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AR107335A1 - Derivados de quinolin-2-ona - Google Patents

Derivados de quinolin-2-ona

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Publication number
AR107335A1
AR107335A1 ARP170100065A ARP170100065A AR107335A1 AR 107335 A1 AR107335 A1 AR 107335A1 AR P170100065 A ARP170100065 A AR P170100065A AR P170100065 A ARP170100065 A AR P170100065A AR 107335 A1 AR107335 A1 AR 107335A1
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AR
Argentina
Prior art keywords
denotes
aza
spiro
nhet
oxa
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ARP170100065A
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English (en)
Inventor
Esdar Christina Dra
Czodrowski Paul Dr
Wucherer-Plietker Margarita Dra
Burgdorf Lars Dr
Mathilde Muzerelle
Dorsch Dieter Dr
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Merck Patent Ges Mit Beschraenkter Haftung
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Publication of AR107335A1 publication Critical patent/AR107335A1/es

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    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
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    • C07D401/02—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 two hetero rings
    • C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
    • A61K31/4704—2-Quinolinones, e.g. carbostyril
    • A—HUMAN NECESSITIES
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    • 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
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    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
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    • 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
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    • 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
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 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
    • 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
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • 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
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    • 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
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    • 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
    • C07D487/10—Spiro-condensed systems
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    • 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
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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
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  • Medicinal Chemistry (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Reivindicación 1: Los compuestos de la fórmula (1), en la cual X¹, X², X³, X⁴ cada uno, independientemente entre sí, denota CH o N; Y denota N o CH; Q denota H o CH₃; R¹ denota H, F, Cl, Br, CN, CH₃, CF₃ u OCH₃; R² denota H, F o Cl; R³ denota fenilo, naftilo, piridilo, pirimidinilo, quinolinilo, isoquinolinilo, indolilo, indazolilo, tiofenilo, dihidroisoindolilo o benzimidazolilo, cada uno de los cuales está sin sustituir o es sustituido una, dos o tres veces con Hal, CN, NO₂, A, (CR⁴)ₙOR⁴, (CR⁴)ₙN(R⁴)₂, (CR⁴)ₙS(O)ₘR⁴, (CR⁴)ₙCON(R⁴)₂, (CR⁴)ₙCOHet, (CR⁴)ₙSO₂N(R⁴)₂, (CR⁴)ₙSO₂Het, (CR⁴)ₙN(R⁴)₂, (CR⁴)ₙHet, O(CR⁴)ₙCOHet, (CR⁴)ₙO(CR⁴)ₙHet, (CR⁴)ₙN(R⁴)(CR⁴)ₙHet, (CR⁴)ₙCON(R⁴)(CR⁴)ₙHet, (CR⁴)ₙCON(R⁴)(CR⁴)ₙN(R⁴)₂, (CR⁴)ₙN(R⁴)COA, (CR⁴)ₙN(R⁴)COHet’, (CR⁴)ₙOCyc y/o (CR⁴)ₙCOOR⁴; R⁴ denota H o A’; A denota alquilo no ramificado o ramificado con 1 - 10 átomos de C, donde dos átomos de carbono adyacentes pueden formar un enlace doble y/o uno o dos grupos CH y/o CH₂ no adyacentes pueden ser reemplazados con átomos de N, O y/o S y donde 1 - 7 átomos de H pueden ser reemplazados con R⁵, o alquilo cíclico que tiene 3 - 7 átomos de C; A’ denota alquilo no ramificado o ramificado con 1 - 6 átomos de C, donde uno o dos grupos CH y/o CH₂ no adyacentes pueden ser reemplazados con átomos de O; Cyc denota ciclobutilo, ciclopentilo o ciclohexilo, cada uno de los cuales está sin sustituir o está sustituido una o dos veces con A, Hal, OR⁴, N(R⁴)₂, Het’, (CR⁴)ₙO(CR⁴)ₙHet’, CON(R⁴)₂ y/o =O; R⁵ denota F, Cl u OH; Het denota pirrolidinilo, morfolinilo, piperidinilo, piperazinilo, [1,4]-diazepanilo, oxazolidinilo, hexahidro-pirrolo[3,4-c]pirrolilo, 2-oxa-6-aza-espiro[3.4]octanilo, 2-oxa-6-aza-espiro[3.5]nonanilo, 2-oxa-7-aza-espiro[3.5]nonanilo, 2,5-dioxa-8-aza-espiro[3.5]nonanilo, oxetanilo, 2-oxa-5-aza-espiro[3.4]octanilo, 2-oxa-6-aza-espiro[3.3]heptanilo, 3-aza-biciclo[3.1.0]hexanilo, 2-oxa-7-aza-espiro[3.5]nonanilo, isoxazolidinilo, azetidinilo, 2,6-diaza-espiro[3.4]octanilo, hexahidro-pirrolo[3,4-b]pirrolilo, tetrahidrofuranilo o isotiazolidinilo, cada uno de los cuales está sin sustituir o está sustituido una, dos o tres veces con A, Hal, OR⁴, OCOA, COA, (CR⁴)ₙN(R⁴)₂, (CR⁴)ₙHet’, (CR⁴)ₙO(CR⁴)ₙHet’, CON(R⁴)₂, COHet’, (CR⁴)ₙS(O)ₘR⁴, y/o =O; Het’ denota pirrolidinilo, morfolinilo, piperidinilo, oxetanilo, tetrahidrofuranilo, tetrahidropiranilo, piridilo, pirazolilo o piperazinilo, cada uno de los cuales está sin sustituir o está sustituido una o dos veces con A, Hal, OR⁴, N(R⁴)₂ y/o =O; Hal denota F, Cl, Br o I; n denota 0, 1, 2 ó 3; m denota 0, 1 ó 2; con la condición de que solamente uno o dos de X¹, X², X³, X⁴ denote N; y sus sales, tautómeros y esteroisómeros farmacéuticamente aceptables, caracterizados porque incluyen las mezclas de los mismos en todas las relaciones.
ARP170100065A 2016-01-11 2017-01-11 Derivados de quinolin-2-ona AR107335A1 (es)

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CR20240382A (es) 2018-05-01 2025-08-29 Revolution Medicines Inc ANÁLOGOS DE RAPAMICINA A C40, C28 Y C32 COMO INHIBIDORES DE MTOR (Divisional 2020-578)
EP3788050B1 (en) 2018-05-01 2024-08-28 Revolution Medicines, Inc. C26-linked rapamycin analogs as mtor inhibitors
WO2020102095A1 (en) * 2018-11-12 2020-05-22 Blueprint Medicines Corporation Avapritinib resistance of kit mutants
ES3015269T3 (en) * 2019-02-11 2025-04-30 Merck Patent Gmbh Indazolyl-isoxazole derivatives for the treatment of diseases such as cancer
CN114364798A (zh) 2019-03-21 2022-04-15 欧恩科斯欧公司 用于治疗癌症的Dbait分子与激酶抑制剂的组合
JP2023500906A (ja) 2019-11-08 2023-01-11 インサーム（インスティテュ ナシオナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシェ メディカル） キナーゼ阻害剤に対する獲得抵抗性を有するがんの処置方法
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