Modification,Biological Evaluation and 3D QSAR Studies of Novel 2-(1,3-Diaryl-4,5-Dihydro-1 H-Pyrazol-5-yl)Phenol Derivatives as Inhibitors of B-Raf Kinase
A series of novel 2-(1,3-diaryl-4,5-dihydro-1H-pyrazol-5-yl)phenol derivatives(C1-C24)have been synthesized.The B-Raf inhibitory activity and anti-proliferation activity of these compounds have been tested.Compound C6 displayed the most potent biological activity against B-RafV600E(IC50=0.15 μM)and WM266.4 human melanoma cell line(GI50 = 1.75 μM),being comparable with the positive control(Vemurafenib and Erlotinib)and more potent than our previous best compounds.The docking simulation was performed to analyze the probable binding models and poses while the QSAR model was built to check the previous work as well as to introduce new directions.This work aimed at seeking more potent inhibitors as well as discussing some previous findings.As a result,the introduction of ortho-hydroxyl group on 4,5-dihydro-1H-pyrazole skeleton did reinforce the anti-tumor activity while enlarging the group on N-1 of pyrazoline was also helpful.
Yu-Shun Yang Fei Zhang Dan-Jie Tang Yong-Hua Yang Hai-Liang Zhu
State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing,P.R.China;Institute State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing,P.R.China
国内会议
大连
英文
543-552
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）