MA46342A - Dérivés de chromane, d'isochromane et de dihydroisobenzofurane en tant que modulateurs allostériques négatifs de mglur2, compositions et leur utilisation - Google Patents

Dérivés de chromane, d'isochromane et de dihydroisobenzofurane en tant que modulateurs allostériques négatifs de mglur2, compositions et leur utilisation

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Publication number
MA46342A
MA46342A MA046342A MA46342A MA46342A MA 46342 A MA46342 A MA 46342A MA 046342 A MA046342 A MA 046342A MA 46342 A MA46342 A MA 46342A MA 46342 A MA46342 A MA 46342A
Authority
MA
Morocco
Prior art keywords
mglur2
pharmaceutically acceptable
compositions
compounds
isochroman
Prior art date
Application number
MA046342A
Other languages
English (en)
Other versions
MA46342B1 (fr
Inventor
Ashok Arasappan
Duane Demong
Scott B Hoyt
Iyassu K Sebhat
Robert R Wilkening
Original Assignee
Merck Sharp & Dohme
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Sharp & Dohme filed Critical Merck Sharp & Dohme
Publication of MA46342A publication Critical patent/MA46342A/fr
Publication of MA46342B1 publication Critical patent/MA46342B1/fr

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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
    • C07D491/12Heterocyclic 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
    • 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
    • C07D491/02Heterocyclic 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Anesthesiology (AREA)
  • Psychology (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 Containing Plant Substances (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne certains composés de chromane, d'isochromane et de dihydroisobenzofurane substitués de formule (i) ou un sel pharmaceutiquement acceptable de celui-ci, le cycle a étant un fragment choisi parmi (ii), (iii), (iv) et (v), et le cycle b, n, r1, r2, r2a, r3, et r3a sont tels que définis dans la description. Les composés de l'invention sont utiles en tant qu'inhibiteurs de mglur2, ou modulateurs allostériques négatifs de mglur2 (nams), et dans des méthodes de traitement d'un patient pour des maladies ou des troubles dans lesquels le récepteur mglur2-nam est impliqué, tels que la maladie d'alzheimer, le déficit cognitif, le déficit cognitif léger, la schizophrénie ou autres troubles de l'humeur, troubles de la douleur et troubles du sommeil, par l'administration au patient d'une quantité thérapeutiquement efficace d'un composé de l'invention ou d'un sel pharmaceutiquement acceptable de celui-ci. L'invention concerne également des compositions pharmaceutiques comprenant un composé de l'invention ou un sel pharmaceutiquement acceptable de celui-ci (facultativement en combinaison avec un ou plusieurs principes actifs supplémentaires) et un support pharmaceutiquement acceptable, et l'utilisation des composés et compositions pharmaceutiques de l'invention dans le traitement de telles maladies.
MA46342A 2016-09-27 2017-09-25 Dérivés de chromane, d'isochromane et de dihydroisobenzofurane en tant que modulateurs allostériques négatifs de mglur2, compositions et leur utilisation MA46342B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662400150P 2016-09-27 2016-09-27
PCT/US2017/053155 WO2018063955A1 (fr) 2016-09-27 2017-09-25 Dérivés de chromane, d'isochromane et de dihydroisobenzofurane en tant que modulateurs allostériques négatifs de mglur2, compositions et leur utilisation

Publications (2)

Publication Number Publication Date
MA46342A true MA46342A (fr) 2019-08-07
MA46342B1 MA46342B1 (fr) 2021-05-31

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
MA46342A MA46342B1 (fr) 2016-09-27 2017-09-25 Dérivés de chromane, d'isochromane et de dihydroisobenzofurane en tant que modulateurs allostériques négatifs de mglur2, compositions et leur utilisation

Country Status (39)

Country Link
US (4) US10335399B2 (fr)
EP (1) EP3519416B1 (fr)
JP (3) JP6681517B2 (fr)
KR (1) KR102296043B1 (fr)
CN (1) CN109983022B (fr)
AR (1) AR109714A1 (fr)
AU (2) AU2017334870C1 (fr)
CA (1) CA3037537C (fr)
CL (1) CL2019000778A1 (fr)
CO (1) CO2019002673A2 (fr)
CR (1) CR20190147A (fr)
CY (1) CY1124346T1 (fr)
DK (1) DK3519416T3 (fr)
DO (1) DOP2019000076A (fr)
EA (1) EA038627B1 (fr)
EC (1) ECSP19020742A (fr)
ES (1) ES2868973T3 (fr)
GE (2) GEP20217266B (fr)
HR (1) HRP20210793T1 (fr)
HU (1) HUE054898T2 (fr)
IL (1) IL265366B (fr)
JO (1) JOP20190058B1 (fr)
LT (1) LT3519416T (fr)
MA (1) MA46342B1 (fr)
MD (1) MD3519416T2 (fr)
MX (1) MX392132B (fr)
MY (1) MY196807A (fr)
NI (1) NI201900025A (fr)
PE (1) PE20190609A1 (fr)
PH (1) PH12019500597B1 (fr)
PL (1) PL3519416T3 (fr)
PT (1) PT3519416T (fr)
RS (1) RS61890B1 (fr)
SI (1) SI3519416T1 (fr)
TN (2) TN2020000160A1 (fr)
TW (1) TWI764934B (fr)
UA (1) UA123687C2 (fr)
WO (1) WO2018063955A1 (fr)
ZA (1) ZA201901701B (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI764934B (zh) * 2016-09-27 2022-05-21 美商默沙東藥廠 作為mGluR2負向異位調節劑之色烷、異色烷及二氫異苯並呋喃衍生物、組合物及其用途
HUE067913T2 (hu) 2018-01-19 2024-11-28 Cytokinetics Inc Dihidrobenzofurán és indén analógok mint szív szarkomer gátlók
US12187712B2 (en) 2018-06-26 2025-01-07 Cytokinetics, Inc. Cardiac sarcomere inhibitors
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
BR112021017276A2 (pt) * 2019-03-01 2021-11-09 Kbp Biosciences Co Ltd Método para preparar composto tricíclico e intermediário do mesmo
CN117083275A (zh) 2021-03-04 2023-11-17 赛特凯恩蒂克公司 心脏肌节抑制剂
US20250340562A1 (en) * 2021-06-30 2025-11-06 The General Hospital Corporation Chromane imaging ligands

