1421372-66-8

Basic information

• Product Name: Mutated EGFR-IN-1
• Synonyms: Mutated EGFR-IN-1;HY-78869;AZD9291DA HCl salt;AZD9291 int-5;N1-[2-(Dimethylamino)ethyl]-5-methoxy-N1-methyl-N4-[4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl]-1,2,4-benzenetriamine;N1-[2-(diMethylaMino)ethyl]-5-Methoxy-N1-Methyl-N4-[4-(1-Methyl-1H-indol-3-yl)-2-pyriMidinyl]benzene-1,2,4-triamine;1,2,4-Benzenetriamine, N1-[2-(dimethylamino)ethyl]-5-methoxy-N1-methyl-N4-[4-(1-methyl-1H-indol-3-yl)-2-pyrimidinyl]-;AZD9291 intermediate 4
• CAS NO: 1421372-66-8
• Molecular Formula: C₂₅H₃₁N₇O
• Molecular Weight: 445.57
• Product Categories: AZD9291;Pharmaceutical intermediate
• Mol File: 1421372-66-8.mol

Chemical Properties

• Boiling Point: 676.5±65.0 °C(Predicted)
• Appearance: /
• Density: 1.21±0.1 g/cm3(Predicted)
• PKA: 9.07±0.28(Predicted)
• CAS DataBase Reference: Mutated EGFR-IN-1(CAS DataBase Reference)
• NIST Chemistry Reference: Mutated EGFR-IN-1(1421372-66-8)
• EPA Substance Registry System: Mutated EGFR-IN-1(1421372-66-8)

Safety Data

• Hazardous Substances Data: 1421372-66-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Mutated EGFR-IN-1 is used as a reactant/reagent for the self-assembly of dual thermoresponsive block copolymers bearing a zwitterionic and a non-ionic hydrophilic block. This application is particularly relevant in the development of novel drug delivery systems and materials for the treatment of Schizophrenia.

Upstream product

• 954421-16-0 (2E)-3-(dimethylamino)-1-(1-methyl-1H-indol-3-yl)-2-propen-1-one 
• 142-25-6 N,N',N'-trimethylenediamine 
• 367-25-9 2,4-difluorophenylamine 
• 123344-02-5 5-amino-2,4-difluoronitrobenzene 
• 603-76-9 1-methylindole 
• 1443291-03-9 3-(dimethylamino)-1-(1-methyl-1H-indol-3-yl)prop-2-en-1-one 
• 19012-02-3 N-methyl-3-acetylindole 
• 703-80-0 3-acetylindole 
• 448-19-1 4-fluoro-2-methoxy-1-nitrobenzene 
• 450-91-9 4-fluoro-2-methoxyaniline 
• 120-72-9 indole 
• 945016-63-7 3-(2-chloro-pyrimidin-4-yl)-1H-indole 
• 1032452-86-0 2-chloro-4-(1'-methyl-1H-indol-3-yl)pyrimidine 

Downstream Products

• 1421373-65-0 [N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl)propen-2-amide] 
• 1421373-66-1 N-(2-(N-(2-(dimethylamino)ethyl)-N-methylamino)-4-methoxy-5-((4-(1-methyl-1H-indole-3-yl)pyrimidine-2-yl)amino)phenyl)acrylamide methanesulfonate 
• 1421373-36-5 3-chloro-N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl)propanamide 

Relevant articles and documents

Design, synthesis, SAR discussion, in?vitro and in?vivo evaluation of novel selective EGFR modulator to inhibit L858R/T790M double mutants

Based upon the modeling binding mode of marketed AZD9291 with T790M, a series of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline derivatives were designed and synthesized with the purpose to overcome the drug resistance resulted from T790M/L858R double mutations. The most potent compound 8 showed excellent enzyme inhibitory activities and selectivity with sub nanomolar IC50 values for both the single L858R and double T790M/L858R mutant EGFRs, and was more than 8-fold selective for wild type EGFR. Compound 8 exhibited good microsomes stabilities and pharmacokinetic properties and lower binding affinity to hERG ion channel than AZD9291 and displayed strong antiproliferative activity against the H1975 non-small cell lung cancer (NSCLC) cells bearing T790M/L858R and in?vivo anticancer efficacy in a human NSCLC (H1975) xenograft mouse model.

