NI201900025A - DERIVADOS DE CROMANO, ISOCROMANO Y DIHIDROISOBENZOFURANOS COMO MODULADORES ALOSTÉRICOS NEGATIVOS DE mGluR2, COMPOSICIONES Y SU USO - Google Patents

DERIVADOS DE CROMANO, ISOCROMANO Y DIHIDROISOBENZOFURANOS COMO MODULADORES ALOSTÉRICOS NEGATIVOS DE mGluR2, COMPOSICIONES Y SU USO

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Publication number
NI201900025A
NI201900025A NI201900025A NI201900025A NI201900025A NI 201900025 A NI201900025 A NI 201900025A NI 201900025 A NI201900025 A NI 201900025A NI 201900025 A NI201900025 A NI 201900025A NI 201900025 A NI201900025 A NI 201900025A
Authority
NI
Nicaragua
Prior art keywords
mglur2
pharmaceutically acceptable
disorders
compounds
acceptable salt
Prior art date
Application number
NI201900025A
Other languages
English (en)
Inventor
K Sebhat Iyassu
Arasappan Ashok
B Hoyt Scott
R Wilkening Robert
Demong Duane
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 NI201900025A publication Critical patent/NI201900025A/es

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    • 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
    • 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

Abstract

La presente invención proporciona ciertos compuestos de cromano, isocromano y dihidroisobenzofurano sustituidos de fórmula (I), o una sal farmacéuticamente aceptable de los mismos, en la que el anillo A es un resto seleccionado de (II), (III), (IV) y (V) y el anillo B, n, R1 , R2 , R2A , R3 , y R3A son como se definen en el presente memoria. Los compuestos de la invención son útiles como inhibidores de mGluR2, o moduladores alostéricos negativos 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.
NI201900025A 2016-09-27 2019-03-20 DERIVADOS DE CROMANO, ISOCROMANO Y DIHIDROISOBENZOFURANOS COMO MODULADORES ALOSTÉRICOS NEGATIVOS DE mGluR2, COMPOSICIONES Y SU USO NI201900025A (es)

Applications Claiming Priority (1)

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US201662400150P 2016-09-27 2016-09-27

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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)
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MA (1) MA46342B1 (es)
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MY (1) MY196807A (es)
NI (1) NI201900025A (es)
PE (1) PE20190609A1 (es)
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PT (1) PT3519416T (es)
RS (1) RS61890B1 (es)
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WO2019144041A1 (en) 2018-01-19 2019-07-25 Cytokinetics, Inc. Dihydrobenzofuran and inden analogs as 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
JP7291426B2 (ja) * 2019-03-01 2023-06-15 山東亨利醫藥科技有限責任公司 縮合三環式化合物を調製するための方法、及びその中間体
CA3209557A1 (en) 2021-03-04 2022-09-09 Bradley P. Morgan Cardiac sarcomere inhibitors
WO2023278729A1 (en) * 2021-06-30 2023-01-05 The General Hospital Corporation Chromane imaging ligands

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JOP20190058B1 (ar) * 2016-09-27 2023-09-17 Merck Sharp And Dohme Llc مشتقات كرومان، أيزوكرومان وداي هيدرو أيزو بنزوفوران كمُعدلات تفارغية سالبة mGluR2، تركيبات، واستخدامها

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CO2019002673A2 (es) 2019-03-29
EA038627B1 (ru) 2021-09-24
ECSP19020742A (es) 2019-04-30
CA3037537A1 (en) 2018-04-05
US10335399B2 (en) 2019-07-02
MD3519416T2 (ro) 2021-09-30
PE20190609A1 (es) 2019-04-23
US20210015800A1 (en) 2021-01-21
TWI764934B (zh) 2022-05-21
AR109714A1 (es) 2019-01-16
GEP20217279B (en) 2021-08-10
JOP20190058B1 (ar) 2023-09-17
DK3519416T3 (da) 2021-05-25
AU2020270468A1 (en) 2020-12-10
AU2020270468B2 (en) 2022-02-17
US20180085358A1 (en) 2018-03-29
CR20190147A (es) 2019-05-17
JOP20190058A1 (ar) 2019-03-24
US10806724B2 (en) 2020-10-20
JP2020111596A (ja) 2020-07-27
HUE054898T2 (hu) 2021-10-28
ZA201901701B (en) 2023-03-29
UA123687C2 (uk) 2021-05-12
AU2017334870B2 (en) 2020-08-20
EP3519416B1 (en) 2021-03-31
BR112019005869A2 (pt) 2019-06-11
CA3037537C (en) 2021-06-15
EP3519416A1 (en) 2019-08-07
HRP20210793T1 (hr) 2021-09-03
WO2018063955A1 (en) 2018-04-05
GEP20217266B (en) 2021-06-25
MA46342A (fr) 2019-08-07
DOP2019000076A (es) 2019-07-15
SI3519416T1 (sl) 2021-08-31
AU2017334870C1 (en) 2020-12-17
MX2019003492A (es) 2019-09-19
AU2017334870A1 (en) 2019-03-28
PH12019500597A1 (en) 2019-07-24
CN109983022B (zh) 2022-06-07
JP6681517B2 (ja) 2020-04-15
MY196807A (en) 2023-05-03
KR102296043B1 (ko) 2021-08-30
BR112019005869A8 (pt) 2023-05-02
CY1124346T1 (el) 2022-07-22
JP6945605B2 (ja) 2021-10-06
CN109983022A (zh) 2019-07-05
JP2019529468A (ja) 2019-10-17
TN2020000161A1 (en) 2022-04-04
IL265366B (en) 2021-12-01
LT3519416T (lt) 2021-06-10
ES2868973T3 (es) 2021-10-22
RS61890B1 (sr) 2021-06-30
EA201990818A1 (ru) 2019-08-30
JP2020011989A (ja) 2020-01-23
IL265366A (en) 2019-05-30
TN2020000160A1 (en) 2022-04-04
KR20190056418A (ko) 2019-05-24
PT3519416T (pt) 2021-05-13
TW201815794A (zh) 2018-05-01
CL2019000778A1 (es) 2019-05-31
US20190247374A1 (en) 2019-08-15
JP6992109B2 (ja) 2022-02-15
MA46342B1 (fr) 2021-05-31
PL3519416T3 (pl) 2021-09-06
US20220218676A1 (en) 2022-07-14

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