WO2013118817A1 - Composé de quinolyl pyrrolopyrimidine ou son sel - Google Patents

Composé de quinolyl pyrrolopyrimidine ou son sel Download PDF

Info

Publication number
WO2013118817A1
WO2013118817A1 PCT/JP2013/052853 JP2013052853W WO2013118817A1 WO 2013118817 A1 WO2013118817 A1 WO 2013118817A1 JP 2013052853 W JP2013052853 W JP 2013052853W WO 2013118817 A1 WO2013118817 A1 WO 2013118817A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
amino
pyrrolo
pyrimidin
quinolin
Prior art date
Application number
PCT/JP2013/052853
Other languages
English (en)
Japanese (ja)
Inventor
武 相良
伊藤　智
幸恵 大槻
和臣 深澤
雅也 橋本
Original Assignee
大鵬薬品工業株式会社
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 大鵬薬品工業株式会社 filed Critical 大鵬薬品工業株式会社
Publication of WO2013118817A1 publication Critical patent/WO2013118817A1/fr

Links

Classifications

    • 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
    • C07D487/04—Ortho-condensed systems
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • non-small cell lung cancer cells expressing high-sensitivity mutant or drug-resistant mutant EGFR can be suppressed at a dose at which side effects in the skin or gastrointestinal tract do not appear strongly, or high-sensitivity mutation Expected to reduce the frequency of drug-resistant mutant EGFR that appears as acquired resistance from non-small cell lung cancer cell carcinomas that express type EGFR, and are expected to contribute to cancer treatment and patient survival and improvement of QOL Is done.
  • the expression of a highly sensitive mutant type or a drug resistant mutant type EGFR can be applied as a stratification index at the treatment site, the patient can be selected, and the ethical contribution is high.
  • the present invention also provides a pharmaceutical such as an EGFR inhibitor and an antitumor agent comprising the compound represented by the above general formula (I) as an active ingredient.
  • C 3 -C 10 cycloalkylene group refers to a monocyclic or polycyclic divalent cycloalkylene group having 3 to 10 carbon atoms. Examples include butylene, cyclopentylene, cyclohexylene, cycloheptylene, and decalylene.
  • the moiety is attached to the pyrrolopyrimidine and the —N (R 4 ) — moiety is attached to the carbonyl group.
  • a — (CH 2 ) n — moiety of the group is bonded to pyrrolopyrimidine,
  • R 6 , R 7 and R 8 in general formula (I) are preferably the same or different and are a hydrogen atom, a C 1 -C 6 alkyl group, a C 4 -C 9 heteroaryl group, or a C 1 -C 6 alkyl.
  • R 5 and R 6 may also form a C 4 -C 8 cycloalkene ring with the two carbon atoms to which they are attached.
  • R 1 is a hydrogen atom or a C 2 -C 6 alkynyl group which may have R 2 ;
  • R 2 may have —OR x , —N (R x ) (R y ), R 3 (preferably an amino group) or a C 3 -C 10 cycloalkyl group or R 3 (preferably an amino group)
  • a C 6 -C 12 aryl group optionally having: R x and R y are the same or different and are a hydrogen atom or a C 1 -C 6 alkyl group;
  • X is a group represented by the general formula (X 3 );
  • n is 0 to 1;
  • R 5 is a C 1 -C 6 alkyl group optionally having a hydrogen atom or a hydroxy group;
  • Y is preferably a vinyl group or a salt thereof.
  • L 1 and L 2 represent a leaving group
  • P 1 represents an amino-protecting group contained in X: X and Y are as defined above.
  • the compound represented by the general formula (IV) thus obtained can be isolated and purified by a known separation and purification means such as concentration, concentration under reduced pressure, crystallization, solvent extraction, reprecipitation, chromatography and the like. It can be subjected to the next step without separation and purification.
  • This step is a method for producing a compound represented by the structural formula (V) by coupling the compound represented by the general formula (IV) with 3-quinolineboronic acid.
