AR092924A1 - Derivados de pirrolidinona como moduladores de gpr119 para el tratamiento de diabetes, obesidad, dislipidemia y trastornos relacionados - Google Patents

Derivados de pirrolidinona como moduladores de gpr119 para el tratamiento de diabetes, obesidad, dislipidemia y trastornos relacionados

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Publication number
AR092924A1
AR092924A1 ARP130103626A ARP130103626A AR092924A1 AR 092924 A1 AR092924 A1 AR 092924A1 AR P130103626 A ARP130103626 A AR P130103626A AR P130103626 A ARP130103626 A AR P130103626A AR 092924 A1 AR092924 A1 AR 092924A1
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AR
Argentina
Prior art keywords
alkyl
series consisting
derivatives
series
gpr119
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ARP130103626A
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English (en)
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Sanofi Sa
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Publication of AR092924A1 publication Critical patent/AR092924A1/es

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    • 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/12—Oxygen or sulfur atoms
    • 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
    • C07D401/02—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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • 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
    • C07D407/00—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
    • 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
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    • 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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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La presente se refiere a derivados de pirrolidinona. Los derivados de pirrolidina son moduladores de GPR119 y son útiles para la prevención y/o el tratamiento de diabetes, obesidad, dislipidemia y trastornos relacionados. La presente se refiere además al uso de derivados de pirrolidinona como ingredientes activos en sustancias farmacéuticas, y composiciones farmacéuticas que los contienen. Reivindicación 1: Un compuesto de la fórmula (1) en la que X se selecciona entre la serie que consiste en CH₂ y CH₂-CH₂; R¹ᵃ se selecciona entre la serie que consiste en H, F, Cl, Br, alquilo C₁₋₆ y CN; R¹ᵇ se selecciona entre la serie que consiste en H, F, Cl y alquilo C₁₋₆: R¹ᶜ se selecciona entre la serie que consiste en H, F, Cl y alquilo C₁₋₆; R²ᵃ se selecciona entre la serie que consiste en H, F, Cl, Br, alquilo C₁₋₆, CN, CO₂R⁵ y CONR⁵R⁵; R²ᵇ se selecciona entre la serie que consiste en H, F, Cl y alquilo C₁₋₆; R²ᶜ se selecciona entre la serie que consiste en H, F, Cl y alquilo C₁₋₆; R⁵, R⁵ se seleccionan independientemente uno de otro entre la serie que consiste en H y alquilo C₁₋₄; uno de los grupos Y¹ e Y² es N, N-óxido o CR²ᵈ, el otro es C-Z-R³-R⁴; R²ᵈ se selecciona entre la serie que consiste en H, F, Cl y alquilo C₁₋₄; Z se selecciona entre la serie que consiste en un enlace, O, CO, COO, S, SO y SO₂; R³ se selecciona entre la serie que consiste en un enlace y (CR⁶R⁶)ₙ; R⁶, R⁶ se seleccionan independientemente uno de otro entre la serie que consiste en H y alquilo C₁₋₆, que es no sustituido o monofluorado; n se selecciona entre la serie que consiste en 1, 2, 3, 4 y 5; R⁴ se selecciona entre la serie que consiste en alquilo C₁₋₆, alquilo C₁₋₆ mono-, di- o tri-fluorado, alquenilo C₂₋₆, alquinilo C₂₋₆, CO₂R⁵, OR⁷, NR⁸R⁸, SR⁹, cicloalquilo C₃₋₈, un heterociclo de 4 a 6 miembros, que comprende uno o dos heteroátomos en el anillo idénticos o diferentes seleccionados entre la serie que consiste en N y O, fenilo, un heteroarilo de 5 a 6 miembros, que comprende uno o dos, o tres heteroátomos en el anillo idénticos o diferentes seleccionados entre la serie que consiste en N, O, y S, en el que todos los grupos cíclicos dentro de R⁴ están sin sustituir o están sustituidos con uno a tres sustituyentes idénticos o diferentes que se seleccionan entre la serie que consiste en alquilo C₁₋₄, alcanoilo C₁₋₄, hidroxialquilo C₀₋₄, alcoxi C₁₋₃-alquilo C₀₋₄, oxo (=O), F y Cl; R⁷ se selecciona entre la serie que consiste en H, alquilo C₁₋₆, hidroxialquilo C₁₋₄, y alcoxi C₁₋₃-alquilo C₁₋₄; R⁸, R⁸ se seleccionan independientemente uno de otro entre la serie que consiste en H y alquilo C₁₋₆; y R⁹ es alquilo C₁₋₆; en cualquiera de sus formas estereoisómeras, o una mezcla de formas estereoisómeras en cualquier proporción, o una sal fisiológicamente aceptable de ellas, o un solvato fisiológicamente aceptable de cualquiera de ellas.
ARP130103626A 2012-10-09 2013-10-07 Derivados de pirrolidinona como moduladores de gpr119 para el tratamiento de diabetes, obesidad, dislipidemia y trastornos relacionados AR092924A1 (es)

