5-methyl-2-(4-nitro-1H-pyrazol-3-yl)-1H-benzo[d]imidazole | 1254229-49-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 5-methyl-2-(4-nitro-1H-pyrazol-3-yl)-1H-benzo[d]imidazole
• 英文别名: 6-methyl-2-(4-nitro-1H-pyrazol-5-yl)-1H-benzimidazole
• CAS: 1254229-49-6
• 化学式: C₁₁H₉N₅O₂
• 分子量: 243.225
• InChiKey: GRQRTQFXOWMEKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-methyl-2-(4-nitro-1H-pyrazol-3-yl)-1H-benzo[d]imidazole 在 5%-palladium/activated carbon 、 氢气 、 N,N-二异丙基乙胺 、 potassium iodide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 N-[4-(4-chloro-6-{[3-(5-methyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazol-4-yl]amino}pyrimidin-2-ylthio)phenyl]cyclopropanecarboxamide
  参考文献：
  名称：

  Design, synthesis, quantum chemical studies and biological activity evaluation of pyrazole–benzimidazole derivatives as potent Aurora A/B kinase inhibitors

  摘要：

  Novel pyrazole-benzimidazole derivatives have been designed and synthesized. The entire target compounds were determined against cancer cell lines U937, K562, A549, LoVo and HT29 and were screened for Aurora A/B kinase inhibitory activity in vitro. The compounds 7a, 7b, 7i, 7k and 7l demonstrated significant cancer cell lines and Aurora A/B kinase inhibitory activities. Molecular modeling studies suggested the derivatives have bound in the active site of Aurora A kinase through the formation of four hydrogen bonds. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity. The cellular activity of 7k was also tested by immunofluorescence. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.04.039
• 作为产物：
  描述：

  3,4-二硝基甲苯 在 5%-palladium/activated carbon 、 氢气 、 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 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 75.0h， 生成 5-methyl-2-(4-nitro-1H-pyrazol-3-yl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Design, synthesis, quantum chemical studies and biological activity evaluation of pyrazole–benzimidazole derivatives as potent Aurora A/B kinase inhibitors

  摘要：

  Novel pyrazole-benzimidazole derivatives have been designed and synthesized. The entire target compounds were determined against cancer cell lines U937, K562, A549, LoVo and HT29 and were screened for Aurora A/B kinase inhibitory activity in vitro. The compounds 7a, 7b, 7i, 7k and 7l demonstrated significant cancer cell lines and Aurora A/B kinase inhibitory activities. Molecular modeling studies suggested the derivatives have bound in the active site of Aurora A kinase through the formation of four hydrogen bonds. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity. The cellular activity of 7k was also tested by immunofluorescence. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.04.039

文献信息

• Discovery of 3-(1H-benzo[d]imidazole-2-yl)-1H-pyrazol-4 -amine derivatives as novel and potent syk inhibitors for the treatment of hematological malignancies
  作者：Bingbing Cui、Yong Wang、Zhipeng Zhao、Lu Fan、Yu Jiao、Hongmei Li、Jie Feng、Weifang Tang、Tao Lu、Yadong Chen

  DOI：10.1016/j.ejmech.2023.115597

  日期：2023.10

  cell receptor (BCR) signaling pathway. Abnormal activation of Syk is closely related to the occurrence and development of hematological malignancies. Therefore, Syk is a potential target for the treatment of various hematologic cancers. Starting from compound 6(Syk, IC50 = 15.8 μM), we performed fragment-based rational drug design for structural optimization based on the specific solvent-accessible region

  脾酪氨酸激酶（Syk）是一种重要的癌基因和信号转导介质，主要在造血细胞中表达。Syk 在B 细胞受体(BCR) 信号通路中发挥关键作用。Syk的异常激活与血液系统恶性肿瘤的发生、发展密切相关。因此，Syk是治疗多种血液癌症的潜在靶点。从化合物6（Syk，IC 50  = 15.8 μM）开始，我们根据Syk特定的溶剂可及区域、疏水区域和核糖区域进行了基于片段的合理药物设计，以进行结构优化。由此发现了一系列新型 3-(1H-苯并[ d ]咪唑-2-基)-1H-吡唑-4-胺 Syk 抑制剂，从而鉴定了19q ，这是一种高效 Syk 抑制剂，对 Syk 酶表现出优异的抑制活性 (IC 50  = 0.52 nM)，并对其他几种激酶表现出效力。此外，化合物19q可有效降低Romos细胞中下游PLCγ2水平的磷酸化。它还对多种血液肿瘤细胞表现出抗增殖活性。更令人高兴的是， 19q在 MV4-11 小鼠异种移植模型中以低剂量（1