  • This step can be carried out according to a generally known method (for example, Chemical Reviews, Vol. 95, p. 2457, 1995), for example, in a solvent that does not adversely influence the reaction in the presence of a transition metal catalyst and a base. Can be implemented.
  • the amount of 3-quinolineboronic acid used can be 1 to 10 mol, preferably 1 to 3 mol, per 1 mol of the compound represented by the general formula (IV).
  • the compound represented by the general formula (X) thus obtained can be isolated and purified by a known separation and purification means such as concentration, concentration under reduced pressure, crystallization, solvent extraction, reprecipitation, chromatography and the like. It can be subjected to the next step without separation and purification.
  • the reaction solvent is not particularly limited as long as it does not interfere with the reaction.
  • isopropanol, tert-butyl alcohol, toluene, benzene, methylene chloride, chloroform, tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethylacetamide N-methylpyrrolidinone, dimethyl sulfoxide, etc., or a mixed solvent thereof is preferred.
  • the reaction temperature is usually ⁇ 78 to 200 ° C., preferably 0 to 50 ° C.
  • the reaction time is usually 1 minute to 3 days, preferably 1 minute to 10 hours.
  • acid chloride is used as the coupling reagent, the acid chloride is used in an amount of 0.5 to 5 mol, preferably 0.9 to 1.1 mol, per 1 mol of the compound represented by the general formula (X).
  • any isomer is included in the compound of the present invention.
  • a pharmaceutical carrier can be blended as necessary, and various administration forms can be adopted depending on the purpose of prevention or treatment. Any of injections, suppositories, ointments, patches and the like may be used, and oral preparations are preferably employed. Each of these dosage forms can be produced by a conventional formulation method known to those skilled in the art.
  • Examples of the disintegrant include dry starch, sodium alginate, agar powder, sodium hydrogen carbonate, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, and lactose.
  • Examples of the lubricant include purified talc, sodium stearate, magnesium stearate, borax, and polyethylene glycol.
  • Examples of the colorant include titanium oxide and iron oxide.
  • Examples of the flavoring / flavoring agent include sucrose, orange peel, citric acid, tartaric acid and the like.
  • the preservative examples include methyl paraoxybenzoate, ethyl paraoxybenzoate, and propyl paraoxybenzoate.
  • the ointment, cream, gel, paste or the like may be applied to a normal support by a conventional method.
  • Example 1 80 mg of 5- (quinolin-3-yl) -7H-pyrrolo [2,3-d] pyrimidin-4-amine obtained in Example 1 (Step 4) was dissolved in 2.0 ml of DMF, and cooled to 0 ° C. 71 mg of 60% sodium hydride was added. After stirring for 20 minutes, 1.0 ml of a DMF solution of 310 mg of the mesyl obtained in the above Step 1 was added and stirred at 85 ° C. overnight. After cooling to 0 ° C. again, water was added to stop the reaction, and the product was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.
  • Example 4 (S) -1- (3- (4-Amino-5- (quinolin-3-yl) -7H-pyrrolo [2,3-d] pyrimidin-7-yl) piperidin-1-yl) prop-2- En-1-one
  • (R)-( ⁇ )-N-Boc-3-piperidinol instead of (R)-( ⁇ )-N-Boc-3-pyrrolidinol, The title compound was obtained as a white solid.
  • Example 13 (3- (4-Amino-5- (quinolin-3-yl) -7H-pyrrolo [2,3-d] pyrimidin-7-yl) azetidin-1-yl) prop-2-en-1- ON (process 1) tert-Butyl 3- (4-Chloro-5-iodo-7H-pyrrolo [2,3-d] pyrimidin-7-yl) azetidine-1-carboxylate
  • Example 23 (R) -1- (3- (4-Amino-5- (quinolin-3-yl) -7H-pyrrolo [2,3-d] pyrimidin-7-yl) pyrrolidin-1-yl) -2-methylprop -2-En-1-one According to Example 17, a colorless amorphous title compound was obtained by using methacrylic acid instead of 4- (dimethylamino) -2-butenoic acid hydrochloride.
