CN111647000B - 吡嗪类衍生物及其在抑制shp2中的应用 - Google Patents

吡嗪类衍生物及其在抑制shp2中的应用 Download PDF

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Publication number
CN111647000B
CN111647000B CN201910160960.7A CN201910160960A CN111647000B CN 111647000 B CN111647000 B CN 111647000B CN 201910160960 A CN201910160960 A CN 201910160960A CN 111647000 B CN111647000 B CN 111647000B
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compound
radical
formula
halogen atom
membered
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CN201910160960.7A
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Chinese (zh)
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CN111647000A (zh
Inventor
孙海丰
王奎锋
李坤
汪波
戴诚
张涛
丁福云
马梦楠
陆金昌
李瑶
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Qinhao Pharmaceutical Suzhou Co Ltd
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Suzhou Genhouse Pharmaceutical Co ltd
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Priority to CN201910160960.7A priority Critical patent/CN111647000B/zh
Application filed by Suzhou Genhouse Pharmaceutical Co ltd filed Critical Suzhou Genhouse Pharmaceutical Co ltd
Priority to AU2020233038A priority patent/AU2020233038B2/en
Priority to IL286069A priority patent/IL286069B2/en
Priority to US17/436,223 priority patent/US12338246B2/en
Priority to PH1/2021/552134A priority patent/PH12021552134A1/en
Priority to NZ780509A priority patent/NZ780509B2/en
Priority to MX2021010625A priority patent/MX2021010625A/es
Priority to PCT/CN2020/077391 priority patent/WO2020177653A1/zh
Priority to CA3132395A priority patent/CA3132395A1/en
Priority to JP2021551865A priority patent/JP2022523786A/ja
Priority to KR1020217031808A priority patent/KR20210135561A/ko
Priority to BR112021017495A priority patent/BR112021017495A2/pt
Priority to SG11202109603S priority patent/SG11202109603SA/en
Priority to CN202080014053.2A priority patent/CN113474338B/zh
Priority to EP20766519.1A priority patent/EP3936502A4/en
Publication of CN111647000A publication Critical patent/CN111647000A/zh
Priority to CL2021002308A priority patent/CL2021002308A1/es
Priority to CONC2021/0013140A priority patent/CO2021013140A2/es
Application granted granted Critical
Publication of CN111647000B publication Critical patent/CN111647000B/zh
Priority to US18/101,511 priority patent/US11827644B2/en
Priority to US19/219,936 priority patent/US20250282791A1/en
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    • 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
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    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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CN201910160960.7A 2019-03-04 2019-03-04 吡嗪类衍生物及其在抑制shp2中的应用 Active CN111647000B (zh)

Priority Applications (19)

Application Number Priority Date Filing Date Title
CN201910160960.7A CN111647000B (zh) 2019-03-04 2019-03-04 吡嗪类衍生物及其在抑制shp2中的应用
BR112021017495A BR112021017495A2 (pt) 2019-03-04 2020-03-02 Derivado de pirazina e sua aplicação na inibição de shp2
US17/436,223 US12338246B2 (en) 2019-03-04 2020-03-02 Pyrazine derivative and application thereof in inhibiting SHP2
PH1/2021/552134A PH12021552134A1 (en) 2019-03-04 2020-03-02 Pyrazine derivative and application thereof in inhibiting shp2
NZ780509A NZ780509B2 (en) 2020-03-02 Pyrazine derivative and application thereof in inhibiting shp2
MX2021010625A MX2021010625A (es) 2019-03-04 2020-03-02 Derivado de pirazina y aplicacion del mismo en la inhibicion de shp2.
PCT/CN2020/077391 WO2020177653A1 (zh) 2019-03-04 2020-03-02 吡嗪类衍生物及其在抑制shp2中的应用
CN202080014053.2A CN113474338B (zh) 2019-03-04 2020-03-02 吡嗪类衍生物及其在抑制shp2中的应用
IL286069A IL286069B2 (en) 2019-03-04 2020-03-02 Pyrazine derivative and application thereof in inhibiting shp2
KR1020217031808A KR20210135561A (ko) 2019-03-04 2020-03-02 피라진 유도체 및 shp2 억제에서의 그의 적용
AU2020233038A AU2020233038B2 (en) 2019-03-04 2020-03-02 Pyrazine derivative and application thereof in inhibiting SHP2
JP2021551865A JP2022523786A (ja) 2019-03-04 2020-03-02 ピラジン誘導体およびｓｈｐ２の阻害の際のその適用
CA3132395A CA3132395A1 (en) 2019-03-04 2020-03-02 Pyrazine derivative and application thereof in inhibiting shp2
EP20766519.1A EP3936502A4 (en) 2019-03-04 2020-03-02 PYRAZINE DERIVATIVES AND THEIR USE TO INHIBIT SHP2
SG11202109603S SG11202109603SA (en) 2019-03-04 2020-03-02 Pyrazine derivative and application thereof in inhibiting shp2
CL2021002308A CL2021002308A1 (es) 2019-03-04 2021-09-03 Derivado de pirazina y aplicación del mismo en la inhibición de shp2
CONC2021/0013140A CO2021013140A2 (es) 2019-03-04 2021-09-30 Derivado de pirazina y aplicación del mismo en la inhibición de shp2
US18/101,511 US11827644B2 (en) 2019-03-04 2023-01-25 Pyrazine derivative and application thereof in inhibiting SHP2
US19/219,936 US20250282791A1 (en) 2019-03-04 2025-05-27 Pyrazine derivative and application thereof in inhibiting shp2

