WO2019112344A1 - Nouveau dérivé de pyrimidine ayant pour effet d'inhiber la croissance de cellules cancéreuses, et composition pharmaceutique contenant celui-ci - Google Patents

Nouveau dérivé de pyrimidine ayant pour effet d'inhiber la croissance de cellules cancéreuses, et composition pharmaceutique contenant celui-ci Download PDF

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WO2019112344A1
WO2019112344A1 PCT/KR2018/015437 KR2018015437W WO2019112344A1 WO 2019112344 A1 WO2019112344 A1 WO 2019112344A1 KR 2018015437 W KR2018015437 W KR 2018015437W WO 2019112344 A1 WO2019112344 A1 WO 2019112344A1
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Prior art keywords
amino
phenyl
methoxy
methylmethanesulfonamide
pyrimidine
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PCT/KR2018/015437
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English (en)
Korean (ko)
Inventor
김성은
이선호
라제쉬랭가사미
강대호
유형철
김재선
이상율
김경철
노진경
이재철
Original Assignee
주식회사 온코빅스
제이투에이치바이오텍(주)
주식회사 천보
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Priority claimed from KR1020180154838A external-priority patent/KR101992621B1/ko
Application filed by 주식회사 온코빅스, 제이투에이치바이오텍(주), 주식회사 천보 filed Critical 주식회사 온코빅스
Priority to AU2018379499A priority Critical patent/AU2018379499B2/en
Priority to RU2020120942A priority patent/RU2744168C1/ru
Priority to CN201880075980.8A priority patent/CN111386266B/zh
Priority to EP18886173.6A priority patent/EP3722292B1/fr
Priority to JP2020550574A priority patent/JP7036939B2/ja
Priority to BR112020011203-8A priority patent/BR112020011203B1/pt
Priority to US16/766,350 priority patent/US11248003B2/en
Priority to CA3083933A priority patent/CA3083933C/fr
Publication of WO2019112344A1 publication Critical patent/WO2019112344A1/fr

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    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—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
    • C07D401/14—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 three or more 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
    • C07D403/14—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

