347161-76-6

Upstream product

• 13425-93-9 6,7-dimethoxyquinoline-4-ol 
• 455-88-9 5-nitro-2-fluorotoluene 
• 144-55-8 sodium hydrogencarbonate 
• 347161-73-3 6,7-dimethoxy-4-(2-methyl-4-nitrophenoxy)quinoline 
• 35654-56-9 6,7-dimethoxy-4-chloroquinoline 
• 99-53-6 2-methyl-4-nitrophenol 

Downstream Products

• 1192299-30-1 N-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-methylphenyl]-2-trifluoromethylbenzenesulfonamide 

Relevant academic research and scientific papers

Discovery of 2-(4-Chloro-3-(trifluoromethyl)phenyl)- N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)acetamide (CHMFL-KIT-64) as a Novel Orally Available Potent Inhibitor against Broad-Spectrum Mutants of c-KIT Kinase for Gastrointestinal Stromal Tumors

Starting from our previously developed c-KIT kinase inhibitor CHMFL-KIT-8140, through a type II kinase inhibitor binding element hybrid design approach, we discovered a novel c-KIT kinase inhibitor compound 18 (CHMFL-KIT-64), which is potent against c-KIT wt and a broad spectrum of drug-resistant mutants with improved bioavailability. 18 exhibits single-digit nM potency against c-KIT kinase and c-KIT T670I mutants in the biochemical assay and displays great potencies against most of the gain-of-function mutations in the juxtamembrane domain, drug-resistant mutations in the ATP binding pocket (except V654A), and activation loops (except D816V). In addition, 18 exhibits a good in vivo pharmacokinetic (PK) profile in different species including mice, rats, and dogs. It also displays good in vivo antitumor efficacy in the c-KIT T670I, D820G, and Y823D mutant-mediated mice models as well as in the c-KIT wt patient primary cells which are known to be imatinib-resistant. The potent activity against a broad spectrum of clinically important c-KIT mutants combining the good in vivo PK/pharmacodynamic properties of 18 indicates that it might be a new potential therapeutic candidate for gastrointestinal stromal tumors.

QUINOLINE DERIVATIVES AS INHIBITORS OF AXL/MER RTK AND CSF1R

The present invention relates to quinoline derivatives which are inhibitors for Axl/Mer RTK (receptor tyrosine kinase) and CSF1R (colony stimulating factor 1 receptor). These compounds are suitable for the treatment of disorders associated with, accompanied by, caused by or induced by Axl/Mer RTK and CSF1R, in particular a hyperfunction thereof. The compounds are suitable for the treatment of hyperproliferative disorders, such as cancer, particularly immune-suppressive cancer (such as those cancers with an immunosuppression of innate immunity in a tumor microenvironment (TME), refractory cancer and cancer metastases. They are also useful in the treatment of inflammatory diseases and/or neurodegenerative diseases.

Discovery of N-[4-(Quinolin-4-yloxy)phenyl]benzenesulfonamides as Novel AXL Kinase Inhibitors

The overexpression of AXL kinase has been described in many types of cancer. Due to its role in proliferation, survival, migration, and resistance, AXL represents a promising target in the treatment of the disease. In this study we present a novel compound family that successfully targets the AXL kinase. Through optimization and detailed SAR studies we developed low nanomolar inhibitors, and after further biological characterization we identified a potent AXL kinase inhibitor with favorable pharmacokinetic profile. The antitumor activity was determined in xenograft models, and the lead compounds reduced the tumor size by 40% with no observed toxicity as well as lung metastasis formation by 66% when compared to vehicle control.

URACIL DERIVATIVES AS AXL AND C-MET KINASE INHIBITORS

The present invention provides compounds of Formula I, or pharmaceutically acceptable salt forms thereof, wherein Ra, Rb, Rc, Rd, D, W, R1a, R1b, R1c,Y, R3, X, E and G are as defined herein, methods of treatment and uses thereof.

PHARMACEUTICALLY ACTIVE COMPOUNDS AS AXL INHIBITORS

The present invention relates to 1-nitrogen-heterocyclic-2-carboxamides of general formula (I): and/or pharmaceutically acceptable salts thereof, the use of these derivatives as pharmaceutically active agents, especially for the treatment and/or prevention of Axl receptor tyrosine kinase subfamily induced disorders, including cancer and primary tumor metastases, and pharmaceutical compositions containing at least one of said 1-nitrogen-heterocyclic-2-carboxamide derivatives and/or pharmaceutically acceptable salts thereof.

Pharmaceutically active compounds as Axl inhibitors

The present invention relates to 1-nitrogen-heterocyclic-2-carboxamides of general formula (I): and/or pharmaceutically acceptable salts thereof, the use of these derivatives as pharmaceutically active agents, especially for the treatment and/or prevention of Axl receptor tyrosine kinase subfamily induced disorders, including cancer and primary tumor metastases, and pharmaceutical compositions containing at least one of said 1-nitrogen-heterocyclic-2-carboxamide derivatives and/or pharmaceutically acceptable salts thereof.

Orally active anti-proliferation agents: Novel diphenylamine derivatives as FGF-R2 autophosphorylation inhibitors

(6,7-Disubstituted-quinolin-4-yloxy-phenyl)(4-substituted-phenyl)amine derivatives were synthesized and evaluated by a cellular autophosphorylation assay for FGF-R2 in the human scirrhous gastric carcinoma cell line, OCUM-2MD3. We also performed metabolic

QUINOLINE AND QUINAZOLINE DERIVATIVES AND DRUGS CONTAINING THE SAME

There are provided compounds which can be used in the treatment of diseases mediated by the autophosphorylation of a PDGF receptor, specifically, compounds which can inhibit neointima formation hypertrophy. The compounds are those represented by formula (