17-Fluoro-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,15(20),16,18-heptaen-14-one | 1394329-65-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 17-Fluoro-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,15(20),16,18-heptaen-14-one
• 英文别名: 17-fluoro-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,15(20),16,18-heptaen-14-one
• CAS: 1394329-65-7
• 化学式: C₁₈H₁₄FN₃O
• 分子量: 307.327
• InChiKey: QBMNCJXJOVDTGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  48.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  17-Fluoro-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,15(20),16,18-heptaen-14-one 在 2-碘酰基苯甲酸 作用下， 以 二甲基亚砜 为溶剂， 以89.9%的产率得到3-fluoro-8,13-dihydroindolo[2',3':3,4]pyrido[2,1-b]quinazolin-5(7H)-one
  参考文献：
  名称：

  New Tricks for an Old Natural Product: Discovery of Highly Potent Evodiamine Derivatives as Novel Antitumor Agents by Systemic Structure–Activity Relationship Analysis and Biological Evaluations

  摘要：

  Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus. Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.

  DOI：

  10.1021/jm300605m
• 作为产物：
  描述：

  N-[2-(1H-吲哚-3-基)乙基]甲酰胺 在 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 17-Fluoro-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,15(20),16,18-heptaen-14-one
  参考文献：
  名称：

  生物活性指导的合成加速了吴茱萸碱衍生物作为强效杀虫剂候选者的发现

  摘要：

  害虫通过降低作物产量和损害其质量来威胁全球粮食安全。基于天然产物的分子设计和结构优化一直是创新农药以实现昆虫综合治理的最有效方法之一。为了继续我们先前对发现杀虫铅的研究，我们设计、合成了一系列吴茱萸碱衍生物，并对其杀虫活性进行了评估。生物测定结果表明，化合物Ian和Iao在 2.5 mg/L 时对Mythimna separata的杀虫活性分别为 90% 和 80%，优于吴茱萸碱（10%，10 mg/L）、苦参碱（45%，600 mg/L）。 L) 和鱼藤酮 (30% at 200 mg/L)。化合物Ian-Iap对小菜蛾的杀虫活性为 1.0 mg/L，远高于吴茱萸碱、苦参碱和鱼藤酮。化合物Ian在5.0 mg/L时对棉铃虫的杀虫活性为60% ，而吴茱萸碱、苦参碱和鱼藤酮的杀虫活性很差。通过钙成像实验对杀虫作用机制的研究表明，昆虫兰尼碱受体（RyRs）可能是Ian的潜在靶点。此外，分子对接

  DOI：

  10.1021/acs.jafc.1c08297

文献信息

• New Tricks for an Old Natural Product: Discovery of Highly Potent Evodiamine Derivatives as Novel Antitumor Agents by Systemic Structure–Activity Relationship Analysis and Biological Evaluations
  作者：Guoqiang Dong、Shengzheng Wang、Zhenyuan Miao、Jianzhong Yao、Yongqiang Zhang、Zizhao Guo、Wannian Zhang、Chunquan Sheng

  DOI：10.1021/jm300605m

  日期：2012.9.13

  Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus. Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.
• Bioactivity-Guided Synthesis Accelerates the Discovery of Evodiamine Derivatives as Potent Insecticide Candidates
  作者：Jingbo Liu、Yabing Shi、Zhicheng Tian、Fengyun Li、Zesheng Hao、Wen Wen、Li Zhang、Yuanhong Wang、Yuxin Li、Zhijin Fan

  DOI：10.1021/acs.jafc.1c08297

  日期：2022.4.27

  design and structural optimization have been one of the most effective ways to innovate pesticides for integrated insect management. To continue our previous studies on the discovery of insecticidal lead, a series of evodiamine derivatives were designed, synthesized, and evaluated for their insecticidal activities. The bioassay results demonstrated that compounds Ian and Iao exhibited 90 and 80% insecticidal

  害虫通过降低作物产量和损害其质量来威胁全球粮食安全。基于天然产物的分子设计和结构优化一直是创新农药以实现昆虫综合治理的最有效方法之一。为了继续我们先前对发现杀虫铅的研究，我们设计、合成了一系列吴茱萸碱衍生物，并对其杀虫活性进行了评估。生物测定结果表明，化合物Ian和Iao在 2.5 mg/L 时对Mythimna separata的杀虫活性分别为 90% 和 80%，优于吴茱萸碱（10%，10 mg/L）、苦参碱（45%，600 mg/L）。 L) 和鱼藤酮 (30% at 200 mg/L)。化合物Ian-Iap对小菜蛾的杀虫活性为 1.0 mg/L，远高于吴茱萸碱、苦参碱和鱼藤酮。化合物Ian在5.0 mg/L时对棉铃虫的杀虫活性为60% ，而吴茱萸碱、苦参碱和鱼藤酮的杀虫活性很差。通过钙成像实验对杀虫作用机制的研究表明，昆虫兰尼碱受体（RyRs）可能是Ian的潜在靶点。此外，分子对接