849217-64-7

Basic information

• Product Name: Foretinib (GSK1363089)
• Synonyms: Foretinib;GSK 1363089;EXEL-2880;XL880;N-[3-Fluoro-4-[[6-(methyloxy)-7-[[3-(morpholin-4-yl)propyl]oxy]quinolin-4-yl]oxy]phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide;N-[3-Fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]-N'-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide;XL880(GSK1363089);foretinib N1-{3-fluoro-4-[(6-(Methyloxy)-7-{[3-(4-Morpholinyl)propyl]oxy}-4-quinolinyl)oxy]phenyl}-N1'-(4-fluorophenyl)-1,1-cyclopropanedicarboxaMide
• CAS NO: 849217-64-7
• Molecular Formula: C₃₄H₃₄F₂N₄O₆
• Molecular Weight: 632.6537664
• Product Categories: Inhibitors
• Mol File: 849217-64-7.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 828.475 °C at 760 mmHg
• Flash Point: 454.846 °C
• Appearance: /
• Density: 1.372
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility: DMSO (Slightly), Ethanol (Slightly)
• PKA: 13.14±0.70(Predicted)
• CAS DataBase Reference: Foretinib (GSK1363089)(CAS DataBase Reference)
• NIST Chemistry Reference: Foretinib (GSK1363089)(849217-64-7)
• EPA Substance Registry System: Foretinib (GSK1363089)(849217-64-7)

Safety Data

• Hazardous Substances Data: 849217-64-7(Hazardous Substances Data)

Usage

Uses

Used in Oncology:
Foretinib (GSK1363089) is used as an anticancer agent for targeting the proliferation and angiogenesis of cancer cells. It inhibits the activity of MET and VEGFR2, which are key drivers of tumor growth and blood vessel formation, leading to the suppression of tumor progression and metastasis.
Used in Drug Development:
Foretinib (GSK1363089) serves as a valuable compound in the development of targeted therapies for various cancers. Its multikinase inhibitory profile allows researchers to study its potential synergistic effects with other drugs and explore its efficacy in combination therapies for improved cancer treatment outcomes.

Clinical Use

Foretinib has also shown to be effective against ROS1 mutations especially when acquired with crizotinib resistance. A clinical trial investigating the dosing and safety profile of combining foretinib and erlotinib was designed for advanced pretreated NSCLC patients.

in vitro

In vitro, foretinib blocks activation of MET and VEGFR2-induced signaling pathways. In vivo experiments show a dose-dependent decrease in tumor burden in a lung metastasis experimental model.

references

[1] qian f1, engst s, yamaguchi k, yu p, won ka, mock l, lou t, tan j, li c, tam d, lougheed j, yakes fm, bentzien f, xu w, zaks t, wooster r,greshock j, joly ah. inhibition of tumor cell growth, invasion, and metastasis by exel-2880 (xl880, gsk1363089), a novel inhibitor of hgf and vegf receptor tyrosine kinases. cancer res. 2009 oct 15;69(20):8009-16. doi: 10.1158/0008-5472.can-08-4889.

Upstream product

• 479690-08-9 1-(2-fluoro-4-nitrophenyl)-6-hydroxy-7-methoxy-quinoline 
• 479690-03-4 7-benzyloxy-4-(2-fluoro-4-nitro-phenoxy)-6-methyloxyquinoline 
• 286371-49-1 7-(benzyloxy)-4-chloro-6-methoxyquinoline 
• 479690-04-5 4-(7-(benzyloxy)-6-methoxyquinolin-4-yloxy)-3-fluorobenzenamine 
• 479690-10-3 3-Fluoro-4-{[6-methoxy-7-(3-morpholinopropoxy)-4-quinolyl]oxy}-aniline 
• 960299-44-9 4-(3-((4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7-yl)oxy)propyl)morpholine 
• 75665-88-2 1-(4-(benzyloxy)-5-methoxy-2-nitrophenyl)ethanone 
• 371-40-4 4-fluoroaniline 
• 498-02-2 1-(3-methoxy-4-hydroxyphenyl)ethanone 
• 403-19-0 2-fluoro-4-nitrophenol 
• 1835-11-6 4-benzyloxy-3-methoxyacetophenone 
• 598-10-7 cyclopropane-1,1-dicarboxylic acid 
• 849217-57-8 N'-(4-(benzyloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dimethylamide 
• 849217-58-9 N'-(3-fluoro-4-hydroxyphenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide 