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Application Number Priority Date Filing Date Title
CN201910160960.7A CN111647000B (zh) 2019-03-04 2019-03-04 吡嗪类衍生物及其在抑制shp2中的应用

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CN111647000B true CN111647000B (zh) 2021-10-12

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CN202080014053.2A Active CN113474338B (zh) 2019-03-04 2020-03-02 吡嗪类衍生物及其在抑制shp2中的应用

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US (3) US12338246B2 (https=)
EP (1) EP3936502A4 (https=)
JP (1) JP2022523786A (https=)
KR (1) KR20210135561A (https=)
CN (2) CN111647000B (https=)
AU (1) AU2020233038B2 (https=)
BR (1) BR112021017495A2 (https=)
CA (1) CA3132395A1 (https=)
CL (1) CL2021002308A1 (https=)
CO (1) CO2021013140A2 (https=)
IL (1) IL286069B2 (https=)
MX (1) MX2021010625A (https=)
PH (1) PH12021552134A1 (https=)
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WO2020051424A1 (en) 2018-09-07 2020-03-12 Pic Therapeutics Eif4e inhibitors and uses thereof
CN112867718B (zh) 2018-09-29 2025-03-04 诺华股份有限公司 用于抑制shp2活性的化合物和组合物的制造
CN111647000B (zh) * 2019-03-04 2021-10-12 勤浩医药（苏州）有限公司 吡嗪类衍生物及其在抑制shp2中的应用
TW202146393A (zh) 2020-03-03 2021-12-16 美商皮克醫療公司 Eif4e抑制劑及其用途
IL299131A (en) 2020-06-18 2023-02-01 Revolution Medicines Inc Methods for delaying, preventing and treating acquired resistance to RAS inhibitors
JP2023530838A (ja) * 2020-06-22 2023-07-20 スーチュアン・コールン－バイオテック・バイオファーマシューティカル・カンパニー・リミテッド 置換されたピラジン化合物、当該化合物を含む医薬組成物、及びその使用
US12441737B2 (en) 2020-07-08 2025-10-14 Novartis Ag Manufacture of compounds and compositions for inhibiting the activity of SHP2
WO2022006780A1 (en) * 2020-07-08 2022-01-13 Novartis Ag Manufacture of compounds and compositions for inhibiting activity of shp2
US20250195521A1 (en) 2020-09-03 2025-06-19 Revolution Medicines, Inc. Use of sos1 inhibitors to treat malignancies with shp2 mutations
CA3194067A1 (en) 2020-09-15 2022-03-24 Revolution Medicines, Inc. Ras inhibitors
CN116348466B (zh) * 2020-09-23 2025-05-30 上海齐鲁制药研究中心有限公司 吡嗪硫联苯基类化合物及其应用
JP2024516997A (ja) * 2021-05-05 2024-04-18 フヤバイオ インターナショナル，エルエルシー Ｓｈｐ２阻害剤単独療法およびその使用
TW202309052A (zh) 2021-05-05 2023-03-01 美商銳新醫藥公司 Ｒａｓ抑制劑
JP2024516450A (ja) 2021-05-05 2024-04-15 レボリューション メディシンズ インコーポレイテッド 共有結合性ｒａｓ阻害剤及びその使用
KR20240017811A (ko) 2021-05-05 2024-02-08 레볼루션 메디슨즈, 인크. 암의 치료를 위한 ras 억제제
MX2023012929A (es) * 2021-05-05 2023-11-13 Huyabio Int Llc Terapias de combinacion que comprenden inhibidores de shp2 e inhibidores de tirosina cinasa egfr.
IL308222A (en) * 2021-05-05 2024-01-01 Huyabio Int Llc Combination therapies that include SHP2 inhibitors and PD-1 inhibitors
TW202244049A (zh) * 2021-05-12 2022-11-16 大陸商藥雅科技（上海）有限公司 Shp2磷酸酶抑制劑的製備及其應用
CN115340559A (zh) * 2021-05-12 2022-11-15 药雅科技(上海)有限公司 Shp2磷酸酶杂环类抑制剂的制备及其应用
CN115340561A (zh) * 2021-05-14 2022-11-15 药雅科技(上海)有限公司 Shp2磷酸酶稠环类抑制剂的制备及其应用
AU2022274936B2 (en) * 2021-05-13 2025-08-21 Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences Heterocyclic compound for inhibiting shp2 activity, preparation method therefor and use thereof
WO2022259157A1 (en) 2021-06-09 2022-12-15 Novartis Ag A triple pharmaceutical combination comprising dabrafenib, trametinib and a shp2 inhibitor