Definitions

  • the present invention relates to a novel pyrimidine derivative which effectively inhibits cancer cell growth and a pharmaceutical composition containing the same.
  • EGFR epidermal growth factor receptor
  • EGFR Gefitnib, Erlotinib, etc. low molecular weight epithelial growth factor receptor
  • C797S EGFR Epidermal growth factor receptor
  • MET amplification which is the major resistance mechanism of the above-described third generation EGFR anticancer drug
  • the present inventors have sought to develop new compounds that effectively inhibit the C797S mutant EGFR and MET amplification cancers, the major resistance mechanisms of the third generation EGFR anticancer agents.
  • a novel pyrimidine derivative effective for cancer treatment was found.
  • the novel pyrimidine derivatives have been found to exert excellent effects in the treatment of lung cancer.
  • X and Y are each independently carbon or nitrogen
  • Z is oxygen or a C1 to C4 alkyl group
  • R 2 is an alkyl group having 1 to 4 carbon atoms
  • R 3 is hydrogen or a halogen group
  • R 4 is hydrogen, a halogen group, CN, CF 3 , an alkyl group having 1 to 4 carbon atoms or an aminocarbonyl group,
  • R < 5 > is hydrogen or a C1 to C4 alkyl group
  • R 6 is an alkyl group having from 1 to 4 carbon atoms
  • R 7 is hydrogen, an amine group substituted with at least one C1 to C4 alkyl group, or a piperazinyl group substituted or unsubstituted with at least one C1 to C4 alkyl group,
  • R 4 and R 5 may be connected to form pyrrole, imidazole and thiophene.
  • compositions for treating lung cancer comprising, as an active ingredient, a compound represented by the above-mentioned formula (1) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
  • novel pyrimidine derivative compounds of the present invention provide excellent effects in the treatment of cancer.
  • the pharmaceutical composition for treating lung cancer of the present invention comprising the pyrimidine derivative compound provides an excellent activity for the treatment of lung cancer, and more particularly, the C797S mutant EGFR and MET amplification due to the major resistance of the third generation EGFR anticancer drug ) Effectively inhibits the growth of cancer cells.
  • alkyl group means straight and branched chain hydrocarbon groups having the specified number of carbon atoms.
  • the alkyl group may be, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl,
  • alkylsulfonyl is alkyl -S (O 2) - refers to. Where alkyl is defined above.
  • the present invention relates to a compound represented by the following general formula (1) or a salt thereof:
  • X and Y are each independently carbon or nitrogen
  • Z is oxygen or a C1 to C4 alkyl group
  • R 1 is an alkyl group having 1 to 4 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, CF 3 , Or a dimethylamine group,
  • R 2 is an alkyl group having 1 to 4 carbon atoms
  • R 3 is hydrogen or a halogen group
  • R 4 is hydrogen, a halogen group, CN, CF 3 , an alkyl group having 1 to 4 carbon atoms or an aminocarbonyl group,
  • R < 5 > is hydrogen or a C1 to C4 alkyl group
  • R 6 is an alkyl group having from 1 to 4 carbon atoms
  • R 7 is hydrogen, an amine group substituted with at least one C1 to C4 alkyl group, or a piperazinyl group substituted or unsubstituted with at least one C1 to C4 alkyl group,
  • R 4 and R 5 may be connected to form pyrrole, imidazole and thiophene.
  • the compound represented by Formula 1 may include the following compounds.
  • Phenyl) amino) < RTI ID 0.0 > pyrimidine < / RTI > (2-methoxy- 4-yl) amino) phenyl) -N-methylmethanesulfonamide;
  • Phenyl) amino) < RTI ID 0.0 > pyrimidine < / RTI > (2-methoxy- 4-yl) amino) -4-fluorophenyl) -N-methylmethanesulfonamide;
  • X is nitrogen
  • Y is carbon
  • Z is oxygen
  • R 1 is an alkyl group having from 1 to 4 carbon atoms
  • R 2 is an alkyl group having 1 to 4 carbon atoms
  • R 3 is hydrogen or a halogen group
  • R 4 is a halogen group
  • R < 5 > is hydrogen
  • R 6 is an alkyl group having from 1 to 4 carbon atoms
  • R 7 may be a piperazinyl group or an amine group substituted with at least one C1 to C4 alkyl group or a piperazinyl group substituted or unsubstituted with at least one C1 to C4 alkyl group or a salt thereof.
  • the compound of formula 1 and salts thereof may be:
  • the compound represented by the formula (1) of the present invention and a salt thereof can be used for the treatment of cancer.
  • it can be used for the treatment of lung cancer.
  • lung cancer treatment of lung cancer with C797S mutant Epidermal growth factor receptor (C797S mutant Epidermal growth factor receptor, C797S EGFR) and MET amplified cancer cell which is the main resistance mechanism of third generation EGFR anticancer drug Can be effectively used.
  • the compound represented by the formula (1) may be used in the form of a salt derived from an inorganic acid or an organic acid, and examples thereof include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, acetic acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, , Benzoic acid, benzoic acid, hydroxybenzoic acid, phenylacetic acid, cinnamic acid, salicylic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, maleic acid, maleic acid, And salts derived from at least one acid selected from the group consisting of phosphoric acid, toluene sulfonic acid and the like.
  • the present invention relates to a compound represented by the above formula (1) or a salt thereof, which is used for treating lung cancer.
  • the present invention also relates to a pharmaceutical composition for the treatment of lung cancer, which comprises a compound represented by the above-mentioned general formula (1) as an active ingredient or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
  • the present invention relates to a method for treating an animal having lung cancer, which comprises administering an effective amount of the compound represented by Formula 1 to an animal.
  • the animal may be a human, and the lung cancer may be lung cancer with C797S mutant EGFR (C797S mutant Epidermal growth factor receptor, C797S EGFR) and MET-amplified resistant cancer cells.
  • C797S mutant EGFR C797S mutant Epidermal growth factor receptor, C797S EGFR
  • MET-amplified resistant cancer cells C797S mutant EGFR (C797S mutant Epidermal growth factor receptor, C797S EGFR) and MET-amplified resistant cancer cells.
  • the pharmaceutical composition of the present invention may be formulated according to a conventional method and may be formulated into various oral dosage forms such as tablets, pills, powders, capsules, syrups, emulsions and microemulsions or by intravenous injection, subcutaneous injection, Intraperitoneal injection, percutaneous injection, direct injection into tissues, and the like.
