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AR088258A1 - Inhibidores de la pde10 de azetidina 1,3-sustituida - Google Patents

Inhibidores de la pde10 de azetidina 1,3-sustituida

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Publication number
AR088258A1
AR088258A1 ARP120103729A ARP120103729A AR088258A1 AR 088258 A1 AR088258 A1 AR 088258A1 AR P120103729 A ARP120103729 A AR P120103729A AR P120103729 A ARP120103729 A AR P120103729A AR 088258 A1 AR088258 A1 AR 088258A1
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AR
Argentina
Prior art keywords
substituted
groups
alkyl
heterocycle
aryl
Prior art date
Application number
ARP120103729A
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English (en)
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Merck Sharp & Dohme
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Application filed by Merck Sharp & Dohme filed Critical Merck Sharp & Dohme
Publication of AR088258A1 publication Critical patent/AR088258A1/es

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    • 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
    • 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
    • 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
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P25/22—Anxiolytics
    • 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
    • A61P25/24—Antidepressants
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • 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

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Psychiatry (AREA)
  • Addiction (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La presente se dirige a compuestos de azetidina sustituida que son útiles como agentes terapéuticos para el tratamiento de los trastornos del sistema nervioso central asociados con la fosfodiesterasa 10 (PDE10). También se refiere al uso de dichos compuestos para tratar trastornos neurológicos y psiquiátricos tales como la esquizofrenia, la psicosis o la enfermedad de Huntington, y aquéllos asociados con la hipofunción del estriado o la disfunción de los ganglios basales. Reivindicación 1: Un compuesto de la fórmula (1), en la que: X¹, X² y X³ son independientemente CH o N; R se selecciona del grupo que consiste en H y alquilo C₁₋₆; R² se selecciona del grupo que consiste en H, O-alquilo C₁₋₆, alquilo C₁₋₆, haloalquilo C₁₋₃, (CH₂)ₙ-cicloalquilo C₃₋₁₀, CN; (CH₂)ₙ-heterociclo C₅₋₁₀, estando dichos alquilo, cicloalquilo y heterociclo opcionalmente sustituidos con 1 a 3 grupos de Rᵃ; R³ se selecciona del grupo que consiste en NRC(O)R⁶, C(O)OR⁶, C(O)NR⁶R⁶ y (CH₂)ₙ-heterociclo C₅₋₁₀, estando dicho heterociclo opcionalmente sustituido con 1 a 3 grupos de Rᵃ; R⁵ es (CH₂)ₙ-arilo C₆₋₁₀, (CH₂)ₙ-heterociclo C₅₋₁₀, (CH₂)ₙ-cicloalquilo C₃₋₁₀, estando dichos cicloalquilo, heterociclo y arilo opcionalmente sustituidos con 1 a 3 grupos de Rᵃ; R⁶ se selecciona de los grupos que consisten en H, alquilo C₁₋₆, OR, (CH₂)ₙ-cicloalquilo C₃₋₁₀, -NH(CH₂)ₙ-OR, (CH₂)ₙ-arilo C₆₋₁₀, -N(R)₂, (CH₂)ₙ-heterociclo C₆₋₁₀, estando dichos alquilo, cicloalquilo, heterociclo y arilo opcionalmente sustituidos con 1 a 3 grupos de Rᵃ; Rᵃ se selecciona del grupo que consiste en: (i) halógeno, (ii) hidroxilo, (iii) alquilo C₁₋₆, que no está sustituido o está sustituido con 1 a 3 grupos de Rᵇ, (iv) -O-alquilo C₁₋₆, que no está sustituido o está sustituido con 1 a 3 grupos de Rᵇ, (v) (CH₂)ₙ-arilo C₆₋₁₀, que no está sustituido o está sustituido con 1 a 3 grupos de Rᵇ, (vi) -O-(CH₂)ₙ-heterociclo C₅₋₁₀, que no está sustituido o está sustituido con 1 a 3 grupos de Rᵇ, (vii) -(CH₂)ₙ-heterociclo C₅₋₁₀, que no está sustituido o está sustituido con 1 a 3 grupos de Rᵇ, (viii) -O-(CH₂)ₙ-arilo C₆₋₁₀, que no está sustituido o está sustituido con 1 a 3 grupos de Rᵇ, (ix) -(CH₂)ₙ-arilo C₆₋₁₀, que no está sustituido o está sustituido con 1 a 3 grupos de Rᵇ, (x) -O-(CH₂)ₙ-cicloalquilo C₃₋₁₀, que no está sustituido o está sustituido con 1 a 3 grupos de Rᵇ, (xi) -(CH₂)ₙ-cicloalquilo C₃₋₁₀, que no está sustituido o está sustituido con 1 a 3 grupos de Rᵇ, (xii) -NH-alquilo C₁₋₆ o -N(alquil C₁₋₆)(alquilo C₁₋₆), que no está sustituido o está sustituido con 1 a 3 grupos de Rᵇ, (xiii) -O-(CH₂)ₙ-SO₂-arilo C₆₋₁₀, que no está sustituido o está sustituido con 1 a 3 grupos de Rᵇ, (xiv) -(CH₂)ₙ-CO₂R, (xv) -CN, (xvi) -NO₂, (xvii) -(O)₀₋₁-haloalquilo C₁₋₅; (xviii) alquinil C₂₋₆-heterociclo C₅₋₁₀, que no está sustituido o está sustituido con 1 a 3 grupos de Rᵇ; (xix) alquenilo C₂₋₆; (xx) C(O)R, (xxi) NH(CH₂)ₙ-OR, -NH(CH₂)ₙ-arilo C₆₋₁₀, -NH(CH₂)ₙ-cicloalquilo C₃₋₁₀, -NH(CH₂)ₙ-alquilo C₁₋₆, -NRR, -NHC(O)alquilo C₁₋₆, -N(alquil C₁₋₆)(CH₂)ₙ-arilo C₆₋₁₀ o -NHSO₂-alquilo C₁₋₆, estando dichos alquilo, cicloalquilo y arilo opcionalmente sustituidos con 1 a 3 grupos de Rᵇ; Rᵇ se selecciona del grupo que consiste en: (i) halógeno, (ii) hidroxilo, (iii) alquilo C₁₋₆, (iv) -O-alquilo C₁₋₆, (v) (CH₂)ₙ-arilo C₆₋₁₀, (vi) (CH₂)ₙ-heterociclo C₅₋₁₀, (vii) haloalquilo C₁₋₅; y n representa 0 - 4; o una de sus sales farmacéuticamente aceptables.
ARP120103729A 2011-10-06 2012-10-05 Inhibidores de la pde10 de azetidina 1,3-sustituida AR088258A1 (es)

