1005782-08-0Relevant academic research and scientific papers
Convergent and streamlined synthesis of 6-etherified imidazo[1,2-b] pyridazine-2-amine derivatives possessing VEGFR-2 kinase inhibitory activity
Ishimoto, Kazuhisa,Sawai, Yasuhiro,Fukuda, Naohiro,Nagata, Toshiaki,Ikemoto, Tomomi
, p. 8564 - 8571 (2013/09/12)
A convergent and streamlined synthesis of selective vascular endothelial growth factor receptor (VEGFR) 2 kinase inhibitors has been achieved using a synthetic strategy based on an SNAr reaction of 6-chloroimidazo[1,2- b]pyridazine with phenols in the final step. For the synthesis of 6-chloroimidazo[1,2-b]pyridazine, a one-pot reaction using 3-amino-6- chloropyridazine, cyclopropanecarboxamide, and bromoacetyl bromide was developed. The phenols were easily prepared by chemoselective acylation of 3-aminophenols with pyrazole carboxylic acids, and an efficient and high-yielding synthesis of N-ethylpyrazole was also developed. The S NAr reaction of 6-chloroimidazo[1,2-b]pyridazine with phenols in DMSO in the presence of cesium carbonate successfully proceeded at 100-110 C to give the target products in good yields. This new chromatography-free process will be not only useful for the further bulk supply of these compounds but also applicable to the synthesis of other compounds containing the 6-etherified imidazo[1,2-b]pyridazin-2-amine core.
FUSED HETEROCYCLIC DERIVATIVE AND USE THEREOF
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, (2009/06/27)
The present invention provides a fused heterocyclic derivative having a potent kinase inhibitory activity and use thereof. A compound represented by the formula (I): wherein each symbol is as defined in the specification, except a particular compound, or a salt thereof, and a pharmaceutical agent containing the compound or a prodrug thereof, which is a kinase (VEGFR, VEGFR2, PDGFR, Raf) inhibitor, an angiogenesis inhibitor, an agent for the prophylaxis or treatment of cancer, a cancer growth inhibitor or a cancer metastasis suppressor.
