5367. Lapatinib

Nomenclature

CAS number: 231277-92-2
N-[3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[[[2-(methylsulfonyl)ethyl]amino]methyl]-2-furanyl]-4-quinazolinamine; GW-572016.
C29H26ClFN4O4S; mol wt 581.06.
C 59.94%, H 4.51%, Cl 6.10%, F 3.27%, N 9.64%, O 11.01%, S 5.52%.

Description and references

Reversible dual inhibitor of ErbB1 (EGFR) and ErbB2 (HER-2) tyrosine kinases. Prepn: M. C. Carter et al., WO 9935146 (1999 to Glaxo); eidem, US 6727256 (2004 to SmithKline Beecham). Mechanism of action study: W. Xia et al., Oncogene 21, 6255 (2002) DOI PubMed; and crystal structure of complex with epidermal growth factor receptor (EGFR, ErbB1): E. R. Wood et al., Cancer Res. 64, 6652 (2004) DOI PubMed. LC-MS/MS determn in plasma: F. Bai et al., J. Chromatogr. B 831, 169 (2006) DOI PubMed. Pharmacokinetics and clinical activity in metastatic carcinomas: H. A. Burris III et al., J. Clin. Oncol. 23, 5305 (2005) DOI PubMed. Clinical trial in combination with capecitabine in HER2-positive breast cancer: C. E. Geyer et al., N. Engl. J. Med. 355, 2733 (2006) DOI PubMed. Review of clinical experience: F. Montemurro et al., Expert Opin. Biol. Ther. 7, 257-268 (2007) DOI PubMed.

Chemical structure

Derivative

Ditoluenesulfonate monohydrate.

Nomenclature

CAS number: 388082-78-8; 388082-77-7 (anhydrous)
Lapatinib ditosylate; GW-572016F; Tykerb (GSK); Tycerb (GSK); Tyverb (GSK).
C29H26ClFN4O4S.2C7H8O3S.H2O; mol wt 943.48.
C 54.74%, H 4.70%, Cl 3.76%, F 2.01%, N 5.94%, O 18.65%, S 10.20%.

Properties

Yellow solid. Soly at 25° (mg/ml): 0.007 in water; 0.001 in 0.1N HCl.

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Tyrosine Kinase Inhibitors