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)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Addiction (AREA)
  • Psychology (AREA)
  • Rheumatology (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) EP3331869B1 (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) ES2980578T3 (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 (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6083818B2 (ja) 2011-11-18 2017-02-22 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ｍ１受容体アゴニスト
GB201404922D0 (en) 2014-03-19 2014-04-30 Heptares Therapeutics Ltd Pharmaceutical compounds
PL3331863T3 (pl) 2015-08-03 2020-08-10 Glenmark Pharmaceuticals S.A. Nowe związki jako modulatory ror gamma
BR112018001960A2 (pt) 2015-08-03 2018-09-18 Bristol-Myers Squibb Company compostos heterocíclicos úteis como moduladores de tnf alfa
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
GB201519352D0 (en) 2015-11-02 2015-12-16 Heptares Therapeutics Ltd Pharmaceutical compounds
ES2789756T3 (es) 2015-12-23 2020-10-26 Merck Sharp & Dohme Moduladores alostéricos de 6,7-dihidro-5H-pirrolo[3,4-b]piridin-5-ona del receptor de acetilcolina muscarínico M4
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
GB201617454D0 (en) 2016-10-14 2016-11-30 Heptares Therapeutics Limited Pharmaceutical compounds
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
WO2018112843A1 (en) 2016-12-22 2018-06-28 Merck Sharp & Dohme Corp. Heteroaryl piperidine ether allosteric modulators of the m4 muscarinic acetylcholine 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
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
JP7166331B2 (ja) * 2017-08-01 2022-11-07 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 中間体化合物及び方法
CA3079188A1 (en) * 2017-10-17 2019-04-25 Vanderbilt University Antagonists of the muscarinic acetylcholine receptor m4
US11299481B2 (en) 2017-10-20 2022-04-12 Vanderbilt University Antagonists of the muscarinic acetylcholine receptor M4
EP3732163A4 (en) * 2017-12-20 2021-07-14 Vanderbilt University MUSCARIN M4 ACETYLCHOLIN RECEPTOR ANTAGONISTS
CA3094366A1 (en) * 2018-03-23 2019-09-26 Pfizer Inc. Piperazine azaspiro derivatives
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
AU2020361735B2 (en) * 2019-10-09 2024-04-18 Novartis Ag 2-azaspiro(3.4)octane derivatives as M4 agonists
KR102798432B1 (ko) 2019-10-09 2025-04-22 노파르티스 아게 M4 작용제로서의 5-옥사-2-아자스피로[3.4]옥탄 유도체
US20250064833A1 (en) 2021-12-13 2025-02-27 Sage Therapeutics, Inc. Combination of muscarinic receptor positive modulators and nmda positive allosteric modulators

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

Family Cites Families (7)

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UY31672A1 (es) * 2008-02-28 2009-09-30 "agonistas de receptores muscarínicos composiciones farmacéuticas métodos de tratamiento de los mismos, y procedimientos para su preparación"
WO2011112825A2 (en) * 2010-03-10 2011-09-15 Vanderbilt University Heterocyclyl-azabicyclo[3.2.1]octane analogs as selective m1 agonists and methods of making and using same
PL3102568T3 (pl) * 2014-02-06 2019-01-31 Heptares Therapeutics Limited Bicykliczne związki aza w postaci agonistów receptorów muskarynowych m1
PL3331863T3 (pl) 2015-08-03 2020-08-10 Glenmark Pharmaceuticals S.A. Nowe związki jako modulatory ror gamma
BR112018001960A2 (pt) 2015-08-03 2018-09-18 Bristol-Myers Squibb Company compostos heterocíclicos úteis como moduladores de tnf alfa
AR105556A1 (es) 2015-08-03 2017-10-18 Hoffmann La Roche Derivados de etinilo
GB201513742D0 (en) 2015-08-03 2015-09-16 Heptares Therapeutics Ltd Muscarinic agonists

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

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