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
WO2023280237A1 (zh) * 2021-07-07 2023-01-12 海创药业股份有限公司 一种磷酸酶降解剂的合成和应用
US12157732B2 (en) 2021-08-25 2024-12-03 PIC Therapeutics, Inc. eIF4E inhibitors and uses thereof
CA3229560A1 (en) 2021-08-25 2023-03-02 Christopher L. Vandeusen Eif4e inhibitors and uses thereof
KR20240055778A (ko) 2021-09-01 2024-04-29 노파르티스 아게 Tead 억제제를 포함하는 제약 조합물 및 암의 치료를 위한 이의 용도
AR127308A1 (es) 2021-10-08 2024-01-10 Revolution Medicines Inc Inhibidores ras
CN116063307B (zh) * 2021-10-29 2025-08-19 中国药科大学 Shp2与cdk4/6双靶点抑制化合物合成及其制备方法与应用
WO2023122938A1 (en) * 2021-12-28 2023-07-06 Js Innomed Holdings Ltd. Heterocyclic compounds as shp2 inhibitors, compositions comprising the heterocyclic compound, and methods of use thereof
JP2025510572A (ja) 2022-03-08 2025-04-15 レボリューション メディシンズ インコーポレイテッド 免疫不応性肺癌を治療するための方法
CN116947867B (zh) * 2022-04-18 2025-12-30 上海茂晟康慧科技有限公司 一种嘧啶-4(3h)-酮类杂环化合物的重要中间体的制备方法
WO2023240263A1 (en) 2022-06-10 2023-12-14 Revolution Medicines, Inc. Macrocyclic ras inhibitors
CN115521305B (zh) * 2022-09-20 2024-11-08 中国药科大学 Shp2&nampt双靶向化合物及其药物组合物和用途
WO2024081674A1 (en) 2022-10-11 2024-04-18 Aadi Bioscience, Inc. Combination therapies for the treatment of cancer
CN115677661B (zh) * 2022-10-27 2024-04-19 中国药科大学 杂环硫醚类化合物及其用途和药物组合物
CN118206550A (zh) * 2022-12-15 2024-06-18 江苏威凯尔医药科技有限公司 Shp2抑制剂及其应用
CN120826403A (zh) * 2023-02-24 2025-10-21 深圳真实生物医药科技有限公司 Shp2抑制剂化合物及其应用
AU2024241633A1 (en) 2023-03-30 2025-11-06 Revolution Medicines, Inc. Compositions for inducing ras gtp hydrolysis and uses thereof
AR132338A1 (es) 2023-04-07 2025-06-18 Revolution Medicines Inc Inhibidores de ras
CR20250420A (es) 2023-04-07 2025-11-20 Revolution Medicines Inc Inhibidores macrocíclicos de ras
CN121100123A (zh) 2023-04-14 2025-12-09 锐新医药公司 Ras抑制剂的结晶形式
CN121464140A (zh) 2023-04-14 2026-02-03 锐新医药公司 Ras抑制剂的结晶形式、含有其的组合物及其使用方法
TW202508595A (zh) 2023-05-04 2025-03-01 美商銳新醫藥公司 用於ｒａｓ相關疾病或病症之組合療法
WO2025011568A1 (zh) * 2023-07-11 2025-01-16 勤浩医药（苏州）有限公司 用作shp2抑制剂的杂环化合物、包含其的药物组合物及其制备方法和用途
US20250049810A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
TW202529768A (zh) 2023-09-29 2025-08-01 大陸商德昇濟醫藥（無錫）有限公司 癌症治療的療法
AU2024360465A1 (en) 2023-10-12 2026-04-09 Revolution Medicines, Inc. Macrocyclic ras inhibitors
CN118108707A (zh) * 2024-02-04 2024-05-31 中国药科大学 吡嗪类化合物及其制备方法、药物组合物和应用
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
TW202547461A (zh) 2024-05-17 2025-12-16 美商銳新醫藥公司 Ｒａｓ抑制劑
WO2025242126A1 (zh) * 2024-05-22 2025-11-27 上海正大天晴医药科技开发有限公司 一种药物组合及其应用
WO2025255438A1 (en) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en) 2024-06-21 2025-12-26 Revolution Medicines, Inc. Therapeutic compositions and methods for managing treatment-related effects
WO2026015796A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015801A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015790A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015825A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Use of ras inhibitor for treating pancreatic cancer
WO2026050446A1 (en) 2024-08-29 2026-03-05 Revolution Medicines, Inc. Ras inhibitors
WO2026072904A2 (en) 2024-09-26 2026-04-02 Revolution Medicines, Inc. Compositions and methods for treating lung cancer

