Chen, Hong; Li, Ridong; Ning, Xianling; Zhao, Xuyang; Jin, Yan; Yin, Yuxin published the artcile< Synthesis and anti-tumor efficacy of novel 2, 4-diarylaminopyrimidine derivatives bearing N-(3-pyridinylmethyl) urea moiety as anaplastic lymphoma kinase inhibitors>, Safety of Pyridin-4-ylmethanamine, the main research area is chloro amino pyrimidinylamino methoxyphenyl pyridinylmethyl urea preparation; antitumor activity anaplastic lymphoma kinase inhibition SAR docking cytotoxicity; ALK inhibitor; Anti-proliferation activity; NSCLC; Structure modification.
A series of novel 2,4-diarylaminopyrimidine derivatives I [R = 3,5-dimethoxyphenyl, 6-quinolyl, 3-methoxy-4-morpholino-Ph, etc.] possessing a unique N-(3-pyridinylmethyl)urea moiety as ALK inhibitors were synthesized. The most promising analog compound I [R = 3-methoxy-4-morpholino-phenyl] significantly inhibited proliferation of ALK pos. H3122 and Karpas-299 cells with IC50 values about 10 nM, which were comparable with pos. control LDK378. Compound I [R = 3-methoxy-4-morpholino-phenyl] suppressed phosphorylation of ALK and its downstream proteins and showed low cytotoxicity on normal human primary fibroblast cells (BJ cells). The binding mode of compound I [R = 3-methoxy-4-morpholino-phenyl] was proposed by docking simulation, which explains the important role of N-(3-pyridinylmethyl)urea moiety. Furthermore, compound I [R = 3-methoxy-4-morpholino-phenyl] exhibited favorable liver microsomal stability and significant efficacy in H3122 xenograft mice model. Interestingly, compound I [R = 3-methoxy-4-morpholino-phenyl] also showed broader anti-proliferative activity on other human tumor cell lines, which was different from other ALK inhibitors.
European Journal of Medicinal Chemistry published new progress about Amines Role: ADV (Adverse Effect, Including Toxicity), PAC (Pharmacological Activity), PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 3731-53-1 belongs to class pyridine-derivatives, and the molecular formula is C6H8N2, Safety of Pyridin-4-ylmethanamine.