35654-56-9

Usage

Uses

Used in Pharmaceutical Industry:
4-Chloro-6,7-dimethoxyquinoline is used as a chemical intermediate for the synthesis of various pharmaceutical compounds. Its primary application is in the preparation of Tivozanib (T447205) and Cabozantinib (C051500), which are employed as anticancer agents. These compounds exhibit significant potential in the treatment of cancer due to their ability to inhibit specific cellular pathways and target cancer cells effectively.
Used in Anticancer Applications:
4-Chloro-6,7-dimethoxyquinoline plays a crucial role in the development of Tivozanib and Cabozantinib, which are used as anticancer agents. These agents target specific cellular pathways involved in cancer cell growth and proliferation, thereby inhibiting tumor progression and offering potential therapeutic benefits to patients suffering from various types of cancer.

InChI:InChI=1/C11H10ClNO2/c1-14-10-5-7-8(12)3-4-13-9(7)6-11(10)15-2/h3-6H,1-2H3

Upstream product

• 13425-93-9 6,7-dimethoxyquinoline-4-ol 
• 127285-54-5 1,4-dihydro-6,7-dimethoxy-4-oxoquinoline 
• 13436-14-1 ethyl 4-hydroxy-6,7-dimethoxyquinoline-3-carboxylate 
• 67000-01-5 methyltertbutyl ether 
• 1634-04-4 tert-butyl methyl ether 
• 96042-30-7 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 
• 1131-62-0 1-(3,4-dimethoxyphenyl)ethanone 
• 4101-32-0 4',5'-dimethoxy-2'-nitroacetophenone 
• 498-02-2 1-(3-methoxy-4-hydroxyphenyl)ethanone 
• 46729-91-3 1-(3,4-dimethoxyphenyl)-2-nitroethan-1-one 
• 26893-22-1 4-hydroxy-6,7-dimethoxy-2-quinolinecarboxylic acid 
• 6315-89-5 3,4-dimethoxyaniline 
• 213699-53-7 5-(((3,4-dimethoxyphenyl)amino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 4101-30-8 2-amino-4,5-dimethoxyacetophenone 

Downstream Products

• 190726-45-5 Ki₆₇₈₃ 
• 202917-05-3 6,7-Dimethoxy-4-(3-nitro-phenoxy)-quinoline 
• 319492-82-5 CA₇₅ 
• 190728-24-6 6,7?dimethoxy?4?(4?nitrophenoxy)quinoline 

Relevant academic research and scientific papers

Design, Synthesis and Biological Evaluation of Novel α-Acyloxycarboxamide-Based Derivatives as c-Met Inhibitors

Dysregulated HGF/c-Met signalling has been associated with many human cancers, poor clinical outcomes, and even resistance acquisition to some approved targeted therapies. As such, c-Met kinase has emerged as an attractive target for anticancer drug discovery. Herein, a series of 6,7-disubstitued-4-(2-fluorophenoxy)quinoline derivatives bearing α-acyloxycarboxamide moiety were designed, synthesized via Passerini reaction as the key step, and evaluated for their in vitro biological activities against c-Met kinase and five selected cancer cell lines. The preliminary structure-activity relationship demonstrated that α-acyloxycarboxamide as the 5-atom linker maintained the potent antitumor potency. Among these compounds, compound 25s (c-Met IC50 = 4.06 nmol/L) was identified as the most promising lead compound and displayed the most potent antiproliferative activities against A549, HT-29 and MDA-MB-231 cell lines with IC50 of 0.39, 0.20, and 0.58 μmol/L, which were 1.3-, 1.4- and 1.2-fold superior to foretinib, respectively. The further studies indicated that compound 25s can induce apoptosis of A549 cells and arrest efficiently the cell cycle distribution in G2/M phase of A549 cells. Moreover, compound 25s can also inhibit c-Met phosphorylation in A549 cells by a dose-dependent manner. Collectively, these results indicated that compound 25s could be a potential anticancer lead compound deserving for further development.

c-Met kinase inhibitor as well as preparation method and application thereof

The invention belongs to the technical field of biological medicines, and particularly provides a c-Met kinase inhibitor represented by a general formula I. An in-vitro anti-tumor activity screening experiment shows that the compound disclosed by the invention shows relatively strong inhibitory activity on four cancer cells, namely human colon cancer cells (HT29), human non-small cell lung cancer cells (A549), human large cell lung cancer cells (H460) and human gastric cancer cells (MKN-45), and has a relatively good clinical application prospect.

Novel substituted pyrazolo [1, 5-a] pyrimidine compound and preparation method and application thereof

The invention provides a novel substituted pyrazolo [1, 5-a]pyrimidine compound and a preparation method and application thereof, and particularly relates to a pyrazolo [1, 5-a]pyrimidine-containing quinoline derivative shown as a general formula (I) and pharmaceutically acceptable salts thereof, and substituent groups X, Ar and A have meanings given in the specification. The invention also relates to a compound represented by the general formula (I), wherein the compound has a strong c-Met kinase inhibition effect. The invention also relates to application of the compound and the pharmaceutically acceptable salt thereof in preparation of drugs for treating and/or preventing diseases caused by abnormal high expression of c-Met kinase, especially application in preparation of drugs for treating and/or preventing cancers.

