N-(4-chlorophenyl)-2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetamide

• 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: N-(4-chlorophenyl)-2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetamide
• 英文别名: N-(4-Chlorophenyl)-2-(3-methyl-2-oxo-1,2-dihydroquinoxalin-1-YL)acetamide；N-(4-chlorophenyl)-2-(3-methyl-2-oxoquinoxalin-1-yl)acetamide
• 化学式: C₁₇H₁₄ClN₃O₂
• mdl: MFCD14729758
• 分子量: 327.77
• InChiKey: BQEIOJGGRPELPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-吡啶甲醛 、 N-(4-chlorophenyl)-2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetamide 在 硫酸 、 溶剂黄146 作用下， 反应 2.0h， 以68%的产率得到(Z)-N-(4-chlorophenyl)-2-(2-oxo-3-(2-(pyridin-4-yl)vinyl)quinoxalin-1(2H)-yl)acetamide
  参考文献：
  名称：

  Quinoxalinone (Part II). Discovery of (Z)-3-(2-(pyridin-4-yl)vinyl)quinoxalinone derivates as potent VEGFR-2 kinase inhibitors

  摘要：

  Inhibition of VEGFR-2 kinase has been highlighted as one of the well-defined strategies to suppress tumor growth via blockade of angiogenesis. Guided by the principles of bioisosteric replacement and pharmacophoric fragment migration, a series of novel quinoxalinone derivates were designed, synthesized and evaluated for their VEGFR-2 inhibitory potencies. Among them, compounds 7c, 8b, 8c, 8e and 10b displayed antiangiogenic abilities via the in vitro tube formation assay (cellular level) and ex vivo rat aortic ring assay (tissue level) at a low concentration (0.1 mu M). By means of in vivo zebrafish embryo model, two (Z)-3-(2-(pyridin-4-yl)vinyl)quinoxalinone derivates 8c and 8e showed significant antiangiogenesis effects, suggesting they have potentials to be developed into antiangiogenesis agents via further structural optimization. Moreover, these two compounds also demonstrated potent inhibition toward VEGFR-2 and B-raf kinases in a low concentration (1 mu M). A possible interpretation of our evaluation result has been presented by a molecular docking study by docking representative compound 8c with VEGFR-2. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.03.008
• 作为产物：
  描述：

  3-甲基-3-喹诺醇 在 N-甲基吗啉 、 potassium carbonate 、 potassium iodide 、 potassium hydroxide 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 乙醇 、 丙酮 为溶剂， 反应 15.5h， 生成 N-(4-chlorophenyl)-2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetamide
  参考文献：
  名称：

  3-(顺式)-乙烯芳基喹喔啉酮类似物、其制备方法和应用

  摘要：

  本发明公开了一种具有VEGFR‑2抑制活性的3‑顺式乙烯芳基喹喔啉酮类似物，其药学上可接受的盐，溶剂合物、其前药、其中间体、其代谢物或者是含有这种化合物为活性物质的药物组合物，其结构通式如式(I)、式(II)所示：其中，R1、R2和Ar中的每一个都如本文中所定义。本发明还阐述了它们的制备方法、它们作为药物的用途和它们在治疗肿瘤中的应用。本发明的化合物疗效确切，毒副作用小，丰富了现有技术中用于与VEGFR‑2表达异常所引起疾病治疗药物的抑制剂的种类，有望成为治疗指数较高的可用于临床的药物。

  公开号：

  CN105936631A

文献信息

• 3-(顺式)-乙烯芳基喹喔啉酮类似物、其制备方法和应用
  申请人：江苏神华药业有限公司

  公开号：CN105936631A

  公开（公告）日：2016-09-14

  本发明公开了一种具有VEGFR‑2抑制活性的3‑顺式乙烯芳基喹喔啉酮类似物，其药学上可接受的盐，溶剂合物、其前药、其中间体、其代谢物或者是含有这种化合物为活性物质的药物组合物，其结构通式如式(I)、式(II)所示：其中，R1、R2和Ar中的每一个都如本文中所定义。本发明还阐述了它们的制备方法、它们作为药物的用途和它们在治疗肿瘤中的应用。本发明的化合物疗效确切，毒副作用小，丰富了现有技术中用于与VEGFR‑2表达异常所引起疾病治疗药物的抑制剂的种类，有望成为治疗指数较高的可用于临床的药物。
• Quinoxalinone (Part II). Discovery of (Z)-3-(2-(pyridin-4-yl)vinyl)quinoxalinone derivates as potent VEGFR-2 kinase inhibitors
  作者：Leilei Shi、Jianfeng Zhou、Jifeng Wu、Junya Cao、Yuemao Shen、Hua Zhou、Xun Li

  DOI：10.1016/j.bmc.2016.03.008

  日期：2016.4

  Inhibition of VEGFR-2 kinase has been highlighted as one of the well-defined strategies to suppress tumor growth via blockade of angiogenesis. Guided by the principles of bioisosteric replacement and pharmacophoric fragment migration, a series of novel quinoxalinone derivates were designed, synthesized and evaluated for their VEGFR-2 inhibitory potencies. Among them, compounds 7c, 8b, 8c, 8e and 10b displayed antiangiogenic abilities via the in vitro tube formation assay (cellular level) and ex vivo rat aortic ring assay (tissue level) at a low concentration (0.1 mu M). By means of in vivo zebrafish embryo model, two (Z)-3-(2-(pyridin-4-yl)vinyl)quinoxalinone derivates 8c and 8e showed significant antiangiogenesis effects, suggesting they have potentials to be developed into antiangiogenesis agents via further structural optimization. Moreover, these two compounds also demonstrated potent inhibition toward VEGFR-2 and B-raf kinases in a low concentration (1 mu M). A possible interpretation of our evaluation result has been presented by a molecular docking study by docking representative compound 8c with VEGFR-2. (C) 2016 Elsevier Ltd. All rights reserved.