1394821-01-2

Upstream product

• 1484-26-0 3-(benzyloxy)aniline 
• 749922-34-7 7-(benzyloxy)quinolin-4-ol 
• 178984-56-0 7-(benzyloxy)-4-chloroquinoline 
• 909345-85-3 5-((3-(benzyloxy)phenylamino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 1394820-97-3 7-benzyloxy-4-(2-fluoro-4-nitrophenoxy)quinoline 
• 1039046-51-9 4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinoline 
• 1394820-98-4 4-(2-fluoro-4-nitrophenoxy)quinolin-7-ol 
• 403-19-0 2-fluoro-4-nitrophenol 

Downstream Products

• 1394820-70-2 (R)-N-(3-fluoro-4-((7-(2-hydroxypropoxy)quinolin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide 
• 1221443-46-4 N-(3-fluoro-4-(7-hydroxyquinolin-4-yloxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide 

Relevant academic research and scientific papers

Discovery of 1,6-naphthyridinone-based MET kinase inhibitor bearing quinoline moiety as promising antitumor drug candidate

A series of 1,6-naphthyridinone-based MET kinase inhibitors bearing quinoline moiety in block A were designed and synthesized based on the structures of Cabozantinib and our reported compound IV. Extensive SAR and DMPK studies led to the identification of 20j, a potent and orally bioavailable MET kinase inhibitor with favorable kinase selectivity. More importantly, 20j exhibited statistically significant tumor growth inhibition (Tumor growth inhibition/TGI of 131%, 4/6 partial regression/PR) in the U-87 MG xeograft model, which is superior to that of Cabozantinib (TGI of 97%, 2/6 PR), and significantly better than that of compound IV (TGI of 15%, 0/6 PR) at the same dose (12.5 mg/kg). Combined with favorable in vitro potency, kinase selectivity, pharmacokinetic profile and in vivo efficacy, the promising antitumor drug candidate 20j has subsequently advanced into preclinical research.

SUBSTITUTED QUINOLINE COMPOUNDS AND METHODS OF USE

The present invention provides novel substituted quinoline compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.