10347. Bosutinib

Nomenclature

CAS number: 380843-75-4
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile; 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile; SKI-606; WAY-173606.
C26H29Cl2N5O3; mol wt 530.45.
C 58.87%, H 5.51%, Cl 13.37%, N 13.20%, O 9.05%.

Description and references

Tyrosine kinase inhibitor with dual activity against Src and Abl kinases. Prepn: A. Wissner et al., WO 9843960; eidem, US 6002008 (1998, 1999 both to American Cyanamid). Structure-activity relationship: D. H. Boschelli et al., J. Med. Chem. 44, 3965 (2001) DOI PubMed. Improved synthesis: eidem, ibid. 47, 1599 (2004) DOI PubMed. Protonation constants and characterization of micro-speciation: K. J. Box et al, J. Pharm. Biomed. Anal. 47, 303 (2008) DOI PubMed. In vitro and in vivo evaluation in imatinib-resistant chronic myelogenous leukemia models: M. Puttini et al., Cancer Res. 66, 11314 (2006) DOI PubMed. In vitro and in vivo inhibition of Src-mediated signaling pathways in breast cancer models: H. Jallal et al., ibid. 67, 1580 (2007) DOI PubMed.

Chemical structure

Properties

Light pink solid from diethyl ether, mp 116-120°. Protonation constants (log K): 11.2, 7.92, 4.75, 3.79.

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Tyrosine Kinase Inhibitors