CN115151532A - 喹喔啉二酮衍生物作为kras g12c突变蛋白的不可逆抑制剂 - Google Patents

喹喔啉二酮衍生物作为kras g12c突变蛋白的不可逆抑制剂 Download PDF

Info

Publication number
CN115151532A
CN115151532A CN202180015895.4A CN202180015895A CN115151532A CN 115151532 A CN115151532 A CN 115151532A CN 202180015895 A CN202180015895 A CN 202180015895A CN 115151532 A CN115151532 A CN 115151532A
Authority
CN
China
Prior art keywords
alkylene
haloalkyl
halogen
cancer
alkyl radical
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
CN202180015895.4A
Other languages
English (en)
Other versions
CN115151532B (zh
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
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beijing Tide Pharmaceutical Co Ltd
Original Assignee
Beijing Tide 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
Publication date
Application filed by Beijing Tide Pharmaceutical Co Ltd filed Critical Beijing Tide Pharmaceutical Co Ltd
Publication of CN115151532A publication Critical patent/CN115151532A/zh
Application granted granted Critical
Publication of CN115151532B publication Critical patent/CN115151532B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (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)
  • Medicinal Preparation (AREA)

Abstract

一种式(I)所示的喹喔啉‑2,3(1H,4H)‑二酮衍生物、其制备方法以及包含所述衍生物的药物组合物。该类化合物可作为KRAS G12C突变蛋白的不可逆抑制剂，用于治疗癌症等疾病。

Description

PCT国内申请，说明书已公开。

Claims (31)

  1. PCT国内申请，权利要求书已公开。
CN202180015895.4A 2020-04-29 2021-04-29 喹喔啉二酮衍生物作为kras g12c突变蛋白的不可逆抑制剂 Active CN115151532B (zh)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
CN2020103544347 2020-04-29
CN202010354434 2020-04-29
CN2020103544370 2020-04-29
CN202010354437 2020-04-29
CN202110390360 2021-04-12
CN2021103903607 2021-04-12
CN202110446892 2021-04-25
CN2021104468928 2021-04-25
PCT/CN2021/091100 WO2021219090A1 (zh) 2020-04-29 2021-04-29 喹喔啉二酮衍生物作为kras g12c突变蛋白的不可逆抑制剂

Publications (2)

Publication Number Publication Date
CN115151532A true CN115151532A (zh) 2022-10-04
CN115151532B CN115151532B (zh) 2023-06-06

Family

ID=78373332

Family Applications (2)

Application Number Title Priority Date Filing Date
CN202180015592.2A Pending CN115135636A (zh) 2020-04-29 2021-04-29 喹喔啉酮衍生物作为kras g12c突变蛋白的不可逆抑制剂
CN202180015895.4A Active CN115151532B (zh) 2020-04-29 2021-04-29 喹喔啉二酮衍生物作为kras g12c突变蛋白的不可逆抑制剂

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CN202180015592.2A Pending CN115135636A (zh) 2020-04-29 2021-04-29 喹喔啉酮衍生物作为kras g12c突变蛋白的不可逆抑制剂

Country Status (3)

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

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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 (es) 2019-09-24 2022-07-11 Mirati Therapeutics Inc Terapias de combinacion.
KR20220130126A (ko) 2019-12-20 2022-09-26 미라티 테라퓨틱스, 인크. Sos1 억제제
WO2022111527A1 (zh) * 2020-11-24 2022-06-02 成都百裕制药股份有限公司 哌嗪-2,3-二酮衍生物及其在医药上的应用
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 cancer treatment
KR20240004960A (ko) 2021-05-05 2024-01-11 레볼루션 메디슨즈, 인크. Ras 억제제
WO2022266206A1 (en) 2021-06-16 2022-12-22 Erasca, Inc. Kras inhibitor conjugates
KR20240041917A (ko) 2021-07-27 2024-04-01 도레이 카부시키가이샤 암의 치료 및/또는 예방을 위한 의약품
TW202340214A (zh) 2021-12-17 2023-10-16 美商健臻公司 做為shp2抑制劑之吡唑并吡𠯤化合物
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 (ko) * 2022-05-25 2023-12-04 주식회사 엘지화학 다이아실글리세롤 키나아제 저해제로서 헤테로사이클 화합물 및 이의 용도
WO2023229378A1 (ko) * 2022-05-25 2023-11-30 주식회사 엘지화학 다이아실글리세롤 키나아제 저해제로서 헤테로사이클 화합물 및 이의 용도
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

