CN119039284A - 作为毒蕈碱m1和/或m4受体的激动剂的噁二唑 - Google Patents

作为毒蕈碱m1和/或m4受体的激动剂的噁二唑 Download PDF

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Publication number
CN119039284A
CN119039284A CN202410873092.8A CN202410873092A CN119039284A CN 119039284 A CN119039284 A CN 119039284A CN 202410873092 A CN202410873092 A CN 202410873092A CN 119039284 A CN119039284 A CN 119039284A
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CN
China
Prior art keywords
optionally substituted
compound
methyl
azabicyclo
oxadiazol
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Pending
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CN202410873092.8A
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English (en)
Chinese (zh)
Inventor
盖尔斯·艾伯特·布朗
巴里·约翰·泰奥巴尔德
本杰明·杰拉尔德·特汉
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Nexla Pharmaceuticals Uk Ltd
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Nexla Pharmaceuticals Uk Ltd
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Publication of CN119039284A publication Critical patent/CN119039284A/zh
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    • C—CHEMISTRY; METALLURGY
    • 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
    • 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
    • A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
    • 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
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/14—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/06—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing isoquinuclidine ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic 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
    • C07D471/02—Heterocyclic 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
    • C07D471/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic 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
    • C07D471/02—Heterocyclic 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
    • C07D471/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic 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
    • C07D491/02—Heterocyclic 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
    • C07D491/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/09—Geometrical isomers

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Epidemiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN202410873092.8A 2018-06-22 2019-06-24 作为毒蕈碱m1和/或m4受体的激动剂的噁二唑 Pending CN119039284A (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GBGB1810245.9A GB201810245D0 (en) 2018-06-22 2018-06-22 Pharmaceutical compounds
GB1810245.9 2018-06-22
CN201980054880.1A CN112585135B (zh) 2018-06-22 2019-06-24 作为毒蕈碱m1和/或m4受体的激动剂的噁二唑
PCT/GB2019/051778 WO2019243850A1 (en) 2018-06-22 2019-06-24 Oxadiazoles as agonists of the muscarinic m1 and/or m4 receptor

Related Parent Applications (1)

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CN201980054880.1A Division CN112585135B (zh) 2018-06-22 2019-06-24 作为毒蕈碱m1和/或m4受体的激动剂的噁二唑

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Publication Number Publication Date
CN119039284A true CN119039284A (zh) 2024-11-29

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CN202410873092.8A Pending CN119039284A (zh) 2018-06-22 2019-06-24 作为毒蕈碱m1和/或m4受体的激动剂的噁二唑
CN201980054880.1A Active CN112585135B (zh) 2018-06-22 2019-06-24 作为毒蕈碱m1和/或m4受体的激动剂的噁二唑

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Country Status (14)

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US (2) US10858352B2 (enExample)
EP (1) EP3810607A1 (enExample)
JP (3) JP7389762B2 (enExample)
KR (1) KR102833588B1 (enExample)
CN (2) CN119039284A (enExample)
AU (1) AU2019289216B2 (enExample)
BR (1) BR112020026437A2 (enExample)
CA (1) CA3104085A1 (enExample)
GB (1) GB201810245D0 (enExample)
MX (1) MX2020014156A (enExample)
SG (1) SG11202012570TA (enExample)
TW (1) TWI872024B (enExample)
WO (1) WO2019243850A1 (enExample)
ZA (1) ZA202007986B (enExample)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2780015B1 (en) 2011-11-18 2017-01-04 Heptares Therapeutics Limited Muscarinic m1 receptor agonists
GB201404922D0 (en) 2014-03-19 2014-04-30 Heptares Therapeutics Ltd Pharmaceutical compounds
GB201513743D0 (en) 2015-08-03 2015-09-16 Heptares Therapeutics Ltd Muscarinic agonists
GB201519352D0 (en) 2015-11-02 2015-12-16 Heptares Therapeutics Ltd Pharmaceutical compounds
GB201617454D0 (en) 2016-10-14 2016-11-30 Heptares Therapeutics Limited Pharmaceutical compounds
GB201810239D0 (en) 2018-06-22 2018-08-08 Heptares Therapeutics Ltd Pharmaceutical compounds
GB201810245D0 (en) 2018-06-22 2018-08-08 Heptares Therapeutics Ltd Pharmaceutical compounds
GB201819961D0 (en) 2018-12-07 2019-01-23 Heptares Therapeutics Ltd Pharmaceutical compounds
GB201819960D0 (en) 2018-12-07 2019-01-23 Heptares Therapeutics Ltd Pharmaceutical compounds
GB202020191D0 (en) * 2020-12-18 2021-02-03 Heptares Therapeutics Ltd Pharmaceutical compounds
WO2021070090A1 (en) * 2019-10-09 2021-04-15 Novartis Ag 2-azaspiro[3.4]octane derivatives as m4 agonists
CN119390705A (zh) 2019-10-09 2025-02-07 诺华股份有限公司 作为m4激动剂的5-氧杂-2-氮杂螺[3.4]辛烷衍生物

