CN106661000A - Egfr抑制剂及其制备和应用 - Google Patents

Egfr抑制剂及其制备和应用 Download PDF

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CN106661000A
CN106661000A CN201580045311.2A CN201580045311A CN106661000A CN 106661000 A CN106661000 A CN 106661000A CN 201580045311 A CN201580045311 A CN 201580045311A CN 106661000 A CN106661000 A CN 106661000A
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compound
methyl
formula
amino
pyrimidine
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CN106661000B (zh
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危明松
孙广俊
谭松良
高鹏
王少宝
修文华
张福军
包如迪
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Jiangsu Hansoh Pharmaceutical Group Co Ltd
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Lianyungang Hongchuang Pharmaceutical Co ltd
Shanghai Hansoh Biomedical Co Ltd
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Priority to CN202311030017.7A priority Critical patent/CN117050062A/zh
Priority to CN201910210386.1A priority patent/CN111171000B/zh
Priority to CN201910210387.6A priority patent/CN111187221B/zh
Priority to CN202311029815.8A priority patent/CN117069700A/zh
Priority to CN201910208542.0A priority patent/CN111170999B/zh
Priority to CN202311339167.6A priority patent/CN117402143A/zh
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    • 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
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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    • A61K31/5375—1,4-Oxazines, e.g. morpholine
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Abstract

一种如式(I)所示的4‑取代‑2‑(N‑(5‑取代烯丙酰胺基)苯基)氨基)嘧啶衍生物以及其作为EGFR抑制剂的制备和应用，该化合物具有抑制L858R EGFR突变体、T790M EGFR突变体和外显子19缺失激活突变体的活性，可以用来治疗单独或部分地由EGFR突变体活性介导疾病，在预防与治疗癌症尤其是非小细胞肺癌药物中的具有广泛应用。

Description

PCT国内申请，说明书已公开。

Claims (49)

  1. PCT国内申请，权利要求书已公开。
CN201580045311.2A 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用 Active CN106661000B (zh)

Priority Applications (6)

Application Number Priority Date Filing Date Title
CN202311030017.7A CN117050062A (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN201910210386.1A CN111171000B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN201910210387.6A CN111187221B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN202311029815.8A CN117069700A (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN201910208542.0A CN111170999B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN202311339167.6A CN117402143A (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN2014105342039 2014-10-11
CN201410534203 2014-10-11
PCT/CN2015/091189 WO2016054987A1 (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用

Related Child Applications (6)

Application Number Title Priority Date Filing Date
CN202311030017.7A Division CN117050062A (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN201910210387.6A Division CN111187221B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN202311339167.6A Division CN117402143A (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN202311029815.8A Division CN117069700A (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN201910210386.1A Division CN111171000B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN201910208542.0A Division CN111170999B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用

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CN106661000A true CN106661000A (zh) 2017-05-10
CN106661000B CN106661000B (zh) 2019-04-09

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CN202311030017.7A Pending CN117050062A (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN202311339167.6A Pending CN117402143A (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN201580045311.2A Active CN106661000B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN201910208542.0A Active CN111170999B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN201910210386.1A Active CN111171000B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN202311029815.8A Pending CN117069700A (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN201910210387.6A Active CN111187221B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用

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CN202311030017.7A Pending CN117050062A (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN202311339167.6A Pending CN117402143A (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用

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CN201910208542.0A Active CN111170999B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN201910210386.1A Active CN111171000B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN202311029815.8A Pending CN117069700A (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
CN201910210387.6A Active CN111187221B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用

