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

Info

Publication number
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
Authority
CN
China
Prior art keywords
compound
methyl
formula
amino
pyrimidine
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
CN201580045311.2A
Other languages
English (en)
Other versions
CN106661000B (zh
Inventor
危明松
孙广俊
谭松良
高鹏
王少宝
修文华
张福军
包如迪
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.)
Jiangsu Hansoh Pharmaceutical Group Co Ltd
Original Assignee
Lianyungang Hongchuang Pharmaceutical Co ltd
Shanghai Hansoh Biomedical 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 Lianyungang Hongchuang Pharmaceutical Co ltd, Shanghai Hansoh Biomedical Co Ltd filed Critical Lianyungang Hongchuang Pharmaceutical Co ltd
Priority to CN202311029815.8A priority Critical patent/CN117069700A/zh
Priority to CN201910210386.1A priority patent/CN111171000B/zh
Priority to CN202311339167.6A priority patent/CN117402143A/zh
Priority to CN202311030017.7A priority patent/CN117050062A/zh
Priority to CN201910208542.0A priority patent/CN111170999B/zh
Priority to CN201910210387.6A priority patent/CN111187221B/zh
Publication of CN106661000A publication Critical patent/CN106661000A/zh
Application granted granted Critical
Publication of CN106661000B publication Critical patent/CN106661000B/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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • 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
    • 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
    • C07D403/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D403/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • C07D471/06—Peri-condensed systems
    • 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
    • C07D471/10—Spiro-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
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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

Publications (2)

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

Family

ID=55652583

Family Applications (7)

Application Number Title Priority Date Filing Date
CN201580045311.2A Active CN106661000B (zh) 2014-10-11 2015-09-30 Egfr抑制剂及其制备和应用
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
CN202311029815.8A Pending CN117069700A (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
CN201910208542.0A Active CN111170999B (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

Family Applications After (6)

Application Number Title Priority Date Filing Date
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
CN202311029815.8A Pending CN117069700A (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
CN201910208542.0A Active CN111170999B (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

Country Status (23)

Country Link
US (2) US10259820B2 (zh)
EP (1) EP3205650B1 (zh)
JP (1) JP6691281B2 (zh)
KR (1) KR102589982B1 (zh)
CN (7) CN106661000B (zh)
AU (1) AU2015330506B2 (zh)
BR (1) BR112017006713B1 (zh)
CA (1) CA2959194A1 (zh)
CY (1) CY1124476T1 (zh)
DK (1) DK3205650T3 (zh)
ES (1) ES2886887T3 (zh)
HR (1) HRP20211392T1 (zh)
HU (1) HUE055233T2 (zh)
LT (1) LT3205650T (zh)
MX (1) MX2017004234A (zh)
PL (1) PL3205650T3 (zh)
PT (1) PT3205650T (zh)
RS (1) RS62350B1 (zh)
RU (1) RU2702631C2 (zh)
SI (1) SI3205650T1 (zh)
TW (1) TWI704138B (zh)
WO (1) WO2016054987A1 (zh)
ZA (1) ZA201701465B (zh)

