AU2017369753A1 - Fused pyrimidine compounds as BRD4 and JAK2 dual inhibitors and methods for use thereof - Google Patents

Fused pyrimidine compounds as BRD4 and JAK2 dual inhibitors and methods for use thereof Download PDF

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Publication number
AU2017369753A1
AU2017369753A1 AU2017369753A AU2017369753A AU2017369753A1 AU 2017369753 A1 AU2017369753 A1 AU 2017369753A1 AU 2017369753 A AU2017369753 A AU 2017369753A AU 2017369753 A AU2017369753 A AU 2017369753A AU 2017369753 A1 AU2017369753 A1 AU 2017369753A1
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Prior art keywords
compound
alkyl
cancer
halogen
optionally substituted
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Abandoned
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AU2017369753A
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Inventor
Raghava KETHIRI
Sachin MADAN
Santosh Kumar Kotturi RAJAIAH
Ram Shankar Upadhayaya
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Aptose Biosciences Inc
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Aptose Biosciences Inc
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Publication of AU2017369753A1 publication Critical patent/AU2017369753A1/en
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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
    • C07D487/02—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
    • 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
    • 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
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
    • C07D405/02—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 two hetero rings
    • C07D405/10—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 two hetero rings linked by a carbon chain containing aromatic 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
    • C07D417/10—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 carbon chain containing aromatic rings
    • 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
    • C07D471/04—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
    • C07D471/18—Bridged 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
    • C07D491/02—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 two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • 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
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/12—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 three hetero rings
    • C07D495/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
AU2017369753A 2016-12-01 2017-12-01 Fused pyrimidine compounds as BRD4 and JAK2 dual inhibitors and methods for use thereof Abandoned AU2017369753A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662428756P 2016-12-01 2016-12-01
US62/428,756 2016-12-01
PCT/CA2017/000258 WO2018098561A1 (en) 2016-12-01 2017-12-01 Fused pyrimidine compounds as brd4 and jak2 dual inhibitors and methods for use thereof

Publications (1)

Publication Number Publication Date
AU2017369753A1 true AU2017369753A1 (en) 2019-07-18

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AU2017369753A Abandoned AU2017369753A1 (en) 2016-12-01 2017-12-01 Fused pyrimidine compounds as BRD4 and JAK2 dual inhibitors and methods for use thereof

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US (1) US11279703B2 (enExample)
EP (1) EP3548496A4 (enExample)
JP (1) JP2019536820A (enExample)
KR (1) KR20190135464A (enExample)
CN (1) CN110691782A (enExample)
AU (1) AU2017369753A1 (enExample)
WO (1) WO2018098561A1 (enExample)

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EP3717475B1 (en) 2017-11-20 2023-06-07 Icahn School of Medicine at Mount Sinai Kinase inhibitor compounds and compositions and methods of use
WO2019136320A1 (en) 2018-01-05 2019-07-11 Icahn School Of Medicine At Mount Sinai Method of increasing proliferation of pancreatic beta cells, treatment method, and composition
AU2019240065A1 (en) 2018-03-20 2020-09-24 Icahn School Of Medicine At Mount Sinai Kinase inhibitor compounds and compositions and methods of use
WO2020051572A1 (en) * 2018-09-07 2020-03-12 H. Lee Moffitt Cancer Center And Research Institute, Inc. Brd4-jak2 inhibitors
KR102377007B1 (ko) * 2018-09-20 2022-03-22 한미약품 주식회사 상피세포 성장인자 수용체 돌연변이 저해 효과를 갖는 신규 융합 피리미딘 골격 설폰아마이드 유도체
EP3842435A4 (en) * 2018-09-20 2022-05-11 Hanmi Pharm. Co., Ltd. NEW SULFONAMIDE DERIVATIVE PRESENTING A FUSED PYRIMIDINE SKELETON, HAVING AN INHIBITOR EFFECT OF EPIDERMAL GROWTH FACTOR RECEPTOR MUTATION
JP2022515650A (ja) * 2018-12-31 2022-02-21 アイカーン スクール オブ メディシン アット マウント サイナイ キナーゼ阻害剤化合物及び組成物ならびに使用方法
CN110305140B (zh) * 2019-07-30 2020-08-04 上海勋和医药科技有限公司 二氢吡咯并嘧啶类选择性jak2抑制剂
WO2021030238A2 (en) * 2019-08-09 2021-02-18 Ohm Oncology Method of synthesis of compound for dual inhibition of jak2 and bet
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GB201914910D0 (en) * 2019-10-15 2019-11-27 Sentinel Oncology Ltd Pharmaceutical compounds
JP7621351B2 (ja) * 2019-11-08 2025-01-24 ネクセラ・ファーマ・ユーケイ・リミテッド Ｇｐｒ５２モジュレーター化合物
CN114728978A (zh) * 2019-11-22 2022-07-08 南京明德新药研发有限公司 作为dna-pk抑制剂的嘧啶并吡咯类螺环化合物及其衍生物
WO2022083560A1 (zh) * 2020-10-19 2022-04-28 南京药石科技股份有限公司 Tyk2选择性抑制剂及其用途
CN117295743A (zh) * 2021-04-30 2023-12-26 微境生物医药科技(上海)有限公司 作为Wee-1抑制剂的吡咯并嘧啶衍生物
GB202113079D0 (en) * 2021-09-14 2021-10-27 Ucl Business Ltd New therapy
JP2024540921A (ja) * 2021-10-19 2024-11-06 上海瑛派▲薬▼▲業▼有限公司 Ｕｓｐ１阻害剤としての置換トリアゾロヘテロアリール化合物及びその応用
US12084453B2 (en) 2021-12-10 2024-09-10 Incyte Corporation Bicyclic amines as CDK12 inhibitors
CN118574832A (zh) * 2022-01-19 2024-08-30 上海奕拓医药科技有限责任公司 三并环化合物、其制备、药物组合物及应用
CN116731035A (zh) * 2022-03-08 2023-09-12 广州再极医药科技有限公司 一种噻吩并嘧啶类化合物、中间体、其制备方法、组合物和应用
CN114957248B (zh) * 2022-05-09 2023-12-29 南开大学 一种吡咯并嘧啶化合物及其制备方法、药物组合物和应用
CN116813624B (zh) * 2023-06-29 2025-10-03 成都金瑞基业生物科技有限公司 一种jak2抑制剂的晶型及制备方法

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US11279703B2 (en) 2022-03-22
CN110691782A (zh) 2020-01-14
JP2019536820A (ja) 2019-12-19
WO2018098561A1 (en) 2018-06-07
EP3548496A4 (en) 2020-05-13
KR20190135464A (ko) 2019-12-06
EP3548496A1 (en) 2019-10-09
US20200095252A1 (en) 2020-03-26

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