CN107949558B - 毒蕈碱激动剂 - Google Patents

毒蕈碱激动剂 Download PDF

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Publication number
CN107949558B
CN107949558B CN201680043661.XA CN201680043661A CN107949558B CN 107949558 B CN107949558 B CN 107949558B CN 201680043661 A CN201680043661 A CN 201680043661A CN 107949558 B CN107949558 B CN 107949558B
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piperidin
azaspiro
amino
octane
ethyl ester
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CN107949558A (zh
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盖尔斯·艾伯特·布朗
迈尔斯·斯图尔特·康格里夫
马克·皮克沃斯
本杰明·杰拉尔德·特汉
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Nexla Pharmaceuticals Uk Ltd
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Heptares Therapeutics Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/04—Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • 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
    • A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
    • 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
    • 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • 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
    • 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
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/08—Heterocyclic 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 carbon chain containing alicyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/14—Heterocyclic 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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/14—Heterocyclic 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 three or more hetero rings
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Psychiatry (AREA)
  • Epidemiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Psychology (AREA)
  • Rheumatology (AREA)
  • Addiction (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
CN201680043661.XA 2015-08-03 2016-08-03 毒蕈碱激动剂 Active CN107949558B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB1513742.5A GB201513742D0 (en) 2015-08-03 2015-08-03 Muscarinic agonists
GB1513742.5 2015-08-03
PCT/GB2016/052386 WO2017021730A1 (en) 2015-08-03 2016-08-03 Muscarinic agonists

Publications (2)

Publication Number Publication Date
CN107949558A CN107949558A (zh) 2018-04-20
CN107949558B true CN107949558B (zh) 2022-03-15

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CN201680043661.XA Active CN107949558B (zh) 2015-08-03 2016-08-03 毒蕈碱激动剂

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US (4) US9758506B2 (enExample)
EP (2) EP3822262B1 (enExample)
JP (1) JP6876675B2 (enExample)
KR (1) KR102664558B1 (enExample)
CN (1) CN107949558B (enExample)
AR (1) AR105593A1 (enExample)
AU (1) AU2016302048B2 (enExample)
BR (1) BR112018002279B1 (enExample)
CA (1) CA2993484C (enExample)
CL (1) CL2018000292A1 (enExample)
CO (1) CO2018002060A2 (enExample)
DK (1) DK3331869T3 (enExample)
ES (2) ES2850298T3 (enExample)
GB (1) GB201513742D0 (enExample)
IL (1) IL257064A (enExample)
MX (1) MX379530B (enExample)
MY (1) MY195244A (enExample)
PH (1) PH12018500259A1 (enExample)
RU (1) RU2737158C2 (enExample)
TW (1) TWI723037B (enExample)
UA (1) UA123315C2 (enExample)
WO (1) WO2017021730A1 (enExample)
ZA (1) ZA201800715B (enExample)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2619829T3 (es) 2011-11-18 2017-06-27 Heptares Therapeutics Limited Agonistas del receptor muscarínico M1
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
CN108137547B (zh) 2015-08-03 2021-11-12 百时美施贵宝公司 可用作TNFα调节剂的杂环化合物
GB201513743D0 (en) 2015-08-03 2015-09-16 Heptares Therapeutics Ltd Muscarinic agonists
HUE048902T2 (hu) 2015-08-03 2020-08-28 Glenmark Pharmaceuticals Sa Új ROR gamma modulátor vegyületek
GB201519352D0 (en) 2015-11-02 2015-12-16 Heptares Therapeutics Ltd Pharmaceutical compounds
WO2017107089A1 (en) 2015-12-23 2017-06-29 Merck Sharp & Dohme Corp. 3- (1h-pyrazol-4-yl) pyridineallosteric modulators of the m4 muscarinic acetylcholine receptor
EP3394061B1 (en) 2015-12-23 2020-03-11 Merck Sharp & Dohme Corp. 6,7-dihydro-5h-pyrrolo[3,4-b]pyridin-5-one allosteric modulators of the m4 muscarinic acetylcholine receptor
GB201617454D0 (en) 2016-10-14 2016-11-30 Heptares Therapeutics Limited Pharmaceutical compounds
WO2018112843A1 (en) 2016-12-22 2018-06-28 Merck Sharp & Dohme Corp. Heteroaryl piperidine ether allosteric modulators of the m4 muscarinic acetylcholine receptor
WO2018112842A1 (en) 2016-12-22 2018-06-28 Merck Sharp & Dohme Corp. 6,6-fused heteroaryl piperidine ether allosteric modulators of m4 muscarinic acetylcholine receptor
WO2019000237A1 (en) 2017-06-27 2019-01-03 Merck Sharp & Dohme Corp. ALLOSTERIC MODULATORS OF 3- (1H-PYRAZOL-4-YL) PYRIDINE FROM THE M4 ACETYLCHOLINE MUSCARINIC RECEPTOR
WO2019000238A1 (en) 2017-06-27 2019-01-03 Merck Sharp & Dohme Corp. 5- (PYRIDIN-3-YL) OXAZOLE ALLOSTERIC MODULATORS OF M4 ACETYLCHOLINE MUSCARINIC RECEPTOR
WO2019000236A1 (en) 2017-06-27 2019-01-03 Merck Sharp & Dohme Corp. ALLOSTERIC MODULATORS OF 3- (1H-PYRAZOL-4-YL) PYRIDINE FROM THE M4 ACETYLCHOLINE MUSCARINIC RECEPTOR
EP3651762B1 (en) 2017-07-12 2024-07-03 Vanderbilt University Antagonists of the muscarinic acetylcholine receptor m4
CN110944999A (zh) * 2017-08-01 2020-03-31 勃林格殷格翰国际有限公司 中间体化合物和方法
WO2019079410A1 (en) 2017-10-17 2019-04-25 Vanderbilt University ANTAGONISTS OF THE MUSCARINIC RECEPTOR OF ACETYLCHOLINE M4
JP7270989B2 (ja) 2017-10-20 2023-05-11 ヴァンダービルト ユニバーシティー ムスカリン性アセチルコリン受容体ｍ４のアンタゴニスト
EP3732163A4 (en) * 2017-12-20 2021-07-14 Vanderbilt University MUSCARIN M4 ACETYLCHOLIN RECEPTOR ANTAGONISTS
EP3768669B1 (en) * 2018-03-23 2023-01-25 Pfizer Inc. Piperazine azaspiro derivaves
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
GB201819960D0 (en) 2018-12-07 2019-01-23 Heptares Therapeutics Ltd Pharmaceutical compounds
GB201819961D0 (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
PH12022550860A1 (en) 2019-10-09 2023-06-14 Novartis Ag 5-oxa-2-azaspiro[3.4]octane derivatives as m4 agonists
UY38906A (es) * 2019-10-09 2021-05-31 Novartis Ag Compuestos 2- derivados de azaspiro[3,4]octano como agonistas de m4 y composiciones de los mismos
US20250064833A1 (en) 2021-12-13 2025-02-27 Sage Therapeutics, Inc. Combination of muscarinic receptor positive modulators and nmda positive allosteric modulators

