CN110386932A - 用于抗肿瘤疗法中的双重atm和dna-pk抑制剂 - Google Patents

用于抗肿瘤疗法中的双重atm和dna-pk抑制剂 Download PDF

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Publication number
CN110386932A
CN110386932A CN201810359447.6A CN201810359447A CN110386932A CN 110386932 A CN110386932 A CN 110386932A CN 201810359447 A CN201810359447 A CN 201810359447A CN 110386932 A CN110386932 A CN 110386932A
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CN
China
Prior art keywords
optionally substituted
pyrrolo
methyl
pyridin
dihydrospiro
Prior art date
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Pending
Application number
CN201810359447.6A
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English (en)
Chinese (zh)
Inventor
付健民
王尧德
孙跃
吴国胜
陆爱军
张双
R.古诺
T.吉尔默
M.卡斯滕
D.基尔什
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Acoslade Pharmaceutical Co Ltd
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Acoslade Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
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Application filed by Acoslade Pharmaceutical Co Ltd filed Critical Acoslade Pharmaceutical Co Ltd
Priority to CN201810359447.6A priority Critical patent/CN110386932A/zh
Priority to KR1020207033463A priority patent/KR20210027251A/ko
Priority to EP23202655.9A priority patent/EP4327877A3/en
Priority to MA052364A priority patent/MA52364A/fr
Priority to AU2019254980A priority patent/AU2019254980B2/en
Priority to CA3096732A priority patent/CA3096732A1/en
Priority to SG11202010212RA priority patent/SG11202010212RA/en
Priority to CN201980040733.9A priority patent/CN112469720B/zh
Priority to EP19787882.0A priority patent/EP3784671B1/en
Priority to PCT/CN2019/083104 priority patent/WO2019201283A1/en
Priority to BR112020021323-3A priority patent/BR112020021323A2/pt
Priority to JP2021506031A priority patent/JP7366996B2/ja
Priority to MX2020010942A priority patent/MX2020010942A/es
Publication of CN110386932A publication Critical patent/CN110386932A/zh
Priority to PH12020551717A priority patent/PH12020551717A1/en
Priority to US17/074,425 priority patent/US12187742B2/en
Pending legal-status Critical Current

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    • 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
    • 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
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with 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
    • A61K31/495—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
    • 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
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • 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
    • 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
    • C07D471/02—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
    • 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
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN201810359447.6A 2018-04-20 2018-04-20 用于抗肿瘤疗法中的双重atm和dna-pk抑制剂 Pending CN110386932A (zh)

Priority Applications (15)

Application Number Priority Date Filing Date Title
CN201810359447.6A CN110386932A (zh) 2018-04-20 2018-04-20 用于抗肿瘤疗法中的双重atm和dna-pk抑制剂
CN201980040733.9A CN112469720B (zh) 2018-04-20 2019-04-17 用于抗肿瘤疗法中的双重atm和dna-pk抑制剂
EP19787882.0A EP3784671B1 (en) 2018-04-20 2019-04-17 Dual atm and dna-pk inhibitors for use in anti-tumor therapy
MA052364A MA52364A (fr) 2018-04-20 2019-04-17 Inhibiteurs doubles d'atm et d'adn-pk pour une utilisation en thérapie antitumorale
AU2019254980A AU2019254980B2 (en) 2018-04-20 2019-04-17 Dual ATM and DNA-PK inhibitors for use in anti-tumor therapy
CA3096732A CA3096732A1 (en) 2018-04-20 2019-04-17 Dual atm and dna-pk inhibitors for use in anti-tumor therapy
SG11202010212RA SG11202010212RA (en) 2018-04-20 2019-04-17 Dual atm and dna-pk inhibitors for use in anti-tumor therapy
KR1020207033463A KR20210027251A (ko) 2018-04-20 2019-04-17 항-종양 요법에서 사용하기 위한 이중 atm 및 dna-pk 억제제
EP23202655.9A EP4327877A3 (en) 2018-04-20 2019-04-17 Dual atm and dna-pk inhibitors for use in anti-tumor therapy
PCT/CN2019/083104 WO2019201283A1 (en) 2018-04-20 2019-04-17 Dual atm and dna-pk inhibitors for use in anti-tumor therapy
BR112020021323-3A BR112020021323A2 (pt) 2018-04-20 2019-04-17 Inibidores duplos de atm e dna-pk para uso em terapia antitumoral
JP2021506031A JP7366996B2 (ja) 2018-04-20 2019-04-17 抗腫瘍療法で使用するためのデュアルａｔｍ及びｄｎａ－ｐｋ阻害剤
MX2020010942A MX2020010942A (es) 2018-04-20 2019-04-17 Inhibidores dobles de atm y adn-pk para uso en terapias antitumorales.
PH12020551717A PH12020551717A1 (en) 2018-04-20 2020-10-16 Dual atm and dna-pk inhibitors for use in anti-tumor therapy
US17/074,425 US12187742B2 (en) 2018-04-20 2020-10-19 Dual ATM and DNA-PK inhibitors for use in anti-tumor therapy

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810359447.6A CN110386932A (zh) 2018-04-20 2018-04-20 用于抗肿瘤疗法中的双重atm和dna-pk抑制剂