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Publication number Priority date Publication date Assignee Title
WO1999032486A1 (en) 1997-12-23 1999-07-01 Alcon Laboratories, Inc. Muscarinic agents and use thereof to treat glaucoma, myopia and various other conditions
US7786141B2 (en) 2004-08-19 2010-08-31 Vertex Pharmaceuticals Incorporated Dihydrospiroindene modulators of muscarinic receptors
AU2006330866A1 (en) 2005-12-22 2007-07-05 Vertex Pharmaceuticals Incorporated Modulators of muscarinic receptors
KR20080098070A (ko) 2006-02-22 2008-11-06 버텍스 파마슈티칼스 인코포레이티드 무스카린성 수용체의 조절제로서의 스피로 축합된 피페리딘
AU2007284548A1 (en) 2006-08-15 2008-02-21 Vertex Pharmaceuticals Incorporated Modulators of muscarinic receptors
WO2008117229A1 (en) * 2007-03-23 2008-10-02 Ranbaxy Laboratories Limited Muscarinic receptor antagonists
EP2616074A1 (en) * 2010-09-17 2013-07-24 Array Biopharma, Inc. Piperidinyl-substituted lactams as gpr119 modulators
CN107098899B (zh) * 2012-09-18 2019-09-06 赫普泰雅治疗有限公司 作为毒蕈碱的m1受体激动剂的二环氮杂化合物
JP6478923B2 (ja) * 2013-02-07 2019-03-06 ヘプタレス セラピューティクス リミテッドＨｅｐｔａｒｅｓ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｌｉｍｉｔｅｄ ムスカリンｍ４受容体アゴニストとしてのピペリジン−１−イル及びアゼピン−１−イルカルボキシレート
SG11201606269WA (en) * 2014-02-06 2016-09-29 Heptares Therapeutics Ltd Bicyclic aza compounds as muscarinic m1 receptor and/or m4 receptor agonists
GB201404922D0 (en) * 2014-03-19 2014-04-30 Heptares Therapeutics Ltd Pharmaceutical compounds
GB201513742D0 (en) * 2015-08-03 2015-09-16 Heptares Therapeutics Ltd Muscarinic agonists
GB201513743D0 (en) * 2015-08-03 2015-09-16 Heptares Therapeutics Ltd Muscarinic agonists
GB201617454D0 (en) * 2016-10-14 2016-11-30 Heptares Therapeutics Limited Pharmaceutical compounds
GB201810245D0 (en) * 2018-06-22 2018-08-08 Heptares Therapeutics Ltd Pharmaceutical compounds

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US20190389849A1 (en) 2019-12-26
AU2019289216A1 (en) 2021-01-14
CA3104085A1 (en) 2019-12-26
AU2019289216B2 (en) 2023-04-06
GB201810245D0 (en) 2018-08-08
US20210101893A1 (en) 2021-04-08
CN112585135A (zh) 2021-03-30
US10858352B2 (en) 2020-12-08
CN112585135B (zh) 2024-08-02
ZA202007986B (en) 2021-10-27
WO2019243850A1 (en) 2019-12-26
BR112020026437A2 (pt) 2021-03-23
KR20210024036A (ko) 2021-03-04
EP3810607A1 (en) 2021-04-28
TW202019918A (zh) 2020-06-01
JP2026002915A (ja) 2026-01-08
JP7389762B2 (ja) 2023-11-30
US11319312B2 (en) 2022-05-03
TWI872024B (zh) 2025-02-11
MX2020014156A (es) 2021-03-09
JP2021528447A (ja) 2021-10-21
SG11202012570TA (en) 2021-01-28
KR102833588B1 (ko) 2025-07-16
JP2023164721A (ja) 2023-11-10

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