956907-14-5

Upstream product

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• 100516-88-9 6-(hydroxymethyl)quinoline 
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• 872047-71-7 2-(quinolin-6-ylmethyl)isoindoline-1,3-dione 
• 5332-25-2 6-bromoquinoline 
• 956907-13-4 6-bromo-N²-(quinolin-6-ylmethyl)pyrazine-2,3-diamine 
• 110-46-3 isopentyl nitrite 
• 23395-72-4 quinoline-6-carbonitrile 

Relevant academic research and scientific papers

Discovery of small-molecule fluorescent probes for C-Met

C-mesenchymal-epithelia transition factor (c-Met) is highly expressed in various solid tumors such as gastric cancer, liver cancer, and lung cancer, playing a pivotal role in the growth, maintenance, and development of different tumor cells. In this study, three small-molecule fluorescent probes (5, 11, 16) targeting c-Met were developed, and their design strategies were also initially explored. In general, the fluorescence properties of the probes themselves could meet the imaging requirements, and they have shown sufficient inhibitory activities against c-Met, especially probe 16, reflecting the targeting and acceptance. Also, fluorescence polarization assays and flow cytometry analysis verified the binding between the probes and c-Met. Cell imaging confirmed that these probes could be used to label c-Met on living cells. It is of positive significance for the development of c-Met kinase inhibitors and tumor pathology research.

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.

Discovery of (S)-1-(1-(Imidazo[1,2- a ]pyridin-6-yl)ethyl)-6-(1-methyl-1 H -pyrazol-4-yl)-1 H -[1,2,3]triazolo[4,5- b ]pyrazine (Volitinib) as a Highly Potent and Selective Mesenchymal-Epithelial Transition Factor (c-Met) Inhibitor in Clinical Development for Treatment of Cancer

HGF/c-Met signaling has been implicated in human cancers. Herein we describe the invention of a series of novel triazolopyrazine c-Met inhibitors. The structure-activity relationship of these compounds was investigated, leading to the identification of compound 28, which demonstrated favorable pharmacokinetic properties in mice and good antitumor activities in the human glioma xenograft model in athymic nude mice.

Discovery of a novel class of exquisitely selective mesenchymal-epithelial transition factor (c-MET) protein kinase inhibitors and identification of the clinical candidate 2-(4-(1-(Quinolin-6-ylmethyl)-1 H -[1,2,3]triazolo[4,5- b ]pyrazin-6-yl)-1 H -pyrazol-1-yl)ethanol (PF-04217903) for the treatment of cancer

The c-MET receptor tyrosine kinase is an attractive oncology target because of its critical role in human oncogenesis and tumor progression. An oxindole hydrazide hit 6 was identified during a c-MET HTS campaign and subsequently demonstrated to have an unusual degree of selectivity against a broad array of other kinases. The cocrystal structure of the related oxindole hydrazide c-MET inhibitor 10 with a nonphosphorylated c-MET kinase domain revealed a unique binding mode associated with the exquisite selectivity profile. The chemically labile oxindole hydrazide scaffold was replaced with a chemically and metabolically stable triazolopyrazine scaffold using structure based drug design. Medicinal chemistry lead optimization produced 2-(4-(1-(quinolin-6- ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol (2, PF-04217903), an extremely potent and exquisitely selective c-MET inhibitor. 2 demonstrated effective tumor growth inhibition in c-MET dependent tumor models with good oral PK properties and an acceptable safety profile in preclinical studies. 2 progressed to clinical evaluation in a Phase I oncology setting.

HETEROCYCLIC HYDRAZONE COMPOUNDS AND THEIR USES TO TREAT CANCER AND INFLAMMATION

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

HETEROCYCLIC OXIME COMPOUNDS

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

CERTAIN TRIAZOLOPYRIDINES AND TRIAZOLOPYRAZINES, COMPOSITIONS THEREOF AND METHODS OF USE THEREFOR

Provided are certain triazolopyridines and triazolopyrazines, compositions thereof and methods of use therefor.

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.