Lapatinib

Base Information

• Chemical Name: Lapatinib
• CAS No.: 231277-92-2
• Molecular Formula: C29H26ClFN4O4S
• Molecular Weight: 581.067
• Hs Code.: 29349990
• European Community (EC) Number: 642-915-3,878-720-7
• NSC Number: 745750
• UNII: 0VUA21238F
• DSSTox Substance ID: DTXSID7046675
• Nikkaji Number: J1.859.987B
• Wikipedia: Lapatinib
• Wikidata: Q420323
• NCI Thesaurus Code: C26653
• RXCUI: 480167
• Pharos Ligand ID: 3GTG4JMBXQKW
• Metabolomics Workbench ID: 43465
• ChEMBL ID: CHEMBL554
• Mol file: 231277-92-2.mol

Synonyms:GW 282974X;GW 572016;GW-282974X;GW-572016;GW282974X;GW572016;lapatinib;lapatinib ditosylate;N-(3-chloro-4-(((3-fluorobenzyl)oxy)phenyl)-6-(5-(((2-methylsulfonyl)ethyl)amino)methyl) -2-furyl)-4-quinazolinamine;Tykerb

Chemical Property of Lapatinib

Chemical Property:

• Appearance/Colour: Powder
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.645
• Boiling Point: 750.7 °C at 760 mmHg
• PKA: 6.34±0.19(Predicted)
• Flash Point: 407.8 °C
• PSA: 114.73000
• Density: 1.381 g/cm³
• LogP: 7.68380
• Storage Temp.: 2-8°C(protect from light)
• Solubility.: Soluble in DMSO (up to 200 mg/ml)
• XLogP3: 5.1
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 11
• Exact Mass: 580.1347324
• Heavy Atom Count: 40
• Complexity: 898

Purity/Quality:

99% ^*data from raw suppliers

N-(3-Chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)furan-2-yl)quinazolin-4-amine 98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,F
• Hazard Codes: T,F

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CS(=O)(=O)CCNCC1=CC=C(O1)C2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl
• Recent ClinicalTrials: LOGiC - Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer: A Phase III Global, Blinded Study Designed to Evaluate Clinical Endpoints and Safety of Chemotherapy Plus Lapatinib
• Recent EU Clinical Trials: The ROME trial from histology to target: the road to personalize target therapy and immunotherapy
• Recent NIPH Clinical Trials: DS-8201a in Pre-treated HER2 Breast Cancer That Cannot be Surgically Removed or Has Spread [DESTINY-Breast02]
• General Description: Lapatinib, also known as GW572016, is a 4-anilinoquinazoline derivative originally developed as an EGFR inhibitor for cancer treatment but has shown potential for repurposing in neglected tropical diseases, such as human African trypanosomiasis (HAT). Its scaffold has been utilized to develop potent inhibitors of *Trypanosoma brucei*, demonstrating low micromolar activity and serving as a foundation for further optimization to enhance pharmacokinetic properties and efficacy against HAT.

Technology Process of Lapatinib

There total 71 articles about Lapatinib which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) + 5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde (231278-84-5) → lapatanib (231277-92-2)

Guidance literature:

2-(methylsulfonyl)ethylamine hydrochloride; With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20 ℃; for 0.333333h;

5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde; With acetic acid; In tetrahydrofuran; at 40 ℃; for 2h;

With sodium tris(acetoxy)borohydride; In tetrahydrofuran; at 25 - 40 ℃; for 3h; Concentration;

Reference yield: 97.0%

C27H19ClFN3O3 + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → lapatanib (231277-92-2)

Guidance literature:

With triethylamine; In dichloromethane; at 25 - 30 ℃; Inert atmosphere;

Reference yield: 90.3%

formaldehyd (50-00-0,30525-89-4,61233-19-0) + 6-(furan-2-yl)-4-[3-chloro-4-(3-fluorobenzyloxy)phenyl]aminoquinazoline + 2-(methylsulfonyl)ethylamine hydrochloride (104458-24-4) → lapatanib (231277-92-2)

Guidance literature:

In tetrahydrofuran; at 35 - 40 ℃; for 4h;

upstream raw materials:

2-Methanesulfonyl-ethylamine

5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-carbaldehyde

3-chloro-4-(3-fluorobenzyloxy)nitrobenzene

4-chloro-6-iodoquinazoline

Downstream raw materials:

lapatinib ditosylate

lapatinib monobesylate

C₂₉H₂₆ClFN₄O₅S

Refernces

Kinase scaffold repurposing for neglected disease drug discovery: Discovery of an efficacious, lapatanib-derived lead compound for trypanosomiasis

10.1021/jm400349k

This research presents the repurposing of kinase scaffolds for the discovery of new drugs to combat neglected tropical diseases, specifically focusing on human African trypanosomiasis (HAT), a disease caused by the protozoan parasite Trypanosoma brucei. The study aims to expedite drug discovery by utilizing chemical scaffolds from drugs approved for other indications, demonstrating the potential of lapatinib and canertinib, two 4-anilinoquinazolines with low micromolar EC50 values against T. brucei. The researchers synthesized and tested several potent 4-anilinoquinazolines, leading to the identification of NEU617 (23a), a highly potent and orally bioavailable inhibitor of trypanosome replication. The compound 23a was found to block kinetoplast duplication and arrest cytokinesis in trypanosomes, offering a new chemical tool for studying the regulation of the trypanosome cell cycle. The study concludes that compounds based on established human EGFR inhibitor chemotypes can be effective against HAT and that further optimization of these chemotypes is necessary to improve their pharmacokinetic properties and effectiveness in treating HAT. The chemicals used in the process include a series of 4-anilinoquinazoline derivatives, with lapatinib (GW572016, 1) and canertinib (CI-1033) as the starting points for optimization.