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EP12306231 2012-10-09

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AR092924A1 true AR092924A1 (es) 2015-05-06

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US (1) US8853412B2 (es)
EP (1) EP2906550B1 (es)
AR (1) AR092924A1 (es)
TW (1) TW201427941A (es)
UY (1) UY35073A (es)
WO (1) WO2014056938A1 (es)

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US9255154B2 (en) 2012-05-08 2016-02-09 Alderbio Holdings, Llc Anti-PCSK9 antibodies and use thereof
US9682085B2 (en) 2013-02-22 2017-06-20 Shifa Biomedical Corporation Anti-proprotein convertase subtilisin kexin type 9 (anti-PCSK9) compounds and methods of using the same in the treatment and/or prevention of cardiovascular diseases
EP2968318A4 (en) 2013-03-15 2016-12-14 Shifa Biomedical Corp ANTI-PCSK9 COMPOUNDS AND METHODS FOR TREATING AND / OR PREVENTING CARDIOVASCULAR DISEASES
MX2016013029A (es) * 2014-04-04 2017-01-18 Sanofi Sa Compuestos de indanona sustituidos como modulares de gpr119 para el tratamiento de diabetes, obesidad, dislipidemia y trastornos relacionados.
BR112016026809A2 (pt) 2014-05-19 2017-12-12 Pfizer compostos de 6,8-dioxabiciclo[3.2.1]octano-2,3-diol substituído como agentes de alvejamento de asgpr
CN104473920A (zh) * 2014-12-20 2015-04-01 长沙佰顺生物科技有限公司 一种用于治疗2型糖尿病的复方制剂及其制备方法
WO2017004797A1 (en) * 2015-07-08 2017-01-12 Eli Lilly And Company Pyrrolidinone compounds
CA3027223A1 (en) 2016-06-21 2017-12-28 Shifa Biomedical Corporation Anti-proprotein convertase subtilisin kexin type 9 (anti-pcsk9) compounds and methods of using the same in the treatment and/or prevention of cardiovascular diseases
US11495339B2 (en) 2018-06-14 2022-11-08 Astrazeneca Uk Limited Methods for lowering blood sugar with a gliflozin sodium-glucose cotransport 2 inhibitor pharmaceutical composition
CN109374783B (zh) * 2018-12-21 2022-02-01 安徽联创生物医药股份有限公司 一种用hplc分离测定卡格列净原料药有关物质的方法
CA3142325A1 (en) * 2019-05-31 2020-12-03 Avolynt Compositions and methods for treating metabolic disease
BR112022023359A2 (pt) 2020-05-19 2023-04-18 Kallyope Inc Ativadores de ampk
CN116390925A (zh) 2020-06-26 2023-07-04 卡尔优普公司 Ampk活化剂
AU2022251165A1 (en) 2021-04-01 2023-11-09 Astrazeneca Uk Limited Systems and methods for managing prediabetes with a gliflozin sodium-glucose cotransport 2 inhibitor pharmaceutical composition

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EP1638932A1 (en) 2003-06-18 2006-03-29 Pfizer Products Inc. Novel piperazinyl-aryloxy and piperazinyl-heteroaryloxy-n-aryl lactams
TW200621677A (en) 2004-09-21 2006-07-01 Astellas Pharma Inc Cyclic amine derivative or salt thereof
WO2010048149A2 (en) 2008-10-20 2010-04-29 Kalypsys, Inc. Heterocyclic modulators of gpr119 for treatment of disease
MX2012013465A (es) 2010-05-17 2013-12-02 Array Biopharma Inc Lactamas sustituidas con piperidinilo como moduladores de gpr119.
RU2013117403A (ru) 2010-09-17 2014-10-27 Эррэй Биофарма Инк. Пиперидинил-замещенные лактамы как модуляторы gpr119
AU2012336157A1 (en) 2011-11-11 2014-05-29 Glaxosmithkline Llc Treatment of blood lipid abnormalities and other conditions

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EP2906550B1 (en) 2016-08-24
US8853412B2 (en) 2014-10-07
WO2014056938A1 (en) 2014-04-17
UY35073A (es) 2014-05-30
EP2906550A1 (en) 2015-08-19
TW201427941A (zh) 2014-07-16
US20140099333A1 (en) 2014-04-10

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