In 2019,Journal of Medicinal Chemistry included an article by Engelhardt, Harald; Boese, Dietrich; Petronczki, Mark; Scharn, Dirk; Bader, Gerd; Baum, Anke; Bergner, Andreas; Chong, Eugene; Doebel, Sandra; Egger, Georg; Engelhardt, Christian; Ettmayer, Peter; Fuchs, Julian E.; Gerstberger, Thomas; Gonnella, Nina; Grimm, Andreas; Grondal, Elisabeth; Haddad, Nizar; Hopfgartner, Barbara; Kousek, Roland; Krawiec, Mariusz; Kriz, Monika; Lamarre, Lyne; Leung, Joyce; Mayer, Moriz; Patel, Nitinchandra D.; Simov, Biljana Peric; Reeves, Jonathan T.; Schnitzer, Renate; Schrenk, Andreas; Sharps, Bernadette; Solca, Flavio; Stadtmueller, Heinz; Tan, Zhulin; Wunberg, Tobias; Zoephel, Andreas; McConnell, Darryl B.. Recommanded Product: 89466-08-0. The article was titled 《Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors》. The information in the text is summarized as follows:
The epidermal growth factor receptor (EGFR), when carrying an activating mutation like del19 or L858R, acts as an oncogenic driver in a subset of lung tumors. While tumor responses to tyrosine kinase inhibitors (TKIs) are accompanied by marked tumor shrinkage, the response is usually not durable. Most patients relapse within two years of therapy often due to acquisition of an addnl. mutation in EGFR kinase domain that confers resistance to TKIs. Crucially, oncogenic EGFR harboring both resistance mutations, T790M and C797S, can no longer be inhibited by currently approved EGFR TKIs. Here, we describe the discovery of BI-4020, which is a noncovalent, wild-type EGFR sparing, macrocyclic TKI. BI-4020 potently inhibits the above-described EGFR variants and induces tumor regressions in a cross-resistant EGFRdel19 T790M C797S xenograft model. Key was the identification of a highly selective but moderately potent benzimidazole followed by complete rigidification of the mol. through macrocyclization. The experimental part of the paper was very detailed, including the reaction process of 2-Hydroxyphenylboronic acid(cas: 89466-08-0Recommanded Product: 89466-08-0)
2-Hydroxyphenylboronic acid(cas: 89466-08-0) belongs to acyl phenylboronic acid. Phenylboronic acid (PBA) has been used to extract β-blockers (a class of aminoalcohol-containing drugs) from aqueous solution, rat, and human plasma. Recommanded Product: 89466-08-0
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts