N-(5-(4-bromophenyl)-1H-pyrazol-3-yl)-2-chloronicotinamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(5-(4-bromophenyl)-1H-pyrazol-3-yl)-2-chloronicotinamide
• 英文别名: N-[5-(4-bromophenyl)-1H-pyrazol-3-yl]-2-chloropyridine-3-carboxamide
• 化学式: C₁₅H₁₀BrClN₄O
• 分子量: 377.628
• InChiKey: VBOODGJKJMKNBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氯烟酸 、 在 1-羟基苯并三唑 、 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 为溶剂， 以85%的产率得到N-(5-(4-bromophenyl)-1H-pyrazol-3-yl)-2-chloronicotinamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel 5-phenyl-1H-pyrazole derivatives as potential BRAFV600E inhibitors

  摘要：

  A series of novel 5-phenyl-1H-pyrazole derivatives (5a-5u) containing niacinamide moiety were synthesized and evaluated for biological activity as potential BRAF(V600E) inhibitors. Among them, compound 5h exhibited the most potent inhibitory activity with an IC50 value of 0.33 mu Mfor BRAF(V600E) . Antiproliferative assay results indicated that compound 5h has better antiproliferative activity against WM266.4 and A375 in vitro with IC50 value of 2.63 and 3.16 mu M, respectively, being comparable with the positive control vemurafenib. Molecular docking of 5h into the BRAF(V600E) active site was performed to determine the probable binding mode. Furthermore, molecular docking and 3D QSAR study by means of DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd) explored the binding modes and the structure and activity relationship (SAR) of these derivatives. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.08.029