1052114-80-3

Upstream product

• 221121-37-5 4-(4-fluorophenyl)-3-oxobutanoic acid ethyl ester 
• 405-50-5 p-Fluorophenylacetic acid 
• 1035695-10-3 5-[2-(4-fluorophenyl)-1-hydroxyethylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 459-04-1 4-Fluorophenylacetyl chloride 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 290-87-9 1,3,5-Triazine 

Downstream Products

• 1052114-81-4 5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridin-3-ylcarboxylic acid 
• 1345855-04-0 ethyl 5-(4-fluorophenyl )-1-methyl-4-oxo-1,4-dihydropyridine-3-carboxylate 
• 1528549-08-7 C₃₀H₂₆F₂N₄O₅ 
• 1528546-94-2 N-(4-(2,3-dihydro-1H-pyrrolo[2,3-b] pyridin-4-yloxy)-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide 
• 1528546-96-4 N-(3-fluoro-4-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-8-yloxy)phenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide 
• 1449300-94-0 1-[2-(dimethylamino)-2-oxoethyl]-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid 
• 1449299-70-0 N-{4-[2-amino-5-(3,4-dimethoxyphenyl)pyridin-3-yl]phenyl}-1-(2-fluoroethyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide 
• 1449300-83-7 1-(2-fluoroethyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid 
• 1449299-66-4 N-{4-[2-amino-5-(3,4-dimethoxyphenyl)pyridin-3-yl]phenyl}-5-(4-fluorophenyl)-1-(2-methoxyethyl)-4-oxo-1,4-dihydropyridine-3-carboxamide 
• 1449300-80-4 5-(4-fluorophenyl)-1-(2-methoxyethyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid 
• 1449300-57-5 N-[4-(6-amino-2'-methyl-3,4'-bipyridin-5-yl)phenyl]-1-(2-fluoroethyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide 
• 1449300-41-7 N-{4-[2-amino-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)pyridin-3-yl]phenyl}-1-(2-fluoroethyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide 
• 1449301-44-3 tert-butyl 4-(4-[6-amino-5-[4-({[1-(2-fluoroethyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridin-3-yl]carbonyl}amino)phenyl]pyridin-3-yl]-1H-pyrazol-1-yl)piperidin-1-carboxylate 
• 1449300-22-4 N-[4-(2-amino-5-{4-[(2R)-1,4-dioxan-2-ylmethoxy]-3-methoxyphenyl}pyridin-3-yl)phenyl]-1-(2-fluoroethyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide 

Relevant academic research and scientific papers

Discovery of pyrrolo[2,3-d]pyrimidine derivatives as potent Axl inhibitors: Design, synthesis and biological evaluation

Axl has emerged as an attractive target for cancer therapy due to its strong correlation with tumor growth, metastasis, poor survival, and drug resistance. Herein, we report the design, synthesis and structure-activity relationship (SAR) investigation of a series of pyrrolo[2,3-d]pyrimidine derivatives as new Axl inhibitors. Among them, the most promising compound 13b showed high enzymatic and cellular Axl potencies. Furthermore, 13b possessed preferable pharmacokinetic properties and displayed promising therapeutic effect in BaF3/TEL-Axl xenograft tumor model. Compound 13b may serve as a lead compound for new antitumor drug discovery.

NOVEL FUSED PYRIDINE DERIVATIVES USEFUL AS c-MET TYROSINE KINASE INHIBITORS

This invention relates to novel fused quinazoline derivatives of Formula I as c-Met inhibitors, their synthesis and uses for treating c-Met mediated disorders.

Bioisosteric replacement of an acylureido moiety attached to an indolin-2-one scaffold with a malonamido or a 2/4-pyridinoylamido moiety produces a selectively potent Aurora-B inhibitor

Bioisosteric replacement of acylureido moiety in 6-acylureido-3- pyrrolylmethylidene-2-oxoindoline derivatives resulted in a series of malonamido derivatives with indolin-2-one scaffold (11-14). Further conformational restrictions of the malonamido moiety led to 2-oxo-1,2-dihydropyridine (21-25) or a 4-oxo-1,4-dihydropyridine derivatives (31-36). 4-Oxo-1,4-dihydropyridine derivatives were more potent Aurora B inhibitors than their 2-oxo-1,2- dihydropyridine counterparts and demonstrated cytotoxicities against A549 and HepG2 cells in the submicromolar range. In A549 cells, 31h decreased phosphorylation of histone H3, triggered polyploidy, induced expression of pro-apoptotic Fas and FasL with subsequent activation of caspase 8, resulting into apoptosis. In a Huh7-xenograft mouse model, 31h demonstrated potent in vivo efficacy with a daily dose of 5 mg/kg.

PYRIDONE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES

Compounds useful in the treatment of mammalian cancers and especially human cancers according to Formula I are disclosed. Formula (I). Pharmaceutical compositions and methods of treatment employing the compounds disclosed herein are also disclosed.

PYRIDONE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITES

Compounds useful in the treatment of mammalian cancers and especially human cancers according to Formula I are disclosed. Pharmaceutical compositions and methods of treatment employing the compounds disclosed herein are also disclosed.

4-PYRIDINONE COMPOUNDS AND THEIR USE FOR CANCER

Disclosed are compounds of Formula (I)and salts thereof. Also, disclosed are methods of using the compounds in the treatment of proliferative diseases, such as cancer, and to pharmaceutical compositions comprising at least one compound of Formula (I) or a

Discovery of pyrrolopyridine-pyridone based inhibitors of met kinase: Synthesis, X-ray crystallographic analysis, and biological activities

Conformationally constrained 2-pyridone analogue 2 is a potent Met kinase inhibitor with an IC50 value of 1.8 nM. Further SAR of the 2-pyridone based inhibitors of Met kinase led to potent 4-pyridone and pyridine N-oxide inhibitors such as 3 and 4. The X-ray crystallographic data of the inhibitor 2 bound to the ATP binding site of Met kinase protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues showed potent antiproliferative activities against the Met dependent GTL-16 gastric carcinoma cell line. Compound 2 also inhibited Flt-3 and VEGFR-2 kinases with IC50 values of 4 and 27 nM, respectively. It possesses a favorable pharmacokinetic profile in mice and demonstrates significant in vivo antitumor activity in the GTL-16 human gastric carcinoma xenograft model.