1-(4-bromophenyl)-3-(2,3-di(furan-2-yl)quinoxalin-6-yl)urea | 1290058-79-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 1-(4-bromophenyl)-3-(2,3-di(furan-2-yl)quinoxalin-6-yl)urea
• 英文别名: 1-(2,3-difuranylquinoxalin-6-yl)-3-(4-bromophenyl)-urea；1-[2,3-Bis(furan-2-yl)quinoxalin-6-yl]-3-(4-bromophenyl)urea
• CAS: 1290058-79-5
• 化学式: C₂₃H₁₅BrN₄O₃
• 分子量: 475.301
• InChiKey: IZDJBLVUPVPPFN-UHFFFAOYSA-N

物化性质

• 沸点：
  505.0±50.0 °C(Predicted)
• 密度：
  1.569±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  93.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-硝基邻苯二胺 在 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 1-(4-bromophenyl)-3-(2,3-di(furan-2-yl)quinoxalin-6-yl)urea
  参考文献：
  名称：

  结构活性关系 (SAR) 研究确定了一种可调节 IKKβ 磷酸化用于胰腺癌治疗的喹喔啉尿素类似物

  摘要：

  遗传模型验证了核因子 (NF) κ B 激酶β (IKKβ) 抑制剂作为 KRAS 突变相关胰腺癌的治疗靶点。IKKβ中激活环丝氨酸残基（S 177，S 181）的磷酸化是驱动肿瘤坏死因子（TNF）α诱导的NF-κB介导的基因表达的关键事件。在这里，我们进行了结构活性关系 (SAR) 研究，以提高喹喔啉类似物 13-197 的效力和口服生物利用度，该类似物先前被报道为胰腺癌治疗的 NFκB 抑制剂。SAR 导致发现了一种新的喹喔啉尿素类似物84，它在剂量和时间依赖性研究中降低了 p-IKKβ 的水平。与 13–197 相比，模拟84对 TNFα 诱导的 NFκB 抑制作用强 2.5 倍，抑制胰腺癌细胞生长的作用强 4 倍。模拟84的暴露量增加了 4.3 倍（AUC 0-∞) 与 13-197 相比，导致口服生物利用度 (%F) 增加约 5.7 倍。重要的是，在异种移植模型中，单独口服84和与吉西他滨联合使用可降低

  DOI：

  10.1016/j.ejmech.2021.113579

文献信息

• CO₂-assisted synthesis of non-symmetric α-diketones directly from aldehydes<i>via</i>C–C bond formation
  作者：Pradipbhai Hirapara、Daniel Riemer、Nabanita Hazra、Jignesh Gajera、Markus Finger、Shoubhik Das

  DOI：10.1039/c7gc02425h

  日期：——

  CO2-assisted various symmetric and non-symmetric α-diketones have been synthesized directly from the corresponding aldehydes using transition metal-free catalysts. This method can even be applied to synthesize pharmaceuticals directly from aldehydes. The crucial role of CO2 has been investigated in detail and the mechanism is proposed on the basis of experiments and DFT calculations.

  已使用无过渡金属的催化剂直接从相应的醛中合成了CO 2辅助的各种对称和非对称α-二酮。该方法甚至可以直接用于从醛合成药物。详细研究了CO 2的关键作用，并在实验和DFT计算的基础上提出了机理。
• QUINOXALINE COMPOUNDS AND USES THEREOF
  申请人：Natarajan Amarnath

  公开号：US20130289041A1

  公开（公告）日：2013-10-31

  Disclosed herein are compounds of formula (I) and methods of inhibiting IKKβ and the NF-κB signaling and mTOR pathways.

  本文披露了式(I)化合物以及抑制IKKβ、NF-κB信号通路和mTOR途径的方法。
• Perturbing pro-survival proteins using quinoxaline derivatives: A structure–activity relationship study
  作者：Rajkumar Rajule、Vashti C. Bryant、Hernando Lopez、Xu Luo、Amarnath Natarajan

  DOI：10.1016/j.bmc.2012.02.022

  日期：2012.4

  In HeLa cells the combinatorial knockdown of Bcl-xL and Mcl-1 is sufficient to induce spontaneous apoptosis. Quinoxaline derivatives were screened for the induction of Mcl-1 dependent apoptosis using a cell line without functional Bcl-xL. Quinoxaline urea analog 1h was able to specifically induce apoptosis in an Mcl-1 dependent manner. We demonstrate that even small changes to 1h results in dramatic loss of activity. In addition, 1h and ABT-737 synergistically inhibit cell growth and induce apoptosis. Our results also suggest that 1h could have therapeutic potential against ABT-737 refractory cancer. (C) 2012 Elsevier Ltd. All rights reserved.
• 2,3-Substituted quinoxalin-6-amine analogs as antiproliferatives: A structure–activity relationship study
  作者：Qianyi Chen、Vashti C. Bryant、Hernando Lopez、David L. Kelly、Xu Luo、Amarnath Natarajan

  DOI：10.1016/j.bmcl.2011.02.055

  日期：2011.4

  The quinoxaline core is considered a privileged scaffold as it is found in a variety of biologically relevant molecules. Here we report the synthesis of a quinoxalin-6-amine library, screening against a panel of cancer cell lines and a structure-activity relationship (SAR). This resulted in the identification of a bisfuranylquinoxalineurea analog (7c) that has low micromolar potency against the panel of cancer cell lines. We also show that cells treated with quinoxalineurea 7c results in caspase 3/7 activation, PARP cleavage and Mcl-1 dependent apoptosis. (C) 2011 Elsevier Ltd. All rights reserved.
• Quinoxaline Compounds and Uses Thereof
  申请人：BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA

  公开号：US20210002258A1

  公开（公告）日：2021-01-07

  Provided herein are compounds having a structure of formula (I) and methods of using the disclosed compounds to inhibit IKKβ activity.