Industrial Cunninghamia lanceolata carbon supported FeO(OH) nanoparticles-catalyzed hydrogenation of nitroarenes

The development of green and efficient methods for hydrogenation of nitroarenes is still highly demanding in organic synthesis. Herein, we report an industrial Cunninghamia lanceolata carbon supported FeO(OH) nanoparticles process for the synthesis of aryl amines with good yields via hydrogenation of nitroarenes. Nine key anti-cancer drug intermediates were successfully achieved with protocol. And Osimertinib intermediate 4m can be smoothly synthesized at a 2.67 kg-scale with >99.5% HPLC purity. This protocol features cheap carbon source, highly catalytic activity, simple operation, kilogram-scalable and recyclable catalysts (eight times without observable losing activity).

Preparation method of osimertinib mesylate

The invention discloses a preparation method of osimertinib mesylate. 4-fluoro-2-methoxy-5-nitroaniline and 3-(2-chloro-4-pyrimidinyl)-1-methyl-1H-indole are subjected to a condensation reaction and then subjected to a nucleophilic substitution reaction with N, N-dimethylethylenediamine, a high-purity compound shown in the formula (6) is obtained through Eschweiler-Clarke amine reductive alkylation, water serves as a solvent, acetic acid and the like serve as a cosolvent, catalytic hydrogenation is performed, amidation reaction with acryloyl chloride is carried out to obtain high-purity osimertinib and salifying with methanesulfonic acid is carried out to obtain osimertinib mesylate, and compared with the patent CN103702990B, the method is simple and convenient to operate, less in environmental pollution, high in yield, low in cost, good in product quality and more suitable for industrial production.

Improvements in the Synthesis of the Third-Generation EGFR Inhibitor Osimertinib

Osimertinib, a third generation potent and specific EGFR inhibitor is an important drug against many forms of cancer. It was synthesized by an improved and highly efficient protocol, revisiting the classical synthetic process and modifying parameters, such as solvents, temperature, reagents, and reaction time. A cost-effective, environmentally friendly methodology for the synthesis of osimertinib was established, which gave shorter reaction times, saved labor by eliminating purification steps through column chromatography, and enhanced yields. Four of the seven steps in total, were proceeded quantitatively or almost quantitatively (ca. 98 %). This synthetic protocol provides a very high overall yield, up to 68 %. In addition, the entire approach enables the preparation of osimertinib analogues and could be extended in the synthesis of other structurally similar bioactive compounds.

Compound for inhibiting three-mutant epidermal growth factor receptor tyrosine kinase and application thereof

The invention discloses a compound for inhibiting three-mutant epidermal growth factor receptor tyrosine kinase, and is characterized in that the structural formula is as follows. Among them: Substituent R1 . One of: Substituent R2 . One of: The substituent X is H or Cl. Substituent R3 To H. One of the following.

Design, synthesis and structure-activity relationship studies of 4-indole-2-arylaminopyrimidine derivatives as anti-inflammatory agents for acute lung injury

