1421372-94-2

Usage

Uses

Used in Pharmaceutical Industry:
N-(4-fluoro-2-Methoxy-5-nitrophenyl)-4-(1-Methylindol-3-yl)pyriMidin-2-aMine is used as a reagent for the synthesis of dihydropyrroloquinoline derivatives. These derivatives possess significant anticancer activity, particularly as modulators of the epidermal growth factor receptor (EGFR). The compound is specifically designed to inhibit the L858R/T790M mutation, which is a common resistance mutation in non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors.
The application reason for using N-(4-fluoro-2-Methoxy-5-nitrophenyl)-4-(1-Methylindol-3-yl)pyriMidin-2-aMine in this context is its ability to form dihydropyrroloquinoline derivatives with potent anticancer properties. These derivatives can effectively target and inhibit the EGFR L858R/T790M mutation, providing a potential therapeutic strategy for overcoming resistance to EGFR-targeted therapies in lung cancer treatment.

Upstream product

• 450-91-9 4-fluoro-2-methoxyaniline 
• 603-76-9 1-methylindole 
• 123344-02-5 5-amino-2,4-difluoronitrobenzene 
• 367-25-9 2,4-difluorophenylamine 
• 448-19-1 4-fluoro-2-methoxy-1-nitrobenzene 
• 1032452-86-0 2-chloro-4-(1'-methyl-1H-indol-3-yl)pyrimidine 
• 1075705-01-9 4-fluoro-2-methoxy-5-nitro-phenylamine 
• 104-15-4 toluene-4-sulfonic acid 
• 120-72-9 indole 
• 945016-63-7 3-(2-chloro-pyrimidin-4-yl)-1H-indole 

Downstream Products

• 1421373-88-7 C₂₉H₃₃N₇O₂ 
• 1421373-99-0 Ν-(4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)acrylamide 
• 1421372-66-8 N?2?[[2?(dimethylamino)ethyl]methylamino]?4?methoxy?5?[[4?(1?methyl?1H?indole-3-yl)-2-pyrimidinyl]amino]aniline 
• 1421372-69-1 4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-6-methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine 
• 1421372-75-9 6-methoxy-N¹-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)benzene-1,3-diamine 
• 1421372-81-7 4-(3-(dimethylamino)cycloazane-1-yl)-6-methoxy-N₁-[4-(1-methylindol-3-yl)pyrimidine- 2-yl]benzene-1,3-diamine 
• 1421373-12-7 4-[(3S)-3-dimethylaminopyrrolidin-1-yl]-6-methoxy-N'-{4-(1-methylindol-3-yl)pyrimidin-2-yl}benzene-1,3-diamine 
• 1421373-33-2 tert-butyl N-[2-[[5-methoxy-4-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]-2-(prop-2-enoylamino)phenyl](methyl)amino]ethyl]-N-methylcarbamate 
• 1421373-34-3 tert-butyl (2-((2-amino-5-methoxy-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)(methyl)amino)ethyl)(methyl)carbamate 
• 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 
• 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 
• 1421373-68-3 C₂₉H₃₃N₇O₂ 
• 1421373-71-8 EB₁₀₄ 

Relevant academic research and scientific papers

Discovery of highly potent and selective EGFRT790M/L858R TKIs against NSCLC based on molecular dynamic simulation

Epidermal growth factor receptor (EGFR) is the most attractive target for drug research in non-small cell lung cancer (NSCLC). There have been three generation drugs developed to treat of NSCLC. The third-generation EGFR tyrosine kinase inhibitors (TKIs)

Refinement of covalent EGFR inhibitor AZD9291 to eliminate off-target activity

Non-small-cell lung cancer (NSCLC) is a major disease that accounts for 85% of all lung cancer cases which claimed around 1.8 billion lives worldwide in 2020. Tyrosine kinase inhibitors (TKIs) that target EGFR have been used for the treatment of NSCLC, but often develop drug resistance, and the covalent inhibitor AZD9291 has been developed to tackle the problem of drug resistance mediated by the T790M EGFR mutation; however, there is a side effect of hyperglycemia that may be due to off-target activity. This study examines analogs of AZD9291 by chemical proteomics, identifying analogs that maintain T790M-EGFR engagement while showing reduced cross-reactivity with off-targets.

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.

P-phenylenediamine LSD1 inhibitor and preparation method thereof

Disclosed are a p-phenylenediamine derivative as represented by general formula I, a pharmaceutically acceptable salt, and a stereoisomer thereof. The p-phenylenediamine derivative as represented by general formula I, the pharmaceutically acceptable salt thereof and the stereoisomer thereof can be used alone or in combination as lysine-specific demethylase-1 (LSD1) inhibitors.

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.

Deuterated pyrimidine derivative and application thereof

The invention discloses a deuterated pyrimidine derivative and application thereof, and belongs to the field of medicines. The deuterated pyrimidine derivative and a pharmaceutically acceptable salt thereof have good activity of selectively inhibiting an

Pyrimidine bis-aromatic ring derivative epidermal growth factor inhibitor, and preparation method and application thereof

The invention relates to a pyrimidine double-aromatic-ring derivative epidermal growth factor inhibitor, and a preparation method and application thereof. The invention discloses a selective inhibitorfor a clinical mutant of EGFR protein tyrosine kinase.

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.).

Discovery and biological evaluation of proteolysis targeting chimeras (PROTACs) as an EGFR degraders based on osimertinib and lenalidomide

Epidermal growth factor receptor (EGFR) is one of the important and valuable drug targets. Overexpression of EGFR is associated with the development of many types of cancer. In this study, three PROTACs small molecules (16a–16c) were designed, synthesized and evaluated for their cytotoxicity against the growth in different NSCLC cell line and the degradation effect. The bioassay results indicated that 16c has a good inhibition in PC9 cells and H1975 cells, and the corresponding IC50 value was 0.413 μM and 0.657 μM, respectively. Western blotting results demonstrated that compound 16c could serve as an effective EGFRdel19-targeting degrader in PC9 cells.