Relevant articles and documents

Preparation methods of tyrosine kinase inhibitor XJF007 and its intermediate

The invention discloses preparation methods of tyrosine kinase inhibitor XJF007 with a general structural formula (I) and its intermediate. The preparation method of the tyrosine kinase inhibitor XJF007 employs a collecting synthesis strategy of construct

A tyrosine kinase inhibitor and intermediate preparation method

The invention provides preparation methods of a tyrosine kinase inhibitor and intermediates thereof, specifically preparation methods of N-[3-fluoro-4-[[6-methoxy-7-[oxy]quinolin-4-yl]oxy]phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (Foretinib), and analogs and intermediates thereof. 1,1-cyclopropane dicarboxylic acid diester is used as the raw material to prepare a compound of the formula VI; and the compound of the formula VI is hydrolyzed and then reacts with a compound of the formula VIII, so as to prepare the Foretinib and the analogs thereof. The condition of each reaction step is mild, the preparation method is easy to operate, the price of the raw materials is low, and thus the production cost is reduced, the yield is relatively high, and the preparation methods are suitable for industrialized production.

Preparation method of tyrosine enzyme inhibitor Foretinib

The present invention provides a preparation method of a tyrosine enzyme inhibitor Foretinib. The method is as below: subjecting 1,1-cyclopropyl dicarboxylic acid diethyl ester to selective hydrolysis; amidating with p-fluoro aniline to obtain a compound shown in a formula 4; hydrolyzing and amidating with 4-amino-2-fluorophenol to obtain a compound shown in a formula 6; conducting substitution on 4-chloro-6-methoxy-7-quinolinol and N-(3-chloropropyl) morpholine to obtain a compound shown in formula 8; conducting substitution on the compound in formula 6 and compound shown in the formula 8 to obtain a target product N-[3-fluoro-4-({6-(methyl oxy)-7-[(3-morpholine-4-yl phenyl)-oxy] quinoline-4-yl}oxy)phenyl]-N'-(4-fluorophenyl) cyclopropane-1,1-dicarboamide crude product. The crude product is re-crystallized in an ethanol / acetone solution to obtain a high purity product with an overall yield of 44-55%. The method has the advantages of easy and feasible process, easily available raw materials, high overall yield and good product quality, and is applicable to industrial production.

CRYSTALLINE FORMS OF N-[3-FLUORO-4-({6-(METHYLOXY)-7-[(3-MORPHOLIN-4-YLPROPYL)OXY]-QUIN0LIN-4-YL}OXY)PHENYL]-N'-(4-FLUOROPHENYL)CYCLOPROPANE-1, 1-DICARBOXAMIDE

This invention relates to three crystalline forms of N-[3-fluoro-4-((6-(methyloxy)- 7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl |oxy)phenyl]-N'-(4- fluorophenyl)cyclopropane-l.l-dicarboxamidc. Compound (I), designated as Form A, Form B, and Form C. The i

METHODS OF PREPARING QUINOLINE DERIVATIVES

A Method of preparing a compound of formula i(1) or a pharmaceutically acceptable salt thereof, wherein: R1 and R2 join together with the nitrogen atom to which they are attached form a 6 membered heterocycloalkyl X1 is H,

Preparation of a Quinolinyloxydiphenylcyclopropanedicarboxamide

The present invention relates to a process of preparing a compound of the following formula III: wherein R1-R4 are as defined herein. The present invention also relates to the preparation of intermediates used to prepare the compound

C-MET MODULATORS AND METHODS OF USE

The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate and/or modulate kinase receptor, particularly c-Met, KDR, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.