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), a clinically high mortality disease, has not been effectively treated till now, and the development of anti-acute lung injury drugs is imminent. Acute lung injury was efficiently treated by inhibiting the cascade of inflammation, and reducing the inflammatory response in the lung. A series of novel compounds with highly efficient inhibiting the expression of inflammatory factors were designed by using 4-indolyl-2-aminopyrimidine as the core skeleton. Totally eleven 4-indolyl-2-arylaminopyrimidine derivatives were designed and synthesized. As well, the related anti-ALI activity of these compounds was evaluated. Compounds 6c and 6h showed a superior activity among these compounds, and the inhibition rate of IL-6 and IL-8 release ranged from 62% to 77%, and from 65% to 72%, respectively. Furthermore, most of compounds had no significant cytotoxicity in vitro. The infiltration of inflammatory cells into lung tissue significantly reduced by using compound 6h (20 mg/kg) in the ALI mice model, which achieved the effect of protecting lung tissue and improving ALI. In addition, the inflammatory response was inhibited by using compound 6h through inhibiting phosphorylation of p-38 and ERK in MAPK signaling pathway, and resulted in protective effect on ALI. These data indicated that compound 6h showed good anti-inflammatory activity in vitro and in vivo, which was expected to become a leading compound for the treatment of ALI.

Compound, containing conjugated dienamide structure, preparation method, pharmaceutical composition and application thereof

The invention relates to a compound containing a conjugated allene amide structure and a preparation method, a medicine composition and application thereof, in particular to a compound containing a conjugated allene amide structure shown in a formula (I), and a preparation method, a medicine composition and application thereof in preparation of an EGFR (epidermal growth factor receptor) inhibitoror a medicine for preventing and/or treating EGFR-related diseases, especially cancers. (The formula (I) is shown in the description.).

Osimertinib dimer, preparation method and application thereof

The invention belongs to the field of medicines, and particularly relates to an osimertinib dimer, a preparation method and application thereof, and the chemical structure of the osimertinib dimer isshown as the specification. The osimertinib dimer is synthesized by taking a compound 1 as a starting material, acrylic anhydride and acrylic acid are gradually added according to a synthesis route inthe intermediate reaction process, and the osimertinib dimer is prepared through reduction, acylation, addition and condensation, and the preparation method is simple, convenient to operate, low in equipment condition requirement, extremely easy to implement, and simple in aftertreatment. The osimertinib dimer synthesized by the preparation method is high in purity, can be used as an impurity reference substance to be applied to qualitative and quantitative research and detection of osimertinib impurities, and has important significance in effectively controlling the quality of osimertinib.

Design, synthesis and biological evaluation of AZD9291 derivatives as selective and potent EGFRL858R/T790M inhibitors

Third-generation epidermal growth factor receptor (EGFR)L858R/T790M inhibitors are still the main drugs for the treatment of advanced non-small cell lung cancer (NSCLC), and these drugs have achieved remarkable clinical efficacy. However, there are still many patients suffering from drug-resistant mutations and drug side effects caused by NSCLC. In this study, guided by the molecular simulation, we applied a structure-based drug design strategy (SBDD) and optimized the structure to obtain a series of potent and selective EGFRL858R/T790M inhibitors. The most potent compound 18e demonstrated excellent kinase inhibitory activity and selectivity for EGFRL858R/T790M double mutants and the IC50 value reached nanomolar level. The selectivity of 18e against wild-type EGFR was near to 200-fold. In addition, compound 18e also inhibited H1975 cells proliferation at G2/M phase and induced apoptosis at a concentration of 0.25 μM, which makes it more valuable for potential lung cancer research.

A phenyl acrylamide structure containing substituted pyrimidine compound and use thereof (by machine translation)

The invention discloses a containing substituted phenyl acrylamide structure of the pyridine compound, its geometric isomer and its pharmaceutically acceptable salt, hydrate, solvate or prodrug. The invention containing substituted phenyl acrylamide structure of pyrimidines, and its pharmaceutically acceptable salt, hydrate or solvate thereof as an active ingredient, with a pharmaceutically acceptable carrier or excipient mixed preparation composition in, and prepared into a clinically acceptable dosage form. The compounds of the invention in preparing and treating and/or preventing proliferative disorders application of the medicament, for treating and/or preventing cancer of application of the medicament, for treating and/or preventing lung cancer, prostate cancer, breast cancer and applied in the medicine of cervical cancer. (by machine translation)