CA2955910C - Tricyclic imidazo-pyrimidinone compounds as lp-pla2 inhibitors - Google Patents

Tricyclic imidazo-pyrimidinone compounds as lp-pla2 inhibitors Download PDF

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CA2955910C
CA2955910C CA2955910A CA2955910A CA2955910C CA 2955910 C CA2955910 C CA 2955910C CA 2955910 A CA2955910 A CA 2955910A CA 2955910 A CA2955910 A CA 2955910A CA 2955910 C CA2955910 C CA 2955910C
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disease
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pharmaceutically acceptable
diseases
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CA2955910A1 (en
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Zehong Wan
Xiaomin Zhang
Jian Wang
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GlaxoSmithKline Intellectual Property Development Ltd
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GlaxoSmithKline Intellectual Property Development Ltd
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    • 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
    • C07D487/12—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 three hetero rings
    • C07D487/14—Ortho-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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • 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
    • A61P25/14—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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/14—Ortho-condensed 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
    • C07D471/12—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 three hetero rings
    • C07D471/20—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
    • C07D487/04—Ortho-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
    • C07D491/12—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 three hetero rings
    • C07D491/20—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
    • C07D498/12—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 three hetero rings
    • C07D498/14—Ortho-condensed systems
    • 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
    • C07D513/12—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 three hetero rings
    • C07D513/14—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Epidemiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Psychology (AREA)
  • Psychiatry (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Emergency Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pulmonology (AREA)
  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
CA2955910A 2014-07-22 2015-07-21 Tricyclic imidazo-pyrimidinone compounds as lp-pla2 inhibitors Active CA2955910C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN2014000695 2014-07-22
CNPCT/CN2014/000695 2014-07-22
PCT/CN2015/084607 WO2016011931A1 (en) 2014-07-22 2015-07-21 Compounds

Publications (2)

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CA2955910A1 CA2955910A1 (en) 2016-01-28
CA2955910C true CA2955910C (en) 2022-07-12

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CA2955910A Active CA2955910C (en) 2014-07-22 2015-07-21 Tricyclic imidazo-pyrimidinone compounds as lp-pla2 inhibitors
CA2970537A Active CA2970537C (en) 2014-07-22 2015-07-21 Tricyclic imidazo-pyrimidinone compounds for the mediation of lipoprotein-associated phospholipase a2

Family Applications After (1)

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CA2970537A Active CA2970537C (en) 2014-07-22 2015-07-21 Tricyclic imidazo-pyrimidinone compounds for the mediation of lipoprotein-associated phospholipase a2

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US (5) US10125141B2 (enExample)
EP (2) EP3172208B1 (enExample)
JP (2) JP6625603B2 (enExample)
KR (2) KR20170029516A (enExample)
CN (2) CN106536521B (enExample)
AR (1) AR101261A1 (enExample)
AU (2) AU2015292048B2 (enExample)
BR (1) BR112016030939B1 (enExample)
CA (2) CA2955910C (enExample)
ES (2) ES2747636T3 (enExample)
RU (2) RU2690190C2 (enExample)
TW (1) TW201617348A (enExample)
UY (1) UY36224A (enExample)
WO (2) WO2016011931A1 (enExample)

