Discovery of (R)-1-(3-(4-Amino-3-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one (CHMFL-EGFR-202) as a Novel Irreversible EGFR Mutant Kinase Inhibitor with a Distinct Binding Mode was written by Wang, Aoli;Li, Xixiang;Wu, Hong;Zou, Fengming;Yan, Xiao-E.;Chen, Cheng;Hu, Chen;Yu, Kailin;Wang, Wenchao;Zhao, Peng;Wu, Jiaxin;Qi, Ziping;Wang, Wei;Wang, Beilei;Wang, Li;Ren, Tao;Zhang, Shanchun;Yun, Cai-Hong;Liu, Jing;Liu, Qingsong. And the article was included in Journal of Medicinal Chemistry in 2017.Computed Properties of C11H21NO3 This article mentions the following:
On the basis of Ibrutinib’s core pharmacophore, which was moderately active to EGFR T790M mutant, we discovered novel epidermal growth factor receptor (EGFR) inhibitor compound 19 (CHMFL-EGFR-202), which potently inhibited EGFR primary mutants (L858R, del19) and drug-resistant mutant L858R/T790M. Compound 19 displayed a good selectivity profile among 468 kinases/mutants tested in the KINOMEscan assay (S score (1) = 0.02). In particular, it did not exhibit apparent activities against INSR and IGF1R kinases. The X-ray crystal structure revealed that this class of inhibitors formed a covalent bond with Cys797 in a distinct “DFG-in-C-helix-out” inactive EGFR conformation. Compound 19 displayed strong antiproliferative effects against EGFR mutant-driven nonsmall cell lung cancer (NSCLC) cell lines such as H1975, PC9, HCC827, and H3255 but not the wild-type EGFR expressing cells. In the H1975 and PC9 cell-inoculated xenograft mouse models, compound 19 exhibited dose-dependent tumor growth suppression efficacy without obvious toxicity. Compound 19 might be a potential drug candidate for EGFR mutant-driven NSCLC. In the experiment, the researchers used many compounds, for example, tert-Butyl (4-hydroxycyclohexyl)carbamate (cas: 224309-64-2Computed Properties of C11H21NO3).
tert-Butyl (4-hydroxycyclohexyl)carbamate (cas: 224309-64-2) belongs to alcohols. Because alcohols are easily synthesized and easily transformed into other compounds, they serve as important intermediates in organic synthesis. Tertiary alcohols cannot be oxidized at all without breaking carbon-carbon bonds, whereas primary alcohols can be oxidized to aldehydes or further oxidized to carboxylic acids.Computed Properties of C11H21NO3
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