  • pharmaceutically acceptable carrier may be any known component in the art without limitation as long as it does not interfere with the active expression of the active ingredient have.
  • Examples of the carrier include, but are not limited to, excipients, diluents, disintegrants, binders, lubricants, surfactants, emulsifiers, suspending agents, and diluents.
  • pharmaceutically acceptable carriers may be used without limitation as long as they do not interfere with the active expression of the active ingredient .
  • the dosage of the pharmaceutical composition of the present invention is preferably determined in consideration of the age, sex, condition of the patient, the degree of absorption of the active ingredient, the inactivation rate of the active ingredient, and the drug to be used. mg / kg (body weight) to 100 mg / kg (body weight).
  • the structure 5 was obtained by dissolving 1-fluoro-2-nitrobenzene (3 g, 21.262 mmol) in acetonitrile (150 mL), adding cesium carbonate (10.4 g, 31.892 mmol) and N -methylmethanesulfonamide did. Then, the mixture was stirred at 80 DEG C for 12 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, filtered, and the filtrate was evaporated under reduced pressure to obtain N -methyl- N- (2-nitrophenyl) methanesulfonamide (Compound 4) . The reaction was carried out without further separation.
  • the pyrimidine derivative (1.37 eq.) Is dissolved in isopropyl alcohol and aniline derivative (1.0 eq.) And para-toluenesulfonic acid (1.37 eq.) Are added at room temperature. Followinged by stirring at 90 ⁇ ⁇ for 12 hours. After completion of the reaction, the solvent is evaporated under reduced pressure, and the mixture is extracted with a mixture of water and 10% methanol / dichloromethane. The separated organic layer is evaporated under reduced pressure and subjected to column chromatography to obtain the target compound (5-10% ammonia / methyl alcohol / dichloromethane).
  • the compound having a protecting group was dissolved in 4M hydrochloric acid (1,4-dioxane). After stirring at room temperature for 3 hours, the reaction was terminated, neutralized with 1N sodium hydroxide solution and extracted with ethyl acetate. The separated organic layer was evaporated under reduced pressure and subjected to column chromatography to obtain the target compound.
  • Method 2 A compound having a protecting group was dissolved in a mixed solvent of methanol, 1,4-dioxane and water (3: 3: 1). Cesium carbonate (10.0 eq.) was added at room temperature and stirred at 80 ⁇ ⁇ for 3 hours. After completion of the reaction, the temperature was lowered to room temperature, and then water was added. The resulting solid was filtered and dried. The target compound was isolated using column chromatography.
  • the final compound was prepared by the above method 1.
  • the final compound was prepared by Method 2 above.
  • the final compound was prepared by Method 2 above.
  • the final compound was prepared by Method 2 above.
  • the final compound was prepared by the above method 1.
  • the final compound was prepared by Method 2 above.
  • the final compound was prepared by Method 2 above.
  • Example 8 N- (2 - ((2 - ((2-Methoxy-4- (4- (4- methylpiperazin- 1 -yl) piperidin- - (trifluoromethyl) pyrimidin-4-yl) amino) phenyl) -N-methylmethanesulfonamide
  • the final compound was prepared by the above method 1.
  • the final compound was prepared by the above method 1.
  • the final compound was prepared by the above method 1.
  • Example 15 ((2 - ((5-Chloro-2 - ((2-methoxy- ) Pyrimidin-4-yl) amino) phenyl) imino) dimethyl- ⁇ 6 -sulfanone
  • the final compound was prepared by Method 2 above.
  • the compound 1 obtained in the above Example was measured for the inhibitory effect of C797S-containing epithelial growth factor (EGFR) kinase and MET kinase inhibitor, and the results are shown in Table 1 below.
  • Kinase inhibitory activity was measured by the following method.
  • Each kinase was incubated with 8 mM MOPS pH 7.0, 0.2 mM EDTA, 250 ⁇ M KKKGQEEEYVFIE, 1 mM sodium orthovanadate, 5 mM sodium-6-glycerophosphate, 10 mM magnesium acetate, [ ⁇ - 33 P] -ATP.
  • reaction solution was divided into 0.5% 10uL and spotted on a P30 filtermat.
  • Example EGFR (del19 / C797S) EGFR (del19 / T790M / C797S) MET (IC 50 ) One 0.4 nM 0.08 nM 1 nM Brigatini - 2nM 70 nM TRE-069 - 6nM 120 nM
  • the compounds prepared by the examples of the present invention show that the inhibitory effect of C797S-containing epithelial growth factor (EGFR) kinase, MET kinase inhibitor, on the activity of brittanyib and TRE-069 It was confirmed to be very good.
  • EGFR epithelial growth factor
  • wild type and mutant EGFR were purchased from Addgene (wild type, # 11011; L858R, # 11012; L858R + T790M, # 32073; del19, # 32062; del19 + T790M, # 32072). All construction was a retroviral vector and finally completed the viral particle for infection.
  • Ba / F3 stable cell line Murine lymphoid cells undergo IL-3 dependent growth. When each mutant EGFR construct is infected with these cell lines, the cells will survive without IL-3 because they become oncogenic addiction due to the expression of mutant EGFR. Using this principle, a stable cell line was constructed without puromycin selection. Briefly, each construction was infected with Ba / F3, and after 48 hours, IL-3 was removed while media exchange and cells were cultured. However, puromycin selection was performed for wild-type EGFR.
  • EBC lysis buffer 50 mM Tris-HCl pH 8.0, 120 mM NaCl, 1% Triton X-100, 1 mM EDTA, 1 mM EGTA, 0.3 mM phenylmethylsulfonylfluoride, 0.2 mM sodium orthovanadate, 0.5% NP- U / mL aprotinin
  • Antibodies to EGFR-related signaling molecules [p-EGFR (Tyr1173), EGFR, Akt, p-Erk, Erk, actin, from SantaCruz; p-Akt, from Cell signaling].
  • Antitumor effect assay by MTT assay 2 X 10 5 cells were seeded in a 96-well plate. After 24 hours, each of the drugs was treated in a dose-dependent manner, incubated for 72 hours, reacted with 15 ⁇ L MTT reagent for 4 hours, and then incubated with 100 ⁇ L 10% SDS for 24 hours. Changes in final OD were read at 595 nm. MTT results were analyzed by IC 50 values through prism software.
  • GI 50 values were calculated for each compound by 50% inhibition of cell growth. The results are shown in Table 2 below.
  • the compounds prepared by the examples of the present invention exhibit a remarkably inhibitory activity against the C797S mutant epithelial cell growth factor receptor-expressing cancer cell line as compared to the brittitanib and TRE-069 Respectively.
  • briatitinib and TRE069 were found to be very inactive compared with the compounds of the present invention.

