51009-52-0Relevant academic research and scientific papers
Design, modification and 3D QSAR studies of novel 2,3-dihydrobenzo[b][1,4] dioxin-containing 4,5-dihydro-1H-pyrazole derivatives as inhibitors of B-Raf kinase
Yang, Yu-Shun,Li, Qing-Shan,Sun, Shuai,Zhang, Yan-Bin,Wang, Xiao-Liang,Zhang, Fei,Tang, Jian-Feng,Zhu, Hai-Liang
, p. 6048 - 6058 (2012/11/07)
Two series of novel 2,3-dihydrobenzo[b][1,4]dioxin-containing 4,5-dihydro-1H-pyrazole derivatives C1-C15 and D1-D15 have been synthesized and evaluated for their B-Raf inhibitory and anti-proliferation activities. Compound C14 ((3-(4-bromophenyl)-5-(2-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2,3- dihydrobenzo[b][1,4]dioxin-6-yl)methanone) showed the most potent biological activity against B-RafV600E (IC50 = 0.11 μM) and WM266.4 human melanoma cell line (GI50 = 0.58 μM), being comparable with the positive control Erlotinib and more potent than our previous best compound, while D10 ((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)(5-(3- fluorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)methanone) performed the best in the D series (IC50 = 1.70 μM; GI50 = 1.45 μM). The docking simulation was performed to analyze the probable binding models and poses and the QSAR model was built for reasonable design of B-Raf inhibitors in future. The introduction of 2,3-dihydrobenzo[b][1,4]dioxin structure reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity.
