1437869-77-6Relevant articles and documents
Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53-MDM2 interaction. Part 2
Wang, Weisi,Lv, Dan,Qiu, Ni,Zhang, Lei,Hu, Chunqi,Hu, Yongzhou
, p. 2886 - 2894 (2013/06/27)
Five series of novel 3,4,5-trisubstituted aminothiophene derivatives and analogs were designed and synthesized based on our previous studies. All target compounds were evaluated for their p53-MDM2 binding inhibitory activities and anti-proliferation activities against A549 and PC3 tumor cell lines. Twelve compounds displayed comparable p53-MDM2 binding inhibitory activities to that of Nutlin-3. Among them, compound 7a exhibited marked binding affinity (IC 50 = 0.086 μM). In addition, most target compounds showed potent anti-proliferation activities with IC50 values at low micromolar level. A good selective profile for wild-type p53 expression cell line was also observed. Molecular docking analysis was performed as well to predict possible binding modes of target compounds with MDM2.