874672B2 (en) 2015-12-10 2020-12-29 Ptc Therapeutics, Inc. Methods for treating Huntington's disease
US12384789B2 (en) 2017-06-05 2025-08-12 Ptc Therapeutics, Inc. Compounds for treating Huntington's disease
US11407753B2 (en) 2017-06-05 2022-08-09 Ptc Therapeutics, Inc. Compounds for treating Huntington's disease
US11395822B2 (en) 2017-06-28 2022-07-26 Ptc Therapeutics, Inc. Methods for treating Huntington's disease
US11382918B2 (en) 2017-06-28 2022-07-12 Ptc Therapeutics, Inc. Methods for treating Huntington's Disease
US12103926B2 (en) 2018-03-27 2024-10-01 Ptc Therapeutics, Inc. Compounds for treating huntington's disease
US11780839B2 (en) 2018-03-27 2023-10-10 Ptc Therapeutics, Inc. Compounds for treating Huntington's disease
US12139499B2 (en) 2018-06-27 2024-11-12 Ptc Therapeutics, Inc. Heteroaryl compounds for treating Huntington's disease
US11685746B2 (en) 2018-06-27 2023-06-27 Ptc Therapeutics, Inc. Heteroaryl compounds for treating Huntington's disease
US11858941B2 (en) 2018-06-27 2024-01-02 Ptc Therapeutics, Inc. Heterocyclic and heteroaryl compounds for treating Huntington's disease
US12577226B2 (en) 2019-05-13 2026-03-17 Ptc Therapeutics, Inc. Compounds for treating Huntington's disease
WO2021014428A1 (en) 2019-07-25 2021-01-28 Novartis Ag Regulatable expression systems
WO2021084495A1 (en) 2019-11-01 2021-05-06 Novartis Ag The use of a splicing modulator for a treatment slowing progression of huntington's disease
US20240226098A1 (en) * 2020-02-28 2024-07-11 Remix Therapeutics Inc. Compounds and methods for modulating splicing
US11806346B2 (en) 2020-05-13 2023-11-07 Chdi Foundation, Inc. HTT modulators for treating Huntington's disease
WO2022006543A1 (en) 2020-07-02 2022-01-06 Remix Therapeutics Inc. 5-[5-(piperidin-4-yl)thieno[3,2-c]pyrazol-2-yl]indazole derivatives and related compounds as modulators for splicing nucleic acids and for the treatment of proliferative diseases
WO2022006550A1 (en) 2020-07-02 2022-01-06 Remix Therapeutics Inc. 2-(indazol-5-yl)-6-(piperidin-4-yl)-1,7-naphthyridine derivatives and related compounds as modulators for splicing nucleic acids and for the treatment of proliferative diseases
JP2023532332A (ja) * 2020-07-02 2023-07-27 リミックス セラピューティクス インコーポレイテッド 核酸のスプライシング及び増殖性疾患の処置のためのモジュレーターとしての２－（インダゾール－５－イル）－６－（ピペリジン－４－イル）－１，７－ナフチリジン誘導体及び関連する化合物
WO2022103980A1 (en) 2020-11-12 2022-05-19 Ptc Therapeutics Inc. Novel rna transcript
US12281116B2 (en) 2021-11-17 2025-04-22 Chdi Foundation, Inc. HTT modulators for treating Huntington's disease
WO2023133225A1 (en) * 2022-01-05 2023-07-13 Remix Therapeutics Inc. Compounds and methods for modulating splicing
US20220151938A1 (en) * 2022-01-28 2022-05-19 Ptc Therapeutics, Inc. Tablet for use in treating huntington's disease and method of making the same
WO2023170115A1 (en) * 2022-03-10 2023-09-14 F. Hoffmann-La Roche Ag Pyrido[1,2-a]pyrimidin-4-one derivatives
WO2023225244A1 (en) * 2022-05-20 2023-11-23 Biogen Ma Inc. Heterocyclic compounds for treating huntington's disease

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