The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity was written by Newton, Rebecca;Bowler, Katherine A.;Burns, Emily M.;Chapman, Philip J.;Fairweather, Emma E.;Fritzl, Samantha J. R.;Goldberg, Kristin M.;Hamilton, Niall M.;Holt, Sarah V.;Hopkins, Gemma V.;Jones, Stuart D.;Jordan, Allan M.;Lyons, Amanda J.;Nikki March, H.;McDonald, Neil Q.;Maguire, Laura A.;Mould, Daniel P.;Purkiss, Andrew G.;Small, Helen F.;Stowell, Alexandra I. J.;Thomson, Graeme J.;Waddell, Ian D.;Waszkowycz, Bohdan;Watson, Amanda J.;Ogilvie, Donald J.. And the article was included in European Journal of Medicinal Chemistry in 2016.Recommanded Product: 5-Amino-2,4-dichlorophenol This article mentions the following:
Deregulation of the receptor tyrosine kinase RET has been implicated in medullary thyroid cancer, a small percentage of lung adenocarcinomas, endocrine-resistant breast cancer and pancreatic cancer. There are several clin. approved multi-kinase inhibitors that target RET as a secondary pharmacol. but addnl. activities, most notably inhibition of KDR, lead to dose-limiting toxicities. There is, therefore, a clin. need for more specific RET kinase inhibitors. Herein we report our efforts towards identifying a potent and selective RET inhibitor using vandetanib 1 as the starting point for structure-based drug design. Phenolic anilinoquinazolines exemplified by 6 showed improved affinities towards RET but, unsurprisingly, suffered from high metabolic clearance. Efforts to mitigate the metabolic liability of the phenol led to the discovery that a flanking substituent not only improved the hepatocyte stability, but could also impart a significant gain in selectivity. This culminated in the identification of 36; a potent RET inhibitor with much improved selectivity against KDR. In the experiment, the researchers used many compounds, for example, 5-Amino-2,4-dichlorophenol (cas: 39489-79-7Recommanded Product: 5-Amino-2,4-dichlorophenol).
5-Amino-2,4-dichlorophenol (cas: 39489-79-7) belongs to organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. Aliphatic organochlorides are often alkylating agents as chlorine can act as a leaving group, which can result in cellular damage.Recommanded Product: 5-Amino-2,4-dichlorophenol
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