  • 4-Bromocrotonic acid methyl ester (1.79 g) was dissolved in tetrahydrofuran (40 ml), diethylamine (2.10 ml) was added at 0 ° C., and the mixture was stirred at room temperature for 1 hr. Diethyl ether and water were added to the reaction solution, and the organic layer was separated. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. To the resulting product, 40 ml of 3N hydrochloric acid was added and heated to reflux at 100 ° C. for 1 hour.
  • Example 31 1- (3- (4-Amino-5- (quinolin-3-yl) -7H-pyrrolo [2,3-d] pyrimidin-7-yl) azetidin-1-yl) -4- (pyrrolidin-1- Yl) but-2-en-1-one
  • 4- (dimethylamino) -2-butenoic acid hydrochloride 4- (pyrrolidine-) obtained in Example 18 (Step 1) was used.
  • 1-yl) -2-butenoic acid hydrochloride the colorless amorphous title compound was obtained.
  • reaction solution was allowed to cool to room temperature, poured into a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the crude title compound.
  • Test Example 1 Measurement of Various EGFR Kinase Activity Inhibitory Actions (In Vitro) 1) Measurement of EGFR (T790M / L858R) Kinase Inhibitory Activity The inhibitory activities of Example compounds on the EGFR (T790M / L858R) kinase activity were measured.
  • the material was a biotinylated amino acid described in reference to Caliper Life Science LabChip (registered trademark) series reagent FL-Peptide 22 (biotin-EEPLYWSFPAKKK) as a substrate peptide, and EGFR (T790M / L858R) Purified recombinant human EGFR (T790M / L858R) protein from Carna Biosciences was purchased.
  • the material is human EGFR (WT) in which FLAG (WT) is fused with a FLAG tag at the N-terminal, and the cytoplasmic domain of human EGFR (WT) is expressed in insect cells Sf9 by a baculovirus expression system, and anti-FLAG antibody agarose (Sigma Aldrich) ) was used.
  • the final concentration of the substrate peptide was 500 nM, and the final concentration of ATP was 4.7 uM.
  • IC50 values (nM) were obtained by the same materials and measurement methods as in the measurement of EGFR (T790M / L858R) kinase inhibitory activity.
  • Example compounds were confirmed to have potent inhibitory activity not only against EGFR (L858R) and EGFR (d746-750), but also against EGFR (T790M / L858R) and EGFR (d746-750 / T790M). Moreover, compared with these, it was confirmed that EGFR (WT) has weak inhibitory activity.
  • Test Example 2 Growth Inhibitory Activity Measurement Test for Wild Type and Mutant EGFR-expressing Cell Lines (In Vitro) 1) NCI-H1975 cell, a lung adenocarcinoma cell line expressing EGFR (T790M / L858R), 2) HCC827 cell, a lung adenocarcinoma cell line expressing EGFR (d746-750), 3) A431 cells, which are human epithelioid cancer cell lines expressing EGFR (WT), were each suspended in a medium recommended by ATCC. The cell suspension was seeded in each well of a 384 well flat bottom microplate or a 96 well flat bottom plate and cultured at 37 ° C.
  • the compound of the present invention and the comparative compound were dissolved in DMSO, and the test compound was diluted with DMSO to a concentration 200 times the final concentration.
  • a DMSO solution of the test compound is diluted with the medium used for suspending each cell, and this is added to each well of the cell culture plate so that the final concentration of DMSO is 0.5%.
  • the number of cells at the start of culture and after culture was measured using Cell titergro (manufactured by Promega) based on the protocol recommended by Promega.
  • the growth inhibition rate was calculated from the following formula, and the concentration of the test compound that inhibited 50% (GI50 (nM)) was determined.
  • Example compounds were confirmed to have a strong growth inhibitory effect not only on EGFR (d746-750) -expressing cells but also on EGFR (T790M / L858R) -expressing cells. Moreover, compared with these, it was confirmed that the growth inhibitory effect is weak with respect to the EGFR (WT) expression cell.

