MX2019003492A - Derivados de cromano, isocromano y dihidroisobenzofuranos como moduladores alostericos negativos de mg1ur2, composiciones y su uso. - Google Patents

Derivados de cromano, isocromano y dihidroisobenzofuranos como moduladores alostericos negativos de mg1ur2, composiciones y su uso.

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Publication number
MX2019003492A
MX2019003492A MX2019003492A MX2019003492A MX2019003492A MX 2019003492 A MX2019003492 A MX 2019003492A MX 2019003492 A MX2019003492 A MX 2019003492A MX 2019003492 A MX2019003492 A MX 2019003492A MX 2019003492 A MX2019003492 A MX 2019003492A
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MX
Mexico
Prior art keywords
mglur2
pharmaceutically acceptable
disorders
compounds
acceptable salt
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MX2019003492A
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English (en)
Inventor
R Wilkening Robert
K Sebhat Iyassu
Arasappan Ashok
B Hoyt Scott
Demong Duane
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Merck Sharp & Dohme
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Publication date
Application filed by Merck Sharp & Dohme filed Critical Merck Sharp & Dohme
Publication of MX2019003492A publication Critical patent/MX2019003492A/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic 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
    • C07D491/02Heterocyclic 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
    • C07D491/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/165Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/166Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
    • 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
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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
    • A61K31/436Heterocyclic 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
    • 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
    • A61K31/435Heterocyclic 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
    • A61K31/439Heterocyclic 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 the ring forming part of a bridged ring system, e.g. quinuclidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/20Hypnotics; Sedatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D221/00Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/22Bridged ring systems
    • C07D221/24Camphidines
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic 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
    • C07D491/12Heterocyclic 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 three hetero rings
    • C07D491/18Bridged systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/01Hydrocarbons
    • A61K31/015Hydrocarbons carbocyclic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/02Halogenated hydrocarbons
    • A61K31/025Halogenated hydrocarbons carbocyclic
    • A61K31/03Halogenated hydrocarbons carbocyclic aromatic

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Anesthesiology (AREA)
  • Psychology (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

La presente invención proporciona ciertos compuestos de cromano, isocromano y dihidroisobenzofurano sustituidos de fórmula (I): (ver Fórmulas) o una sal farmacéuticamente aceptable de los mismos, en la que el anillo A es un resto seleccionado de: (ver Fórmula) y el anillo B, n, R1, R2, R2A, R3 y R3A son como se definen en la presente memoria. Los compuestos de la invención son útiles como inhibidores de mGluR2, o moduladores alostéricos negativos de mGluR2 (NAM), y pueden ser útiles en procedimientos de tratamiento de un paciente para enfermedades o trastornos en los que está implicado el receptor mGluR2-NAM, tales como la enfermedad de Alzheimer, deterioro cognitivo, deterioro cognitivo leve, esquizofrenia y otros trastornos del estado de ánimo, trastornos del dolor y trastornos del sueño, mediante la administración al paciente de una cantidad terapéuticamente eficaz de un compuesto de la invención, o una sal farmacéuticamente aceptable del mismo. La invención también se refiere a composiciones farmacéuticas que comprenden un compuesto de la invención, o una sal farmacéuticamente aceptable del mismo, (opcionalmente en combinación con uno o más ingredientes activos adicionales), y un vehículo farmacéuticamente aceptable, y al uso de los compuestos y composiciones farmacéuticas de la invención en el tratamiento de tales enfermedades.
MX2019003492A 2016-09-27 2017-09-25 Derivados de cromano, isocromano y dihidroisobenzofuranos como moduladores alostericos negativos de mg1ur2, composiciones y su uso. MX2019003492A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662400150P 2016-09-27 2016-09-27
PCT/US2017/053155 WO2018063955A1 (en) 2016-09-27 2017-09-25 CHROMANE, ISOCHROMANE AND DIHYDROISOBENZOFURAN DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE

Publications (1)

Publication Number Publication Date
MX2019003492A true MX2019003492A (es) 2019-09-19

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US (4) US10335399B2 (es)
EP (1) EP3519416B1 (es)
JP (3) JP6681517B2 (es)
KR (1) KR102296043B1 (es)
CN (1) CN109983022B (es)
AR (1) AR109714A1 (es)
AU (2) AU2017334870C1 (es)
CA (1) CA3037537C (es)
CL (1) CL2019000778A1 (es)
CO (1) CO2019002673A2 (es)
CR (1) CR20190147A (es)
CY (1) CY1124346T1 (es)
DK (1) DK3519416T3 (es)
DO (1) DOP2019000076A (es)
EA (1) EA038627B1 (es)
EC (1) ECSP19020742A (es)
ES (1) ES2868973T3 (es)
GE (2) GEP20217279B (es)
HR (1) HRP20210793T1 (es)
HU (1) HUE054898T2 (es)
IL (1) IL265366B (es)
JO (1) JOP20190058B1 (es)
LT (1) LT3519416T (es)
MA (1) MA46342B1 (es)
MD (1) MD3519416T2 (es)
MX (1) MX2019003492A (es)
MY (1) MY196807A (es)
NI (1) NI201900025A (es)
PE (1) PE20190609A1 (es)
PH (1) PH12019500597A1 (es)
PL (1) PL3519416T3 (es)
PT (1) PT3519416T (es)
RS (1) RS61890B1 (es)
SI (1) SI3519416T1 (es)
TN (2) TN2020000161A1 (es)
TW (1) TWI764934B (es)
UA (1) UA123687C2 (es)
WO (1) WO2018063955A1 (es)
ZA (1) ZA201901701B (es)

