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

Description

Different sources of media describe the Description of 849217-64-7 differently. You can refer to the following data:
1. Foretinib (GSK1363089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met and KDR with IC50 of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit, PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR. Phase 2.
2. Foretinib is a multikinase inhibitor that targets MET and VEGFR2 and also exhibits an inhibitory effect against KIT, Flt-3, PDGFRb, and Tie-2.

Uses

Foretinib (GSK1363089) is an ATP-competitive inhibitor of hepatocyte growth factor (HGF) and Vascular endothelial growth factor (VEGF) Receptor Tyrosine Kinases.

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

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.

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,