Abstract

La présente invention concerne un nouveau composé dérivé de pyrimidine et un sel correspondant. Le composé dérivé de pyrimidine inhibe efficacement la croissance de cellules cancéreuses dans lesquelles l'expression du récepteur EGFR muté en c797s et l'amplification MET, qui constituent des mécanismes de résistance majeurs de médicaments anticancéreux EGFR de troisième génération, se sont produites, et peut par conséquent être utilisé efficacement dans le traitement du cancer du poumon.
PCT/KR2018/015437 2017-12-07 2018-12-06 Nouveau dérivé de pyrimidine ayant pour effet d'inhiber la croissance de cellules cancéreuses, et composition pharmaceutique contenant celui-ci WO2019112344A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
AU2018379499A AU2018379499B2 (en) 2017-12-07 2018-12-06 Novel pyrimidine derivative having effect of inhibiting cancer cell growth and pharmaceutical composition containing same
RU2020120942A RU2744168C1 (ru) 2017-12-07 2018-12-06 Новое пиримидиновое производное, обладающее эффектом ингибирования роста раковых клеток, и содержащая его фармацевтическая композиция
CN201880075980.8A CN111386266B (zh) 2017-12-07 2018-12-06 具有抑制癌细胞生长作用的新型嘧啶衍生物及包含其的药物组合物
EP18886173.6A EP3722292B1 (fr) 2017-12-07 2018-12-06 Nouveau dérivé de pyrimidine ayant pour effet d'inhiber la croissance de cellules cancéreuses, et composition pharmaceutique contenant celui-ci
JP2020550574A JP7036939B2 (ja) 2017-12-07 2018-12-06 癌細胞の成長抑制効果を示す新規なピリミジン誘導体及びそれを含む薬剤学的組成物
BR112020011203-8A BR112020011203B1 (pt) 2017-12-07 2018-12-06 Composto derivado de pirimidina, composição farmacêutica compreendendo o mesmo e uso do dito composto para o tratamento de câncer de pulmão
US16/766,350 US11248003B2 (en) 2017-12-07 2018-12-06 Pyrimidine derivative having effect of inhibiting cancer cell growth and pharmaceutical composition containing same
CA3083933A CA3083933C (fr) 2017-12-07 2018-12-06 Nouveau derive de pyrimidine ayant pour effet d'inhiber la croissance de cellules cancereuses, et composition pharmaceutique contenant celui-ci