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un nouveau composé présentant un effet inhibiteur sur EGFR et ayant un effet cytostatique. L'invention concerne également un médicament utile dans la prévention et/ou le traitement du cancer sur la base de l'effet inhibiteur sur EGFR. L'invention concerne un composé représenté par la formule générale (I) ou son sel.
PCT/JP2013/052853 2012-02-07 2013-02-07 Composé de quinolyl pyrrolopyrimidine ou son sel WO2013118817A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2012-024200 2012-02-07
JP2012024200 2012-02-07

Publications (1)

Publication Number Publication Date
WO2013118817A1 true WO2013118817A1 (fr) 2013-08-15

Family

ID=48947574

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2013/052853 WO2013118817A1 (fr) 2012-02-07 2013-02-07 Composé de quinolyl pyrrolopyrimidine ou son sel

Country Status (2)

Country Link
TW (1) TW201336847A (fr)
WO (1) WO2013118817A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015025936A1 (fr) * 2013-08-22 2015-02-26 大鵬薬品工業株式会社 Nouveau composé substitué par une quinoline
JP2016534059A (ja) * 2013-10-25 2016-11-04 ブループリント メディシンズ コーポレイション 繊維芽細胞成長因子受容体の阻害剤
JP2019526550A (ja) * 2016-08-15 2019-09-19 ニューファーマ， インコーポレイテッド 特定の化学的実体、組成物、および方法
WO2020166680A1 (fr) 2019-02-15 2020-08-20 大鵬薬品工業株式会社 Dérivé de 7h-pyrrolo [2,3-d] pyrimidine-4-amine
CN113271950A (zh) * 2019-01-11 2021-08-17 大鹏药品工业株式会社 嘧啶化合物或其盐
WO2022014639A1 (fr) * 2020-07-15 2022-01-20 大鵬薬品工業株式会社 Inhibiteur du récepteur du facteur de croissance épidermique
WO2022014638A1 (fr) * 2020-07-15 2022-01-20 大鵬薬品工業株式会社 Cristal de composé pyrimidine
WO2022109551A1 (fr) * 2020-11-17 2022-05-27 Relay Therapeutics, Inc. Inhibiteurs de src et leurs utilisations
RU2796605C2 (ru) * 2019-02-15 2023-05-26 Тайхо Фармасьютикал Ко., Лтд. Производное 7h-пирроло[2,3-d]пиримидин-4-амина
US11701359B2 (en) 2017-09-01 2023-07-18 Taiho Pharmaceutical Co., Ltd. Exon 18 and/or exon 21 mutant EGFR selective inhibitor
US11857513B2 (en) 2016-10-31 2024-01-02 Taiho Pharmaceutical Co., Ltd. Selective inhibitor of exon 20 insertion mutant EGFR
US11865120B2 (en) 2013-08-23 2024-01-09 Neupharma, Inc. Substituted quinazolines for inhibiting kinase activity

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112961159B (zh) * 2020-03-05 2022-07-01 四川大学华西医院 氨基嘧啶并吡唑/吡咯类衍生物及其制备方法和用途

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007075554A2 (fr) * 2005-12-19 2007-07-05 Osi Pharmaceuticals, Inc. Traitement combine avec une composition d’inhibiteur de proteine kinase heterobicyclique a noyau 6,6-bicyclique et d'agents anticancereux
WO2007114926A2 (fr) * 2006-04-04 2007-10-11 The Regents Of The University Of California Antagonistes de la kinase
WO2008018881A1 (fr) * 2006-08-10 2008-02-14 Osi Pharmaceuticals, Inc. Soufre porteur d'une substitution à noyau 6,6-bicyclique contenant des inhibiteurs hétérobicycliques de la protéine kinase
WO2008039218A2 (fr) * 2006-09-22 2008-04-03 Pharmacyclics, Inc. Inhibiteurs de la tyrosine kinase de bruton
WO2008121742A2 (fr) * 2007-03-28 2008-10-09 Pharmacyclics, Inc. Inhibiteurs de la tyrosine kinase de bruton
WO2011046964A2 (fr) * 2009-10-12 2011-04-21 Pharmacyclics, Inc. Inhibiteurs de tyrosine kinase de bruton

