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

Foretinib (GSK1363089) is an ATP-competitive multikinase inhibitor that targets hepatocyte growth factor receptor (HGFR) and vascular endothelial growth factor receptor (VEGFR), with high specificity for Met and KDR, and moderate inhibitory effects against Ron, Flt-1/3/4, Kit, PDGFRα/β, and Tie-2. It is currently in Phase 2 of clinical development.

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

• 849217-50-1 N-[3-fluoro-4-[[7-hydroxy-6-methoxy-quinolin-4-yl]oxy]phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide 
• 57616-74-7 N-(3-chloropropyl)morpholine hydrochloride 
• 205448-32-4 4-chloro-6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinoline 
• 849217-58-9 N'-(3-fluoro-4-hydroxyphenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide 
• 479690-10-3 3-Fluoro-4-{[6-methoxy-7-(3-morpholinopropoxy)-4-quinolyl]oxy}-aniline 
• 849217-48-7 ((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid 
• 3697-66-3 1,1-cyclopropanedicarboxylic acid monoethyl ester 
• 1559-02-0 diethyl cyclopropane-1,1-dicarboxylate 
• 1245931-90-1 ethyl 1-(4-fluorophenylcarbamoyl)cyclopropanecarboxylate 
• 7357-67-7 4-(3-chloropropyl)morpholine 
• 205448-31-3 4-chloro-6-methoxy-7-hydroxyquinoline 
• 371-40-4 4-fluoroaniline 
• 168268-00-6 4-(benzyloxy)-3-fluoroaniline 
• 76243-24-8 1-(benzyloxy)-2-fluoro-4-nitrobenzene 

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.

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