Citations (3)

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Publication number Priority date Publication date Assignee Title
WO2007100670A1 (en) * 2006-02-22 2007-09-07 Vertex Pharmaceuticals Incorporated Spiro condensed piperidnes as modulators of muscarinic receptors
CN104039321A (zh) * 2011-11-18 2014-09-10 赫普泰雅治疗有限公司 药物化合物
CN104640851A (zh) * 2012-09-18 2015-05-20 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

Family Cites Families (7)

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US20090221567A1 (en) * 2008-02-28 2009-09-03 Astrazeneca Ab Muscarinic receptor agonists, compositions, methods of treatment thereof, and processes for preparation thereof 177
US20130197027A1 (en) * 2010-03-10 2013-08-01 Craig Lindsley Heterocyclyl-azabicyclo[3.2.1]octane analogs as selective m1 agonists and methods of making and using same
RU2685230C2 (ru) 2014-02-06 2019-04-17 Хептарес Терапьютикс Лимитед Бициклические азотсодержащие соединения как агонисты М1 мускариновых рецепторов
CN108137547B (zh) 2015-08-03 2021-11-12 百时美施贵宝公司 可用作TNFα调节剂的杂环化合物
GB201513742D0 (en) * 2015-08-03 2015-09-16 Heptares Therapeutics Ltd Muscarinic agonists
AR105556A1 (es) 2015-08-03 2017-10-18 Hoffmann La Roche Derivados de etinilo
HUE048902T2 (hu) 2015-08-03 2020-08-28 Glenmark Pharmaceuticals Sa Új ROR gamma modulátor vegyületek

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007100670A1 (en) * 2006-02-22 2007-09-07 Vertex Pharmaceuticals Incorporated Spiro condensed piperidnes as modulators of muscarinic receptors
CN104039321A (zh) * 2011-11-18 2014-09-10 赫普泰雅治疗有限公司 药物化合物
CN104640851A (zh) * 2012-09-18 2015-05-20 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

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WO2017021730A1 (en) 2017-02-09
PH12018500259A1 (en) 2018-08-13
ES2980578T3 (es) 2024-10-02
ZA201800715B (en) 2018-12-19
RU2018105020A (ru) 2019-09-06
AR105593A1 (es) 2017-10-18
EP3331869B1 (en) 2020-12-23
RU2737158C2 (ru) 2020-11-25
MX2018001564A (es) 2018-09-06
AU2016302048A1 (en) 2018-02-22
US9758506B2 (en) 2017-09-12
EP3331869A1 (en) 2018-06-13
IL257064A (en) 2018-03-29
EP3822262B1 (en) 2024-03-27
US10167272B2 (en) 2019-01-01
HK1250160A1 (en) 2018-11-30
CO2018002060A2 (es) 2018-06-20
DK3331869T3 (da) 2021-02-15
CN107949558A (zh) 2018-04-20
US10351545B2 (en) 2019-07-16
JP6876675B2 (ja) 2021-05-26
RU2018105020A3 (enExample) 2019-09-06
UA123315C2 (uk) 2021-03-17
US20190270718A1 (en) 2019-09-05
EP3822262C0 (en) 2024-03-27
US20170037025A1 (en) 2017-02-09
KR102664558B1 (ko) 2024-05-09
MY195244A (en) 2023-01-11
JP2018522032A (ja) 2018-08-09
CA2993484C (en) 2023-10-24
TWI723037B (zh) 2021-04-01
CL2018000292A1 (es) 2018-06-29
US20180155315A1 (en) 2018-06-07
EP3822262A1 (en) 2021-05-19
BR112018002279A2 (enExample) 2018-10-02
TW201716391A (zh) 2017-05-16
MX379530B (es) 2025-03-11
GB201513742D0 (en) 2015-09-16
AU2016302048B2 (en) 2020-09-10
KR20180039657A (ko) 2018-04-18
US20180022726A1 (en) 2018-01-25
CA2993484A1 (en) 2017-02-09
ES2850298T3 (es) 2021-08-26
US11091456B2 (en) 2021-08-17
BR112018002279B1 (pt) 2024-01-30

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