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007075554A2 (fr) * 2005-12-19 2007-07-05 Osi Pharmaceuticals, Inc. Traitement combine avec une composition d’inhibiteur de proteine kinase heterobicyclique a noyau 6,6-bicyclique et d'agents anticancereux
WO2007114926A2 (fr) * 2006-04-04 2007-10-11 The Regents Of The University Of California Antagonistes de la kinase
WO2008018881A1 (fr) * 2006-08-10 2008-02-14 Osi Pharmaceuticals, Inc. Soufre porteur d'une substitution à noyau 6,6-bicyclique contenant des inhibiteurs hétérobicycliques de la protéine kinase
WO2008039218A2 (fr) * 2006-09-22 2008-04-03 Pharmacyclics, Inc. Inhibiteurs de la tyrosine kinase de bruton
WO2008121742A2 (fr) * 2007-03-28 2008-10-09 Pharmacyclics, Inc. Inhibiteurs de la tyrosine kinase de bruton
WO2011046964A2 (fr) * 2009-10-12 2011-04-21 Pharmacyclics, Inc. Inhibiteurs de tyrosine kinase de bruton

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ZAPF,C.W. ET AL.: "Covalent Inhibitors of Interleukin-2 Inducible T Cell Kinase (Itk) with Nanomolar Potency in a Whole-Blood Assay", JOURNAL OF MEDICINAL CHEMISTRY, vol. 55, no. 22, November 2012 (2012-11-01), pages 10047 - 10063, XP055082084, DOI: doi:10.1021/jm301190s *