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018013597A1 (en) * 2016-07-12 2018-01-18 Revolution Medicines, Inc. 2,5-disubstituted 3-methyl pyrazines and 2,5,6-trisubstituted 3-methyl pyrazines as allosteric shp2 inhibitors
CN107922388A (zh) * 2015-06-19 2018-04-17 诺华股份有限公司 用于抑制shp2活性的化合物和组合物
WO2018172984A1 (en) * 2017-03-23 2018-09-27 Jacobio Pharmaceuticals Co., Ltd. Novel heterocyclic derivatives useful as shp2 inhibitors
CN109311848A (zh) * 2016-06-07 2019-02-05 北京加科思新药研发有限公司 可用作shp2抑制剂的新型杂环衍生物
CN109415360A (zh) * 2016-06-14 2019-03-01 诺华股份有限公司 用于抑制shp2活性的化合物和组合物

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JO3517B1 (ar) * 2014-01-17 2020-07-05 Novartis Ag ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2
WO2015107494A1 (en) * 2014-01-17 2015-07-23 Novartis Ag 1 -(triazin-3-yi_/pyridazin-3-yl)-piper(-azine)idine derivatives and compositions thereof for inhibiting the activity of shp2
CA3048340A1 (en) 2017-01-10 2018-07-19 Novartis Ag Pharmaceutical combination comprising an alk inhibitor and a shp2 inhibitor
CA3074690A1 (en) 2017-09-07 2019-03-14 Revolution Medicines, Inc. Shp2 inhibitor compositions and methods for treating cancer
TW201930292A (zh) 2017-10-12 2019-08-01 美商銳新醫藥公司 作為變構ｓｈｐ２抑制劑的吡啶、吡嗪和三嗪化合物
US11110171B2 (en) 2017-12-21 2021-09-07 New York University PD-1 related cancer therapy
WO2019152454A1 (en) 2018-01-30 2019-08-08 Research Development Foundation Shp2 inhibitors and methods of use thereof
RU2020133727A (ru) 2018-03-21 2022-04-21 Сучжоу Пухе Биофарма Ко., Лтд. Ингибиторы shp2 и их применение
MX2020010719A (es) 2018-04-10 2020-11-06 Revolution Medicines Inc Composiciones de inhibidores de shp2, metodos para tratar el cancer y metodos para identificar a un sujeto con mutaciones en shp2.
CN111647000B (zh) * 2019-03-04 2021-10-12 勤浩医药（苏州）有限公司 吡嗪类衍生物及其在抑制shp2中的应用

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107922388A (zh) * 2015-06-19 2018-04-17 诺华股份有限公司 用于抑制shp2活性的化合物和组合物
CN109311848A (zh) * 2016-06-07 2019-02-05 北京加科思新药研发有限公司 可用作shp2抑制剂的新型杂环衍生物
CN109415360A (zh) * 2016-06-14 2019-03-01 诺华股份有限公司 用于抑制shp2活性的化合物和组合物
WO2018013597A1 (en) * 2016-07-12 2018-01-18 Revolution Medicines, Inc. 2,5-disubstituted 3-methyl pyrazines and 2,5,6-trisubstituted 3-methyl pyrazines as allosteric shp2 inhibitors
WO2018172984A1 (en) * 2017-03-23 2018-09-27 Jacobio Pharmaceuticals Co., Ltd. Novel heterocyclic derivatives useful as shp2 inhibitors

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