CO2023004366A2 - Preparación de derivados de oxindol como nuevos inhibidores de la diacilglicerol o-aciltransferasa 2 - Google Patents

Preparación de derivados de oxindol como nuevos inhibidores de la diacilglicerol o-aciltransferasa 2

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Publication number
CO2023004366A2
CO2023004366A2 CONC2023/0004366A CO2023004366A CO2023004366A2 CO 2023004366 A2 CO2023004366 A2 CO 2023004366A2 CO 2023004366 A CO2023004366 A CO 2023004366A CO 2023004366 A2 CO2023004366 A2 CO 2023004366A2
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Colombia
Prior art keywords
formula
compounds
acyltransferase
diacylglycerol
preparation
Prior art date
Application number
CONC2023/0004366A
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English (en)
Inventor
Yeon-Hee Lim
Jianming Bao
James P Roane
Original Assignee
Merck Sharp & Dohme Llc
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Filing date
Publication date
Application filed by Merck Sharp & Dohme Llc filed Critical Merck Sharp & Dohme Llc
Publication of CO2023004366A2 publication Critical patent/CO2023004366A2/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic 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
    • A61K31/403Heterocyclic 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 condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404Indoles, e.g. pindolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/30Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32Oxygen atoms
    • C07D209/34Oxygen atoms in position 2
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/30Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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 two hetero rings
    • C07D405/12Heterocyclic 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 two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/02Heterocyclic 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 two hetero rings
    • C07D417/12Heterocyclic 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 two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Cardiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Indole Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Se inventan compuestos de fórmula I y sales farmacéuticamente aceptables, ésteres y profármacos de los mismos, que son inhibidores de DGAT2. También se proporcionan métodos de preparación de compuestos de Fórmula I, composiciones farmacéuticas que comprenden compuestos de Fórmula I y métodos de uso de estos compuestos para tratar la esteatosis hepática, esteatohepatitis no alcohólica (EHNA), fibrosis, diabetes mellitus de tipo 2, obesidad, hiperlipidemia, hipercolesterolemia, ateroesclerosis, declive cognitivo, demencia, enfermedades cardiorrenales tales como enfermedades renales crónicas e insuficiencia cardíaca y enfermedades y afecciones relacionadas, que comprenden administrar un compuesto de Fórmula I a un paciente que lo necesita.
CONC2023/0004366A 2020-10-08 2023-04-05 Preparación de derivados de oxindol como nuevos inhibidores de la diacilglicerol o-aciltransferasa 2 CO2023004366A2 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202063089063P 2020-10-08 2020-10-08
PCT/US2021/053681 WO2022076496A1 (en) 2020-10-08 2021-10-06 Preparation of oxindole derivatives as novel diacylglyceride o-acyltransferase 2 inhibitors

Publications (1)

Publication Number Publication Date
CO2023004366A2 true CO2023004366A2 (es) 2023-04-27

Family

ID=78709520

Family Applications (1)

Application Number Title Priority Date Filing Date
CONC2023/0004366A CO2023004366A2 (es) 2020-10-08 2023-04-05 Preparación de derivados de oxindol como nuevos inhibidores de la diacilglicerol o-aciltransferasa 2

Country Status (18)

Country Link
US (2) US20220112181A1 (es)
EP (1) EP4225735A1 (es)
JP (1) JP7482324B2 (es)
KR (1) KR20230079427A (es)
CN (1) CN116457346A (es)
AR (1) AR123701A1 (es)
AU (1) AU2021358946A1 (es)
CA (1) CA3195032A1 (es)
CL (1) CL2023000978A1 (es)
CO (1) CO2023004366A2 (es)
CR (1) CR20230160A (es)
DO (1) DOP2023000068A (es)
EC (1) ECSP23034049A (es)
IL (1) IL301799A (es)
MX (1) MX2023003844A (es)
PE (1) PE20240217A1 (es)
TW (1) TW202229232A (es)
WO (1) WO2022076496A1 (es)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023233033A1 (en) * 2022-06-03 2023-12-07 Domain Therapeutics Novel par-2 inhibitors
US20240254114A1 (en) 2022-12-02 2024-08-01 Merck Sharp & Dohme Llc Preparation of fused azole derivatives as novel diacylglyceride 0-acyltransferase 2 inhibitors

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080287479A1 (en) * 2006-12-20 2008-11-20 Pfizer Inc Inhibitors of serine palmitoyltransferase
WO2010077839A1 (en) * 2008-12-15 2010-07-08 Wyeth Llc (Formerly Known As Wyeth) Substituted oxindol cb2 agonists for pain treatment
MX2019005679A (es) * 2016-11-18 2019-08-14 Merck Sharp & Dohme Derivados de indol de utilidad como inhibidores de diacilglicerido o-aciltransferasa 2.
MA46856A (fr) * 2016-11-18 2019-09-25 Merck Sharp & Dohme Dérivés d'indazole utiles en tant qu'inhibiteurs de la diacylglycéride o-acyltransférase 2

Also Published As

Publication number Publication date
AU2021358946A1 (en) 2023-06-08
MX2023003844A (es) 2023-04-14
CL2023000978A1 (es) 2023-09-29
CR20230160A (es) 2023-06-02
US20240327391A1 (en) 2024-10-03
DOP2023000068A (es) 2023-05-31
KR20230079427A (ko) 2023-06-07
CN116457346A (zh) 2023-07-18
JP7482324B2 (ja) 2024-05-13
CA3195032A1 (en) 2022-04-14
JP2023541714A (ja) 2023-10-03
EP4225735A1 (en) 2023-08-16
US20220112181A1 (en) 2022-04-14
PE20240217A1 (es) 2024-02-16
WO2022076496A1 (en) 2022-04-14
AU2021358946A9 (en) 2024-02-08
AR123701A1 (es) 2023-01-04
ECSP23034049A (es) 2023-06-30
IL301799A (en) 2023-05-01
TW202229232A (zh) 2022-08-01

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