CN110650950B - 用于治疗或预防prmt5介导的疾病的化合物 - Google Patents

用于治疗或预防prmt5介导的疾病的化合物 Download PDF

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CN110650950B
CN110650950B CN201880032332.4A CN201880032332A CN110650950B CN 110650950 B CN110650950 B CN 110650950B CN 201880032332 A CN201880032332 A CN 201880032332A CN 110650950 B CN110650950 B CN 110650950B
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CN110650950A (zh
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安德鲁·莫利
丽贝卡·米勒
尼古拉斯·拉·唐格
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Aguno Treatment Co 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
    • C07D401/12—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
    • 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
    • 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
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4365—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
    • 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
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • 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
    • C07D491/18—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-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
    • C07D498/08—Bridged systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201880032332.4A 2017-03-17 2018-03-16 用于治疗或预防prmt5介导的疾病的化合物 Active CN110650950B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB1704327.4 2017-03-17
GBGB1704327.4A GB201704327D0 (en) 2017-03-17 2017-03-17 Compounds
PCT/EP2018/056663 WO2018167269A1 (en) 2017-03-17 2018-03-16 Compounds useful in the treatment or prevention of a prmt5-mediated disorder

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CN110650950A CN110650950A (zh) 2020-01-03
CN110650950B true CN110650950B (zh) 2023-09-19

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US (1) US11485731B2 (OSRAM)
EP (1) EP3596061B1 (OSRAM)
JP (1) JP7211982B2 (OSRAM)
KR (1) KR102616970B1 (OSRAM)
CN (1) CN110650950B (OSRAM)
AU (2) AU2018235139A1 (OSRAM)
CA (1) CA3056724A1 (OSRAM)
GB (1) GB201704327D0 (OSRAM)
IL (1) IL269354B2 (OSRAM)
MX (1) MX2019011061A (OSRAM)
SG (1) SG11201908598PA (OSRAM)
WO (1) WO2018167269A1 (OSRAM)
ZA (1) ZA201906269B (OSRAM)

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US11807622B2 (en) 2019-01-30 2023-11-07 Insilico Medicine Ip Limited TLR 9 inhibitors
US10689360B1 (en) * 2019-01-30 2020-06-23 Insilico Medicine Ip Limited TLR inhibitors
GB201905780D0 (en) 2019-04-25 2019-06-05 La Thangue Nicholas Cancer therapy
CA3139365A1 (en) * 2019-06-06 2020-12-10 Aligos Therapeutics, Inc. Heterocyclic compounds
CN110950841A (zh) * 2019-11-22 2020-04-03 济南大学 一类新型三唑类化合物的合成及应用
WO2021126728A1 (en) * 2019-12-17 2021-06-24 Merck Sharp & Dohme Corp. Prmt5 inhibitors
AU2021283568B2 (en) * 2020-06-02 2023-12-14 Cspc Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd 3,4-dihydroisoquinoline compound and use thereof
PH12022553378A1 (en) 2020-06-10 2024-03-25 Univ Leuven Kath Anti-viral compounds for treating coronavirus, picornavirus, and norovirus infections
AU2021300483A1 (en) * 2020-06-30 2023-02-09 Nanjing Zaiming Pharmaceutical Co., Ltd. Tetrahydroisoquinoline compounds and use thereof
CN116113626B (zh) 2020-09-04 2025-10-10 上海翊石医药科技有限公司 一种具有抗肿瘤活性的化合物及其用途
KR20230159421A (ko) 2021-02-19 2023-11-21 수도 바이오사이언시즈 리미티드 Tyk2 억제제 및 이의 용도
TW202246233A (zh) 2021-02-19 2022-12-01 英商蘇多生物科學有限公司 Tyk2抑制劑及其用途
AU2022271927B2 (en) 2021-05-13 2025-07-10 Innovstone Therapeutics Limited Compound having anti-tumor activity and use thereof
GB202108383D0 (en) 2021-06-11 2021-07-28 Argonaut Therapeutics Ltd Compounds useful in the treatment or prevention of a prmt5-mediated disorder
EP4366831A4 (en) 2021-07-09 2025-06-11 Aligos Therapeutics, Inc. ANTI-VIRAL COMPOUNDS
US12065428B2 (en) 2021-09-17 2024-08-20 Aligos Therapeutics, Inc. Anti-viral compounds
GB202117230D0 (en) 2021-11-29 2022-01-12 Argonaut Therapeutics Ltd Peptide vaccine
JP7704986B2 (ja) * 2021-12-08 2025-07-08 石薬集団中奇制薬技術（石家庄）有限公司 ３，４－ジヒドロイソキノリン類化合物の塩及びその応用
WO2023125947A1 (zh) * 2021-12-30 2023-07-06 江苏先声药业有限公司 四氢异喹啉类化合物的可药用盐、晶型及其用途
WO2023131305A1 (zh) * 2022-01-06 2023-07-13 江苏先声药业有限公司 Prmt5抑制剂和抗癌治疗剂的组合
GB202203588D0 (en) 2022-03-15 2022-04-27 Argonaut Therapeutics Ltd Cancer diagnostic

