WO2021219091A3 - Quinoxalinone derivative as irreversible inhibitor of kras g12c mutant protein - Google Patents

Quinoxalinone derivative as irreversible inhibitor of kras g12c mutant protein Download PDF

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Publication number
WO2021219091A3
WO2021219091A3 PCT/CN2021/091102 CN2021091102W WO2021219091A3 WO 2021219091 A3 WO2021219091 A3 WO 2021219091A3 CN 2021091102 W CN2021091102 W CN 2021091102W WO 2021219091 A3 WO2021219091 A3 WO 2021219091A3
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WO
WIPO (PCT)
Prior art keywords
kras
mutant protein
irreversible inhibitor
quinoxalinone derivative
derivative
Prior art date
Application number
PCT/CN2021/091102
Other languages
French (fr)
Chinese (zh)
Other versions
WO2021219091A2 (en
Inventor
赵焰平
王红军
张道广
肖绪枝
叶佳
冒莉
姜媛媛
禄立彦
黄淮
牛海涛
黄建宝
刘森
刘雪莲
周丽莹
刘亚男
Original Assignee
北京泰德制药股份有限公司
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
Publication date
Application filed by 北京泰德制药股份有限公司 filed Critical 北京泰德制药股份有限公司
Priority to CN202180015592.2A priority Critical patent/CN115135636A/en
Publication of WO2021219091A2 publication Critical patent/WO2021219091A2/en
Publication of WO2021219091A3 publication Critical patent/WO2021219091A3/en

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    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
    • 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
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/42—Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/44—Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • 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
    • 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
    • C07D403/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • 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

Abstract

The present invention relates to a novel quinoxalinone derivative, which can be used as an irreversible inhibitor of the KRAS G12C mutant protein. The present invention also relates to a pharmaceutical composition containing the quinoxalinone derivative, and a preparation method and use thereof.
PCT/CN2021/091102 2020-04-29 2021-04-29 Quinoxalinone derivative as irreversible inhibitor of kras g12c mutant protein WO2021219091A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202180015592.2A CN115135636A (en) 2020-04-29 2021-04-29 Quinoxalinone derivatives as irreversible inhibitors of KRAS G12C mutant proteins

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
CN202010354437.0 2020-04-29
CN202010354434 2020-04-29
CN202010354434.7 2020-04-29
CN202010354437 2020-04-29
CN202110390360 2021-04-12
CN202110390360.7 2021-04-12
CN202110446892 2021-04-25
CN202110446892.8 2021-04-25

Publications (2)

Publication Number Publication Date
WO2021219091A2 WO2021219091A2 (en) 2021-11-04
WO2021219091A3 true WO2021219091A3 (en) 2021-12-23

Family

ID=78373332

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/CN2021/091102 WO2021219091A2 (en) 2020-04-29 2021-04-29 Quinoxalinone derivative as irreversible inhibitor of kras g12c mutant protein
PCT/CN2021/091100 WO2021219090A1 (en) 2020-04-29 2021-04-29 Quinoxaline dione derivative as irreversible inhibitor of kras g12c mutant protein

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/091100 WO2021219090A1 (en) 2020-04-29 2021-04-29 Quinoxaline dione derivative as irreversible inhibitor of kras g12c mutant protein

Country Status (3)

Country Link
CN (2) CN115135636A (en)
TW (2) TW202200562A (en)
WO (2) WO2021219091A2 (en)

Families Citing this family (18)

