4379. Gefitinib

Nomenclature

CAS number: 184475-35-2
N-(3-Chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-4-quinazolinamine; 4-(3′-chloro-4′-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline; ZD-1839; Iressa (AstraZeneca).
C22H24ClFN4O3; mol wt 446.90.
C 59.13%, H 5.41%, Cl 7.93%, F 4.25%, N 12.54%, O 10.74%.

Description and references

Selective epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor which blocks signal transduction pathways implicated in the proliferation and survival of cancer cells. Prepn: K. H. Gibson, WO 9633980; idem, US 5770599 (1996, 1998 both to Zeneca). LC/MS/MS determn in biological samples: M. Zhao et al., J. Chromatogr. B 819, 73 (2005). Clinical pharmacokinetics and tolerability: H. Swaisland et al., Clin. Pharmacokinet. 40, 297 (2001). In vitro and in vivo inhibition of EGFR-expressing cancer lines: N. G. Anderson et al., Int. J. Cancer 94, 774 (2001). Proposed mechanism of action: A. Hirata et al., Cancer Res. 62, 2554 (2002). Clinical study in non-small cell lung cancer: M. G. Kris et al., J. Am. Med. Assoc. 290, 2149 (2003). Review: C. L. Arteaga, D. H. Johnson, Curr. Opin. Oncol. 13, 491-498 (2001). Review of clinical evaluations: D. Raben et al., Semin. Oncol. 29, Suppl. 4, 37-46 (2002); of use in non-small cell lung cancer: K. Tamura, M. Fukuoka, Expert Opin. Pharmacother. 6, 985-993 (2005).

Chemical structure

Properties

White powder. Crystals from toluene, mp 119-120°. pKa 5.4, 7.2. Freely sol in glacial acetic acid, DMSO; sol in pyridine; sparingly sol in tetrahydrofuran; slightly sol in methanol, ethanol (99.5%), ethyl acetate, propan-2-ol, and acetonitrile.

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Tyrosine Kinase Inhibitors