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US5552437A (en) 1994-10-27 1996-09-03 Merck Frosst Canada, Inc. Bisarylcarbinol derivatives as inhibitors of leukotriene biosynthesis
US5576338A (en) 1995-02-15 1996-11-19 Merck Frosst Canada, Inc. Bis (biaryl) compounds as inhibitors of leukotriene biosynthesis
WO2005014543A1 (fr) 2003-08-06 2005-02-17 Japan Tobacco Inc. Compose a cycle condense utilise comme inhibiteur de la polymerase du vhc
JP2009510132A (ja) 2005-10-05 2009-03-12 メルク フロスト カナダ リミテツド ロイコトリエン生合成の阻害剤としての置換キノリン
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WO2016029454A1 (fr) 2014-08-29 2016-03-03 Merck Sharp & Dohme Corp. Dérivés de tétrahydronaphtyridine comme modulateurs allostériques négatifs de mglur2, compositions et leur utilisation
US9382208B1 (en) 2015-01-26 2016-07-05 Vanderbilt University Negative allosteric modulators of metabotropic glutamate receptor 2
WO2016149324A1 (fr) 2015-03-16 2016-09-22 Vanderbilt University Modulateurs allostériques négatifs du récepteur métabotropique du glutamate de type 2
JP6471614B2 (ja) 2015-05-29 2019-02-20 株式会社リコー 通信端末、通信システム、通信制御方法、及びプログラム
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
TWI764934B (zh) * 2016-09-27 2022-05-21 美商默沙東藥廠 作為mGluR2負向異位調節劑之色烷、異色烷及二氫異苯並呋喃衍生物、組合物及其用途

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Publication number Publication date
JP2020111596A (ja) 2020-07-27
JP2020011989A (ja) 2020-01-23
JP6992109B2 (ja) 2022-02-15
BR112019005869A8 (pt) 2023-05-02
MD3519416T2 (ro) 2021-09-30
US20220218676A1 (en) 2022-07-14
JP6945605B2 (ja) 2021-10-06
CA3037537C (fr) 2021-06-15
US20180085358A1 (en) 2018-03-29
SI3519416T1 (sl) 2021-08-31
TN2020000161A1 (en) 2022-04-04
PL3519416T3 (pl) 2021-09-06
PE20190609A1 (es) 2019-04-23
ECSP19020742A (es) 2019-04-30
AR109714A1 (es) 2019-01-16
AU2017334870C1 (en) 2020-12-17
MX2019003492A (es) 2019-09-19
AU2017334870B2 (en) 2020-08-20
UA123687C2 (uk) 2021-05-12
IL265366B (en) 2021-12-01
KR102296043B1 (ko) 2021-08-30
CR20190147A (es) 2019-05-17
AU2020270468A1 (en) 2020-12-10
MA46342B1 (fr) 2021-05-31
EP3519416B1 (fr) 2021-03-31
US10806724B2 (en) 2020-10-20
US20210015800A1 (en) 2021-01-21
CL2019000778A1 (es) 2019-05-31
US10335399B2 (en) 2019-07-02
TW201815794A (zh) 2018-05-01
JOP20190058B1 (ar) 2023-09-17
PH12019500597B1 (en) 2023-05-10
JOP20190058A1 (ar) 2019-03-24
HUE054898T2 (hu) 2021-10-28
EP3519416A1 (fr) 2019-08-07
EA038627B1 (ru) 2021-09-24
JP6681517B2 (ja) 2020-04-15
AU2017334870A1 (en) 2019-03-28
DK3519416T3 (da) 2021-05-25
US20190247374A1 (en) 2019-08-15
AU2020270468B2 (en) 2022-02-17
MX392132B (es) 2025-03-12
RS61890B1 (sr) 2021-06-30
IL265366A (en) 2019-05-30
CY1124346T1 (el) 2022-07-22
TWI764934B (zh) 2022-05-21
CN109983022B (zh) 2022-06-07
CO2019002673A2 (es) 2019-03-29
TN2020000160A1 (en) 2022-04-04
GEP20217266B (en) 2021-06-25
PT3519416T (pt) 2021-05-13
ZA201901701B (en) 2023-03-29
JP2019529468A (ja) 2019-10-17
MY196807A (en) 2023-05-03
ES2868973T3 (es) 2021-10-22
WO2018063955A1 (fr) 2018-04-05
PH12019500597A1 (en) 2019-07-24
HRP20210793T1 (hr) 2021-09-03
EA201990818A1 (ru) 2019-08-30
LT3519416T (lt) 2021-06-10
GEP20217279B (en) 2021-08-10
CN109983022A (zh) 2019-07-05
CA3037537A1 (fr) 2018-04-05
NI201900025A (es) 2019-05-27
DOP2019000076A (es) 2019-07-15
BR112019005869A2 (pt) 2019-06-11
KR20190056418A (ko) 2019-05-24

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