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 (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110526912B (zh) 2014-06-19 2023-02-14 武田药品工业株式会社 用于激酶抑制的杂芳基化合物
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
US10266517B2 (en) * 2014-12-23 2019-04-23 Dana-Farber Cancer Institute, Inc. 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
EP3426772A4 (en) 2016-03-09 2019-08-28 Beijing Percans Oncology Co. Ltd. TUMOR CELL SUSPENSION CULTURES AND ASSOCIATED 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
US10513509B2 (en) 2016-05-26 2019-12-24 Recurium Ip Holdings, Llc EGFR inhibitor compounds
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
WO2018019204A1 (zh) 2016-07-26 2018-02-01 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
WO2018050108A1 (zh) * 2016-09-19 2018-03-22 江苏正大丰海制药有限公司 氘代3-(4,5-取代氨基嘧啶)苯基衍生物及其应用
CN107973783A (zh) * 2016-10-21 2018-05-01 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
CR20190542A (es) * 2017-06-02 2020-01-14 Hoffmann La Roche Compuestos
AU2018306726B2 (en) * 2017-07-28 2023-08-03 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 ***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
US20210069190A1 (en) 2018-05-15 2021-03-11 Jiangsu Hansoh Pharmaceutical Group Co., Ltd. Pharmaceutical composition comprising small molecule egfr inhibitor and preparation method therefor
MX2020012540A (es) 2018-05-23 2021-02-16 Jiangsu Hengrui Medicine Co Uso de inhibidor de cdk4/6 en combinacion con inhibidor del egfr en la preparacion de medicamento para tratar enfermedades tumorales.
WO2019228330A1 (zh) * 2018-05-29 2019-12-05 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***疾病的药物中的用途
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
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
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
WO2020188015A1 (en) 2019-03-21 2020-09-24 Onxeo A dbait molecule in combination with kinase inhibitor for the treatment of cancer
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
US20220229072A1 (en) 2019-06-04 2022-07-21 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
US20220227781A1 (en) * 2019-06-20 2022-07-21 Oncobix Co., Ltd. Pyrimidine derivative inhibiting growth of cancer cell and medicinal use thereof
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
US20230056604A1 (en) 2020-01-20 2023-02-23 Astrazeneca Ab Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of cancer
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
CN115175902A (zh) * 2020-03-13 2022-10-11 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
CN116018141A (zh) * 2020-11-19 2023-04-25 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
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
KR20220085735A (ko) * 2020-12-14 2022-06-22 보로노이바이오 주식회사 아이소옥사졸리딘 유도체 화합물 및 이의 용도
TW202241890A (zh) * 2020-12-30 2022-11-01 ***聯邦商拜奧卡德聯合股份公司 表皮生長因子受體之抑制劑
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
EP4335847A1 (en) * 2021-05-07 2024-03-13 Voronoi Inc. Heteroaryl derivative, method for preparing same, and pharmaceutical composition comprising same as active ingredient
AU2022272575A1 (en) * 2021-05-14 2024-01-04 Nanjing Chuangte Pharmaceutical Technology Co., Ltd Pharmaceutical composition
CA3180295A1 (en) * 2021-05-17 2022-11-24 Youn Ho Lee Heteroaryl derivative compounds, and uses thereof
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
WO2023209086A1 (en) 2022-04-28 2023-11-02 Astrazeneca Ab Bicyclic heteroaromatic compounds for treating cancer
WO2023209084A1 (en) 2022-04-28 2023-11-02 Astrazeneca Ab Condensed bicyclic heteroaromatic compounds and their use in the treatment of cancer
WO2023209090A1 (en) 2022-04-28 2023-11-02 Astrazeneca Ab Bicyclic heteroaromatic compounds and their application 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
WO2024002938A1 (en) 2022-06-27 2024-01-04 Astrazeneca Ab Combinations involving epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of cancer
WO2024008929A1 (en) 2022-07-08 2024-01-11 Astrazeneca Ab Epidermal growth factor receptor tyrosine kinase inhibitors in combination with hgf-receptor inhibitors for the treatment of cancer

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
TWI546290B (zh) * 2008-06-27 2016-08-21 賽基艾維洛米斯研究股份有限公司 雜芳基化合物及其用途
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
WO2011140338A1 (en) 2010-05-05 2011-11-10 Gatekeeper Pharmaceuticals, Inc. Compounds that modulate egfr activity and methods for treating or preventing conditions therewith
CN103501612B (zh) * 2011-05-04 2017-03-29 阿里亚德医药股份有限公司 抑制表皮生长因子受体导致的癌症中细胞增殖的化合物
AU2013204563B2 (en) * 2012-05-05 2016-05-19 Takeda Pharmaceutical Company Limited Compounds for inhibiting cell proliferation in EGFR-driven cancers
MX368491B (es) * 2013-07-11 2019-10-04 Acea Biosciences Inc Derivados de pirimidina como inhibidores de cinasa.
WO2015188777A1 (en) * 2014-06-12 2015-12-17 Shanghai Fochon Pharmaceutical Co Ltd Certain protein kinase inhibitors
CN110526912B (zh) * 2014-06-19 2023-02-14 武田药品工业株式会社 用于激酶抑制的杂芳基化合物
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
US10266517B2 (en) * 2014-12-23 2019-04-23 Dana-Farber Cancer Institute, Inc. Pyrimidines as EGFR inhibitors and methods of treating disorders
JP6970081B2 (ja) * 2015-07-16 2021-11-24 正大天晴▲藥▼▲業▼集▲団▼股▲フン▼有限公司 アニリンピリミジン誘導体及びその使用
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