Publications (1)

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CN110386932A true CN110386932A (zh) 2019-10-29

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CN201810359447.6A Pending CN110386932A (zh) 2018-04-20 2018-04-20 用于抗肿瘤疗法中的双重atm和dna-pk抑制剂
CN201980040733.9A Active CN112469720B (zh) 2018-04-20 2019-04-17 用于抗肿瘤疗法中的双重atm和dna-pk抑制剂

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Country Status (10)

Country Link
US (1) US12187742B2 (https=)
EP (2) EP3784671B1 (https=)
JP (1) JP7366996B2 (https=)
KR (1) KR20210027251A (https=)
CN (2) CN110386932A (https=)
BR (1) BR112020021323A2 (https=)
CA (1) CA3096732A1 (https=)
MA (1) MA52364A (https=)
MX (1) MX2020010942A (https=)
SG (1) SG11202010212RA (https=)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021022078A1 (en) * 2019-07-30 2021-02-04 Xrad Therapeutics, Inc. Dual atm and dna-pk inhibitors for use in anti-tumor therapy
WO2021098813A1 (zh) * 2019-11-22 2021-05-27 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
WO2021098734A1 (zh) * 2019-11-19 2021-05-27 南京明德新药研发有限公司 作为atm抑制剂的有取代的喹啉吡咯酮类合物及其应用
WO2021136462A1 (zh) * 2019-12-31 2021-07-08 成都百裕制药股份有限公司 呋喃衍生物及其在医药上的应用
WO2021197339A1 (zh) * 2020-03-30 2021-10-07 南京明德新药研发有限公司 作为atm抑制剂的喹啉并吡咯烷-2-酮类化合物的晶型及其应用
CN114634521A (zh) * 2020-12-15 2022-06-17 首药控股(北京)股份有限公司 Dna-pk选择性抑制剂及其制备方法和用途
WO2025247391A1 (en) * 2024-05-31 2025-12-04 Hutchmed Limited Novel pi3k and/or pikk inhibitors, antibody-drug conjugates comprising the same and uses thereof
WO2026006954A1 (en) * 2024-07-01 2026-01-08 Xrad Holding Cayman Limited Dual atm and dna-pk inhibitors for use in anti-tumor therapy

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WO2019201283A1 (en) 2018-04-20 2019-10-24 Xrad Therapeutics, Inc. Dual atm and dna-pk inhibitors for use in anti-tumor therapy
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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021022078A1 (en) * 2019-07-30 2021-02-04 Xrad Therapeutics, Inc. Dual atm and dna-pk inhibitors for use in anti-tumor therapy
WO2021098734A1 (zh) * 2019-11-19 2021-05-27 南京明德新药研发有限公司 作为atm抑制剂的有取代的喹啉吡咯酮类合物及其应用
CN114746421A (zh) * 2019-11-19 2022-07-12 南京明德新药研发有限公司 作为atm抑制剂的有取代的喹啉吡咯酮类合物及其应用
WO2021098813A1 (zh) * 2019-11-22 2021-05-27 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
TWI768550B (zh) * 2019-11-22 2022-06-21 大陸商南京明德新藥研發有限公司 作為dna-pk抑制劑的嘧啶并吡咯類螺環化合物及其衍生物
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
WO2021136462A1 (zh) * 2019-12-31 2021-07-08 成都百裕制药股份有限公司 呋喃衍生物及其在医药上的应用
WO2021197339A1 (zh) * 2020-03-30 2021-10-07 南京明德新药研发有限公司 作为atm抑制剂的喹啉并吡咯烷-2-酮类化合物的晶型及其应用
CN115380031A (zh) * 2020-03-30 2022-11-22 南京明德新药研发有限公司 作为atm抑制剂的喹啉并吡咯烷-2-酮类化合物的晶型及其应用
CN114634521A (zh) * 2020-12-15 2022-06-17 首药控股(北京)股份有限公司 Dna-pk选择性抑制剂及其制备方法和用途
WO2025247391A1 (en) * 2024-05-31 2025-12-04 Hutchmed Limited Novel pi3k and/or pikk inhibitors, antibody-drug conjugates comprising the same and uses thereof
WO2026006954A1 (en) * 2024-07-01 2026-01-08 Xrad Holding Cayman Limited Dual atm and dna-pk inhibitors for use in anti-tumor therapy

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CN112469720B (zh) 2024-03-29
JP2021522316A (ja) 2021-08-30
KR20210027251A (ko) 2021-03-10
MA52364A (fr) 2021-03-03
US12187742B2 (en) 2025-01-07
SG11202010212RA (en) 2020-11-27
JP7366996B2 (ja) 2023-10-23
CA3096732A1 (en) 2019-10-24
EP4327877A2 (en) 2024-02-28
AU2019254980A1 (en) 2020-12-03
MX2020010942A (es) 2021-01-15
EP3784671B1 (en) 2023-10-11
EP4327877A3 (en) 2024-04-24
US20220315606A1 (en) 2022-10-06
BR112020021323A2 (pt) 2021-01-19
CN112469720A (zh) 2021-03-09
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EP3784671A4 (en) 2021-11-17

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