Gefitinib

Base Information

• Chemical Name: Gefitinib
• CAS No.: 184475-35-2
• Molecular Formula: C22H24ClFN4O3
• Molecular Weight: 446.909
• Hs Code.: 29349990
• European Community (EC) Number: 643-034-7
• NSC Number: 759856,715055
• UNII: S65743JHBS
• DSSTox Substance ID: DTXSID8041034
• Nikkaji Number: J1.437.124I
• Wikipedia: Gefitinib
• Wikidata: Q417824
• NCI Thesaurus Code: C1855
• RXCUI: 328134
• Pharos Ligand ID: 8BUJWRVF2MJG
• Metabolomics Workbench ID: 42702
• ChEMBL ID: CHEMBL939
• Mol file: 184475-35-2.mol

Synonyms:gefitinib;Iressa;N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)-4-quinazolinamide;ZD 1839;ZD1839

Chemical Property of Gefitinib

Chemical Property:

• Appearance/Colour: light-yellow crystalline powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 119-120 °C
• Refractive Index: 1.621
• Boiling Point: 586.8 °C at 760 mmHg
• PKA: 7.00±0.10(Predicted)
• Flash Point: 308.7 °C
• PSA: 68.74000
• Density: 1.322 g/cm³
• LogP: 4.28650
• Storage Temp.: Store at RT
• Solubility.: Soluble in DMSO (up to 40 mg/ml) or in Ethanol (up to 4 mg/ml).
• XLogP3: 4.1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 8
• Exact Mass: 446.1520965
• Heavy Atom Count: 31
• Complexity: 545

Purity/Quality:

98%, ^*data from raw suppliers

Gefitinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4
• Recent ClinicalTrials: Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)
• Recent EU Clinical Trials: A Phase III, Randomized, Double-blind Study to Assess the Efficacy and Safety of Lazertinib versus Gefitinib as the First-line Treatment in Patients with Epidermal Growth Factor Receptor Sensitizing Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer
• Recent NIPH Clinical Trials: Phase II trial of induction gefitinib followed by cisplatin and docetaxel with concurrent radiotherapy in locally advanced non-small cell lung cancer with EGFR activating mutation
• Mechanism of Action: Gefitinib is a tyrosine kinase inhibitor used in targeted treatment for malignant conditions, particularly non-small cell lung cancer (NSCLC). It inhibits epidermal growth factor receptor (EGFR) signaling by binding to adenosine triphosphate (ATP) sites, leading to suppression of downstream signaling cascades that promote tumor cell proliferation.
• Therapeutic Use and Approval: Approved in several countries globally as second-line and third-line treatment for NSCLC. Often used as a first-line therapeutic strategy for NSCLC.
• Pharmacokinetics: Belongs to Biopharmaceutics Classification System class II.; Exhibits high hydrophobicity with a log P value of 4.15.; The daily administration dose is 250 mg, with an absorption rate of 44%.; Common adverse reactions include hepatobiliary disorders and gastrointestinal complications like diarrhea, nausea, and stomatitis.
• Combination Therapy and Nanoparticles: Used in combination with other therapeutic agents like natural compounds, small interfering RNA, and in photodynamic therapy to enhance efficacy.; Nanoparticles offer advantages such as site-specificity, surface charge, and high surface area, potentially improving gefitinib delivery and effectiveness.
• Clinical Trial Data: Gefitinib is well tolerated in patients with various tumor types. Demonstrates anti-proliferative and anti-tumoral activity, particularly in breast cancer (BC).; Some tumor types, like MDAMB-231 cells in triple-negative breast cancer (TNBC), show resistance to clinically relevant doses of gefitinib.
• Challenges and Limitations: Gefitinib has low solubility, delayed absorption, and low bioavailability, leading to significant side effects. Its therapeutic application is limited due to unavoidable side effects and the availability of alternative treatments for lung cancer.
• Future Directions: Understanding cellular targets of gefitinib can aid in predicting outcomes and overcoming resistance in certain tumor types, such as TNBC.

Technology Process of Gefitinib

There total 85 articles about Gefitinib 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: 99.0%

3-chloro-4-fluorophenylamine (367-21-5) + 4-chloro-7-methoxy-6-(3-morpholinopropoxy)quinazoline (199327-59-8) → gefitinib (184475-35-2)

Guidance literature:

With potassium hydroxide; In isopropyl alcohol; at 20 ℃;

Reference yield: 92.46%

3-chloro-4-fluorophenylamine (367-21-5) + 4-iodo-7-methoxy-6-[3-(4- morpholinyl)propoxy]quinazoline → gefitinib (184475-35-2)

Guidance literature:

In isopropyl alcohol; Reflux;

Reference yield: 92.06%

3-chloro-4-fluorophenylamine (367-21-5) + 4-bromo-7-methoxy-6-[3-(4- morpholinyl)propoxy]quinazoline → gefitinib (184475-35-2)

Guidance literature:

In isopropyl alcohol; Reflux;

upstream raw materials:

3-chloro-4-fluorophenylamine

4-chloro-7-methoxy-6-(3-morpholinopropoxy)quinazoline

4-(3-chloropropyl)morpholine

4-(3-chloro-4-fluorophenylamino)-6-hydroxy-7-methoxyquinazoline

Downstream raw materials:

7-methoxy-6-(3-morpholinopropoxy)-3,4-dihydroquinazolin-4-one

thyl 2-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)acetate

trifluoro-methanesulfonic acid 4-(3-chloro-4-fluoro-phenylamino)-6-(3-morpholin-4-yl-propoxy)-quinazolin-7-yl ester

Refernces

• 1、 Ming, Dong Li,You, Guang Zheng,Ji, Min. "Synthesis of gefitinib from methyl 3-hydroxy-4-methoxy-benzoate". . p. 673 - 678. Retrieved 2007.
• 2、 Wang, Ji-Quan,Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Zheng, Qi-Huang. "Synthesis of [11C]Iressa as a new potential PET cancer imaging agent for epidermal growth factor receptor tyrosine kinase". . p. 4102 - 4106. Retrieved 2006.
• 3、 Sequeira, André,Louren?o, Ana,Ferreira, Luísa Maria,Branco, Paula Sério,Mendes, Zita,Louren?o, Nuno M. T.,Figueiredo, Margarida,Carvalho, Luísa C. R.. "A Different Approach to the EGFR Inhibitor Gefitinib Involving Solid-Phase Synthesis". . p. 1346 - 1350. Retrieved 2018.
• 4、 -. "Synthesis of gefitinib". Paragraph 0021-0026. . Retrieved 2021/09/29.
• 5、 -. "Purification process of gefitinib". Paragraph 0038; 0045-0085. . Retrieved 2020/08/25.