1-cyanomethyl-5-fluoroindole-2-carboxylic acid ethyl ester | 796069-30-2

• 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: 1-cyanomethyl-5-fluoroindole-2-carboxylic acid ethyl ester
• 英文别名: Ethyl 1-cyanomethyl-5-fluoro-1H-indole-2-carboxylate；Ethyl 1-(cyanomethyl)-5-fluoro-1h-indole-2-carboxylate；ethyl 1-(cyanomethyl)-5-fluoroindole-2-carboxylate
• CAS: 796069-30-2
• 化学式: C₁₃H₁₁FN₂O₂
• 分子量: 246.241
• InChiKey: LXWLQBQGBYRRLR-UHFFFAOYSA-N

物化性质

• 沸点：
  413.1±35.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-cyanomethyl-5-fluoroindole-2-carboxylic acid ethyl ester 在 sodium tetrahydroborate 、 cobalt(II) chloride 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 4.75h， 生成
  参考文献：
  名称：

  Scaffold Hopping of Natural Product Evodiamine: Discovery of a Novel Antitumor Scaffold with Excellent Potency against Colon Cancer

  摘要：

  Inspired by the natural product evodiamine, a novel antitumor indolopyrazinoquinazolinone scaffold was designed by scaffold hopping. Structure-activity relationship studies led to the discovery of compound 15j, which shows low nanomolar inhibitory activity against the HCT116 cell line. Further antitumor mechanism studies indicated that compound 15j acted by the dual inhibition of topoisomerase 1 and tubulin and induced apoptosis with G2 cell-cycle arrest. The quaternary ammonium salt of compound 15j (compound 15js) exhibited excellent in vivo antitumor activity (TGI = 66.6%) in the HCT116 xenograft model with low toxicity. Indolopyrazinoquinazolinone derivatives represent promising multitargeting antitumor leads for the development of novel antitumor agents.

  DOI：

  10.1021/acs.jmedchem.9b01626
• 作为产物：
  描述：

  5-氟吲哚-2-甲酸 在 硫酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 12.5h， 生成 1-cyanomethyl-5-fluoroindole-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  Scaffold Hopping of Natural Product Evodiamine: Discovery of a Novel Antitumor Scaffold with Excellent Potency against Colon Cancer

  摘要：

  Inspired by the natural product evodiamine, a novel antitumor indolopyrazinoquinazolinone scaffold was designed by scaffold hopping. Structure-activity relationship studies led to the discovery of compound 15j, which shows low nanomolar inhibitory activity against the HCT116 cell line. Further antitumor mechanism studies indicated that compound 15j acted by the dual inhibition of topoisomerase 1 and tubulin and induced apoptosis with G2 cell-cycle arrest. The quaternary ammonium salt of compound 15j (compound 15js) exhibited excellent in vivo antitumor activity (TGI = 66.6%) in the HCT116 xenograft model with low toxicity. Indolopyrazinoquinazolinone derivatives represent promising multitargeting antitumor leads for the development of novel antitumor agents.

  DOI：

  10.1021/acs.jmedchem.9b01626

文献信息

• Heterocyclyl-substituted dihydroquinazolines and their use as antiviral agents
  申请人：Wunberg Tobias

  公开号：US20070185121A1

  公开（公告）日：2007-08-09

  The invention relates to heterocyclyl-substituted dihydroquinazolines of formula (I), to processes for their preparation, to medicaments containing them, and to methods for the treatment and/or prophylaxis of diseases, in particular, for use as anti-viral agents, in particular, against cytomegaloviruses.

  这项发明涉及公式（I）的杂环基取代的二氢喹唑啉，以及它们的制备方法、含有它们的药物，以及用于治疗和/或预防疾病的方法，特别是作为抗病毒剂，特别是针对巨细胞病毒。
• HETEROCYCLYL-SUBSTITUIERTE DIHYDROCHINAZOLINE UND IHRE VERWENDUNG ALS ANTIVIRALE MITTEL
  申请人：Bayer HealthCare AG

  公开号：EP1625129B1

  公开（公告）日：2008-03-05
• US8343981B2
  申请人：——

  公开号：US8343981B2

  公开（公告）日：2013-01-01
• Scaffold Hopping of Natural Product Evodiamine: Discovery of a Novel Antitumor Scaffold with Excellent Potency against Colon Cancer
  作者：Lei Wang、Kun Fang、Junfei Cheng、Yu Li、Yahui Huang、Shuqiang Chen、Guoqiang Dong、Shanchao Wu、Chunquan Sheng

  DOI：10.1021/acs.jmedchem.9b01626

  日期：2020.1.23

  Inspired by the natural product evodiamine, a novel antitumor indolopyrazinoquinazolinone scaffold was designed by scaffold hopping. Structure-activity relationship studies led to the discovery of compound 15j, which shows low nanomolar inhibitory activity against the HCT116 cell line. Further antitumor mechanism studies indicated that compound 15j acted by the dual inhibition of topoisomerase 1 and tubulin and induced apoptosis with G2 cell-cycle arrest. The quaternary ammonium salt of compound 15j (compound 15js) exhibited excellent in vivo antitumor activity (TGI = 66.6%) in the HCT116 xenograft model with low toxicity. Indolopyrazinoquinazolinone derivatives represent promising multitargeting antitumor leads for the development of novel antitumor agents.