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WO2019063634A1 (en) * 2017-09-26 2019-04-04 INSERM (Institut National de la Santé et de la Recherche Médicale) DARAPLADIB RADIOMARQUÉ, ITS ANALOGUES AND THEIR USE AS IMAGING COMPOUNDS
CN109988126B (zh) * 2017-12-29 2023-05-16 南京富润凯德生物医药有限公司 一种3-氨基-氧杂环丁烷衍生物及其制备方法和应用
CN109134523A (zh) * 2018-09-30 2019-01-04 中昊(大连)化工研究设计院有限公司 一种3，6-二氢-2h-吡喃-4-硼酸频哪醇酯的合成新工艺
JP2022116370A (ja) * 2019-06-13 2022-08-10 アグロカネショウ株式会社 新規な１－ベンジルアミン誘導体及びこれを有効成分とする農園芸用薬剤
CN112574221B (zh) * 2019-09-30 2022-03-04 上海纽思克生物科技有限公司 四环嘧啶酮类化合物、其制备方法、其组合物和用途
EP4056571A4 (en) * 2019-11-09 2024-01-24 Shanghai Simr Biotechnology Co., Ltd. Tricyclic dihydroimidazopyrimidone derivative, preparation method therefor, pharmaceutical composition and use thereof
WO2021228159A1 (zh) * 2020-05-13 2021-11-18 上海纽思克生物科技有限公司 桥环嘧啶酮类化合物、其制备方法、其组合物和用途
CN113666930B (zh) * 2020-05-13 2022-10-25 上海纽思克生物科技有限公司 桥环嘧啶酮类化合物、其制备方法、其组合物和用途
CN113861220B (zh) * 2020-06-30 2023-06-16 上海纽思克生物科技有限公司 三环嘧啶酮类化合物、其制备方法、其组合物和用途
CN113912622B (zh) * 2020-07-10 2023-12-01 上海纽思克生物科技有限公司 三环嘧啶酮类化合物、其制备方法、其组合物和用途
CN115304620A (zh) 2021-05-07 2022-11-08 上海赛默罗生物科技有限公司 嘧啶酮衍生物、其制备方法、药物组合物和用途
CN114057740B (zh) * 2021-12-15 2024-04-02 上海赛默罗生物科技有限公司 螺环嘧啶酮衍生物、其制备方法、药物组合物和用途
JP2025527291A (ja) * 2022-08-04 2025-08-20 ４ビー テクノロジーズ （ベイジン） カンパニー リミテッド Ｌｐ－ＰＬＡ２阻害剤としてのジヒドロイミダゾピリミジノン化合物およびその使用
CN121311231A (zh) * 2023-04-18 2026-01-09 赛神医药有限公司 Lp-PLA2抑制剂和第二药剂的联合治疗
WO2025015951A1 (zh) * 2023-07-17 2025-01-23 上海枢境生物科技有限公司 双环[5,6]咪唑嘧啶酮类衍生物、其制备方法和应用
WO2025217646A1 (en) * 2024-04-12 2025-10-16 Scineuro Therapeutics Inc. Method of treating neurodegenerative and ocular neovascular diseases

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KR20170029516A (ko) 2017-03-15
US9783546B2 (en) 2017-10-10
RU2017105476A (ru) 2018-08-28
CN106536525A (zh) 2017-03-22
JP6625604B2 (ja) 2019-12-25
CN106536525B (zh) 2019-05-03
RU2017105476A3 (enExample) 2019-02-28
BR112016028591A2 (pt) 2017-08-22
JP6625603B2 (ja) 2019-12-25
RU2690190C2 (ru) 2019-05-31
US20170204109A1 (en) 2017-07-20
EP3172211A1 (en) 2017-05-31
EP3172208A1 (en) 2017-05-31
EP3172208A4 (en) 2017-12-06
JP2017521456A (ja) 2017-08-03
AU2015292048A1 (en) 2016-12-15
TW201617348A (zh) 2016-05-16
US10125141B2 (en) 2018-11-13
AR101261A1 (es) 2016-12-07
RU2017105353A3 (enExample) 2018-11-26
CN106536521B (zh) 2018-08-03
US20240300965A1 (en) 2024-09-12
US11999746B2 (en) 2024-06-04
US20190023715A1 (en) 2019-01-24
CN106536521A (zh) 2017-03-22
US20170204108A1 (en) 2017-07-20
US10428078B2 (en) 2019-10-01
ES2747636T3 (es) 2020-03-11
ES2744339T3 (es) 2020-02-24
EP3172211B1 (en) 2019-07-03
UY36224A (es) 2016-01-29
CA2970537A1 (en) 2016-01-28
EP3172208B1 (en) 2019-06-12
AU2015292049B2 (en) 2017-06-15
EP3172211A4 (en) 2018-02-14
WO2016011931A1 (en) 2016-01-28
US20200055863A1 (en) 2020-02-20
BR112016030939A2 (enExample) 2017-08-22
AU2015292049A1 (en) 2016-12-15
JP2017520613A (ja) 2017-07-27
CA2970537C (en) 2023-02-21
BR112016030939B1 (pt) 2023-10-24
AU2015292048B2 (en) 2017-06-29
CA2955910A1 (en) 2016-01-28
RU2017105353A (ru) 2018-08-22
KR20170034889A (ko) 2017-03-29
WO2016011930A1 (en) 2016-01-28

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