179873-51-9

Upstream product

• 1117-97-1 N,0-dimethylhydroxylamine 
• 10349-57-2 Quinoline-6-carboxylic acid 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 

Downstream Products

• 73013-68-0 1-(quinolin-6-yl)ethan-1-one 
• 4113-04-6 quinoline-6-carbaldehyde 
• 878495-86-4 (3,5-dimethoxy-phenyl)-quinolin-6-yl-methanone 
• 878495-85-3 (3-ethoxy-4-methoxy-phenyl)-quinolin-6-yl-methanone 

Relevant academic research and scientific papers

Potent Inhibition of Nicotinamide N-Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics

Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, with the most potent inhibitors sharing structural features based on elements of the nicotinamide substrate and the S-adenosyl-l-methionine (SAM) cofactor. We here report the development of new bisubstrate inhibitors that include electron-deficient aromatic groups to mimic the nicotinamide moiety. In addition, a trans-alkene linker was found to be optimal for connecting the substrate and cofactor mimics in these inhibitors. The most potent NNMT inhibitor identified exhibits an IC50 value of 3.7 nM, placing it among the most active NNMT inhibitors reported to date. Complementary analytical techniques, modeling studies, and cell-based assays provide insights into the binding mode, affinity, and selectivity of these inhibitors.

Discovery and optimization of a series of imidazo[4,5-b]pyrazine derivatives as highly potent and exquisitely selective inhibitors of the mesenchymal–epithelial transition factor (c-Met) protein kinase

Aberrant c-Met activation has been implicated in multiple tumor oncogenic processes and drug resistance. In this study, a series of imidazo[4,5-b]pyrazine derivatives was designed and synthesized, and their inhibitory activities were evaluated in vitro. Structure–activity relationship (SAR) was investigated systematically and docking analysis was performed to elucidate the binding mode, leading to the identification of the most promising compound 1D-2 which exhibited significant inhibitory effect on both enzymatic (IC50?=?1.45?nM) and cellular (IC50?=?24.7?nM in H1993 cell line) assays, as well as exquisite selectivity and satisfactory metabolic stability in human and rat liver microsomes.

Quinoline compounds and preparation method thereof, and intermediate, pharmaceutical composition and application of quinoline compounds

The invention discloses quinoline compounds and a preparation method thereof, and an intermediate, a pharmaceutical composition and application of quinoline compounds. The invention provides quinoline compounds disclosed as Formula 1, and pharmaceutically acceptable salts, solvates, metabolites, metabolism precursors or pharmaceutical precursors thereof. The quinoline compounds have favorable inhibitory effects on tyrosine kinase C-Met, and can be used for preparing drugs for prevention, treatment or auxiliary treatment on multiple diseases related to C-Met expression or activity, and especially neoplastic diseases.

Lessons from (S)-6-(1-(6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3- b ]pyridazin-3-yl)ethyl)quinoline (PF-04254644), an inhibitor of receptor tyrosine kinase c-met with high protein kinase selectivity but broad phosphodiesterase family inhibition lea

The hepatocyte growth factor (HGF)/c-Met signaling axis is deregulated in many cancers and plays important roles in tumor invasive growth and metastasis. An exclusively selective c-Met inhibitor (S)-6-(1-(6-(1-methyl-1H-pyrazol-4-yl)- [1,2,4]triazolo[4,3-

Synthesis and biological evaluation of 4(5)-(6-methylpyridin-2-yl)imidazoles and -pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors

A series of 4(5)-(6-methylpyridin-2-yl)imidazoles 16-19 and -pyrazoles 22-29, 33, and 34 have been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in cell-based luciferase reporter assays. The 6-quinolinyl imidazole analogs 16 and 18 inhibited ALK5 phosphorylation with IC50 values of 0.026 and 0.034 μM, respectively. In a luciferase reporter assay using HaCaT cells transiently transfected with p3TP-luc reporter construct, 18 displayed 66% inhibition at 0.05 μM, while competitor compounds 2 and 3 showed 44% inhibition. The binding mode of 18 generated by flexible docking studies with ALK5:18 complex shows that it fits well into the active site cavity of ALK5 by forming broad and tight interactions.

IMIDAZO [1,2-B] PYRIDAZINE DERIVATIVES FOR THE TREATMENT OF C-MET TYROSINE KINASE MEDIATED DISEASE

The invention relates to compounds of formula (I) and salts thereof, formula (I) wherein the substituents are as defined in the specification, the application of a compound of formula (I) in a process for the treatment of the human or animal body, in particular with regard to C-Met tyrosine kinase mediated disease; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharamaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner; processes for the preparation of a compound of formula (I).

TRIAZOLOPYRAZINE DERIVATIVES

The invention relates to compounds of the formula I or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3 and R4 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula I and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula I.