Gefitinib

Iupac Name：N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

CAS No.: 184475-35-2

Molecular Weight：446.907

Introduction: Gefitinib was introduced in Japan as a daily oral monotherapy for the treatment ofinoperable or recurrent non-small cell lung cancers (NSCLC). This anilinoquinazolinederivative can be synthesized in 6 steps starting from 6,7-dimethoxyquinazolin-4(3H)-oneby successive monodemethylationlacetylation of the 6-hydroxy-group followed bychlorination and reaction with 3-chloro-4-fluoroaniline, finally deacetylation and alkylationwith 3-(4-morpholinyl)propylbromide complete the synthesis. Gefitinib reversibly inhibitsthe activity of the epidermal growth factor receptor tyrosine kinase (EGRF TK). Thisinhibits autophosphorylation of EGRF and blocks the cascade of intracellular events whichhave been implicated in the proliferation, survival and metastasis of cancer cells. Gefitinibdiplays good selectivity for the EGRF TK relative to other growth factors in humanumbilical endothelial cells. It is similarly selective relative to other kinases, for example cerB2.Data from two large phase II studies in patients with pretreated NSCLC have shownthat gefitinib induces a response rate approaching 20% in patients receiving the agent as a second line therapy and approximately 10% in those pretreated with more lines ofchemotherapy. Gefitinib has good bioavailability and is metabolized in the liver via thecytochrome P450 3A4 enzyme system with a mean elimination half life of 28 h. Gefitinibhas been generally well tolerated in cancer patients with predominant side effects beingacne-like skin-rash, diarrhea, nausea, vomiting and mild to moderate myelosuppression..