1421372-75-9

Basic information

• Product Name: 6-methoxy-N¹-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)benzene-1,3-diamine
• Synonyms: 6-methoxy-N¹-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)benzene-1,3-diamine
• CAS NO: 1421372-75-9
• Molecular Weight: 443.552
• Mol File: 1421372-75-9.mol
• Article Data: 6

Chemical Properties

• CAS DataBase Reference: 6-methoxy-N¹-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)benzene-1,3-diamine(CAS DataBase Reference)
• NIST Chemistry Reference: 6-methoxy-N¹-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)benzene-1,3-diamine(1421372-75-9)
• EPA Substance Registry System: 6-methoxy-N¹-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)benzene-1,3-diamine(1421372-75-9)

Safety Data

• Hazardous Substances Data: 1421372-75-9(Hazardous Substances Data)

Upstream product

• 109-01-3 1-methyl-piperazine 
• 603-76-9 1-methylindole 
• 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 
• 1421372-94-2 N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methyl-1H-indole-3-yl)-pyrimidine-2-amine 
• 1421372-76-0 N-(4-(4-methylpiperazinyl)-2-methoxy-5-nitrophenyl)-4-(1-methyl-1H-indole-3-yl)pyrimidin-2-yl-amine 
• 1075705-01-9 4-fluoro-2-methoxy-5-nitro-phenylamine 

Downstream Products

• 1421373-71-8 EB₁₀₄ 

Relevant articles and documents

Discovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands

Drug resistance caused by epidermal growth factor receptor (EGFR) mutation has largely limited the clinical use of EGFR tyrosine kinase inhibitors (EGFR-TKIs) for the treatment of non-small-cell lung cancer (NSCLC). Herein, to overcome the intractable problem of drug resistance, proteolysis targeting chimeras (PROTACs) targeting EGFR mutants were developed by optimizing covalent EGFR ligands. Covalent or reversible covalent pyrimidine- or purine-containing PROTACs were designed, synthesized, and evaluated. As a consequence, covalent PROTAC CP17, with a novel purine-containing EGFR ligand, was discovered as a highly potent degrader against EGFRL858R/T790M and EGFRdel19, reaching the lowest DC50 values among all reported EGFR-targeting PROTACs. Furthermore, CP17 exhibited excellent cellular activity against the H1975 and HCC827 cell lines with high selectivity. Mechanism investigation indicated that the lysosome was involved in the degradation process. Importantly, the covalent binding strategy was proven to be an effective approach for the design of PROTACs targeting EGFRL858R/T790M, which laid the practical foundation for further development of potent EGFR-targeting PROTACs.

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.

4-indole-2-arylaminopyrimidine compound and application thereof in inflammation treatment

The invention belongs to the field of medicinal chemistry, and particularly discloses an N-(4-(1-methyl-1H-indole-3-yl) pyrimidine-2-yl)benzene-1,3-diamine analogue shown as the following formula (I),in the formula, R1 is selected from H, halogen or C1-C5 alkoxy, R2 is selected from H, halogen a C1-C12 chain alkyl substituted nitrogen-containing group, a C3-C6 cyclic group substituted nitrogen-containing group, a five-membered nitrogen-containing heterocyclic ring, a six-membered nitrogen-containing heterocyclic ring or a seven-membered nitrogen-containing heterocyclic ring. The invention further discloses an application of the compound shown in the formula (I) in preparation of drugs for inflammation-related diseases, and pharmacological results show that the N-(4-(1-methyl-1H-indol-3-yl)pyrimidine-2-yl)benzene-1,3-diamine analogue can effectively inhibit release of IL-6 and IL-8 inflammatory factors and has good anti-inflammatory activity.