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EP (1) EP3205650B1 (zh)
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KR (1) KR102589982B1 (zh)
CN (7) CN117050062A (zh)
AU (1) AU2015330506B2 (zh)
BR (1) BR112017006713B1 (zh)
CA (1) CA2959194A1 (zh)
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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105384694A (zh) * 2014-08-22 2016-03-09 四川海思科制药有限公司 一种取代的氨基嘧啶衍生物及其制备方法和药物用途
CN106928150A (zh) * 2015-12-31 2017-07-07 恩瑞生物医药科技（上海）有限公司 丙烯酰胺苯胺衍生物及其药学上的应用
CN108017633A (zh) * 2018-01-30 2018-05-11 天津大学 N-[5-(嘧啶-2-氨基)-2,4-二取代苯基]-2-氟代丙烯酰胺衍生物及应用
CN110652514A (zh) * 2018-06-29 2020-01-07 上海翰森生物医药科技有限公司 第三代egfr抑制剂的制药用途
CN110684016A (zh) * 2019-09-27 2020-01-14 上海应用技术大学 一种含氟的azd9291衍生物及其制备方法和应用
CN112645932A (zh) * 2016-03-22 2021-04-13 江苏豪森药业集团有限公司 Egfr抑制剂游离碱或其酸式盐的多晶型、其制备方法和应用
CN113387935A (zh) * 2021-07-23 2021-09-14 苏州雅深智慧科技有限公司 抑制三突变表皮生长因子受体酪氨酸激酶的化合物及用途
CN114605400A (zh) * 2019-03-19 2022-06-10 株式会社沃若诺伊 杂芳基衍生物、其制备方法、及含其作为有效成分的药物组合物