Structure-based discovery of novel 4-(2-fluorophenoxy)quinoline derivatives as c-Met inhibitors using isocyanide-involved multicomponent reactions

The c-Met kinase has emerged as a promising target for the development of small molecule antitumor agents because of its close relationship with the progression of many human cancers, poor clinical outcomes and even drug resistance. In this study, two novel series of 6,7-disubstitued-4-(2-fluorophenoxy)quinoline derivatives containing α-acyloxycarboxamide or α-acylaminoamide scaffolds were designed, synthesized, and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (H460, HT-29, MKN-45, and MDA-MB-231). Most of the target compounds exhibited moderate to significant potency and possessed selectivity for H460 and HT-29 cancer cell lines. The preliminary structure-activity relationships indicated that α-acyloxycarboxamide or α-acylaminoamide as 5-atom linker contributed to the antitumor potency. Among these compounds, compound 10m (c-Met IC50 = 2.43 nM, a multitarget tyrosine kinase inhibitor) exhibited the most potent inhibitory activities against H460, HT-29 and MDA-MB-231 cell lines with IC50 of 0.14 ± 0.03 μM, 0.20 ± 0.02 μM and 0.42 ± 0.03 μM, which were 1.7-, 1.3- and 1.6-fold more active than foretinib, respectively. In addition, concentration-dependent assay and time-dependent assay indicated compound 10m can inhibit the proliferation of H460 cell in a time and concentration dependent manner. Moreover, docking studies revealed the common mode of interaction with the c-Met binding site, suggesting that 10m is a potential candidate for cancer therapy deserving further study.

Design, synthesis and biological evaluation of novel N-sulfonylamidine-based derivatives as c-Met inhibitors via Cu-catalyzed three-component reaction

In our continuing efforts to develop novel c-Met inhibitors as potential anticancer candidates, a series of new N-sulfonylamidine derivatives were designed, synthesized via Cu-catalyzed multicomponent reaction (MCR) as the key step, and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (A549, HT-29, MKN-45 and MDA-MB-231). Most of the target compounds showed moderate to significant potency at both the enzyme-based and cell-based assay and possessed selectivity for A549 and HT-29 cancer cell lines. The preliminary SAR studies demonstrated that compound 26af (c-Met IC50 = 2.89 nM) was the most promising compound compared with the positive foretinib, which exhibited the remarkable antiproliferative activities, with IC50 values ranging from 0.28 to 0.72 μM. Mechanistic studies of 26af showed the anticancer activity was closely related to the blocking phosphorylation of c-Met, leading to cell cycle arresting at G2/M phase and apoptosis of A549 cells by a concentration-dependent manner. The promising compound 26af was further identified as a relatively selective inhibitor of c-Met kinase, which also possessed an acceptable safety profile and favorable pharmacokinetic properties in BALB/c mouse. The favorable drug-likeness of 26af suggested that N-sulfonylamidines may be used as a promising scaffold for antitumor drug development. Additionally, the docking study and molecular dynamics simulations of 26af revealed a common mode of interaction with the binding site of c-Met. These positive results indicated that compound 26af is a potential anti-cancer candidate for clinical trials, and deserves further development as a selective c-Met inhibitor.

Preparation method of cabozantinib defluorination impurity

The invention discloses a preparation method of a cabozantinib defluorination impurity. The method comprises the following steps: preparing an intermediate 1, preparing 4-chloro-6, 7-dimethoxyquinoline, preparing an intermediate 2, and removing fluorine i

Synthesis method of cabozantinib dimer

The invention discloses a synthesis method of a cabozantinib dimer. The method comprises the following steps: preparation of 4-chloro-6,7-dimethoxyquinoline, preparation of an intermediate 1, and preparation of a cabozantinib dimer impurity; and preparati

Preparation method of cabozantinib nitrogen oxide impurity

The invention discloses a preparation method of a cabozantinib nitrogen oxide impurity. The method comprises the following steps: preparation of an intermediate 1, preparation of 4-chloro-6, 7-dimethoxyquinoline, preparation of an intermediate 2, and prep

Preparation method for cabozantinib degradation impurity without p-fluoroaniline

The invention discloses a preparation method for a cabozantinib degradation impurity without p-fluoroaniline. The method comprises the following steps: preparation of 4-chloro-6,7-dimethoxyquinoline;preparation of an intermediate 1; and preparation of p-f

Method of Treating Cancer and Bone Cancer Pain

This invention is directed to the treatment of cancer, particularly lung cancer, breast cancer, melanoma, renal cell carcinoma, thyroid cancer that has metastasized to the bone. The invention is also directed to a method for treating bone cancer pain in a