877399-49-0

Basic information

• Product Name: 2-PYRIDINAMINE, 3-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-5-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-YL)-
• Synonyms: 2-PYRIDINAMINE, 3-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-5-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-YL)-;3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine
• CAS NO: 877399-49-0
• Molecular Weight: 427.111
• Mol File: 877399-49-0.mol
• Article Data: 7

Chemical Properties

• CAS DataBase Reference: 2-PYRIDINAMINE, 3-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-5-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-YL)-(CAS DataBase Reference)
• NIST Chemistry Reference: 2-PYRIDINAMINE, 3-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-5-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-YL)-(877399-49-0)
• EPA Substance Registry System: 2-PYRIDINAMINE, 3-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-5-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-YL)-(877399-49-0)

Safety Data

• Hazardous Substances Data: 877399-49-0(Hazardous Substances Data)

Upstream product

• 877399-47-8 (R)-5-bromo-N,N-bis-(tert-butoxycarbonyl)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridine-2-amine 
• 1448326-33-7 5-bromo-3-[1 (R)-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine 
• 877397-71-2 (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethyoxyl)-2-aminopyridine 
• 877397-70-1 (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethyoxyl)-2-nitropyridine 
• 15128-82-2 3-hydroxy-2-nitropyridine 
• 877397-65-4 (S)‐1‐(2,6-dichloro-3-fluorophenyl)ethanol 
• 73183-34-3 bis(pinacol)diborane 
• 877399-48-9 (R)-N,N-bis(tert-butoxycarbonyl)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine 

Downstream Products

• 877399-52-5 crizotinib 
• 1421270-73-6 (R)-tert-butyl 2-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate 
• 1428476-86-1 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester 

Relevant articles and documents

Discovery of 2-aminopyridines bearing a pyridone moiety as potent ALK inhibitors to overcome the crizotinib-resistant mutants

Despite the initial benefit demonstrated in clinical setting with ALK inhibitors, the challenging resistant mutants (F1174L, L1196M and G1202R) invariably developed. In this work, a series of 2-aminopyridine derivatives were designed and synthesized by C-5 position incorporation of a 2-pyridone moiety and bioisosteric replacement of the C-3 position linkers. Optimization of the 2-aminopyridine derivatives led to the identification of hit 18d displaying a significant growth inhibition against a variety of ALK-addicted cancer cells. Especially in the case of ALK-positive Karpas-299 cell, 18d exhibited excellent anti-proliferative potency with an IC50 value of about 40 nM. Moreover, 18d demonstrated encouraging activities against wild-type ALK (19 nM), ROS1 (2.3 nM) as well as challenging crizotinib-resistant ALKL1196M and ALKG1202R mutants with IC50 values of 45 nM and 22 nM, respectively. Additionally flow cytometric analysis indicates that 18d inhibited Karpas-299 cell viability via G1 phase arrest. Taken together, this work provided a promising ALK inhibitor to circumvent the clinical crizotinib-resistant mutants.

PYRIDINE-SUBSTITUTED 2-AMINOPYRIDINE PROTEIN KINASE INHIBITORS

The present invention discloses pharmaceutically acceptable acid salts of pyridine-substituted 2-aminopyridine derivatives as protein kinase inhibitors, preparation methods, pharmaceutical compositions thereof, and use thereof for the treatment of diseases associated with protein kinase.

SUBSTITUTED 2-AMINOPYRIDINE PROTEIN KINASE INHIBITOR

Disclosed are a 2-aminopyridine derivative having protein kinase inhibition activity, a preparation method and a pharmaceutical composition thereof Also disclosed are uses of the compounds and the pharmaceutical compositions thereof in the preparation of drugs for treating and/or preventing protein kinase-related diseases.