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MA40240B1 (fr) 2014-06-19 2019-03-29 Ariad Pharma Inc Composés hétéroaryle d'inhibition de la kinase
CN111170998B (zh) * 2014-11-05 2023-04-11 益方生物科技(上海)股份有限公司 嘧啶或吡啶类化合物、其制备方法和医药用途
WO2016105525A2 (en) 2014-12-23 2016-06-30 Dana-Farber Cancer Institute, Inc. Novel pyrimidines as egfr inhibitors and methods of treating disorders
CN106117185B (zh) * 2015-08-31 2017-11-07 广州必贝特医药技术有限公司 2,4‑二含氮基团取代嘧啶类化合物及其制备方法和应用
CN106749193B (zh) * 2015-11-23 2020-11-20 南京圣和药业股份有限公司 吲唑取代的表皮生长因子受体抑制剂及其应用
TWI726968B (zh) 2016-01-07 2021-05-11 開曼群島商Ｃｓ醫藥技術公司 Egfr酪胺酸激酶之臨床重要突變體之選擇性抑制劑
WO2017119732A1 (en) 2016-01-08 2017-07-13 Samsung Electronics Co., Ltd. Electronic device and operating method thereof
US11753626B2 (en) 2016-03-09 2023-09-12 Beijing Percans Oncology Co., Ltd. Tumor cell suspension cultures and related methods
CN107344934B (zh) * 2016-05-04 2019-08-23 江苏正大丰海制药有限公司 药物活性物质的固体形式
CN107417626B (zh) * 2016-05-23 2020-01-24 江苏奥赛康药业有限公司 一种2-氨基嘧啶类化合物的多晶型形式
AR110038A1 (es) * 2016-05-26 2019-02-20 Kalyra Pharmaceuticals Inc Compuestos inhibidores de egfr; composición farmacéutica que lo comprende; métodos para mejorar o tratar un cáncer; método para inhibir la replicación de un crecimiento maligno o un tumor; métodos para inhibir la actividad del egfr; y usos de los compuestos
CN106083736A (zh) * 2016-06-21 2016-11-09 郑州泰基鸿诺医药股份有限公司 一种嘧啶类化合物、egfr抑制剂及其应用
CN110818690B (zh) * 2016-07-26 2021-08-10 深圳市塔吉瑞生物医药有限公司 用于抑制蛋白酪氨酸激酶活性的氨基嘧啶类化合物
CN107793413B (zh) * 2016-09-05 2021-09-28 上海科州药物研发有限公司 嘧啶杂环化合物及其制备方法和应用
CN109689657B (zh) * 2016-09-19 2021-06-11 南京创特医药科技有限公司 氘代3-(4,5-取代氨基嘧啶)苯基衍生物及其应用
CN107973783B (zh) * 2016-10-21 2024-09-06 正大天晴药业集团股份有限公司 作为erk抑制剂的苯胺嘧啶衍生物
CN108057036B (zh) * 2016-11-07 2023-06-13 正大天晴药业集团股份有限公司 一种egfr抑制剂的固体药物组合物
CN108503627A (zh) * 2017-04-19 2018-09-07 郑州泰基鸿诺医药股份有限公司 用作egfr抑制剂的2,4-二取代苯-1,5-二胺衍生物及其应用
KR20200015595A (ko) * 2017-06-02 2020-02-12 에프. 호프만-라 로슈 아게 화합물
CA3071345A1 (en) * 2017-07-28 2019-01-31 Yale University Anticancer drugs and methods of making and using same
EP3653622B1 (en) * 2017-08-30 2022-12-28 Shenzhen TargetRx, Inc. Aminopyrimidine compound and composition comprising same and use thereof
CN109503573A (zh) * 2017-09-14 2019-03-22 昆明圣加南生物科技有限公司 2-取代苯胺基嘧啶衍生物及其用途
TWI702205B (zh) * 2017-10-06 2020-08-21 俄羅斯聯邦商拜奧卡德聯合股份公司 表皮生長因子受體抑制劑
KR20190108079A (ko) * 2018-03-13 2019-09-23 보로노이바이오 주식회사 2,4,5-치환된 피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 암의 예방 또는 치료용 약학적 조성물
CN110272420A (zh) 2018-03-16 2019-09-24 江苏正大丰海制药有限公司 氘代3-(4,5-取代氨基嘧啶)苯基化合物单甲磺酸盐晶型及其制备方法
AU2019269372A1 (en) 2018-05-14 2020-11-26 Takeda Pharmaceutical Company Limited Pharmaceutical salts of pyrimidine derivatives and method of treating disorders
CN110719782B (zh) * 2018-05-15 2023-02-07 江苏豪森药业集团有限公司 包含第三代小分子egfr抑制剂的药物组合物及其制备方法
CN111818925B (zh) * 2018-05-23 2023-12-12 江苏恒瑞医药股份有限公司 Cdk4/6抑制剂与egfr抑制剂联合在制备治疗肿瘤疾病的药物中的用途
CN110066272B (zh) * 2018-05-29 2022-09-13 深圳市塔吉瑞生物医药有限公司 取代的苯并[d]咪唑类化合物及其药物组合物
CN110698461B (zh) * 2018-07-09 2024-04-05 上海翰森生物医药科技有限公司 第三代egfr抑制剂的制备方法
WO2020052575A1 (zh) * 2018-09-12 2020-03-19 江苏恒瑞医药股份有限公司 Jak激酶抑制剂与egfr抑制剂联合在制备治疗肿瘤疾病的药物中的用途
CN113773304B (zh) * 2019-02-25 2023-03-10 江苏豪森药业集团有限公司 抗耐药抗肿瘤egfr抑制剂的制备方法
CN111606889B (zh) * 2019-02-25 2023-03-07 上海翰森生物医药科技有限公司 4-(1-环丙基-1h-吲哚-3-基)-n-苯基嘧啶-2-胺衍生物的制备方法
CN110041302B (zh) * 2019-03-01 2021-11-30 南方医科大学 2-氨基-4-取代吡啶衍生物及其合成方法和应用
KR102220624B1 (ko) * 2019-03-15 2021-02-25 김민서 드라이 플라워의 처리 방법 및 드라이 플라워의 처리제