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US11932633B2 (en) 2018-05-07 2024-03-19 Mirati Therapeutics, Inc. KRas G12C inhibitors
EP3908283A4 (en) 2019-01-10 2022-10-12 Mirati Therapeutics, Inc. Kras g12c inhibitors
US11453683B1 (en) 2019-08-29 2022-09-27 Mirati Therapeutics, Inc. KRas G12D inhibitors
MX2022003537A (en) 2019-09-24 2022-07-11 Mirati Therapeutics Inc Combination therapies.
KR20220130126A (en) 2019-12-20 2022-09-26 미라티 테라퓨틱스, 인크. SOS1 inhibitor
WO2022111527A1 (en) * 2020-11-24 2022-06-02 成都百裕制药股份有限公司 Piperazine-2,3-dione derivative and application thereof in medicine
US20230107642A1 (en) 2020-12-18 2023-04-06 Erasca, Inc. Tricyclic pyridones and pyrimidones
IL308195A (en) 2021-05-05 2024-01-01 Revolution Medicines Inc Ras inhibitors for the treatment of cancer
KR20240004960A (en) 2021-05-05 2024-01-11 레볼루션 메디슨즈, 인크. RAS inhibitors
WO2022266206A1 (en) 2021-06-16 2022-12-22 Erasca, Inc. Kras inhibitor conjugates
KR20240041917A (en) 2021-07-27 2024-04-01 도레이 카부시키가이샤 Medicines for the treatment and/or prevention of cancer
TW202340214A (en) 2021-12-17 2023-10-16 美商健臻公司 Pyrazolopyrazine compounds as shp2 inhibitors
EP4227307A1 (en) 2022-02-11 2023-08-16 Genzyme Corporation Pyrazolopyrazine compounds as shp2 inhibitors
WO2023172940A1 (en) 2022-03-08 2023-09-14 Revolution Medicines, Inc. Methods for treating immune refractory lung cancer
KR20230164602A (en) * 2022-05-25 2023-12-04 주식회사 엘지화학 Heterocyclic compound as diacrylglycerol kinases inhibitor and use thereof
WO2023229378A1 (en) * 2022-05-25 2023-11-30 주식회사 엘지화학 Heterocyclic compound as diacylglycerol kinase inhibitor and use thereof
WO2023240263A1 (en) 2022-06-10 2023-12-14 Revolution Medicines, Inc. Macrocyclic ras inhibitors
WO2024019995A1 (en) * 2022-07-19 2024-01-25 Dana-Farber Cancer Institute, Inc. Quinoxalinedione and pyrido [2, 3-b]pyrazine-2, 3-dione b cell lymphoma 6 (bcl6) degraders and uses thereof

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WO2014152588A1 (en) * 2013-03-15 2014-09-25 Araxes Pharma Llc Covalent inhibitors of kras g12c
WO2015095829A1 (en) * 2013-12-20 2015-06-25 Biomed Valley Discoveries, Inc. Cancer treatments using combinations of pi3k/akt pathway and erk inhibitors
WO2016044772A1 (en) * 2014-09-18 2016-03-24 Araxes Pharma Llc Combination therapies for treatment of cancer
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US8110578B2 (en) * 2008-10-27 2012-02-07 Signal Pharmaceuticals, Llc Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway
ES2751705T3 (en) * 2009-10-26 2020-04-01 Signal Pharm Llc Synthesis and purification methods of heteroaryl compounds
DE102017005091A1 (en) * 2016-05-30 2017-11-30 Bayer Pharma Aktiengesellschaft Substituted 3,4-dihydropyrido [2,3-b] pyrazine-2 (1H) -one
DE102017005089A1 (en) * 2016-05-30 2017-11-30 Bayer Pharma Aktiengesellschaft Substituted 3,4-dihydroquinoxaline-2 (1H) -one
CN110092782B (en) * 2018-01-30 2022-10-21 中国科学院广州生物医药与健康研究院 Benzo-hexaazacyclo compound and preparation method and application thereof

Patent Citations (4)

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WO2014152588A1 (en) * 2013-03-15 2014-09-25 Araxes Pharma Llc Covalent inhibitors of kras g12c
WO2015095829A1 (en) * 2013-12-20 2015-06-25 Biomed Valley Discoveries, Inc. Cancer treatments using combinations of pi3k/akt pathway and erk inhibitors
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WO2017058805A1 (en) * 2015-09-28 2017-04-06 Araxes Pharma Llc Inhibitors of kras g12c mutant proteins

Also Published As

Publication number Publication date
TW202200563A (en) 2022-01-01
TW202200562A (en) 2022-01-01
CN115151532A (en) 2022-10-04
CN115151532B (en) 2023-06-06
WO2021219091A2 (en) 2021-11-04
WO2021219090A1 (en) 2021-11-04
CN115135636A (en) 2022-09-30

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