Yi, Yuanyuan; Wang, Luhong; Zhao, Dan; Huang, Shanshan; Wang, Changyuan; Liu, Zhihao; Sun, Huijun; Liu, Kexin; Ma, Xiaodong; Li, Yanxia published an article in 2018, the title of the article was Structural optimization of diphenylpyrimidine scaffold as potent and selective epidermal growth factor receptor inhibitors against L858R/T790M resistance mutation in non-small cell lung cancer.HPLC of Formula: 16230-24-3 And the article contains the following content:
A new class of thiodiphenylpyrimidine analogs (Thio-DPPY) were synthesized as potent and selective EGFR T790M inhibitors to overcome gefitinib resistance in non-small cell lung cancer (NSCLC). This structural optimization led to the identification of two potent EGFRT790M/L858R inhibitors, 14a (N-[3-[[5-chloro-2-[4-((1-morpholino)propylthio)phenylamino]-4-pyrimidinyl]amino]phenyl]-2-propenamide) and 14e (N-[3-[[5-chloro-2-[4-((1-morpholino)ethanethioate)phenylamino]-4-pyrimidinyl]oxygen]phenyl]-2-propenamide), which possess IC50 values of 27.5 and 9.1 nM, resp. Moreover, compounds 14a (SI > 36.4) and 14e (SI > 109.9) exhibited high selectivity and low activity against the wild-type EGFR (IC50 > 1000 nM). In particular, compound 14a also displayed strong potency against EGFRT790M-mutated H1975 cells (IC50 = 0.074 μM), but weak activity toward normal cells HBE (IC50 > 40 μM) and LO-2 (IC50 = 9.891 μM). It is important that compound 14a (SI = 52.6) significantly improved the selectivity against mutant H1975 cells over wild-type A431 cells than rociletinib (SI = 6.0), thus revealing its slight cell cytotoxicity. This study provides a promising Thio-DPPY derivative as enhanced EGFR T790M inhibitor, and also revealed valuable clues for further optimization of DPPY scaffold to overcome NSCLC resistance. The experimental process involved the reaction of N-(3-Aminophenyl)acrylamide(cas: 16230-24-3).HPLC of Formula: 16230-24-3
The Article related to diphenylpyrimidine preparation egf receptor inhibitor mutation antitumor lung nsclc, egfr t790m, nsclc, inhibitors, pyrimidine, resistance, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.HPLC of Formula: 16230-24-3
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