Cited By (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105683195B (zh) * 2013-08-22 2017-11-10 大鹏药品工业株式会社 喹啉取代的化合物
CN105683195A (zh) * 2013-08-22 2016-06-15 大鹏药品工业株式会社 新的喹啉取代的化合物
JPWO2015025936A1 (ja) * 2013-08-22 2017-03-02 大鵬薬品工業株式会社 新規キノリン置換化合物
US9650386B2 (en) 2013-08-22 2017-05-16 Taiho Pharmaceutical Co., Inc. Quinoline-substituted compound
US9758526B2 (en) 2013-08-22 2017-09-12 Taiho Pharmaceutical Co., Ltd. Quinoline-substituted compound
RU2797117C2 (ru) * 2013-08-22 2023-05-31 Тайхо Фармасьютикал Ко., Лтд. Новое хинолин-замещенное соединение
KR101906688B1 (ko) 2013-08-22 2018-10-10 다이호야쿠힌고교 가부시키가이샤 신규 퀴놀린 치환 화합물
RU2689158C2 (ru) * 2013-08-22 2019-05-24 Тайхо Фармасьютикал Ко., Лтд. Новое хинолин-замещенное соединение
WO2015025936A1 (fr) * 2013-08-22 2015-02-26 大鵬薬品工業株式会社 Nouveau composé substitué par une quinoline
US11865120B2 (en) 2013-08-23 2024-01-09 Neupharma, Inc. Substituted quinazolines for inhibiting kinase activity
JP2016534059A (ja) * 2013-10-25 2016-11-04 ブループリント メディシンズ コーポレイション 繊維芽細胞成長因子受容体の阻害剤
US10221154B2 (en) 2013-10-25 2019-03-05 Blueprint Medicines Corporation Inhibitors of the fibroblast growth factor receptor
US10875837B2 (en) 2013-10-25 2020-12-29 Blueprint Medicines Corporation Inhibitors of the fibroblast growth factor receptor
JP2019526550A (ja) * 2016-08-15 2019-09-19 ニューファーマ， インコーポレイテッド 特定の化学的実体、組成物、および方法
US12018002B2 (en) 2016-08-15 2024-06-25 Neupharma, Inc Certain chemical entities, compositions, and methods
JP7101165B2 (ja) 2016-08-15 2022-07-14 ニューファーマ， インコーポレイテッド 特定の化学的実体、組成物、および方法
JP2022058912A (ja) * 2016-08-15 2022-04-12 ニューファーマ， インコーポレイテッド 特定の化学的実体、組成物、および方法
US11857513B2 (en) 2016-10-31 2024-01-02 Taiho Pharmaceutical Co., Ltd. Selective inhibitor of exon 20 insertion mutant EGFR
US11701359B2 (en) 2017-09-01 2023-07-18 Taiho Pharmaceutical Co., Ltd. Exon 18 and/or exon 21 mutant EGFR selective inhibitor
CN113271950A (zh) * 2019-01-11 2021-08-17 大鹏药品工业株式会社 嘧啶化合物或其盐
CN113271950B (zh) * 2019-01-11 2024-04-30 大鹏药品工业株式会社 嘧啶化合物或其盐
KR20210116598A (ko) 2019-02-15 2021-09-27 다이호야쿠힌고교 가부시키가이샤 7H-피롤로[2,3-d]피리미딘-4-아민 유도체
AU2020221744B2 (en) * 2019-02-15 2022-06-23 Taiho Pharmaceutical Co., Ltd. 7H-pyrrolo(2,3-d)pyrimidine-4-amine derivative
RU2796605C2 (ru) * 2019-02-15 2023-05-26 Тайхо Фармасьютикал Ко., Лтд. Производное 7h-пирроло[2,3-d]пиримидин-4-амина
JPWO2020166680A1 (ja) * 2019-02-15 2021-11-04 大鵬薬品工業株式会社 ７Ｈ−ピロロ［２，３−ｄ］ピリミジン−４−アミン誘導体
CN113453764A (zh) * 2019-02-15 2021-09-28 大鹏药品工业株式会社 7H-吡咯并[2,3-d]嘧啶-4-胺衍生物
US11786534B2 (en) 2019-02-15 2023-10-17 Taiho Pharmaceutical Co., Ltd. Substituted pyrrolo[2,3-d]pyrimidines as EGFR inhibitors
CN113453764B (zh) * 2019-02-15 2024-04-16 大鹏药品工业株式会社 7H-吡咯并[2,3-d]嘧啶-4-胺衍生物
KR102645237B1 (ko) 2019-02-15 2024-03-07 다이호야쿠힌고교 가부시키가이샤 7H-피롤로[2,3-d]피리미딘-4-아민 유도체
WO2020166680A1 (fr) 2019-02-15 2020-08-20 大鵬薬品工業株式会社 Dérivé de 7h-pyrrolo [2,3-d] pyrimidine-4-amine
TWI828861B (zh) * 2019-02-15 2024-01-11 日商大鵬藥品工業股份有限公司 7H-吡咯并[2,3-d]嘧啶-4-胺衍生物
WO2022014638A1 (fr) * 2020-07-15 2022-01-20 大鵬薬品工業株式会社 Cristal de composé pyrimidine
RU2817044C1 (ru) * 2020-07-15 2024-04-09 Тайхо Фармасьютикал Ко., Лтд. Ингибитор egfr
JP7391226B2 (ja) 2020-07-15 2023-12-04 大鵬薬品工業株式会社 ピリミジン化合物の結晶
JP7495983B2 (ja) 2020-07-15 2024-06-05 大鵬薬品工業株式会社 Ｅｇｆｒ阻害剤
WO2022014639A1 (fr) * 2020-07-15 2022-01-20 大鵬薬品工業株式会社 Inhibiteur du récepteur du facteur de croissance épidermique
WO2022109551A1 (fr) * 2020-11-17 2022-05-27 Relay Therapeutics, Inc. Inhibiteurs de src et leurs utilisations

Also Published As

Publication number Publication date
TW201336847A (zh) 2013-09-16

Similar Documents

Publication Publication Date Title
JP6161705B2 (ja) 新規キノリン置換化合物
WO2013118817A1 (fr) Composé de quinolyl pyrrolopyrimidine ou son sel
JP6084292B2 (ja) Ｆｇｆｒ阻害剤耐性癌の治療薬
JP5355825B1 (ja) ３，５−二置換ベンゼンアルキニル化合物及びその塩
JP6035423B2 (ja) 新規な縮合ピリミジン化合物又はその塩
JP5557963B2 (ja) キノリルピロロピリミジル縮合環化合物又はその塩
WO2020221209A1 (fr) Inhibiteur de cd73, son procédé de préparation et son utilisation
TW202045509A (zh) 7H-吡咯并[2,3-d]嘧啶-4-胺衍生物
RU2797117C2 (ru) Новое хинолин-замещенное соединение

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13746778

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13746778

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP