CN111630053A - 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物 - Google Patents

作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物 Download PDF

Info

Publication number
CN111630053A
CN111630053A CN201980009147.8A CN201980009147A CN111630053A CN 111630053 A CN111630053 A CN 111630053A CN 201980009147 A CN201980009147 A CN 201980009147A CN 111630053 A CN111630053 A CN 111630053A
Authority
CN
China
Prior art keywords
compound
isomer
group
pharmaceutically acceptable
acceptable salt
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.)
Pending
Application number
CN201980009147.8A
Other languages
English (en)
Inventor
蔡亚仙
徐招兵
杨海龙
韩世启
胡国平
胡利红
丁照中
黎健
陈曙辉
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.)
Medshine Discovery Inc
Original Assignee
Medshine Discovery Inc
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 Medshine Discovery Inc filed Critical Medshine Discovery Inc
Priority to CN202110310525.5A priority Critical patent/CN113121530B/zh
Priority to CN202011378153.1A priority patent/CN112442031B/zh
Priority to CN202011378149.5A priority patent/CN112442030B/zh
Publication of CN111630053A publication Critical patent/CN111630053A/zh
Pending legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/495—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
    • 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

Landscapes

  • 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)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

提供了一类KRAS G12C突变蛋白抑制剂，具体涉及式(I)所示化合物及其异构体、药学上可接受的盐。

Description

PCT国内申请，说明书已公开。

Claims (26)

  1. PCT国内申请，权利要求书已公开。
CN201980009147.8A 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物 Pending CN111630053A (zh)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CN202110310525.5A CN113121530B (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物
CN202011378153.1A CN112442031B (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物
CN202011378149.5A CN112442030B (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
CN2018100553968 2018-01-19
CN201810055396 2018-01-19
CN201810712103 2018-06-29
CN2018107121039 2018-06-29
PCT/CN2019/072393 WO2019141250A1 (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物

Related Child Applications (3)

Application Number Title Priority Date Filing Date
CN202011378149.5A Division CN112442030B (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物
CN202110310525.5A Division CN113121530B (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物
CN202011378153.1A Division CN112442031B (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物

Publications (1)

Publication Number Publication Date
CN111630053A true CN111630053A (zh) 2020-09-04

Family

ID=67301292

Family Applications (4)

Application Number Title Priority Date Filing Date
CN202011378149.5A Active CN112442030B (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物
CN201980009147.8A Pending CN111630053A (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物
CN202110310525.5A Active CN113121530B (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物
CN202011378153.1A Active CN112442031B (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CN202011378149.5A Active CN112442030B (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物

Family Applications After (2)

Application Number Title Priority Date Filing Date
CN202110310525.5A Active CN113121530B (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物
CN202011378153.1A Active CN112442031B (zh) 2018-01-19 2019-01-18 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物

Country Status (7)

Country Link
US (2) US11453667B2 (zh)
EP (2) EP3741756B1 (zh)
JP (2) JP7289839B2 (zh)
CN (4) CN112442030B (zh)
ES (1) ES2969284T3 (zh)
SG (2) SG10202102462SA (zh)
WO (1) WO2019141250A1 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116171155A (zh) * 2020-12-08 2023-05-26 上海和誉生物医药科技有限公司 吡啶并[2,3-d]嘧啶-2(1H)-酮衍生物及其制备方法和应用

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112442030B (zh) * 2018-01-19 2022-09-27 南京明德新药研发有限公司 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物
SG11202103839UA (en) 2018-10-31 2021-05-28 Gilead Sciences Inc Substituted 6-azabenzimidazole compounds as hpk1 inhibitors
AU2019373221B2 (en) 2018-10-31 2022-05-26 Gilead Sciences, Inc. Substituted 6-azabenzimidazole compounds having HPK1 inhibitory activity
EP3924053A1 (en) 2019-02-12 2021-12-22 Novartis AG Pharmaceutical combination comprising tno155 and a krasg12c inhibitor
WO2020237025A1 (en) 2019-05-23 2020-11-26 Gilead Sciences, Inc. Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors
AU2020350745A1 (en) * 2019-09-20 2022-04-07 Jiangxi Jemincare Group Co., Ltd Fused pyridone compound, and preparation method therefor and use thereof
WO2021058018A1 (en) * 2019-09-29 2021-04-01 Beigene, Ltd. Inhibitors of kras g12c
CN113286794B (zh) * 2019-11-04 2024-03-12 北京加科思新药研发有限公司 Kras突变蛋白抑制剂
CN112824410A (zh) * 2019-11-21 2021-05-21 苏州泽璟生物制药股份有限公司 氮杂七元环类抑制剂及其制备方法和应用
CN114349750A (zh) * 2019-12-19 2022-04-15 北京加科思新药研发有限公司 Kras突变蛋白抑制剂
CN113527293B (zh) * 2020-04-20 2023-09-08 苏州璞正医药有限公司 Kras g12c突变蛋白抑制剂及其药物组合物、制备方法和用途
CN111423366B (zh) * 2020-04-28 2022-05-27 山东汇海医药化工有限公司 一种吡非尼酮的制备方法
CN113880827A (zh) * 2020-07-03 2022-01-04 苏州闻天医药科技有限公司 一种用于抑制krasg12c突变蛋白的化合物及其制备方法和用途
WO2022048545A1 (zh) * 2020-09-01 2022-03-10 勤浩医药（苏州）有限公司 一种吡啶并嘧啶化合物的晶型
CN116133662A (zh) * 2020-09-11 2023-05-16 南京明德新药研发有限公司 氮杂环丁烷取代化合物的晶型
WO2022133345A1 (en) 2020-12-18 2022-06-23 Erasca, Inc. Tricyclic pyridones and pyrimidones
WO2022140246A1 (en) 2020-12-21 2022-06-30 Hangzhou Jijing Pharmaceutical Technology Limited Methods and compounds for targeted autophagy
WO2022222871A1 (en) * 2021-04-21 2022-10-27 Beijing Innocare Pharma Tech Co., Ltd. Heterocyclic compounds as kras g12c inhibitors
WO2022266206A1 (en) 2021-06-16 2022-12-22 Erasca, Inc. Kras inhibitor conjugates
TW202317100A (zh) 2021-06-23 2023-05-01 瑞士商諾華公司 包含ｋｒａｓ ｇ１２ｃ抑制劑的藥物組合及其用於治療癌症之用途
CA3224341A1 (en) 2021-09-01 2023-03-09 Novartis Ag Pharmaceutical combinations comprising a tead inhibitor and uses thereof for the treatment of cancers
EP4389751A1 (en) 2021-09-03 2024-06-26 Kumquat Biosciences Inc. Heterocyclic compounds and uses thereof
IL314296A (en) * 2022-01-21 2024-09-01 Usynova Pharmaceuticals Ltd Benzopyrimidine compounds and their use
WO2023173017A1 (en) * 2022-03-09 2023-09-14 Blossomhill Therapeutics, Inc. Kras inhibitors for treating disease
WO2023199180A1 (en) 2022-04-11 2023-10-19 Novartis Ag Therapeutic uses of a krasg12c inhibitor
WO2023205701A1 (en) 2022-04-20 2023-10-26 Kumquat Biosciences Inc. Macrocyclic heterocycles and uses thereof
WO2024017392A1 (zh) * 2022-07-22 2024-01-25 上海医药集团股份有限公司 嘧啶环类化合物、其中间体、其药物组合物及其应用
WO2024081674A1 (en) 2022-10-11 2024-04-18 Aadi Bioscience, Inc. Combination therapies for the treatment of cancer

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015054572A1 (en) * 2013-10-10 2015-04-16 Araxes Pharma Llc Inhibitors of kras g12c
WO2016164675A1 (en) * 2015-04-10 2016-10-13 Araxes Pharma Llc Substituted quinazoline compounds and methods of use thereof
WO2017087528A1 (en) * 2015-11-16 2017-05-26 Araxes Pharma Llc 2-substituted quinazoline compounds comprising a substituted heterocyclic group and methods of use thereof
WO2017100546A1 (en) * 2015-12-09 2017-06-15 Araxes Pharma Llc Methods for preparation of quinazoline derivatives
WO2017201161A1 (en) * 2016-05-18 2017-11-23 Mirati Therapeutics, Inc. Kras g12c inhibitors
WO2018064510A1 (en) * 2016-09-29 2018-04-05 Araxes Pharma Llc Inhibitors of kras g12c mutant proteins

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2836154B1 (en) * 2012-03-30 2019-06-26 Orthodontic Research and Development, S.L. Method of assembling a distalizer
JP6789239B2 (ja) * 2015-04-15 2020-11-25 アラクセス ファーマ エルエルシー Ｋｒａｓの縮合三環系インヒビターおよびその使用の方法
RS62456B1 (sr) 2016-12-22 2021-11-30 Amgen Inc Derivati benzizotiazola, izotiazolo[3,4-b]piridina, hinazolina, ftalazina, pirido[2,3-d]piridazina i pirido[2,3-d]pirimidina kao kras g12c inhibitori za tretman raka pluća, pankreasa ili debelog creva
WO2018140600A1 (en) * 2017-01-26 2018-08-02 Araxes Pharma Llc Fused hetero-hetero bicyclic compounds and methods of use thereof
EP3621968A1 (en) 2017-05-11 2020-03-18 Astrazeneca AB Heteroaryl compounds that inhibit g12c mutant ras proteins
CN112442030B (zh) * 2018-01-19 2022-09-27 南京明德新药研发有限公司 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015054572A1 (en) * 2013-10-10 2015-04-16 Araxes Pharma Llc Inhibitors of kras g12c
WO2016164675A1 (en) * 2015-04-10 2016-10-13 Araxes Pharma Llc Substituted quinazoline compounds and methods of use thereof
WO2017087528A1 (en) * 2015-11-16 2017-05-26 Araxes Pharma Llc 2-substituted quinazoline compounds comprising a substituted heterocyclic group and methods of use thereof
WO2017100546A1 (en) * 2015-12-09 2017-06-15 Araxes Pharma Llc Methods for preparation of quinazoline derivatives
WO2017201161A1 (en) * 2016-05-18 2017-11-23 Mirati Therapeutics, Inc. Kras g12c inhibitors
WO2018064510A1 (en) * 2016-09-29 2018-04-05 Araxes Pharma Llc Inhibitors of kras g12c mutant proteins

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116171155A (zh) * 2020-12-08 2023-05-26 上海和誉生物医药科技有限公司 吡啶并[2,3-d]嘧啶-2(1H)-酮衍生物及其制备方法和应用

Also Published As

Publication number Publication date
JP2021510721A (ja) 2021-04-30
SG11202012697QA (en) 2021-02-25
EP3842433A1 (en) 2021-06-30
EP3842433B1 (en) 2023-11-01
US20210147418A1 (en) 2021-05-20
EP3741756A4 (en) 2020-12-09
ES2969284T3 (es) 2024-05-17
JP2021091691A (ja) 2021-06-17
JP7352587B2 (ja) 2023-09-28
CN112442030A (zh) 2021-03-05
CN112442030B (zh) 2022-09-27
US11655248B2 (en) 2023-05-23
US11453667B2 (en) 2022-09-27
SG10202102462SA (en) 2021-04-29
CN112442031A (zh) 2021-03-05
CN113121530B (zh) 2022-08-05
EP3741756B1 (en) 2023-11-01
CN112442031B (zh) 2022-07-12
JP7289839B2 (ja) 2023-06-12
WO2019141250A1 (zh) 2019-07-25
CN113121530A (zh) 2021-07-16
EP3741756A1 (en) 2020-11-25
US20210371411A1 (en) 2021-12-02

Similar Documents

Publication Publication Date Title
CN112442031B (zh) 作为krasg12c突变蛋白抑制剂的吡啶酮并嘧啶类衍生物
JP7377798B2 (ja) ｃ－ＭＥＴ／ＡＸＬ阻害剤としてのウラシル系化合物
CN115192577A (zh) Kras突变蛋白抑制剂
CN116964036A (zh) Kras g12d抑制剂
JP2022543767A (ja) 四環式化合物、その調製と使用の方法
KR20210121168A (ko) 복소환식 화합물인 벤조피리돈 및 그 사용
JP6600365B2 (ja) Ｊａｋ阻害剤
JP7290651B2 (ja) Ａｔｒ阻害剤及びその応用
CN109415341B (zh) 作为TGF-βR1抑制剂的苯并三氮唑衍生的α，β不饱和酰胺类化合物
CN113993860B (zh) 作为kras g12c突变蛋白抑制剂的七元杂环类衍生物
CN111372937B (zh) 噻吩并二氮杂卓衍生物及其应用
JP2023554506A (ja) Ｆｇｆｒ阻害剤化合物及びその使用
CN112867717A (zh) 用作激酶抑制剂的化合物及其应用
CN116425770A (zh) 作为Cdc7抑制剂的四并环类化合物
CN113929676A (zh) 吡啶并杂环类衍生物及其制备方法和用途
CN111315750B (zh) 作为mTORC1/2双激酶抑制剂的吡啶并嘧啶类化合物
JP6900406B2 (ja) Ａｋｔ阻害剤としてのジヒドロピラゾロアゼピン系化合物
WO2022198904A1 (zh) 一种kras抑制剂关键中间体及其制备方法
CN115677831A (zh) 拟肽类stat降解药物、组合物及应用
AU2022412827A1 (en) Heterocyclic compound having anti-tumor activity and use thereof
CN115611898A (zh) 四环类衍生物、其制备方法及其在医药上的应用
CN112384506A (zh) 吲哚啉-1-甲酰胺类化合物、其制备方法及其在医药学上的应用

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: 40029747

Country of ref document: HK

WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20200904

WD01 Invention patent application deemed withdrawn after publication