CN110198944A - 作为单酰基甘油脂肪酶抑制剂的杂环螺环化合物 - Google Patents

作为单酰基甘油脂肪酶抑制剂的杂环螺环化合物 Download PDF

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Publication number
CN110198944A
CN110198944A CN201880007992.7A CN201880007992A CN110198944A CN 110198944 A CN110198944 A CN 110198944A CN 201880007992 A CN201880007992 A CN 201880007992A CN 110198944 A CN110198944 A CN 110198944A
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formula
alkyl
group
compound
pharmaceutically acceptable
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Chinese (zh)
Inventor
M·A·布罗德尼
C·R·巴特勒
C·J·赫拉尔
L·A·麦卡利斯特
S·V·奥尼尔
P·R·费尔赫斯特
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SmithKline Beecham Ltd
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SmithKline Beecham Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/10—Spiro-condensed systems
    • 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
    • A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic 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
    • C07D221/20—Spiro-condensed ring systems
    • 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
    • C07D401/12—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 chain containing hetero atoms as chain links
    • 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
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/10—Spiro-condensed 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN201880007992.7A 2017-01-23 2018-01-09 作为单酰基甘油脂肪酶抑制剂的杂环螺环化合物 Pending CN110198944A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201762449242P 2017-01-23 2017-01-23
US62/449,242 2017-01-23
PCT/IB2018/050128 WO2018134698A1 (en) 2017-01-23 2018-01-09 Heterocyclic spiro compounds as magl inhibitors

Publications (1)

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CN110198944A true CN110198944A (zh) 2019-09-03

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CN201880007992.7A Pending CN110198944A (zh) 2017-01-23 2018-01-09 作为单酰基甘油脂肪酶抑制剂的杂环螺环化合物

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US (2) US20180208608A1 (enExample)
EP (1) EP3571202B1 (enExample)
JP (1) JP2020506903A (enExample)
KR (1) KR20190097242A (enExample)
CN (1) CN110198944A (enExample)
AU (1) AU2018208848A1 (enExample)
BR (1) BR112019014099A2 (enExample)
CA (1) CA3050853A1 (enExample)
IL (1) IL267781A (enExample)
MX (1) MX2019008690A (enExample)
RU (1) RU2726631C1 (enExample)
SG (1) SG11201906427QA (enExample)
TW (1) TWI665199B (enExample)
WO (1) WO2018134698A1 (enExample)

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WO2021228123A1 (zh) * 2020-05-12 2021-11-18 北京广为医药科技有限公司 调节nmda受体活性的化合物、其药物组合物及用途
WO2022135462A1 (zh) * 2020-12-22 2022-06-30 鲁南制药集团股份有限公司 Magl抑制剂的医药用途
CN115335365A (zh) * 2020-03-26 2022-11-11 詹森药业有限公司 氨基环丁烷作为单酰基甘油脂肪酶调节剂
CN116547274A (zh) * 2020-11-13 2023-08-04 H.隆德贝克有限公司 Magl抑制剂

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BR112019014688A2 (pt) * 2017-01-20 2020-02-18 Pfizer Inc. Derivados de carbamato de 1,1,1-trifluoro-3-hidroxipropan-2-il como inibidores de magl
US10927105B1 (en) 2017-05-23 2021-02-23 Lundbeck La Jolla Research Center, Inc. Pyrazole MAGL inhibitors
CN111148746B (zh) * 2017-09-29 2022-08-05 武田药品工业株式会社 杂环化合物
US10662159B2 (en) * 2017-11-22 2020-05-26 Makscientific, Llc ABHD6 and dual ABHD6/MGL inhibitors and their uses
CN111566105A (zh) 2018-01-08 2020-08-21 豪夫迈·罗氏有限公司 作为MAGL抑制剂的八氢吡啶并[1,2-α]吡嗪类化合物
KR20210033504A (ko) * 2018-07-19 2021-03-26 화이자 인코포레이티드 Magl 억제제로서 헤테로환형 스피로 화합물
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CN109485656A (zh) * 2018-12-17 2019-03-19 上海药明康德新药开发有限公司 3-氧亚基-7-氧杂-2,10-二氮杂螺[4.6]十一烷-10-甲酸叔丁酯的制法
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CN114555596B (zh) 2019-09-30 2025-02-25 詹森药业有限公司 放射性标记的mgl pet配体
EP4217062B1 (en) 2020-09-22 2024-10-09 JANSSEN Pharmaceutica NV Cyclobutyl amide monoacylglycerol lipase modulators
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CN119137114A (zh) 2022-05-04 2024-12-13 H.隆德贝克有限公司 作为单酰基甘油脂肪酶抑制剂的(s)-1-(哒嗪-3-基氨基甲酰基)-6-氮杂螺[2.5]辛烷-6-甲酸1,1,1,3,3,3-六氟丙-2-酯的结晶形式
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JAYENDRA Z. PATEL 等: "Loratadine analogues as MAGL inhibitors", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 *

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* Cited by examiner, † Cited by third party
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CN115335365A (zh) * 2020-03-26 2022-11-11 詹森药业有限公司 氨基环丁烷作为单酰基甘油脂肪酶调节剂
WO2021228123A1 (zh) * 2020-05-12 2021-11-18 北京广为医药科技有限公司 调节nmda受体活性的化合物、其药物组合物及用途
CN113966337A (zh) * 2020-05-12 2022-01-21 北京广为医药科技有限公司 调节nmda受体活性的化合物、其药物组合物及用途
CN113966337B (zh) * 2020-05-12 2024-01-02 北京广为医药科技有限公司 调节nmda受体活性的化合物、其药物组合物及用途
CN116547274A (zh) * 2020-11-13 2023-08-04 H.隆德贝克有限公司 Magl抑制剂
WO2022135462A1 (zh) * 2020-12-22 2022-06-30 鲁南制药集团股份有限公司 Magl抑制剂的医药用途

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IL267781A (en) 2019-09-26
TWI665199B (zh) 2019-07-11
SG11201906427QA (en) 2019-08-27
RU2726631C1 (ru) 2020-07-15
KR20190097242A (ko) 2019-08-20
WO2018134698A1 (en) 2018-07-26
MX2019008690A (es) 2019-09-18
EP3571202B1 (en) 2021-06-30
EP3571202A1 (en) 2019-11-27
JP2020506903A (ja) 2020-03-05
AU2018208848A1 (en) 2019-07-18
BR112019014099A2 (pt) 2020-02-11
US20190292203A1 (en) 2019-09-26
US20180208608A1 (en) 2018-07-26
US10858373B2 (en) 2020-12-08
CA3050853A1 (en) 2018-07-26

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