(5-(4-bromophenyl)-3-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2-chloro-6-methylpyridin-3-yl)methanone | 1381883-59-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (5-(4-bromophenyl)-3-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2-chloro-6-methylpyridin-3-yl)methanone
• 英文别名: (5-(4-bromophenyl)-3-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2-chloro-6-methyl-3-pyridyl)methanone；[3-(4-Bromophenyl)-5-(4-chlorophenyl)-3,4-dihydropyrazol-2-yl]-(2-chloro-6-methylpyridin-3-yl)methanone
• CAS: 1381883-59-5
• 化学式: C₂₂H₁₆BrCl₂N₃O
• 分子量: 489.199
• InChiKey: PZVRAGAZWNCMMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-(4-溴苯基)-1-(4-氯苯基)-2-丙烯-1-酮 在 1-羟基苯并三唑 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 16.0h， 生成 (5-(4-bromophenyl)-3-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2-chloro-6-methylpyridin-3-yl)methanone
  参考文献：
  名称：

  Synthesis, biological evaluation and 3D-QSAR studies of novel 4,5-dihydro-1H-pyrazole niacinamide derivatives as BRAF inhibitors

  摘要：

  A series of novel 4,5-dihydropyrazole derivatives containing niacinamide moiety as potential V600E mutant BRAF kinase (BRAF(V600E)) inhibitors were designed and synthesized. Results of the bioassays against BRAF(V600E) and WM266.4 human melanoma cell line showed several compounds to be endowed potent activities with IC50 and GI(50) value in low micromolar range, among which compound 27e, (5-(4-Chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)6-methylpyridin-3-yl methanone (IC50 = 0.20 mu M, GI(50) = 0.89 mu M) was bearing the best bioactivity comparable with the positive control Sorafenib. Docking simulation was performed to determine the probable binding model and 3D-QSAR model was built to provide more pharmacophore understanding that could use to design new agents with more potent BRAF(V600E) inhibitory activity. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2012.04.047

文献信息

• Synthesis, biological evaluation and 3D-QSAR studies of novel 4,5-dihydro-1H-pyrazole niacinamide derivatives as BRAF inhibitors
  作者：Cui-Yun Li、Qing-Shan Li、Li Yan、Xiao-Guang Sun、Ran Wei、Hai-Bin Gong、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2012.04.047

  日期：2012.6

  A series of novel 4,5-dihydropyrazole derivatives containing niacinamide moiety as potential V600E mutant BRAF kinase (BRAF(V600E)) inhibitors were designed and synthesized. Results of the bioassays against BRAF(V600E) and WM266.4 human melanoma cell line showed several compounds to be endowed potent activities with IC50 and GI(50) value in low micromolar range, among which compound 27e, (5-(4-Chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)6-methylpyridin-3-yl methanone (IC50 = 0.20 mu M, GI(50) = 0.89 mu M) was bearing the best bioactivity comparable with the positive control Sorafenib. Docking simulation was performed to determine the probable binding model and 3D-QSAR model was built to provide more pharmacophore understanding that could use to design new agents with more potent BRAF(V600E) inhibitory activity. (C) 2012 Published by Elsevier Ltd.