COA of Formula: C6H13NOIn 2019 ,《An exploration of solvent-front region high affinity moiety leading to novel potent ALK & ROS1 dual inhibitors with mutant-combating effects》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Lei, Hongrui; Jia, Fang; Cao, Meng; Wang, Jie; Guo, Ming; Zhu, Minglin; Zuo, Daiying; Zhai, Xin. The article conveys some information:
The pyrimidine-2,4-diamine analogs exerted excellent activities in down-regulation of ALK phosphorylation. However, the prevalent drug-resistant site-mutation has gradually prevented the agents from being widely used. Herein, we conducted an exploration of high affinity moiety that bound to the solvent-front region (G1202R located) within the ATP binding site of ALK leading to the synthesis of thirty-five pyrimidine-2,4-diamine derivatives Among these compounds, urea group was extensively derivatized which finally resulted in the identification of the ‘semi-free urea’ compound 39. All compounds were assayed cytotoxicity and enzymic activities and 39 turned out to be the most potent one with IC50 values of 2.1, 0.91, 4.3 and 0.73 nM towards ALKwt, ALKL1196M, ALKG1202R and ROS1, resp. The performances of 39 on ALK- & ROS1-dependent cell lines were in good accordance with enzymic activities with IC50 values below 0.06μM. Besides, 39 induced cell apoptosis in a dose-dependent manner in H2228 cells. Finally, the binding models of 39 with ALKwt, ROS1, ALKL1196M and ALKG1202R were ideally established which further clearly elucidated their mode of action within the active site. In the experimental materials used by the author, we found trans-4-Aminocyclohexanol(cas: 27489-62-9COA of Formula: C6H13NO)
trans-4-Aminocyclohexanol(cas: 27489-62-9) belongs to anime. Primary amines having a tertiary alkyl group (R3CNH2) are difficult to prepare with most methods but are made industrially by the Ritter reaction. In this method a tertiary alcohol reacts with hydrogen cyanide (HCN) in the presence of a concentrated strong acid; a formamide, RNH―CHO, is formed first, which then undergoes hydrolysis.COA of Formula: C6H13NO
Referemce:
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