CN114364798A (zh) 2019-03-21 2022-04-15 欧恩科斯欧公司 用于治疗癌症的Dbait分子与激酶抑制剂的组合
CN111747950B (zh) * 2019-03-29 2024-01-23 深圳福沃药业有限公司 用于治疗癌症的嘧啶衍生物
EP3974423A4 (en) * 2019-05-22 2023-06-21 Shanghai Hansoh Biomedical Co., Ltd. INHIBITOR CONTAINING AN INDOLE DERIVATIVE, METHOD FOR PREPARING IT AND ITS USE
WO2020245208A1 (en) 2019-06-04 2020-12-10 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of cd9 as a biomarker and as a biotarget in glomerulonephritis or glomerulosclerosis
CN110183399A (zh) * 2019-06-05 2019-08-30 辽宁科隆精细化工股份有限公司 一种合成4-(2-(n,n-二甲氨基)乙基)吗啉的方法
CN114008028B (zh) * 2019-06-20 2024-07-09 昂科比克斯有限公司 抑制癌细胞生长的嘧啶衍生物及其医药用途
KR102383200B1 (ko) * 2019-10-18 2022-04-06 한국화학연구원 피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물
WO2021089791A1 (en) 2019-11-08 2021-05-14 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the treatment of cancers that have acquired resistance to kinase inhibitors
US20210161897A1 (en) 2019-11-12 2021-06-03 Astrazeneca Ab Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of cancer
TW202128670A (zh) * 2019-11-26 2021-08-01 大陸商上海翰森生物醫藥科技有限公司 含氮多環類衍生物抑制劑、其製備方法和應用
KR20220130190A (ko) 2020-01-20 2022-09-26 아스트라제네카 아베 암 치료를 위한 표피성장인자 수용체 티로신 키나제 억제제
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
WO2021180238A1 (zh) * 2020-03-13 2021-09-16 郑州同源康医药有限公司 一类用作激酶抑制剂的化合物及其应用
CN113493420A (zh) * 2020-03-18 2021-10-12 南京药石科技股份有限公司 Egfr酪氨酸激酶抑制剂及其用途
US20210369709A1 (en) 2020-05-27 2021-12-02 Astrazeneca Ab EGFR TKIs FOR USE IN THE TREATMENT OF NON-SMALL CELL LUNG CANCER
WO2021243596A1 (en) * 2020-06-03 2021-12-09 InventisBio Co., Ltd. Aminopyrimidine compounds, preparation methods and uses thereof
TW202227425A (zh) * 2020-09-18 2022-07-16 南韓商沃若諾伊生物公司 雜芳基衍生物、彼之製法、及包含彼作為活性成份之藥學組成物
WO2022105882A1 (zh) * 2020-11-19 2022-05-27 上海翰森生物医药科技有限公司 一种含吲哚类衍生物的盐、晶型及其制备方法和应用
WO2022131741A1 (ko) * 2020-12-14 2022-06-23 보로노이바이오 주식회사 아이소옥사졸리딘 유도체 화합물 및 이의 용도
CN112457299B (zh) * 2020-12-14 2021-12-17 江苏豪森药业集团有限公司 Egfr抑制剂的纯化方法
UY39600A (es) * 2020-12-30 2022-05-31 Biocad Joint Stock Co Inhibidores del receptor del factor de crecimiento epidérmico
CN112679448B (zh) * 2020-12-31 2022-08-19 苏州昊帆生物股份有限公司 N-(2-氨基乙基)吗啉的制备方法
CN117255792A (zh) * 2021-05-07 2023-12-19 沃若诺伊公司 杂芳基衍生物、其制备方法以及包括其作为活性成分的药物组合物
US20240252481A1 (en) * 2021-05-14 2024-08-01 Nanjing Chuangte Pharmaceutical Technology Co., Ltd. Pharmaceutical formulations
BR112022024068A2 (pt) * 2021-05-17 2023-12-05 Voronoi Inc Compostos de derivado de heteroarila e usos dos mesmos
WO2023187037A1 (en) 2022-03-31 2023-10-05 Astrazeneca Ab Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors in combination with an akt inhibitor for the treatment of cancer
WO2023209084A1 (en) 2022-04-28 2023-11-02 Astrazeneca Ab Condensed bicyclic heteroaromatic compounds and their use in the treatment of cancer
WO2023209088A1 (en) 2022-04-28 2023-11-02 Astrazeneca Ab Bicyclic heteroaromatic compounds and their use in the treatment of cancer
US20240116926A1 (en) 2022-04-28 2024-04-11 Astrazeneca Ab Heteroaromatic compounds
WO2023209090A1 (en) 2022-04-28 2023-11-02 Astrazeneca Ab Bicyclic heteroaromatic compounds and their application in the treatment of cancer
WO2024002938A1 (en) 2022-06-27 2024-01-04 Astrazeneca Ab Combinations involving epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of cancer
TW202421146A (zh) 2022-07-08 2024-06-01 瑞典商阿斯特捷利康公司 用於治療癌症的上皮生長因子受體酪胺酸激酶抑制劑與ｈｇｆ受體抑制劑的組合

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103702990A (zh) * 2011-07-27 2014-04-02 阿斯利康(瑞典)有限公司 2-(2,4,5-取代苯胺)嘧啶衍生物作为egfr调谐子用于治疗癌症
CN104140418A (zh) * 2014-08-15 2014-11-12 朱孝云 新的2-(2,4,5-取代苯胺)嘧啶衍生物及其用途
CN104761544A (zh) * 2014-01-03 2015-07-08 南京波尔泰药业科技有限公司 Egfr酪氨酸激酶的临床重要突变体的选择性抑制剂
CN104860941A (zh) * 2014-02-25 2015-08-26 上海海雁医药科技有限公司 2,4-二取代苯-1,5-二胺衍生物及其应用以及由其制备的药物组合物和药用组合物
CN105085489A (zh) * 2014-11-05 2015-11-25 上海页岩科技有限公司 嘧啶或吡啶类化合物、其制备方法和医药用途
CN106458969A (zh) * 2014-08-25 2017-02-22 四川海思科制药有限公司 一种(取代的苯基)(取代的嘧啶)胺基衍生物及其制备方法和药物用途
CN106687457A (zh) * 2014-05-13 2017-05-17 阿里亚德医药股份有限公司 用于激酶抑制的杂芳基化合物

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG10201510696RA (en) * 2008-06-27 2016-01-28 Celgene Avilomics Res Inc Heteroaryl compounds and uses thereof
US8338439B2 (en) * 2008-06-27 2012-12-25 Celgene Avilomics Research, Inc. 2,4-disubstituted pyrimidines useful as kinase inhibitors
ES2659725T3 (es) * 2009-05-05 2018-03-19 Dana-Farber Cancer Institute, Inc. Inhibidores de EGFR y procedimiento de tratamiento de trastornos
US20130137709A1 (en) * 2010-05-05 2013-05-30 Nathanael S. Gray Compounds that modulate EGFR activity and methods for treating or preventing conditions therewith
JP5999177B2 (ja) * 2011-05-04 2016-09-28 アリアド・ファーマシューティカルズ・インコーポレイテッド Ｅｇｆｒ発動性がんの細胞増殖阻害用化合物
AU2013204563B2 (en) * 2012-05-05 2016-05-19 Takeda Pharmaceutical Company Limited Compounds for inhibiting cell proliferation in EGFR-driven cancers
CA2917364C (en) * 2013-07-11 2020-09-29 Acea Biosciences Inc. Heterocyclic compounds and uses thereof
WO2015188777A1 (en) * 2014-06-12 2015-12-17 Shanghai Fochon Pharmaceutical Co Ltd Certain protein kinase inhibitors
MA40240B1 (fr) * 2014-06-19 2019-03-29 Ariad Pharma Inc Composés hétéroaryle d'inhibition de la kinase
CN105461695B (zh) * 2014-09-29 2018-03-27 齐鲁制药有限公司 嘧啶或三嗪衍生物及其制备方法和用途
WO2016105525A2 (en) * 2014-12-23 2016-06-30 Dana-Farber Cancer Institute, Inc. Novel pyrimidines as egfr inhibitors and methods of treating disorders
US10329277B2 (en) * 2015-07-16 2019-06-25 Chia Tai Tianqing Pharmaceutical Group Co., Ltd. N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(3-methyl-2-OXO-2,3-dihydro-1h-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino)phenyl)acrylamide hydrochloride as an inhibitor of epidermal growth factor receptor activity
CN106117185B (zh) * 2015-08-31 2017-11-07 广州必贝特医药技术有限公司 2,4‑二含氮基团取代嘧啶类化合物及其制备方法和应用