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WO2014100764A2 (en) * 2012-12-21 2014-06-26 Epizyme, Inc. Methods of inhibiting prmt5
WO2014100695A1 (en) * 2012-12-21 2014-06-26 Epizyme, Inc. Prmt5 inhibitors and uses thereof
WO2015200677A2 (en) * 2014-06-25 2015-12-30 Epizyme, Inc. Prmt5 inhibitors and uses thereof
WO2015200680A2 (en) * 2014-06-25 2015-12-30 Epizyme, Inc. Prmt5 inhibitors and uses thereof
WO2016034673A1 (en) * 2014-09-03 2016-03-10 Ctxt Pty Ltd Tetrahydroisoquinoline derived prmt5-inhibitors
CN105452226A (zh) * 2012-12-21 2016-03-30 Epizyme股份有限公司 四氢-和二氢-异喹啉prmt5抑制剂及其用途

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US8940726B2 (en) 2012-12-21 2015-01-27 Epizyme, Inc. PRMT5 inhibitors and uses thereof
GB201415573D0 (en) 2014-09-03 2014-10-15 Cancer Therapeutics Crc Pty Ltd Compounds

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WO2014100764A2 (en) * 2012-12-21 2014-06-26 Epizyme, Inc. Methods of inhibiting prmt5
WO2014100695A1 (en) * 2012-12-21 2014-06-26 Epizyme, Inc. Prmt5 inhibitors and uses thereof
CN105452226A (zh) * 2012-12-21 2016-03-30 Epizyme股份有限公司 四氢-和二氢-异喹啉prmt5抑制剂及其用途
WO2015200677A2 (en) * 2014-06-25 2015-12-30 Epizyme, Inc. Prmt5 inhibitors and uses thereof
WO2015200680A2 (en) * 2014-06-25 2015-12-30 Epizyme, Inc. Prmt5 inhibitors and uses thereof
WO2016034673A1 (en) * 2014-09-03 2016-03-10 Ctxt Pty Ltd Tetrahydroisoquinoline derived prmt5-inhibitors

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Also Published As

Publication number Publication date
WO2018167269A1 (en) 2018-09-20
IL269354B2 (en) 2023-11-01
AU2018235139A1 (en) 2019-10-17
IL269354A (en) 2019-11-28
EP3596061C0 (en) 2023-09-06
EP3596061A1 (en) 2020-01-22
AU2022202389B2 (en) 2024-04-18
BR112019019358A2 (pt) 2020-04-14
KR20190129936A (ko) 2019-11-20
IL269354B1 (en) 2023-07-01
CN110650950A (zh) 2020-01-03
ZA201906269B (en) 2024-03-27
GB201704327D0 (en) 2017-05-03
EP3596061B1 (en) 2023-09-06
MX2019011061A (es) 2019-12-19
CA3056724A1 (en) 2018-09-20
SG11201908598PA (en) 2019-10-30
JP7211982B2 (ja) 2023-01-24
US20200325128A1 (en) 2020-10-15
US11485731B2 (en) 2022-11-01
KR102616970B1 (ko) 2023-12-22
AU2022202389A1 (en) 2022-05-05
JP2020510091A (ja) 2020-04-02

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