5-(4-bromophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole | 202827-81-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(4-bromophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole
• CAS: 202827-81-4
• 化学式: C₁₆H₁₅BrN₂O
• 分子量: 331.212
• InChiKey: RSTOPUSHOIJVHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  33.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氯烟酸 、 5-(4-bromophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole 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， 反应 8.0h， 以75%的产率得到(5-(4-bromophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-1-pyrazolyl)(2-chloro-3-pyridyl)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
• 作为产物：
  描述：

  4-bromo-4'-methoxychalcone 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 5-(4-bromophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole
  参考文献：
  名称：

  新型吡唑类抗黑色素瘤药物的发现和药效团研究

  摘要：

  由于发病率不断上升且缺乏有效的治疗方法，恶性黑色素瘤是最危险的皮肤癌形式，因此迫切需要新的治疗策略。最近的几项进展表明，V600E 突变体 BRAF（BRAFV600E）是抗黑色素瘤药物开发的有效靶点。基于计算机筛选结果，设计、合成了一系列新型吡唑衍生物，并在体外评估了它们对 BRAFV600E 黑色素瘤细胞的抑制活性。化合物 3d 表现出最有效的抑制活性，对 BRAFV600E 的 IC50 值为 0.63 μM，对突变型 BRAF 依赖性细胞的 GI50 值为 0.61 μM。此外，QSAR 建模和抑制剂类似物的对接模拟为进一步的结构优化提供了重要的药效团线索。

  DOI：

  10.1002/cbdv.201400143

文献信息

• Identification of novel 3,5-diarylpyrazoline derivatives containing salicylamide moiety as potential anti-melanoma agents
  作者：Qing-Shan Li、Xian-Hai Lv、Yan-Bin Zhang、Jing-Jun Dong、Wen-Ping Zhou、Yang Yang、Hai-Liang Zhu

  DOI：10.1016/j.bmcl.2012.09.004

  日期：2012.11

  There is an accumulating body of experimental evidences validating oncogenic BRAF(V600E) as a therapeutic target and offering opportunities for anti-melanoma drug development. Encouraged by the positive results of pyrazole derivatives as BRAF(V600E) inhibitors, we sought to design diverse novel potential BRAF(V600E) inhibitors as antitumor agents based on pyrazole skeleton. In silico and in vitro screening of our designed pyrazole derivatives has identified Hit 1 as BRAF(V600E) inhibitor. Based on its structure and through further structure modification, compound 25, which exhibited the most potent inhibitory activity with an IC50 value of 0.16 mu M for BRAF(V600E) and GI(50) value of 0.24 mu M for mutant BRAF-dependent melanoma cells, was obtained. The 3D-QSAR models and the molecular docking simulation were introduced to analyze the structure-activity relationship. (C) 2012 Elsevier Ltd. All rights reserved.