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103702990A (zh) * 2011-07-27 2014-04-02 阿斯利康(瑞典)有限公司 2-(2,4,5-取代苯胺)嘧啶衍生物作为egfr调谐子用于治疗癌症
CN104761544A (zh) * 2014-01-03 2015-07-08 南京波尔泰药业科技有限公司 Egfr酪氨酸激酶的临床重要突变体的选择性抑制剂
CN104860941A (zh) * 2014-02-25 2015-08-26 上海海雁医药科技有限公司 2,4-二取代苯-1,5-二胺衍生物及其应用以及由其制备的药物组合物和药用组合物
CN106687457A (zh) * 2014-05-13 2017-05-17 阿里亚德医药股份有限公司 用于激酶抑制的杂芳基化合物
CN104140418A (zh) * 2014-08-15 2014-11-12 朱孝云 新的2-(2,4,5-取代苯胺)嘧啶衍生物及其用途
CN106458969A (zh) * 2014-08-25 2017-02-22 四川海思科制药有限公司 一种(取代的苯基)(取代的嘧啶)胺基衍生物及其制备方法和药物用途
CN105085489A (zh) * 2014-11-05 2015-11-25 上海页岩科技有限公司 嘧啶或吡啶类化合物、其制备方法和医药用途

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105384694A (zh) * 2014-08-22 2016-03-09 四川海思科制药有限公司 一种取代的氨基嘧啶衍生物及其制备方法和药物用途
CN105384694B (zh) * 2014-08-22 2020-09-04 四川海思科制药有限公司 一种取代的氨基嘧啶衍生物及其制备方法和药物用途
CN106928150A (zh) * 2015-12-31 2017-07-07 恩瑞生物医药科技（上海）有限公司 丙烯酰胺苯胺衍生物及其药学上的应用
CN106928150B (zh) * 2015-12-31 2020-07-31 恩瑞生物医药科技（上海）有限公司 丙烯酰胺苯胺衍生物及其药学上的应用
CN112645932A (zh) * 2016-03-22 2021-04-13 江苏豪森药业集团有限公司 Egfr抑制剂游离碱或其酸式盐的多晶型、其制备方法和应用
CN112645932B (zh) * 2016-03-22 2022-01-14 江苏豪森药业集团有限公司 Egfr抑制剂游离碱或其酸式盐的多晶型、其制备方法和应用
CN108017633A (zh) * 2018-01-30 2018-05-11 天津大学 N-[5-(嘧啶-2-氨基)-2,4-二取代苯基]-2-氟代丙烯酰胺衍生物及应用
CN110652514A (zh) * 2018-06-29 2020-01-07 上海翰森生物医药科技有限公司 第三代egfr抑制剂的制药用途
CN114605400A (zh) * 2019-03-19 2022-06-10 株式会社沃若诺伊 杂芳基衍生物、其制备方法、及含其作为有效成分的药物组合物
CN110684016A (zh) * 2019-09-27 2020-01-14 上海应用技术大学 一种含氟的azd9291衍生物及其制备方法和应用
CN113387935A (zh) * 2021-07-23 2021-09-14 苏州雅深智慧科技有限公司 抑制三突变表皮生长因子受体酪氨酸激酶的化合物及用途

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