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20170167809 2017-12-07
KR10-2017-0167809 2017-12-07
KR1020180154838A KR101992621B1 (ko) 2017-12-07 2018-12-05 암세포 성장 억제 효과를 나타내는 신규한 피리미딘 유도체 및 그를 포함하는 약제학적 조성물
KR10-2018-0154838 2018-12-05

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111233834A (zh) * 2020-03-09 2020-06-05 北京师范大学 一类靶向fak的化合物和其标记物、及它们的制备方法和应用
CN112739701A (zh) * 2018-09-20 2021-04-30 韩美药品株式会社 具有表皮生长因子受体突变的抑制效果的新型融合嘧啶骨架磺酰胺衍生物
CN113896744A (zh) * 2020-07-06 2022-01-07 成都先导药物开发股份有限公司 一种选择性egfr抑制剂
CN114671861A (zh) * 2022-04-12 2022-06-28 安徽医科大学 一种汉黄芩素衍生物及其制备方法与应用
CN114829352A (zh) * 2019-12-16 2022-07-29 昂科比克斯有限公司 新型氘代嘧啶衍生物及包含其的药物组合物
JP2022538014A (ja) * 2019-06-20 2022-08-31 オンコビクス・カンパニー・リミテッド 癌細胞の成長を抑制するピリミジン誘導体およびその医薬用途
WO2022211573A1 (fr) 2021-04-01 2022-10-06 주식회사 테라펙스 Dérivé de pyrimidine ayant une activité inhibitrice de protéine kinase, et composition pharmaceutique thérapeutique le comprenant
WO2022208454A1 (fr) * 2021-04-02 2022-10-06 Bridge Biotherapeutics, Inc. Composés de n2-phénylpyrimidine-2,4-diamine et procédés de préparation et procédés d'utilisation correspondants
KR20220136931A (ko) 2021-04-01 2022-10-11 주식회사 테라펙스 단백질 키나아제 저해 활성을 갖는 피리미딘 유도체 및 이를 포함하는 치료용 약학 조성물
CN115304550A (zh) * 2022-07-25 2022-11-08 南通大学 哌嗪苯基氨基取代的嘧啶氨基酸衍生物及制备方法与应用
KR20240046408A (ko) 2022-09-30 2024-04-09 주식회사 테라펙스 단백질 키나아제 저해 활성을 갖는 피리미딘 유도체 및 이를 포함하는 치료용 약학 조성물

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009032703A1 (fr) * 2007-08-28 2009-03-12 Irm Llc Composés et compositions inhibiteurs de kinase
WO2009112490A1 (fr) * 2008-03-11 2009-09-17 Cellzome Limited Sulfonamides en tant qu'inhibiteurs de zap-70
WO2009143389A1 (fr) 2008-05-21 2009-11-26 Ariad Pharmaceuticals, Inc. Dérivés phosphorés servant d'inhibiteurs de kinase
WO2016022460A1 (fr) * 2014-08-03 2016-02-11 H. Lee Moffitt Cancer Center And Research Institute, Inc. Puissants doubles inhibiteurs de brd4 et de kinase à utiliser en tant qu'agents thérapeutiques anticancéreux
CN106188060A (zh) * 2015-04-29 2016-12-07 厦门大学 嘧啶并吡咯类化合物、其制备方法、药用组合物及其应用

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009032703A1 (fr) * 2007-08-28 2009-03-12 Irm Llc Composés et compositions inhibiteurs de kinase
WO2009112490A1 (fr) * 2008-03-11 2009-09-17 Cellzome Limited Sulfonamides en tant qu'inhibiteurs de zap-70
WO2009143389A1 (fr) 2008-05-21 2009-11-26 Ariad Pharmaceuticals, Inc. Dérivés phosphorés servant d'inhibiteurs de kinase
WO2016022460A1 (fr) * 2014-08-03 2016-02-11 H. Lee Moffitt Cancer Center And Research Institute, Inc. Puissants doubles inhibiteurs de brd4 et de kinase à utiliser en tant qu'agents thérapeutiques anticancéreux
CN106188060A (zh) * 2015-04-29 2016-12-07 厦门大学 嘧啶并吡咯类化合物、其制备方法、药用组合物及其应用