Applications Claiming Priority (1)

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US201161544065P 2011-10-06 2011-10-06

Publications (1)

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AR088258A1 true AR088258A1 (es) 2014-05-21

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US (1) US9365562B2 (es)
EP (1) EP2763672B1 (es)
JP (1) JP2014528446A (es)
AR (1) AR088258A1 (es)
AU (1) AU2012318874A1 (es)
CA (1) CA2851082A1 (es)
TW (1) TW201321369A (es)
WO (1) WO2013052395A1 (es)

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GEP20166432B (en) 2011-09-27 2016-02-10 Novartis Ag 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant idh
UY34632A (es) 2012-02-24 2013-05-31 Novartis Ag Compuestos de oxazolidin- 2- ona y usos de los mismos
US9296733B2 (en) 2012-11-12 2016-03-29 Novartis Ag Oxazolidin-2-one-pyrimidine derivative and use thereof for the treatment of conditions, diseases and disorders dependent upon PI3 kinases
EP2919783B1 (en) 2012-11-15 2018-01-31 Merck Sharp & Dohme Corp. Cyclopropyl imidazopyridine pde10 inhibitors
WO2014078216A1 (en) * 2012-11-15 2014-05-22 Merck Sharp & Dohme Corp. Cyclobutyl benzimidazoles as pde10 inhibitors
TW201422610A (zh) * 2012-11-15 2014-06-16 Merck Sharp & Dohme 作爲ｐｄｅ１０抑制劑之經二級醇取代之三唑
US9663513B2 (en) 2012-11-20 2017-05-30 Merck Sharp & Dohme Corp. Pyrimidine PDE10 inhibitors
US9273033B2 (en) 2012-11-20 2016-03-01 Merck Sharp & Dohme Corp. Substituted pyridone derivatives as PDE10 inhibitors
ES2480341B1 (es) * 2013-01-24 2015-01-22 Palobiofarma S.L Nuevos derivados de pirimidina como inhibidores de la fosfodiesterasa 10 (PDE-10)
WO2014141104A1 (en) 2013-03-14 2014-09-18 Novartis Ag 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant idh
FR3040057A1 (fr) * 2015-08-13 2017-02-17 Inventiva Composes de type azetidine carboxylique
US10583269B2 (en) 2016-06-01 2020-03-10 Becton, Dickinson And Company Magnetized catheters, devices, uses and methods of using magnetized catheters
US20200199136A1 (en) * 2017-08-28 2020-06-25 Acurastem Inc. Pikfyve kinase inhibitors
RS65335B1 (sr) 2018-10-05 2024-04-30 Annapurna Bio Inc Jedinjenja i kompozicije za lečenje stanja povezanih sa aktivnošću receptora apj
WO2021163727A1 (en) * 2020-02-11 2021-08-19 AcuraStem Incorporated Pikfyve kinase inhibitors
WO2025049402A1 (en) * 2023-08-28 2025-03-06 Quanta Therapeutics, Inc. Kras modulators and uses thereof

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EP1863797A1 (en) * 2005-03-23 2007-12-12 AstraZeneca AB 2-AZETIDINYL-4-(lH-PYRAZOL-3-YLAMINO)PYRIMIDINES AS INHIBITORS OF INSULIN-LIKE GROWTH FACTOR-I RECEPTOR ACTIVITY
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ME02419B (me) 2011-08-25 2016-09-20 Merck Sharp & Dohme Inhibitori pirimidina pde10

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Publication number Publication date
CA2851082A1 (en) 2013-04-11
EP2763672B1 (en) 2016-08-10
TW201321369A (zh) 2013-06-01
US9365562B2 (en) 2016-06-14
EP2763672A1 (en) 2014-08-13
JP2014528446A (ja) 2014-10-27
EP2763672A4 (en) 2015-03-04
WO2013052395A1 (en) 2013-04-11
AU2012318874A1 (en) 2014-05-15
US20140256708A1 (en) 2014-09-11

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