Nan, Xiang published the artcileDesign, synthesis and biological evaluation of novel N-sulfonylamidine-based derivatives as c-Met inhibitors via Cu-catalyzed three-component reaction, Synthetic Route of 939-99-1, the publication is European Journal of Medicinal Chemistry (2020), 112470, database is CAplus and MEDLINE.
A series of new N-sulfonylamidine derivatives were designed, synthesized via Cu-catalyzed multicomponent reaction (MCR) as the key step, and evaluated for their in vitro biol. activities against c-Met kinase and four cancer cell lines (A549, HT-29, MKN-45 and MDA-MB-231). Most of the target compounds showed moderate to significant potency at enzyme and cell-based assay. The preliminary SAR studies demonstrated that compound I (c-Met IC50 = 2.89 nM) was the most promising compound compared with the pos. foretinib, which exhibited the remarkable antiproliferative activities, with IC50 values ranging from 0.28 to 0.72μM. Mechanistic studies of compound I showed the anticancer activity was closely related to the blocking phosphorylation of c-Met, leading to cell cycle arresting at G2/M phase and apoptosis of A549 cells by a concentration-dependent manner. The promising compound I was further identified as a relatively selective inhibitor of c-Met kinase, which also possessed an acceptable safety profile and favorable pharmacokinetic properties in BALB/c mouse. The favorable drug-likeness of I suggested that N-sulfonylamidines may be used as a promising scaffold for antitumor drug development. Addnl., the docking study and mol. dynamics simulations of I revealed a common mode of interaction with the binding site of c-Met. These pos. results indicated that I is a potential anti-cancer candidate for clin. trials, and deserves further development as a selective c-Met inhibitor.
European Journal of Medicinal Chemistry published new progress about 939-99-1. 939-99-1 belongs to chlorides-buliding-blocks, auxiliary class Fluoride,Chloride,Benzyl chloride,Benzene, name is 1-(Chloromethyl)-4-(trifluoromethyl)benzene, and the molecular formula is C8H6ClF3, Synthetic Route of 939-99-1.
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