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
BULL. KOREAN CHEM. SOC., vol. 38, 2017, pages 1353 - 1357
CHOE, H. ET AL.: "Structure-Activity Relationship Study of 2,4-Dianilinopyrimidine Containing Methanesulfonamide (TRE-069) as Potent and Selective Epidermal Growth Factor Receptor T790M/C797S Mutant Inhibitor for Anticancer Treatment", BULL. KOREAN CHERN. SOC., vol. 38, 2017, pages 1353 - 1357, XP055561541, [retrieved on 20171013], DOI: doi:10.1002/bkcs.11287 *
CLINICAL CANCER RESEARCH, vol. 19, 2013, pages 2240 - 7
J HEMATOL ONCOL., vol. 9, no. 1, 22 July 2016 (2016-07-22), pages 59
LUNG CANCER, vol. 118, 2018, pages 105 - 110
LUNG CANCER: TARGETS AND THERAPY, vol. 8, 2017, pages 169 - 177
NATURE COMMUNICATIONS, 13 March 2017 (2017-03-13)
NATURE MEDICINE, vol. 21, 2015, pages 560 - 562
NATURE, vol. 534, 2016, pages 129 - 132
NEW ENGLAND JOURNAL OF MEDICINE, vol. 350, 2004, pages 2129 - 39
SCIENCE, vol. 304, 2004, pages 1497 - 500
See also references of EP3722292A4 *

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112739701A (zh) * 2018-09-20 2021-04-30 韩美药品株式会社 具有表皮生长因子受体突变的抑制效果的新型融合嘧啶骨架磺酰胺衍生物
US20210380589A1 (en) * 2018-09-20 2021-12-09 HAN Ml PHARM. CO., LTD. Novel sulfonamide derivative with fused pyrimidine skeleton, having epidermal growth factor receptor mutation inhibitory effect
CN112739701B (zh) * 2018-09-20 2024-02-13 韩美药品株式会社 具有表皮生长因子受体突变的抑制效果的融合嘧啶骨架磺酰胺衍生物
JP7330546B2 (ja) 2019-06-20 2023-08-22 オンコビクス・カンパニー・リミテッド 癌細胞の成長を抑制するピリミジン誘導体およびその医薬用途
JP7330546B6 (ja) 2019-06-20 2024-02-21 オンコビクス・カンパニー・リミテッド 癌細胞の成長を抑制するピリミジン誘導体およびその医薬用途
JP2022538014A (ja) * 2019-06-20 2022-08-31 オンコビクス・カンパニー・リミテッド 癌細胞の成長を抑制するピリミジン誘導体およびその医薬用途
CN114829352A (zh) * 2019-12-16 2022-07-29 昂科比克斯有限公司 新型氘代嘧啶衍生物及包含其的药物组合物
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CN111233834A (zh) * 2020-03-09 2020-06-05 北京师范大学 一类靶向fak的化合物和其标记物、及它们的制备方法和应用
CN113896744A (zh) * 2020-07-06 2022-01-07 成都先导药物开发股份有限公司 一种选择性egfr抑制剂
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WO2022211573A1 (fr) 2021-04-01 2022-10-06 주식회사 테라펙스 Dérivé de pyrimidine ayant une activité inhibitrice de protéine kinase, et composition pharmaceutique thérapeutique le comprenant
WO2022208454A1 (fr) * 2021-04-02 2022-10-06 Bridge Biotherapeutics, Inc. Composés de n2-phénylpyrimidine-2,4-diamine et procédés de préparation et procédés d'utilisation correspondants
CN114671861B (zh) * 2022-04-12 2023-11-24 安徽医科大学 一种汉黄芩素衍生物及其制备方法与应用
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CN115304550A (zh) * 2022-07-25 2022-11-08 南通大学 哌嗪苯基氨基取代的嘧啶氨基酸衍生物及制备方法与应用
KR20240046408A (ko) 2022-09-30 2024-04-09 주식회사 테라펙스 단백질 키나아제 저해 활성을 갖는 피리미딘 유도체 및 이를 포함하는 치료용 약학 조성물

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