Also Published As

Publication number Publication date
US10259820B2 (en) 2019-04-16
CN111170999A (zh) 2020-05-19
CN111170999B (zh) 2023-06-30
RU2017114687A3 (zh) 2019-01-31
HUE055233T2 (hu) 2021-11-29
CN106661000B (zh) 2019-04-09
CN111187221B (zh) 2023-09-26
PL3205650T3 (pl) 2021-12-06
US10428081B2 (en) 2019-10-01
DK3205650T3 (da) 2021-09-13
PT3205650T (pt) 2021-09-02
HRP20211392T1 (hr) 2021-12-10
CN111171000B (zh) 2023-09-01
CA2959194A1 (en) 2016-04-14
BR112017006713A2 (pt) 2017-12-26
EP3205650A4 (en) 2018-09-26
RU2017114687A (ru) 2018-11-20
MX2017004234A (es) 2017-06-08
ZA201701465B (en) 2019-08-28
JP2017532326A (ja) 2017-11-02
US20190100528A1 (en) 2019-04-04
KR20170118681A (ko) 2017-10-25
EP3205650A1 (en) 2017-08-16
CN111171000A (zh) 2020-05-19
CN117050062A (zh) 2023-11-14
TWI704138B (zh) 2020-09-11
TW201613875A (en) 2016-04-16
JP6691281B2 (ja) 2020-04-28
CY1124476T1 (el) 2022-07-22
KR102589982B1 (ko) 2023-10-17
AU2015330506A1 (en) 2017-04-06
CN117069700A (zh) 2023-11-17
AU2015330506B2 (en) 2020-01-30
WO2016054987A1 (zh) 2016-04-14
BR112017006713B1 (pt) 2023-11-21
US20170313714A1 (en) 2017-11-02
RU2702631C2 (ru) 2019-10-09
LT3205650T (lt) 2021-09-10
ES2886887T3 (es) 2021-12-21
SI3205650T1 (sl) 2021-10-29
CN111187221A (zh) 2020-05-22
RS62350B1 (sr) 2021-10-29
EP3205650B1 (en) 2021-08-04
CN117402143A (zh) 2024-01-16

Similar Documents

Publication Publication Date Title
CN106661000A (zh) Egfr抑制剂及其制备和应用
CN111377917B (zh) 杂环类化合物、中间体、其制备方法及应用
CN107793413B (zh) 嘧啶杂环化合物及其制备方法和应用
CN104080774B (zh) 吡嗪甲酰胺化合物
CN106977495B (zh) Dna-pk抑制剂
CN105315285B (zh) 2,4‑二取代7H‑吡咯并[2,3‑d]嘧啶衍生物、其制法与医药上的用途
CN113544128A (zh) Kras-g12c抑制剂
CN109952295A (zh) 一种cdk4/6抑制剂及其制备方法和应用
CN110746424A (zh) Mk2抑制剂和其用途
JP2017518276A (ja) ブルトン型チロシンキナーゼ（ｂｔｋ）インヒビターとしての多フルオロ置換化合物
CN107141293A (zh) 一种含氮杂环化合物、制备方法、中间体、组合物和应用
CN109310671A (zh) 布鲁顿酪氨酸激酶抑制剂
CN101805309A (zh) 用作组蛋白脱乙酰基酶抑制剂的苯甲酰胺衍生物
CN107252429A (zh) 新抗炎剂
CN103421005A (zh) 具有抗肿瘤活性的乙炔衍生物
CN101119996A (zh) 化学化合物
CN114728926A (zh) 一种rock抑制剂及其制备方法和用途
KR20170054421A (ko) 브로모도메인 억제제로서의 테트라하이드로퀴놀린 유도체
CN109810098B (zh) 含有酞嗪-1(2h)-酮结构的parp-1和pi3k双靶点抑制剂
CN112313207B (zh) 一种氰基取代吡啶及氰基取代嘧啶类化合物、制备方法及其应用
CN106565674A (zh) 一种八氢环戊烷并[c]吡咯衍生物及其制备方法和在医药上的用途
WO2023244430A1 (en) Pyrimidine amide compounds and use thereof
CN109666022B (zh) 三氮唑衍生物及其制备方法和用途
CN110177784A (zh) 一种含芳环化合物、其制备方法、药物组合物及应用
CN113880816A (zh) 一种含哌嗪类的氨基嘧啶衍生物及应用

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
GR01 Patent grant
GR01 Patent grant
TR01 Transfer of patent right

Effective date of registration: 20210107

Address after: 222047 Lianyungang economic and Technological Development Zone, Jiangsu

Patentee after: JIANGSU HANSOH PHARMACEUTICAL GROUP Co.,Ltd.

Address before: 201203 Building 2, 3728 Jinke Road, Zhangjiang hi tech park, Shanghai

Patentee before: SHANGHAI HANSOH BIOMEDICAL Co.,Ltd.

Patentee before: JIANGSU HANSOH PHARMACEUTICAL GROUP Co.,Ltd.

TR01 Transfer of patent right