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102245611A (zh) * 2008-10-27 2011-11-16 西格诺药品有限公司 用于与 mTOR/PI3K/AKT/途径相关的肿瘤适应症和疾病的 mTOR激酶抑制剂
CN102686225A (zh) * 2009-10-26 2012-09-19 西格诺药品有限公司 杂芳基化合物的合成和纯化方法
WO2017058805A1 (en) * 2015-09-28 2017-04-06 Araxes Pharma Llc Inhibitors of kras g12c mutant proteins
DE102017005091A1 (de) * 2016-05-30 2017-11-30 Bayer Pharma Aktiengesellschaft Substituierte 3,4-Dihydropyrido[2,3-b]pyrazin-2(1H)-one
DE102017005089A1 (de) * 2016-05-30 2017-11-30 Bayer Pharma Aktiengesellschaft Substitulerte 3,4-Dihydrochinoxalin-2(1H)-one
CN110092782A (zh) * 2018-01-30 2019-08-06 中国科学院广州生物医药与健康研究院 一种苯并六元氮杂环化合物及其制备方法和应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW201524952A (zh) * 2013-03-15 2015-07-01 Araxes Pharma Llc Ｋｒａｓ ｇ１２ｃ之共價抑制劑
AU2014368916B2 (en) * 2013-12-20 2020-04-30 Biomed Valley Discoveries, Inc. Cancer treatments using combinations of PI3K/Akt pathway and ERK inhibitors
JO3556B1 (ar) * 2014-09-18 2020-07-05 Araxes Pharma Llc علاجات مدمجة لمعالجة السرطان

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102245611A (zh) * 2008-10-27 2011-11-16 西格诺药品有限公司 用于与 mTOR/PI3K/AKT/途径相关的肿瘤适应症和疾病的 mTOR激酶抑制剂
CN102686225A (zh) * 2009-10-26 2012-09-19 西格诺药品有限公司 杂芳基化合物的合成和纯化方法
WO2017058805A1 (en) * 2015-09-28 2017-04-06 Araxes Pharma Llc Inhibitors of kras g12c mutant proteins
DE102017005091A1 (de) * 2016-05-30 2017-11-30 Bayer Pharma Aktiengesellschaft Substituierte 3,4-Dihydropyrido[2,3-b]pyrazin-2(1H)-one
DE102017005089A1 (de) * 2016-05-30 2017-11-30 Bayer Pharma Aktiengesellschaft Substitulerte 3,4-Dihydrochinoxalin-2(1H)-one
CN110092782A (zh) * 2018-01-30 2019-08-06 中国科学院广州生物医药与健康研究院 一种苯并六元氮杂环化合物及其制备方法和应用

Also Published As

Publication number Publication date
TW202200563A (zh) 2022-01-01
WO2021219091A3 (zh) 2021-12-23
TW202200562A (zh) 2022-01-01
CN115151532B (zh) 2023-06-06
WO2021219091A2 (zh) 2021-11-04
WO2021219090A1 (zh) 2021-11-04
CN115135636A (zh) 2022-09-30

Similar Documents

Publication Publication Date Title
CN115151532A (zh) 喹喔啉二酮衍生物作为kras g12c突变蛋白的不可逆抑制剂
JP7353682B2 (ja) 置換された縮合芳香環誘導体、その組成物、およびそれらの使用
CN111587249A (zh) 吲哚化合物及其用途
CN108699039B (zh) 用于抑制蛋白激酶活性的(杂)芳基酰胺类化合物
CN112047938B (zh) 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物
CN108191857B (zh) 6-取代的吡啶并[2,3-d]嘧啶类化合物作为蛋白激酶抑制剂
WO2023134266A1 (zh) 2-哌啶基或2-吡唑基取代的嘧啶化合物作为egfr抑制剂
CN110343092B (zh) 用于抑制蛋白激酶活性的(杂)芳基酰胺类化合物
CN114149409A (zh) 一种具有蛋白激酶抑制活性的（杂）芳基酰胺类化合物
CN115698005A (zh) 稠环类AhR抑制剂
CN115551860A (zh) 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物
CN115181104A (zh) 取代的稠合三环衍生物及其组合物及用途
JP7323218B2 (ja) 置換された縮合芳香環誘導体、その組成物、およびそれらの使用
CN112625027B (zh) 杂环衍生物及其用途
CN111349084B (zh) 用于抑制蛋白激酶活性的氨基嘧啶类化合物
CN113754685B (zh) 二氢硫代色烯并吡唑类衍生物、其制备方法及其在医药上的应用
WO2023078267A1 (zh) 作为蛋白激酶调节剂的含氨基大环化合物
CN116096721A (zh) 作为新型选择性flt3抑制剂的1h-咪唑并[4,5-h]喹唑啉化合物
WO2023216910A1 (zh) 取代的双环杂芳基化合物作为usp1抑制剂
WO2023207556A1 (zh) Prmt5-mta抑制剂
CN117402142A (zh) 用于抑制蛋白激酶活性的(杂)芳基酰胺类化合物
CN115943145A (zh) 作为atr激酶抑制剂的吡唑并嘧啶化合物

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 40073782

Country of ref document: HK

GR01 Patent grant
GR01 Patent grant