Design,synthesis and biological evaluation of(1,3-diphenyl-1H-pyrazol-4-yl)methyl benzoate derivatives as potential BRAF V600E inhibitors

摘要：

　　A series of ”1,3-diphenyl-1H-pyrazol-4-yl)methyl benzoate derivatives(6a-10d)were designed,synthesized and evaluated as BRAFV600E inhibitors.Biological evaluation assays indicated that compound 10a showed the most potent inhibitory activity against A375.WM266.4 and BRAFV600E in vitro with IC50 values of 1.36 μM.0.94 μM and 0.11 μM respectively compared with the positive compound vemurafenib Furthermore,compound 10a showed highly selective BRAFV600E inhibitory activity in vitro.A docking simulation displayed that compound 10a could tightly bind the crystal structure of BRAFV600E at the active site.3D-QSAR would provide a guideline to design and optimize more potent and positive BRAFV600E inhibitors based on the(1,3-diphenyl-1H-pyrazol-4-yl)methyl benzoate derivatives skeleton.

作者: Ya-Juan Qin Man Xing Ya-Liang Zhang Jigar A.Makawana Ai-Qin Jiang Hai-Liang Zhu

作者单位: State Key Laboratory of Pharmaceutical Biotechnology,School of Life Science,Nanjing University,Nanji School of Medicine,Nanjing University,Nanjing,210093,P.R.China

会议类型: 国内会议

会议名称: 第八届国际分子模拟与信息技术应用学术会议

会议地点: 大连

会议语种:英文

页码: 183-192

在线出版日期: 2016-09-24（万方平台首次上网日期，不代表论文的发表时间）