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ES2868973T3 (es) * 2016-09-27 2021-10-22 Merck Sharp & Dohme Derivados de cromano, isocromano y dihidroisobenzofurano como moduladores alostéricos negativos para mGluR2, composiciones y su uso
CN117964573A (zh) 2018-01-19 2024-05-03 赛特凯恩蒂克公司 作为心肌节抑制剂的二氢苯并呋喃和茚类似物
JP7438148B2 (ja) 2018-06-26 2024-02-26 サイトキネティックス, インコーポレイテッド 心臓サルコメア阻害剤
AU2020230627B2 (en) * 2019-03-01 2023-01-19 Novo Nordisk A/S Method for preparing tricyclic compound, and intermediate thereof
US11919909B2 (en) 2021-03-04 2024-03-05 Cytokinetics, Inc. Cardiac sarcomere inhibitors
WO2023278729A1 (en) * 2021-06-30 2023-01-05 The General Hospital Corporation Chromane imaging ligands

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JP2018154554A (ja) 2015-07-29 2018-10-04 大日本住友製薬株式会社 新規リンカー部位を持つ縮合ピラゾール誘導体およびその医薬用途
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TW201815794A (zh) 2018-05-01
IL265366B (en) 2021-12-01
ECSP19020742A (es) 2019-04-30
EA201990818A1 (ru) 2019-08-30
TWI764934B (zh) 2022-05-21
CR20190147A (es) 2019-05-17
CL2019000778A1 (es) 2019-05-31
ZA201901701B (en) 2023-03-29
GEP20217266B (en) 2021-06-25
EP3519416B1 (en) 2021-03-31
EA038627B1 (ru) 2021-09-24
MD3519416T2 (ro) 2021-09-30
WO2018063955A1 (en) 2018-04-05
PL3519416T3 (pl) 2021-09-06
JP2020011989A (ja) 2020-01-23
CN109983022A (zh) 2019-07-05
ES2868973T3 (es) 2021-10-22
US20210015800A1 (en) 2021-01-21
CN109983022B (zh) 2022-06-07
TN2020000161A1 (en) 2022-04-04
AU2017334870A1 (en) 2019-03-28
US20190247374A1 (en) 2019-08-15
EP3519416A1 (en) 2019-08-07
NI201900025A (es) 2019-05-27
JP2020111596A (ja) 2020-07-27
MA46342B1 (fr) 2021-05-31
AR109714A1 (es) 2019-01-16
MA46342A (fr) 2019-08-07
JP6992109B2 (ja) 2022-02-15
US20220218676A1 (en) 2022-07-14
GEP20217279B (en) 2021-08-10
KR102296043B1 (ko) 2021-08-30
CA3037537A1 (en) 2018-04-05
JOP20190058A1 (ar) 2019-03-24
LT3519416T (lt) 2021-06-10
HUE054898T2 (hu) 2021-10-28
US10335399B2 (en) 2019-07-02
PE20190609A1 (es) 2019-04-23
BR112019005869A8 (pt) 2023-05-02
JP6945605B2 (ja) 2021-10-06
CA3037537C (en) 2021-06-15
JOP20190058B1 (ar) 2023-09-17
PH12019500597A1 (en) 2019-07-24
BR112019005869A2 (pt) 2019-06-11
PT3519416T (pt) 2021-05-13
US20180085358A1 (en) 2018-03-29
AU2020270468B2 (en) 2022-02-17
HRP20210793T1 (hr) 2021-09-03
JP2019529468A (ja) 2019-10-17
MY196807A (en) 2023-05-03
US10806724B2 (en) 2020-10-20
IL265366A (en) 2019-05-30
KR20190056418A (ko) 2019-05-24
SI3519416T1 (sl) 2021-08-31
DOP2019000076A (es) 2019-07-15
AU2020270468A1 (en) 2020-12-10
DK3519416T3 (da) 2021-05-25
CO2019002673A2 (es) 2019-03-29
JP6681517B2 (ja) 2020-04-15
CY1124346T1 (el) 2022-07-22
RS61890B1 (sr) 2021-06-30
AU2017334870C1 (en) 2020-12-17
UA123687C2 (uk) 2021-05-12
TN2020000160A1 (en) 2022-04-04
AU2017334870B2 (en) 2020-08-20

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